Abstract: The use of meshes to repair incisional hernias has been shown to reduce the recurrence rate, though it may increase the risk of surgical site infection. This is one of the most feared and devastating complications of surgical abdominal wall repair. The aim of this work is to describe a new surgical technique that was used to treat two patients suffering from chronic prosthesis infection. Additionally, the outcome of this procedure will be analyzed in terms of its safety, subsequent site infection and recurrence prevention. Two case reports are presented. The procedure was based on a wide surgical excision of the infected prosthesis and the surrounding tissues, plus abdominal wall repair with biological prosthesis. Both patients experienced an uneventful postoperative course. Infection of the surgical site resolved following the procedure and, after a mean follow-up of 36 months, no recurrences of the incisional hernia had occurred. This unique surgical technique not only proved to be safe, but it also solved the chronic prosthesis infection through its use of radical excision, without any postoperative complications or recurrence. This technique confirmed that biological prostheses can be used safely and effectively for implantation in sites of infection.
Abstract: There is still some debate on whether hepatic resection or liver transplantation should be the initial treatment for hepatocellular carcinoma (HCC) in compensated cirrhosis. Clinical data and observed survivals of 150 transplantable patients (within Milan criteria) resected for HCC were reviewed and their predicted survival after listing for liver transplantation was calculated using a Markov model simulation. Differences between observed and predicted survival estimates were explored by standardized differences (d). The mean observed survival within 5 years after surgery was 45.35 months, and the predicted survival after listing was 49.18 months (d = 0.265). The largest gain in life-expectancy with liver transplantation would be obtained in patients with Model for End-stage Liver Disease (MELD) score >9 (d = 0.403); conversely, observed and predicted survivals were similar in HCV+ patients (d = -0.002) and in patients with MELD ≤9 (d = -0.057). For T1 tumors, the observed mean estimate of survival after hepatic resection was higher than that predicted by the simulation (d = -0.606). In conclusion, in HCV patients and in those with very well compensated cirrhosis, hepatic resection could lead to results similar to those of transplantation strategy for HCC within Milan criteria; HCC T1 patients are probably best served by resection as first-line therapy rather than listing for transplantation.
Abstract: Systemic inflammation markers, such as neutrophil-to-lymphocyte ratio (NLR), have recently emerged as the prognostic factors for recurrence of liver tumors.
Abstract: Although standard treatment typically consists of an early appendectomy, there has recently been an increase in the use of antibiotic therapy as primary treatment for acute appendicitis (AA). The aim of this analysis is to systematically evaluate the evidence available in relevant literature in order to compare the relative effectiveness of antibiotic therapy as a viable alternative to appendectomies in the treatment of AA.
Abstract: The simultaneous incremental increase in incidence of both obesity and hepatocellular carcinoma (HCC) will soon lead to more overweight and obese patients with cirrhosis needing surgery. At present, little is known about postoperative mortality and morbidity in such patients. This study investigated outcomes after hepatectomy in relation to obesity in a homogeneous cohort of patients with cirrhosis.
Abstract: The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation.
Abstract: Terlipressin plus albumin is first-line treatment for hepatorenal syndrome (HRS). Therapy lasts from a few days to two weeks, whereas the efficacy and safety of long-term administration remain unsettled.
Abstract: The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19. Histopathological and immunohistochemical features were therefore compared to recipient follow-up data. Thirty-four (45%) HCCs were completely OATP-, and 18 (24%) showed positivity for K7 and/or K19. We observed a significant inverse correlation between OATP and K7/19 expression (P < 0.001): all OATP+ cases were K7/19-, while all K7+ and/or K19+ cases were OATP-. Sixteen cases were negative for all antibodies. No correlation was found between histopathological features and immunohistochemistry. Twenty-five recipients experienced HCC recurrence, and ten died from neoplastic recurrence. Neither OATP nor keratin expressions were correlated with HCC recurrence, while OATP negativity significantly correlated with HCC-related death after recurrence (P = 0.036). In conclusion, HCCs show a progressive loss in OATP immunoreactivity that correlates with the gain of a biliary phenotype. Although further studies are required to define these findings better, our results support the idea that OATP could be used together with K7/19 to identify a phenotypical "spectrum" in HCC progression.
Abstract: The use of kidneys from expanded criteria donors (ECD) is an attractive strategy to enlarge the pool of organs available for transplantation. Considering the fact that ECD organs have a reduced nephron mass, they are preferentially allocated for dual-kidney transplantation (DKT). Authors have reported excellent results of DKT when pretransplant ECD organs are evaluated for histological scores. The aim of this study was to evaluate DKT donor and recipient characteristics for comparison with DKT posttransplant outcomes versus those of recipients of single-kidney transplantations from expanded criteria (edSKT) and ideal donors (idSKT). We analyzed the potential prognostic factors involved in DKT among a population derived from three transplant centers.
Abstract: Transarterial chemoembolization (TACE) is commonly used as a bridge therapy for patients awaiting liver transplantation (LT) and for downstaging patients initially not meeting the Milan criteria. The primary aim of this study was to analyze whether a difference exists between selective/superselective and lobar TACE in determining tumor necrosis by a pathological analysis of the whole lesion at the time of LT. The secondary aim was to investigate the relationship between the tumor size and the capacity of TACE to induce necrosis. Data were extracted from a prospective database of 67 consecutive patients who underwent LT for hepatocellular carcinoma and cirrhosis from 2003 to 2009 and were treated exclusively with TACE as a bridging (n = 53) or downstaging therapy (n = 14). We identified 122 nodules; 53.3% were treated with selective/superselective TACE. The mean histological necrosis level was 64.7%; complete tumor necrosis was obtained in 42.6% of the nodules. In comparison with lobar TACE, selective/superselective TACE led to significantly higher mean levels of necrosis (75.1% versus 52.8%, P = 0.002) and a higher rate of complete necrosis (53.8% versus 29.8%, P = 0.013). A significant direct relationship was observed between the tumor diameter and the mean tumor necrosis level (59.6% for lesions < 2 cm, 68.4% for lesions of 2.1-3 cm, and 76.2% for lesions > 3 cm). Histological necrosis was maximal for tumors > 3 cm: 91.8% after selective/superselective TACE and 66.5% after lobar procedures. Independent predictors of complete tumor necrosis were selective/superselective TACE (P = 0.049) and the treatment of single nodules (P = 0.008). Repeat sessions were more frequently needed for nodules treated with lobar TACE (31.6% versus 59.3%, P = 0.049). CONCLUSION: Selective/superselective TACE was more successful than lobar procedures in achieving complete histological necrosis, and TACE was more effective in 3- to 5-cm tumors than in smaller ones.
Abstract: In the last US national conference on liver transplantation for hepatocellular carcinoma (HCC), a continuous priority score, that incorporates model for end-stage liver disease (MELD), alpha-fetoprotein and tumor size, was recommended to ensure a more equitable liver allocation. However, prioritizing highest alpha-fetoprotein levels or largest tumors may select lesions at a higher risk for recurrence; similarly, patients with higher degree of liver failure could have lower postoperative survival. Data from 300 adult HCC recipients were reviewed and the proposed HCC-MELD equation was applied to verify if it can predict post-transplantation survival. The 5-year survival and recurrence rates after transplantation were 72.8 and 13.5%, respectively. Cox regression analysis confirmed HCC-MELD as predictive of both postoperative survival and recurrence (p < 0.001). The 5-year predicted survival and recurrence rates were plotted against the HCC-MELD-based dropout probability: the higher the dropout probability while on waiting list, the lower the predicted survival after transplantation, that is worsened by hepatitis C positivity; similarly, the higher the predicted HCC recurrence rate after transplantation. The HCC priority score could predict the postoperative survival of HCC recipients and could be useful in selecting patients with greater possibilities of survival, resulting in higher post-transplantation survival rates of HCC populations.
Abstract: With substantial improvements in perioperative care and surgical technique, both mortality and morbidity after liver resection have progressively decreased; however, long-term prognosis is greatly affected by tumor recurrence, which represents the most frequent cause of death. The aim of this study is to analyze the outcome after hepatic resection in the present clinical scenario, where great improvements in diagnostic techniques, surveillance schedules, in other active treatments will potentially have a positive impact on survival.
Abstract: The incidence of abdominal tuberculosis (TB) is increasing in western and developed countries. This pathology has several complications, including free intestinal perforation. The aim of this study was to analytically summarize all the pertinent literature discussing the various treatments for TB-related perforations.
Abstract: Emergency surgery of the small bowel represents a challenge for the surgeon, in the third millennium as well. There is a wide number of pathologies which involve the small bowel. The present review, by analyzing the recent and past literature, resumes the more commons. The aim of the present review is to provide the main indications to face the principal pathologies an emergency surgeon has to face with during his daily activity.
Abstract: Intra-abdominal infections are still associated with high rate of morbidity and mortality.A multidisciplinary approach to the management of patients with intra-abdominal infections may be an important factor in the quality of care. The presence of a team of health professionals from various disciplines, working in concert, may improve efficiency, outcome, and the cost of care.A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bologna on July 2010, during the 1st congress of the WSES, involving surgeons, infectious disease specialists, pharmacologists, radiologists and intensivists with the goal of defining recommendations for the early management of intra-abdominal infections.This document represents the executive summary of the final guidelines approved by the consensus conference.
Abstract: Accurate knowledge of biliary anatomy and its variants is essential to ensure successful hepatic surgery; however, data from European countries are lacking.
Abstract: The authors describe a case of a 34-year-old woman who presented to the ER with acute epigastric pain caused by an 8-cm celiac artery aneurysm. The patient underwent total aneurysmectomy, distal splenopancreasectomy, and reconstruction of the hepatic arterial inflow using a fresh cadaveric iliac artery homograft. The patient was discharged home on postoperative day 8 in good clinical condition. After 60 months of follow-up, the patient is well and with a patent vascular homograft. The use of a fresh cadaveric iliac homograft described here may represent an option in young patients with low operative risk undergoing visceral artery aneurysm repair.
Abstract: The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.
Abstract: Malignant portal vein thrombosis is a contraindication for liver transplantation. Patients with cirrhosis and early hepatocellular carcinoma (HCC) may have either malignant or benign (fibrin clot) portal vein thrombosis. The aim of this study was to assess prospectively whether well-defined diagnostic criteria would enable the nature of portal vein thrombosis to be established in patients with HCC under consideration for liver transplantation. Benign portal vein thrombosis was diagnosed by the application of the following criteria: lack of vascularization of the thrombus on contrast-enhanced ultrasound and on computed tomography or magnetic resonance imaging, absence of mass-forming features of the thrombus, absence of disruption of the walls of veins, and, if uncertainty persisted, biopsy of the thrombus for histological examination. Patients who did not fulfill the criteria for benign thrombosis were not placed on the transplantation list. In this study, all patients evaluated at our center during 2001-2007 with a diagnosis of HCC in whom portal vein thrombosis was concurrently or subsequently diagnosed were discussed by a multidisciplinary group to determine their suitability for liver transplantation. The outcomes for 33 patients who met the entry criteria of the study were as follows: in 14 patients who were placed on the transplantation list and underwent liver transplantation, no malignant thrombosis was detected when liver explants were examined histologically; 5 patients who were placed on the transplantation list either remained on the list or died from causes unrelated to HCC; in 9 patients, liver transplantation was contraindicated on account of a strong suspicion, or confirmation, of the presence of malignant portal vein thrombosis; and 5 patients who were initially placed on the transplantation list were subsequently removed from it on account of progression of HCC in the absence of evidence of neoplastic involvement of thrombosis. In conclusion, for a patient with HCC and portal vein thrombosis, appropriate investigations can establish whether the thrombosis is benign; patients with HCC and benign portal vein thrombosis are candidates for liver transplantation.
Abstract: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations (SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients.
Abstract: To assess the safety and effectiveness of prophylaxis for venous thromboembolism (VTE) in a large population of patients with hepatocellular carcinoma (HCC) on cirrhosis.
Abstract: Orthotopic liver transplantation (OLT) has been performed for several benign hepatic tumors. Most of these diseases are usually managed conservatively, or treated by liver resection. OLT might be required when the lesions are symptomatic, diffuse in hepatic parenchyma, causing life-threatening complications or malignant transformation cannot be ruled out. Polycystic liver disease is the most common indication for OLT. We present a review of transplantable benign hepatic lesions to evaluate the need of OLT for these diseases, to summarize in which OLT is a good therapeutic option, and to show the early and long-term survival which might be expected.
Abstract: Hepatocellular carcinoma (HCC) prognosis strongly depends upon nuclear grade and the presence of microscopic vascular invasion (MVI). The aim of this study was to develop an artificial neural network (ANN) that is able to predict tumour grade and MVI on the basis of non-invasive variables.
Abstract: To evaluate the results of surgical therapy for intrahepatic cholangiocarcinoma (ICC), the incidence and the management of recurrence, and to analyze the change in approach during 2 different periods.
Abstract: Even though the standard treatment of patients affected by gastrointestinal stromal tumors has been well defined by clinical trials and clinical guidelines, in practice it may be different from those proposed in the literature. This paper reports and comments on a critical picture of the management of patients with gastrointestinal stromal tumors who received at least one treatment before arriving at our GIST Study Group.
Abstract: Many prognostic systems have been devised to predict the outcome of liver transplantation (LT) candidates. Today, the Model for End-Stage Liver Disease (MELD) is widely used for organ allocation, but it has shown some limitations. The aim of this study was to investigate the performance of MELD compared to 5 different score models. We evaluated the prognostic ability of MELD, modified Child-Turcotte-Pugh, MELD-sodium, United Kingdom MELD, updated MELD, and integrated MELD in 487 candidates with cirrhosis for LT at the Bologna Transplant Centre, Bologna, Italy, between 2003 and 2008. Calibration analysis by Hosmer-Lemeshow test, calibration curves, and concordance c-statistics (area under the receiver operating characteristic curve [AUC]) were calculated at 3, 6, and 12 months. Actual cumulative survival curves, taking into account the event of interest in the presence of competing risk, were obtained using the best cutoffs identified by AUC. For each score, the Hosmer-Lemeshow test revealed a good calibration. Integrated MELD showed calibration curves closer to the line of perfect predicting ability, followed by MELD-sodium at 3 months and modified Child-Turcotte-Pugh at 6 months. MELD-sodium AUCs at 3 and 6 months (0.798 and 0.765, respectively) and integrated MELD AUC at 6 months (0.792) were better than standard MELD (P < 0.05). Actual survival curves showed that these 2 scores were able to identify the patients with the highest drop-out risk. In conclusion, MELD-sodium and integrated MELD were the best prognostic models to predict drop-out rates among patients awaiting LT.
Abstract: Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation.
Abstract: Cytomegalovirus (CMV) is a major cause of graft failure and posttransplantation mortality in intestinal/multivisceral transplantation. CMV infection exhibits a wide range of clinical manifestations from asymptomatic infection to severe CMV disease. STUDY'S PURPOSE: The purposes of this study were to assess the utility of measuring CMV-specific cellular immunity in bowel/multivisceral transplant recipients and to provide additional information on the risk of infection and development of CMV disease.
Abstract: Background. Factors affecting outcomes after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS) in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12%) patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP) levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio = 2.88; 95% C.I. = 1.43-5.80; P = .003), preoperative tumor treatments (Odds Ratio = 4.84; 95% C.I. = 1.42-16.42; P = .01), and microvascular invasion (Odds Ratio = 4.82; 95% C.I. = 1.87-12.41; P = .001) were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.
Abstract: Liver resection is the only potential curative treatment for hilar cholangiocarcinoma. In this article, we evaluate mortality, survival, prognostic factors, and changes in surgical approach during the last two decades at a Western hepato-biliary center.
Abstract: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.
Abstract: Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.
Abstract: Use of pulsatile perfusion (PP) to optimize outcomes in deceased donor renal transplantation remains controversial. This prospective analysis describes all cadaveric renal allografts transplanted at our center that were preserved with PP using Celsior solution.
Abstract: Non-carcinoid appendiceal malignancies are rare entities, representing less than 0.5% of all gastrointestinal malignancies. Because of their rarity and particular biological behavior, a substantial number of patients affected by these neoplasms do not receive appropriate surgical resection. In this report, we describe a rare case of primary signet-ring cell carcinoma of the appendix with peritoneal seeding which occurred in a 40-year old man admitted at the Emergency Surgery Department with the clinical suspicion of acute appendicitis. After a surgical debulking and right hemicolectomy, the patient had systemic chemotherapy according to FOLFOX protocol. After completion of the latter, the patient underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. This report offers a brief review of the literature and suggests an algorithm for the management of non-carcinoid appendiceal tumors with peritoneal dissemination.
Abstract: Sirolimus (SRL) is a newer immunosuppressant whose possible benefits and side effects in comparison to calcineurin inhibitors (CNIs) still have to be addressed in the liver transplantation setting. We report the results of the use of SRL in 86 liver transplant recipients, 38 of whom received SRL as the main immunosuppressant in a CNI-sparing regimen. Indications for the use of SRL were: impaired renal function (n = 32), CNI neurotoxicity (n = 16), hepatocellular carcinoma (HCC) at high risk of recurrence (n = 21), recurrence of HCC (n = 6), de novo malignancies (n = 4), cholangiocarcinoma (n = 1), and the need to reinforce immunosuppression (n = 6). Among patients on SRL-based treatment, four episodes of acute rejection were observed, three of which occurred during the first postoperative month. Renal function significantly improved when sirolimus was introduced within the third postoperative month, while no change was observed when it was introduced later. Neurological symptoms resolved completely in 14/16 patients. The 3-year recurrence-free survival of patients with HCC on SRL was 84%. Sixty-two patients developed side effects that required drug withdrawal in seven cases. There was a reduced prevalence of hypertension and new-onset diabetes among patients under SRL. In conclusion, SRL was an effective immunosuppressant even when used in a CNI-sparing regimen. It was beneficial for patients with recently developed renal dysfunction or neurological disorders.
Abstract: Esophageal gastrointestinal stromal tumors (GISTs) are extremely uncommon, representing approximately 5% of GISTs with the majority of esophageal GISTs occurring at the esophagogastric junction (EGJ). The treatment options available for these GISTs are fairly controversial. Many different options are nowadays at our disposal. From surgery to the target therapies we have the possibility to treat the majority of GISTs, including those which are defined as unresectable. The EGJ GISTs represent a stimulating challenge for the surgeon. The anatomical location increases the possibility of post-operative complications. As the role of negative margins in GIST surgery is still controversial and the efficacy of target therapy has been demonstrated, why not treat EGJ GISTs with enucleation and, where indicated, adjuvant target therapy?
Abstract: Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.
Abstract: Several effective treatments are available for patients with small solitary hepatocellular carcinomas (HCCs). Conversely, the management of patients with large or multinodular HCCs is controversial, and the role of surgical resection is not well defined. Between 2000 and 2006, 51 patients with large or multinodular HCC underwent liver resection. Clinicopathologic and follow-up data were prospectively collected and retrospectively reviewed. The perioperative and long-term outcomes were analyzed. Univariate and multivariate analysis of prognostic factors were conducted. Although 20 patients had multinodular HCCs, 31 had large solitary tumors. Perioperative mortality occurred in eight patients and complications in 15. In patients with large solitary tumors, 5-year disease-free and overall survival were 41.3 per cent and 56.1 per cent, respectively. Those with multinodular HCCs demonstrated 5-year disease-free and overall survival rates of 0 per cent and 33.6 per cent, respectively. Liver resection can result in long-term survival in select patients with large or multinodular HCCs, even in select patients with impaired liver function. Large solitary HCCs seem to have better prognoses than multinodular tumors, with lower recurrence and higher survival rates after surgery. Randomized controlled trials comparing resection to other treatment modalities are indicated to determine optimal patient management.
Abstract: Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an important complication posttransplantation. Induction therapy has enabled improvement in graft and patient survival rates.
Abstract: Surgical approaches to complicated benign intestinal failure are accepted worldwide, especially in the pediatric population. Intestinal transplant surgery is thought to rescue patients in whom complications of total parenteral nutrition (TPN) develop.
Abstract: Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors.
Abstract: Routine regional lymphadenectomy for colorectal liver metastases and primary liver tumors is still a subject for debate. During 2001-2005, we performed a prospective study of cases in which regional lymphadenectomy around the hepato-duodenal ligament and common hepatic artery was applied (group R+ LN) or not (group R- LN). Pre-operative clinical features of patients were comparable among groups as well as the operative data. There were 108 (67%) males; the median age was 66 years; 124 cases had a single lesion (77%), and the median diameter was 4 cm. The type of lesion was: 77 (48%) colorectal liver metastases (M-CR), 75 (46%) hepatocellular carcinomas (HCC) and 10 (6%) cholangiocellular carcinomas. In the R+ LN group, the mean number of lymph nodes removed was 6.7 ± 4.8 (range 4-26), and seven cases (8.6%) presented lymph node metastasis. The median follow-up was 3.5 years. M-CR patients showed comparable hospital mortality (R+ LN 0% vs. R- LN 2.6%) and morbidity (R+ LN 17.9% vs. R- LN 21.1%), but R+ LN had higher 5-year disease-free survival (31 vs. 16%, p < 0.05). HCC cases in the R+ LN group presented higher hospital mortality (13.5 vs. 0%, p < 0.05) without any improvement in disease-free survival (it was at 5-year disease-free survival 34 vs. 33%, respectively, p = n.s.). Routine regional lymphadenectomy should be performed for colorectal liver metastases, and avoided in patients with hepatocellular carcinoma.
Abstract: Intestinal transplantation has become an accepted therapy for individuals permanently dependent on total parenteral nutrition (TPN) with life-threatening complications. Quality of life and psychological well-being can be seen as important outcome measures of transplantation surgery.
Abstract: We describe the first case of West Nile virus (WNV) infection in Europe with transmission from donor to recipient following liver transplantation. The infection was detected in the recipient 3 days after transplantation, during the asymptomatic phase. We also report an innovative prophylactic strategy based on infusion of WNV hyperimmune plasma and gamma globulins that could be effective in preventing the appearance of a neuroinvasive disease.
Abstract: In this study we compared the content of muscle free [Mg2+] assessed by 31P MRS to that of serum total Mg assessed by routine colorimetric assays in 15 patients affected by Chronic Intestinal Failure (CIF) on long-term Home Parenteral Nutrition (HPN) or who had undergone isolated intestinal transplantation. We also investigated in the same cohort of patients the relationship of muscle free [Mg2+] and serum total Mg with parathyroid hormone (PTH) serum content. All patients showed a normal cytosolic free [Mg2+] in the calf muscle despite about half of them having a content of total serum [Mg] below or at the lower edge of the boundary limits. Muscle free Mg2+ and serum total Mg displayed an opposite correlation versus serum PTH, showing that the intracellular free form possesses a different functional metabolic meaning in the regulation of PTH secretion.
Abstract: INTRODUCTION: The incidence of gastrointestinal (GI) complication in renal transplantation is relatively high. These complications may be severe, leading to graft loss and patient death. MATERIALS AND METHODS: We reviewed 1651 patients who underwent renal transplantation between 1976 and 2007, analyzing the incidence of colonic perforations and the clinical prognostic factors. RESULTS: Twenty-one patients (1.3%) developed colonic perforations with 7 subsequent deaths. Diverticulitis and ischemia were the most common causes of perforation. Eleven patients (52.3%) were diagnosed and treated within the first 24 hours; their mortality was 18.1%. The 10 patients (47.7%) who were diagnosed and treated 24 hours after the clinical event displayed an high mortality rate (50%). Diverting stoma procedures were performed in all cases. CONCLUSIONS: The follow-up of the kidney transplant patients should include a careful evaluation for possible GI complications and colonic perforations. Early diagnosis and timely treatment were associated with improved outcomes, regardless of the surgical procedures, the cause of perforation or the clinical and laboratory parameters.
Abstract: Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10(5) PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.
Abstract: Split liver transplantation (SLT) for two adult recipients is still considered a challenging procedure, especially when subjected to model for end-stage liver disease (MELD)-based allocation criteria.
Abstract: BACKGROUND: Frequently, hernia repair requires polypropylene (PP) meshes, which carry a well-known adhesiogenic risk when placed in contact to the intestine. The aim of this experimental study in a rat model was to assess the role of some materials, when combined with PP, in preventing the adhesions' formation. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were assigned to five groups for intraperitoneal mesh placement: untreated PP, PP+polyurethane (PP+PU), PP+Surgisis (PP+SIS), PP+expanded polytetrafluoroethylene (PP+ePTFE), and a control group without mesh. Twenty-one days and 3 and 6 months after the operation, an assessment of adhesion formation was performed, scoring adhesions in terms of extent and type and the adhesion index (AI; product of adhesions' extent and type). RESULTS: No significant difference was seen between PP+SIS, PP+PU, and control groups in adhesions extent/quality and in AI. The PP+SIS group had significantly lower adhesions' quality value and AI than PP+ePTFE. PP+PU had significantly lower adhesions' extent/quality value and AI than PP+ePTFE. The control group had adhesions with significantly lower extent/quality and AI than PP+ePTFE. The PP group had significantly more and denser adhesions, compared to PP+ePTFE, as well as a significantly higher AI. CONCLUSIONS: Adhesions' incidence is reduced by using treated PP meshes. PP+PU and PP+SIS were superior to PP+ePTFE in adhesion prevention.
Abstract: ABSTRACT: Emergency surgery is performed in every hospital with a A and E unit all around the world. However it is organized in different ways with different results.Aim of this paper is to present history, current scope, current training program and new politics for training national program of 3 countries of different continents.Brazil, Finland and US emergency surgery models are presented discussing all criticisms showed during the WSES Summer Meeting 2008.
Abstract: BACKGROUND: The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat. METHODS: Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection. RESULTS: Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05). CONCLUSIONS: In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.
Abstract: We assessed the efficacy and outcome of low through level of calcineurin inhibitors (CNI) and introducing mycophenolate mofetil (MMF) in liver transplant (LT) patients with CNI-related renal dysfunction. Thirty LT patients were converted to combined therapy and compared with 30 patients used as a contemporary control group receiving CNI only. The two groups were matched for sex, age, months after LT, immunosuppressive treatment, creatinine level, presence of diabetes and calculated glomerular filtration rate (GFR) via Cockroft-Gault method. After two years, in the MMF serum creatinine decreased from 1.65 mg/dL (range 1.33-3.5) to 1.4 mg/dL (range 0.9-4.7) (p = 0.002) and GFR increased from 51 mL/min (range 18.9-72.2) to 57.6 mL/min (range 16-92.2) (p < 0.001), whereas the controls not showed any improvement. The logistic regression models employing improvement of creatinine and GFR of at least 10% with respect to baseline as dependent variables showed the use of MMF (p = 0.004 and p = 0.019, respectively) as the only statistically significant parameter. Multiple linear regression analysis identified only MMF as independent predictor of Deltacreatinine and DeltaGFR (p = 0.002 and p < 0.001, respectively). No rejection episode was observed (three in controls). This study demonstrates the medium-term efficacy and safety of MMF plus low dose CNI in reducing nephrotoxicity in LT recipients.
Abstract: BACKGROUND: The aim of this study was to evaluate the safety and efficacy of Lichtenstein's hernioplasty using Surgisis Inguinal Hernia Matrix (SIHM; Cook, Bloomington, Indiana) compared with polypropylene (PP; Angiologica, Pavia, Italy). METHODS: This was a prospective, randomized, double-blind trial comparing Lichtenstein's inguinal hernioplasty using SIHM versus PP. RESULTS: Seventy male patients underwent Lichtenstein's hernioplasty (n = 35 in the SIHM group and n = 35 in the PP group). At 3 years after surgery, there were 2 deaths (5.7%) in the PP group and 1 death (2.9%) in the SIHM group (not significant [NS]). Although the study was underpowered to evaluate the recurrence rate, only 1 recurrence (2.9%) was seen in the PP group (NS). Although a significant decrease in postsurgical pain incidence was never observed among patients in the SIHM group, a significantly lower degree of pain was detected at rest and on coughing at 1, 3, and 6 months and on movement at 1, 3, and 6 months and 1, 2, and 3 years. A significant decrease in postsurgical incidence and degree of discomfort when coughing and moving were observed among patients in the SIHM group at 3 and 6 months and at 1, 2, and 3 years after surgery. COMMENTS: SIHM hernioplasty seems to be a safe and effective procedure.
Abstract: Abdominal wall transplantation is a type of composite tissue allograft that can be utilized to reconstitute the abdominal domain of patients undergoing intestinal transplantation. We have presented herein combined experience and long-term follow-up results of a series of abdominal wall transplants performed at 2 institutions. A total of 15 abdominal wall transplants from cadaveric donors were performed in 14 patients at the end of intestinal transplant surgery or, in 2 cases, a few days after the primary intestinal transplant. The vascular supply was through the inferior epigastric vessels, from the iliac vessels in 12 cases and via a microsurgical technique in 3 cases. Immunosuppression consisted of induction with alemtuzumab and maintenance treatment with tacrolimus monotherapy. Two grafts lost to vascular thrombosis were removed. Five patients are still alive, although all deaths were unrelated to the abdominal wall transplant. There were 3 episodes of abdominal wall graft rejection, treated with steroids; the abdominal wall graft and the intestinal grafts experienced rejection independent from each other. In summary, abdominal wall transplantation is a feasible technique for recipients of intestinal or multivisceral transplants, when the closure of the abdominal cavity by primary intention is technically impossible.
Abstract: BACKGROUND/AIMS: The efficacy of ischemic preconditioning (IPC) in preventing reperfusion injury in human liver transplants is still questioned. Phosphoinositide-3-kinase (PI3K) is essential for IPC development in rodent livers. This work investigates whether PI3K-dependent signals might account for the inconsistent responses to IPC of transplanted human livers. METHODS: Forty livers from deceased donors were randomized to receive or not IPC before recovery. PI3K activation was evaluated in biopsies obtained immediately before IPC and 2 h after reperfusion by measuring the phosphorylation of the PI3K downstream kinase PKB/Akt and the levels of the PI3K antagonist phosphatase tensin-homologue deleted from chromosome 10 (PTEN). RESULTS: IPC increased PKB/Akt phosphorylation (p = 0.01) and decreased PTEN levels (p = 0.03) in grafts, but did not significantly ameliorate post-transplant reperfusion injury. By calculating T(2h)/T(0) PKB/Akt phosphorylation ratios, 10/19 (53%) of the preconditioned grafts had ratios above the control threshold (IPC-responsive), while the remaining nine grafts showed ratios comparable to controls (IPC-non-responsive). T(2h)/T(0) PTEN ratios were also decreased (p < or = 0.03) only in IPC-responsive grafts. The patients receiving IPC-responsive organs had ameliorated (p < or = 0.05) post-transplant aminotransferase and bilirubin levels, while prothrombin activity was unchanged. CONCLUSIONS: Impaired PI3K signaling might account for the variability in the responses to IPC of human grafts from deceased donors.
Abstract: The outcome of hepatic resection in cirrhotic patients has improved remarkably in recent years with improved surgical techniques and perioperative care; however, the role of portal hypertension is still uncertain. The aim of this study was to elucidate surgical outcomes of hepatectomy in patients with portal hypertension.
Abstract: The role of hepatitis B virus (HBV) infection in determining the prognosis after hepatectomy for hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial.
Abstract: BACKGROUND: Alcoholic liver cirrhosis (ALC) is a leading indication for orthotopic liver transplantation (OLT). GOALS: To investigate the long-term outcome of OLT for ALC compared with patients transplanted for hepatitis C virus (HCV) infection. STUDY: From 1987 to 2001, 49 OLT were performed for ALC and 173 for HCV. From these contemporary groups we matched 1:2 ALC patients (cases) to 98 HCV (controls). The following variables were analyzed: survival, retransplantation, rejection, primary nonfunction, infections, de novo tumors, cardiovascular and neurologic complications, and alcoholic recurrence. RESULTS: Actuarial survival rate at 9 years was comparable for cases and controls. Actuarial graft survival rate at 9 years was significantly higher in cases (78% vs. 60%; P=0.026). The retransplantation rate was higher in controls (21% vs. 4%; P=0.007). Post-OLT complications were not significantly different. The alcoholic recidivism rate was 28% without influence on patients or graft survival, whereas relapse of HCV caused the majority of death in controls (30%; P=0.042). At multivariate analysis retransplantation was the only predictor of patient survival (odds ratio: 4.35; 95% confidence interval: 2.16-8.74; P<0.001), whereas HCV was associated with a 2-fold probability of graft failure (odds ratio: 1.97; 95% confidence interval: 1.02-3.81; P=0.032). CONCLUSIONS: The long-term outcome of OLT for ALC is comparable to that for HCV, even if graft survival is significantly better among ALC. These data support ALC as an excellent indication for OLT.
Abstract: Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety-nine HCV-positive/hepatitis B surface antigen-negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty-five patients (25%) achieved an SVR. Twenty-seven donor-related, recipient-related, HCV-related, and immunosuppression-related variables were investigated for their association with SVR. In logistic regression analysis, donor age < 60 years (odds ratio = 4.45, 95% confidence interval = 1.39-14.19, P = 0.01), viral genotype other than 1 (odds ratio = 4.97, 95% confidence interval = 1.59-15.48, P = 0.006), and the use of CyA during treatment (odds ratio = 6.85, 95% confidence interval = 2.15-21.73, P = 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P = 0.02 and P = 0.005, respectively) and a greater use of anti-CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P = 0.03, P < 0.001, and P = 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P = 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT.
Abstract: BACKGROUND & AIMS: Data on the safety of bevacizumab-based therapies for patients carrying a self-expandable metallic stent (SEMS) for occlusive colon cancer are lacking. We report 2 cases of colon perforation observed in our case-series of patients with SEMS for occlusive colon cancer. METHODS: Patients with occlusive symptoms caused by colon cancer received a WallFlex colonic stent (Boston Scientific, Natick, MA) under endoscopic and radiologic guidance. RESULTS: Over a 10-month period, 28 patients with occlusive colon cancer were treated with stent placement. The stent was placed as a bridge to surgery in 12 patients who were treated surgically within 4 to 78 days after the endoscopic procedures, without any stent-related complications. Seven patients did not receive any other antitumor treatment as a result of concomitant comorbidities. Nine patients with both primary tumor and metastatic lesions were treated with medical therapy. Over a median follow-up period of 131 days colonic perforation occurred in the 2 patients treated with a combination of capecitabine and oxaliplatin plus bevacizumab. CONCLUSIONS: Further studies are needed to clarify whether SEMS placement increases the risk of perforation caused by bevacizumab-based therapies.
Abstract: BACKGROUND: Videolaparocholecystectomy (VLC) for acute cholecystitis (AC) is a technically demanding procedure, feasible by experienced surgeons, still affected by high conversion rate. Aim of this study was to prospectively evaluate whether the use of harmonic scalpel (HA) during VLC for AC, allowing a potentially better hemostasis and biliostasis, can decrease the conversion rate. METHODS: Hundred and one patients, with the mean age of 61.2+/-8.2 years (range: 39 to 81 y), admitted for AC, have been submitted to early VLC with HA within 6 years (from January 1, 2003 to December 31, 2008) at the Department of General, Emergency, and Transplant Surgery of St Orsola-Malpighi University Hospital in Bologna, Italy. The design of the study was prospective observational non-randomized. The control group consisted of 100 patients who underwent VLC for AC without HA at the same department in the same period. RESULTS: Mean operative time in VLC group with HA has been 71.4+/-14.3 minutes (range: 42 to 112 min) versus 87.4+/-10.8 minutes in the control group (P<0.001). Blood losses were significantly lower with the use of HA. Conversion rate has been 4.9%, mortality was 1%, and postoperative morbidity 7.9% in HA treated group, versus 12% conversion rate, 1% and 9% mortality and morbidity, respectively in the control group (P value not significant). CONCLUSIONS: The use of HA seems to be associated with lower conversion rate in VLC for AC, without any significant increase of morbidity. HA might be even more useful in the most technically demanding cases but further investigations are required. A prospective randomized trial comparing harmonic versus monopolar diathermy in laparoscopic cholecystectomy for AC in adults (Harmonic for Acute Cholecystitis Trial, NCT00746850) is currently enrolling patients and will clarify these observations.
Abstract: INTRODUCTION: Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long-term patient survival. PATIENTS AND METHODS: Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low-dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups. RESULTS: There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT. CONCLUSION: There was no difference in incidence of bacterial infections and long-term patient survival between the two groups.
Abstract: Malignant mixed tumors of the liver in adults are extremely rare. To our knowledge, only a few cases have been reported in the literature. Nested stromal-epithelial tumors (NSET) of the liver are characterized by non-hepatocytic, non-biliary tumors with nests of epithelial and spindle cells, an associated myofibroblastic stroma, as well as variable calcifications and ossifications. We report a case of NSET of the liver affecting a young woman and provide detailed histological and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature.
Abstract: The application of intestinal transplantation is limited by the high rate of infectious complications that can occur; the migration of enteric microorganisms to extraintestinal sites (bacterial translocation) has been suggested to be responsible for this event. We reviewed 95 intestinal biopsies performed on 28 transplanted patients to identify histologic features predictive of isolation of enteric microorganisms in extraintestinal sites within the first month after transplantation. At least 1 isolation of enteric microorganisms in the peritoneal cavity and/or in blood samples was obtained in 13 patients (46.4%); this event led to higher 1-year mortality (38.5% vs. 6.7%; P = .041). Of the 95 biopsies, 38 were followed by positive cultures (40.0%), showing higher degrees of mucosal vascular alterations (Ruiz grade) and ischemia/reperfusion injuries (Park/Chiu grade) compared with the negative cases (P < .05). We also observed an higher prevalence of positive cultures in relation to acute cellular rejection episodes (P = .091). Neither clinical or surgical factors nor immunosuppressive therapy were observed to be significantly related to positive cultures. Histologic alterations of the small bowel allograft are related to isolation of enteric microorganisms in extraintestinal sites. The degree of these histologic features can identify patients at high risk of potentially life-threatening infectious complications and death.
Abstract: The model for end-stage liver disease (MELD) is used to determine organ allocation priorities for orthotopic liver transplantation (OLT), although its value to predict posttransplantation mortality and morbility is controversial. The aim of this study was to analyze postoperative courses and (to evaluate the relationships between MELD score and postoperative) complications. We retrospectively examined the courses of 242 patients including 186 males and 56 females of overall mean age of 53 +/- 10 years who underwent primary liver transplantation. The classification of Dindo-characterized 5 grades of severity to evaluate postoperative events. The data showed that 171 patients (70.7%) experienced complications, while 71 (29.3%) had none. We observed that MELD score and complications were related (P < .05). Patients with complicated courses post-OLT displayed a 22.80 mean value of the MELD score, while those without complications showed a 17.64 mean value. The MELD score was also significantly associated with the time of intensive care unit stay and in hospital. Finally, we noted that MELD score and mortality were significantly correlated (P < .05). In conclusion, MELD score can be considered to be an objective system to predict the prevalence and severity of postoperative complications after liver transplantation.
Abstract: BACKGROUND: In the developmental stage of laparoscopic cholecystectomy (LC) it was considered 'unsafe' or 'technically difficult' to perform laparoscopic cholecystectomy for acute cholecystitis (AC). With increasing experience in laparoscopic surgery, a number of centers have reported on the use of laparoscopic cholecystectomy for acute cholecystitis, suggesting that it is technically feasible but at the expense of a high conversion rate, which can be up to 35 per cent and common bile duct lesions.The HARMONIC SCALPEL (H) is the leading ultrasonic cutting and coagulating surgical device, offering surgeons important benefits including: minimal lateral thermal tissue damage, minimal charring and desiccation.Harmonic Scalpel technology reduces the need for ligatures with simultaneous cutting and coagulation: moreover there is not electricity to or through the patient Harmonic Scalpel has a greater precision near vital structures and it produces minimal smoke with improved visibility in the surgical field.In retrospective series LC performed with H was demonstrated feasible and effective with minimal operating time and blood loss: it was reported also a low conversion rate (3.9%).However there are not prospective randomized controlled trials showing the advantages of H compared to MD (the commonly used electrical scalpel) in LC. METHODS/DESIGN: Aim of this RCT is to demonstrate that H can decrease the conversion rate compared to MD in LC for AC, without a significant increase of morbidity.The patients will be allocated in two groups: in the first group the patient will be submitted to early LC within 72 hours after the diagnosis with H while in the second group will be submitted to early LC within 72 hours with MD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00746850.
Abstract: OBJECTIVE: To estimate risk factors affecting the early outcome after hepatic resection in a high volume center specialized in hepatobiliary surgery and to analyze the changing of results during 3 different periods of treatment. DESIGN: Retrospective review. PATIENTS: A series of 1500 consecutive patients who underwent hepatic resection. METHODS: Postoperative morbidity and mortality were analyzed in relation to indications for surgery, period of operation, patient characteristics, and intraoperative variables. Patients were classified into 4 groups, according to the indication for surgery: primary liver tumors with cirrhosis (group 1, G1); other liver malignancies (group 2, G2); biliary malignancies (group 3, G3); and benign diseases (group 4, G4). Patients were also divided into 3 groups, according to the year of operation (period 1: June 1985 to October 1993; period 2: November 1993 to September 1999; period 3: October 1999 to September 2007). RESULTS: Overall mortality and morbidity were 3% and 22.5%, respectively. Multivariate analysis revealed that blood transfusions, G1, and additional procedures were associated with an increased risk of postoperative complications, whereas blood transfusions, G1, G3, and extended hepatectomy were associated with an increased risk of postoperative mortality. G1 decreased, whereas G3, extended hepatectomies and additional procedures significantly increased between periods 2 and 3 (P < 0.05). The complication rate was significantly lower in period 2 (18.8%) compared with period 1 (23.8%) and period 3 (24.8%). Similarly, there was a significantly lower mortality rate in period 2 (1.6%) compared with period 1 (3.4%) and period 3 (4%). CONCLUSIONS: Slightly worse short-term outcomes in liver surgery were observed in recent years, with a concomitant increase of the aggressiveness of operative strategies. Nevertheless, the present results still justify an aggressive approach in liver resections.
Abstract: BACKGROUND: Macrovesicular steatosis of the liver is associated with early dysfunction or poor function of the graft after transplantation; however, it can be quantified accurately only through a liver biopsy that sometimes may not be available and whose result is anyway known when the recipient has already been selected. It would, therefore, be helpful to be able to predict the degree of steatosis, on the basis of non-invasive readily available variables. METHODS: Data from 374 deceased liver donors from whom a liver biopsy had been taken were analyzed with the receiver operating characteristic area [area under the curve (AUC)] to identify variables that could predict the degree of macrovesicular steatosis classified as: absent to mild (0-30%) and moderate to severe (>30%). RESULTS: Steatosis was associated significantly with donor age, increased body mass index (BMI), presence of type II diabetes, ultrasonographic features, heavy alcohol consumption, transaminases [aspartate-aminotransferase and alanine-aminotransferase (ALT)], gamma-glutamyl-transpeptidase, and glucose blood levels. The combination of BMI, elevation of ALT, presence of type II diabetes, history of heavy alcohol consumption, and ultrasonography signs of steatosis could identify steatosis >30% accurately with an AUC of 0.86 (95% CI = 0.81-0.91). CONCLUSION: Fatty infiltration in liver donors can be estimated based on clinical and biochemical parameters.
Abstract: BACKGROUND/AIMS: Orthotopic liver transplantation (OLT) is an important therapeutic option for HBV-related end-stage-liver disease, yet it is often hampered by a scarcity of organ availability. One option to increase organ availability is the use of virologically compromised organs from HBV-infected donors. Transplantation of anti-HBcore positive grafts has been associated with a low risk of HBV recurrence if adequately treated with nucleoside analogs, irrespective of concomitant HBV-specific immunoglobulin therapy. Experience using HBsAg positive grafts is, however, very limited. METHODS: Here, the analysis of the cellular and humoral HBV-specific immunity of a subject with past HBV infection (anti-HBs and anti-HBc positive) receiving an HBsAg positive liver graft is reported. RESULTS: Nine months post-OLT, the patient experienced a spontaneous anti-HBs re-seroconversion allowing the discontinuation of HBIG. The data show a concurrent increase in the cellular and humoral immunity at times of reduced viral antigenemia, demonstrating effective immune control of HBV post-OLT. CONCLUSIONS: These data support the use of marginal organs in this setting, providing a potential strategy to further alleviate organ shortage.
Abstract: According to transplant registries, grafts from elderly donors have lower survival rates. During 1999-2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged > or = 60 years and managed with the low liver-damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D > or = 60-LLDS). Group D > or = 60-LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60-no-LLDS and 89 donors aged > or =60 years, group D > or = 60-no-LLDS). In the donors proposed from the age group of > or =60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end-stage liver disease score) were comparable among groups, but group D > or = 60-LLDS had a lower mean ischemia time: 415 +/- 106 min vs. 465 +/- 111 (D < 60-no-LLDS), P < 0.05 and vs. 476 +/- 94 (D > or = 60-no-LLDS), P < 0.05. After a median follow-up of 3 years, the 1- and 3-year graft survival rates of group D > or = 60-LLDS (84% and 76%) were comparable with group D < 60-no-LLDS (89% and 76%) and were significantly higher than group D > or = 60-no-LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.
Abstract: PURPOSE: The aim of the study was to evaluate the diagnostic capability of contrast-enhanced ultrasonography (CEUS) in a large series of patients with blunt abdominal trauma. MATERIALS AND METHODS: We studied 133 haemodynamically stable patients with blunt abdominal trauma. Patients were assessed by ultrasonography (US), CEUS and multislice computed tomography (MSCT) with and without administration of a contrast agent. The study was approved by our hospital ethics committee (clinical study no. 1/2004/O). RESULTS: In the 133 selected patients, CT identified 84 lesions; namely, 48 splenic, 21 hepatic, 13 renal or adrenal and two pancreatic. US identified free fluid or parenchymal alterations in 59/84 patients with positive CT and free fluid in 20/49 patients with negative CT. CEUS detected 81/84 traumatic lesions identified on CT and ruled out traumatic lesions in 48/49 patients with negative CT. The sensitivity, specificity and positive and negative predictive values of US were 70.2%, 59.2%, 74.7% and 53.7%, respectively, whereas those of CEUS were 96.4%, 98%, 98.8% and 94.1%, respectively. CONCLUSIONS: Our study showed that CEUS is an accurate technique for evaluating traumatic lesions of solid abdominal organs. The technique is able to detect active bleeding and vascular lesions, avoids exposure to ionising radiation and is useful for monitoring patients undergoing conservative treatment.
Abstract: Histological quality assessment of donated livers is a key factor for extending the cadaveric donor pool for liver transplantation. We retrospectively compared frozen-section analysis with routine histological permanent slides and the outcomes of grafts in liver biopsies from 294 candidate donors. The kappa concordance coefficient of agreement between frozen-section analysis and routine histological analysis was very good for macrosteatosis (kappa = 0.934), microsteatosis (kappa = 0.828), and total steatosis (kappa = 0.814). The correlation between the mean amounts of macrosteatosis, microsteatosis, and total steatosis in frozen and permanent sections was also significant (P < 0.001, Spearman's test). Macrosteatosis and microsteatosis were overestimated to >30% in 4 of 32 cases (12.5%) and in 23 of 62 cases (37.1%), respectively. The only 2 histological parameters of frozen sections able to predict graft dysfunction within 7 days of transplantation were macrosteatosis and total steatosis (P = 0.018 and P = 0.015, respectively, Mann-Whitney test). None of the other histopathological features evaluated in frozen sections, including portal inflammation, lobular necrosis, myointimal thickening, biliocyte regression, cholestasis, hepatocellular polymorphism, lipofuscin storage, and fibrous septa, were significantly correlated with the graft outcome. The frozen-section histological evaluation of biopsies from cadaveric liver donors is an accurate, time-effective, and predictive method for the assessment of graft suitability.
Abstract: The presence of cirrhosis is the only risk factor that is advocated for recurrence of hepatocellular carcinoma (HCC) 2 years after hepatic resection compared with noncirrhotic control subjects; however, data for cohorts of exclusively patients with cirrhosis are lacking. This study was designed to assess risk factors and annual incidence of early (<2 years) and late (>2 years) recurrence after resection of cirrhosis and to compare these findings with those of patients with cirrhosis enrolled in HCC surveillance programs (HCC occurrence). Data from 204 patients with cirrhosis resected for HCC and 150 surveilled for cirrhosis were retrospectively collected and compared using propensity score matching to overcome biases of nonrandomized study. Risk factors for early recurrence (incidence = 21.8%/year) were higher serum alpha-fetoprotein (AFP) levels, poorly differentiated tumor, and presence of microvascular invasion (P < 0.05). Risk factors for both late recurrence (18.4%/year) and HCC occurrence (3.3%/year) were male gender, older age, and higher serum transaminase levels; multiple primary tumors and higher AFP were additional risk factors for late recurrence and HCC occurrence respectively (P < 0.05). After propensity adjustment, resected patients with less than two risk factors for late recurrence showed an annual incidence of HCC (6.2%/year) similar to that of surveilled patients with > or =2 risk factors (5.8%/year; P = 0.898). Early and late recurrence of HCC for patients with cirrhosis after resection have distinct risk factors. Annual incidence of HCC 2 years or more after resection may be similar to that of general patients because the same risk factors are involved; assessment of these characteristics could be useful in tailoring clinical management.
Abstract: The evaluation of the survival achieved with liver transplantation (LT) compared with remaining on the waiting list, the transplant benefit, should be the underlying principle of organ allocation.
Abstract: OBJECTIVE: To produce a model indicating the extent of hepatectomy for hepatocellular carcinoma on cirrhosis based on easily available preoperative data. DESIGN: Retrospective study based on multicenter prospectively updated databases. SETTING: Two tertiary referral centers specializing in hepatobiliary surgery. PATIENTS: A total of 466 patients undergoing hepatectomy for hepatocellular carcinoma on cirrhosis between 1995 and 2006. MAIN OUTCOME MEASURES: To create a decision tree for safe liver resection based on factors affecting irreversible postoperative liver failure (IPLF). RESULTS: A total of 23 patients (4.9%) developed IPLF. The model for end-stage liver disease (MELD) score (categorized as <9, 9-10, and >10; P < .05 for all comparisons) and extent of hepatectomy were independent predictors of IPLF. In patients with a MELD score of less than 9, the IPLF rate was 0.4%. In patients with a MELD score of 9 or 10, the IPLF rate was 1.2% for resections of less than 1 segment, 5.1% for segmentectomies or bisegmentectomies, and 11.1% for major hepatectomies. In this category of MELD, serum sodium levels identified a low-risk group (sodium > or =140 mEq/L; to convert to millimoles per liter, multiply by 1.0) not experiencing IPLF and a high-risk group (sodium <140 mEq/L) in which resections of less than 1 segment led to an IPLF rate of 2.5% and resections of 1 segment or more led to an IPLF rate of more than 5% (P < .05). In patients with a MELD score of more than 10, the IPLF rate was more than 15% in all types of hepatectomies. CONCLUSION: A simple algorithm based on the MELD score and serum sodium level can indicate the maximum tolerable extent of hepatectomy for hepatocellular carcinoma on cirrhosis.
Abstract: Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.
Abstract: Advanced donor age is a risk factor for poor outcome in liver transplantation (LT). We reviewed 553 consecutive transplants according to donor age categories [group 1 (n = 173): <50 years; group 2 (n = 96): 50-59 years; group 3 (n = 132): 60-69 years; group 4 (n = 111): 70-79 years; group 5 (n = 41): > or =80 years]. Clinical parameters were comparable between groups. Group 5 had the highest proportion of pretransplant liver biopsy (85%), with only 1 graft showing macrovesicular steatosis > 30%, and the lowest ischemia time. Five-year graft survival was significantly higher in group 1 (75%) versus groups 3 (60%) and 4 (62%; P = 0.01 and P = 0.001, respectively) and in group 5 (81%) versus groups 3 and 4 (P = 0.04 and P = 0.01, respectively). Donor age of 60-79 years, recipient hepatitis C virus-positive status, Model for End-Stage Liver Disease score > or = 25, and emergency LT were predictors of poor survival. In hepatitis C virus-positive patients, 5-year graft survival was 72% in group 1, 85% in group 2, 52% in group 3, 65% in group 4, and 71% in group 5 (group 1 versus group 3, P = 0.04; group 2 versus group 3, P = 0.03). In conclusion, older donor grafts managed with routine graft biopsy and short ischemia time may work effectively, regardless of the severity of the recipient's liver disease.
Abstract: BACKGROUND: We sought to determine the best strategy to overcome difficult abdominal wall closures in intestinal transplantation (ITx). METHODS: Among 38 adult recipients of 39 ITxs from deceased donors, the median number of previous laparotomies was 2.0 per patient, with a median donor-to-recipient body weight ratio of 1.1. Eight patients (21%) had full residual intestinal length before transplant. Abdominal wall closure after transplant was considered difficult in 15 (39.5%) patients (group A). To overcome size mismatching, we performed two graft reductions, five skin-only closures, one two-step abdominal wall closure, four prosthetic mesh closures, and three abdominal wall transplants. In the remaining 23 (60.5%) patients, a regular abdominal closure was performed (group B). RESULTS: Twelve patients (32%) experienced complications related to abdominal wall closure, 10 (67%) in group A and 2 (8.7%) in group B (P<0.0001). Abdominal closure-related mortality was 6.7% (1/15) and 4.3% (1/23), respectively (P=1.0). In group A, there were six incisional hernias (one of them after abdominal wall transplant), although all four patients with mesh experienced mesh infection. Two of them developed intestinal fistulae, leading to patient death in one case. In group B, one patient with unfavorable donor/recipient size matching had fatal vascular thrombosis of a multivisceral graft caused by compression after abdominal closure. CONCLUSIONS: A careful evaluation of abdominal cavity is necessary in candidates for ITx. In our experience, closure with mesh should be avoided because of the high rate of complications. Abdominal wall transplantation is a feasible option when a difficult abdominal wall closure is expected.
Abstract: INTRODUCTION: In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS: The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS: The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION: Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.
Abstract: BACKGROUND: Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates. AIM: To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response. METHODS: Fifty-three patients with post-LT HCV recurrence were enrolled. Patients received PEG-IFN alfa-2b 1.0 micro/kg/week plus RBV 8-10 mg/kg/day for 24 weeks. Those with 'early virological response at week 24' (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C). RESULTS: Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV-RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02-106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end-of-treatment response. One patient in group B had SVR. CONCLUSIONS: Pegylated-interferon alfa-2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with > or =2 log10 drop in HCV-RNA at week 24.
Abstract: We compared tissue hepatitis C virus (HCV) RNA polymerase chain reaction quantification and HCV immunohistochemistry (IHC) to histology in biopsy tissues in order to differentiate between acute rejection and HCV hepatitis recurrence early after orthotopic liver transplantation (OLT). We analyzed the first biopsy performed because of alteration of serum aminotransferases in 65 consecutive OLT patients with HCV genotype 1b. In the histological analysis, we quantified the portal tracts, Councilman bodies, Councilman body/portal tract (CP) ratio, steatosis, and Knodell and Ishak scores. The 52 patients (80%) with histological HCV recurrence [recurrence-positive (Rec+)] were separated from the 6 (9%) with acute rejection and the 7 (11%) with undetermined pathological features [recurrence-negative (Rec-)]. HCV RNA strongly correlated with HCV IHC, regardless of the histological diagnosis (P < 0.001). Both HCV RNA and HCV IHC were significantly associated with CP ratio (P = 0.041 and P = 0.008). No statistical correlation was found between HCV RNA, HCV IHC, and the other histopathologic features or the hepatitis scores. HCV RNA, HCV IHC, and CP ratio were the only variables able to discriminate between Rec+ and Rec- patients (Mann-Whitney test P < 0.001, P < 0.001, P = 0.014). In conclusion, a combined evaluation of histology, tissue HCV RNA, and HCV IHC significantly discriminated between OLT patients with or without HCV recurrence.
Abstract: Hepatic resection is today the treatment of choice for cirrhotic patients affected by hepatocellular carcinoma (HCC). Short term results are now definitely satisfactory, with a mortality rate in the referral centers lower than 5%. However, long term results are affected by a high recurrence rate, between 50% and 100%, due to the underlying cirrhosis. Notwithstanding the high recurrence rate, the hepatic resection guarantees a five years survival between 40% and 60%, comparable to the one offered by liver transplantation. The aim of this paper is to review the results of studies on resected cirrhotic patients affected by HCC.
Abstract: BACKGROUND: The use of biomarkers for rejection monitoring represents a major goal in intestinal transplantation. We analyzed the blood expression of Granzyme B (GB) and Perforin (PF) in the following pathological conditions after intestinal transplantation: acute rejection (AR), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). The diagnostic accuracy and the clinical utility of these tests are finally discussed. METHODS: GB and PF levels were measured by real time polymerase chain reaction on peripheral blood samples from 32 intestinal recipients. Blood samples (n=494) after comparison of clinical, histological, and microbiological data were assigned to the following groups: normal (n=307), AR (n=30), EBV infection (n=107), CMV infection (n=25), and PTLD (n=25). RESULTS: Mean levels of GB and PF in the AR (GB=279.7; PF=256.7), PTLD (GB=199; PF=185.9), EBV (GB=133.2; PF=143.7), and CMV (GB=151.3; PF=144) groups were significantly higher than in the normal group (GB=100.1; PF=101.1) (all P<0.05, except for PF in CMV infection). The best accuracy was obtained for the diagnosis of AR with sensitivity and specificity of 80% and 79% for GB and 70% and 79% for PF, respectively. The area under the receiver-operator characteristics curve was 0.87 for GB and 0.82 for PF. CONCLUSIONS: GB and PF are diagnostic molecular markers of AR. GB and PF blood levels are also increased in case of viral infections or PTLD. Serial blood testing for GB and PF might be predictive of early intestinal graft dysfunction and should be interpreted in the context of the histological and virological analyses.
Abstract: HYPOTHESIS: Several techniques have been introduced to minimize intraoperative bleeding in hepatic surgery. Ischemia-reperfusion injuries and intestinal congestion are the main drawbacks of vascular clamping. We hypothesized possible negative effects on early postoperative outcomes associated with different types of vascular clamping during liver resections and evaluated how attitudes have changed in the past 20 years. DESIGN: Retrospective review. SETTING: Academic research institute. PATIENTS: Patients who underwent 1260 consecutive liver resections, 338 of them (26.8%) in patients with cirrhosis. MAIN OUTCOME MEASURES: Postoperative complications and mortality were analyzed relative to liver disease, blood transfusion, vascular clamping, and type of liver resection. RESULTS: Vascular clamping was applied in 594 patients (47.1%). Operative mortality was 4.4% in the vascular clamping group and 2.9% in the nonclamped group, a statistically nonsignificant difference. On multivariate analysis, blood transfusion, major hepatectomies, and the presence of cirrhosis were statistically significantly associated with postoperative complications. Among the overall cohort and among patients with cirrhosis, there was statistically significantly reduced use of vascular clamping and of blood transfusion during the past 20 years. The lowest incidences of severe complications occurred among cases of continuous or hemihepatic clamping. Among 338 patients with cirrhosis, 155 (45.9%) received some type of vascular control; morbidity and mortality rates were similar in the groups with vs those without vascular control. On multivariate analysis, only blood transfusion was statistically significantly associated with postoperative morbidity. Postoperative complications were statistically significantly reduced among patients receiving intermittent compared with continuous clamping. CONCLUSIONS: Vascular clamping can be applied without additional risk during partial hepatectomy. Intermittent or hemihepatic clamping is preferable in patients with cirrhosis.
Abstract: BACKGROUND: We retrospectively reviewed our experience in combined liver-kidney (L-KT) and heart-kidney (H-KT) transplantations. PATIENTS AND METHODS: Between January 1997 and April 2007, we performed 25 L-KT and 5 H-KT. Patient mean age was 51+/-8 years in L-KT and 43+/-11 years in H-KT. The main cause of liver failure was chronic viral hepatitis (14 cases). Etiology of heart failure was dilated cardiomyopathy and hypertrophic cardiomyopathy (4 and 1 patients, respectively). The main causes of renal failure in L-KT were chronic glomerulonephritis (n=8) and polycystic disease (n=7). Etiology of renal failure in H-KT was interstitial nephropathy (n=2), vascular nephropathy (n=2), and chronic glomerulonephritis (n=1). RESULTS: Mean follow-up was 32+/-26 months in L-KT and 24+/-17 months in H-KT. Immunosuppression was cyclosporine-based (n=4) or tacrolimus-based (n=21) in L-KT and cyclosporine-based in H-KT. Acute rejection rate was 8% for both liver and kidney in L-KT; 80% (mild) for heart and 40% for kidney in H-KT. In the L-KT group, there was no primary graft nonfunction (PGNF). Two patients experienced liver delayed graft function (DGF); 1 patient required postoperative dialysis. One-year graft and patient survivals were both 84% and overall graft and patient survival was 76%. In the H-KT group, 3 patients needed postoperative dialysis and 1 required a cardiac assistance device for 48 hours; overall graft and patient survival was 100% with good cardiac and renal functions. CONCLUSION: Our experience confirmed that H-KT and L-KT are safe procedures, offering good long-term results.
Abstract: OBJECTIVE: We assessed the effect of tacrolimus on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) and compared it with that of the other calcineurin inhibitor, cyclosporine. INTRODUCTION: HCC recurrence after LT can be favored by overexposure to cyclosporine. Tacrolimus is now the most widely used main immunosuppressant after LT; its possible effect on HCC recurrence has never been investigated. MATERIALS AND METHODS: One hundred and thirty nine HCC patients who had LT were reviewed; 60 of them were administered tacrolimus, and 79, cyclosporine. The exposure to the drugs was calculated with the trapezoidal rule in each patient, using blood levels measured after transplantation and compared with HCC recurrence together with several clinical and pathologic risk factors. RESULTS: HCC recurred in 12 of the 60 (20%) patients under tacrolimus in comparison with that in 9 of the 79 (11.4%) patients under cyclosporine; however, the proportion of poorly differentiated and more advanced tumors was significantly higher in the tacrolimus group than in the cyclosporine group. Exposure to tacrolimus was 11.6 +/- 1.5 ng/mL in patients with recurrence and 8.6 +/- 1.7 ng/mL in those without recurrence (P < 0.001). The optimal cut-off values of exposure identified with receiver operating characteristics analysis to categorize the risk of recurrence were 10 ng/mL for tacrolimus (area under the curve (AUC) = 0.913) and 220 ng/mL for cyclosporine (AUC = 0.752). In the tacrolimus group, high drug exposure independently predicted recurrence (P = 0.005). Multivariate analysis, including all patients (tacrolimus + cyclosporine) characterized higher exposure to immunosuppression (P = 0.01), alpha-fetoprotein levels (P = 0.001), tumor grading (P = 0.009), and microvascular invasion (P = 0.04) as independent predictors of HCC recurrence. CONCLUSIONS: Just as it is with cyclosporine, overexposure to tacrolimus increases the risk of HCC recurrence after LT. Careful management of calcineurin inhibitors is recommended in HCC patients.
Abstract: At present no reports on gene expression profiling of liver metastases from colorectal cancer are available. We identified two different signatures using Affymetrix platform: epidermal growth factor receptor pathway was upregulated in metachronous lesions, whereas the pathway mainly related to angiogenesis was in synchronous lesions. Synchronous or metachronous liver metastases could be treated differently on the basis of different molecular pathways.
Abstract: Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed in patients having undergone liver transplantation (LTx). These alterations are probably multifactorial in origin, and cluster to generate a metabolic syndrome (MS), increasing the risk of cardiovascular events. We assessed the prevalence of MS (National Cholesterol Education Program-Adult Treatment Panel III criteria) in 296 LTx patients in the course of regular follow-up, at least 6 months after transplantation (median, 38 months). Several pre-LTx and post-LTx data were collected to identify the factors associated with the presence of MS. In a subset of 99 patients, insulin resistance was measured by the homeostasis model assessment. High blood pressure was present in 53% of cases, hyperlipidemia in 51%, high glucose in 37%, and enlarged waist circumference in 32%. Overall, MS (defined as 3 or more of the above features) was present in 44.5% of cases. Insulin resistance (homeostasis model assessment > 2.7) was observed in 41% of cases. Hypertension and hyperlipidemia were more frequent in subjects on cyclosporine than in tacrolimus-treated cases, whereas the type of immunosuppressive drug had no effect on the prevalence of diabetes, enlarged waist, and MS. In a logistic regression analysis, only pre-LTx body mass index (odds ratio, 1.20), body mass index increase (odds ratio, 1.18), and pre-LTx diabetes (odds ratio, 2.36) predicted MS; age, gender, etiology of liver disease, time from LTx, type of immunosuppressive drug, and previous hepatocellular carcinoma were removed from the model. Disorders related to MS are frequent in LTx patients, and are related to both pre-LTx conditions and to weight gain. Weight control is mandatory in LTx patients to prevent risk factors of premature atherosclerosis.
Abstract: Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC <or= 5 cm or less than or equal to three HCCs <or= 3 cm. We prospectively evaluated the possibility of slightly extending these criteria in a down-staging protocol, which included patients initially outside conventional criteria: single HCC 5-6 cm or two HCCs <or= 5 cm or less than six HCCs <or= 4 cm and sum diameter <or= 12 cm, but within Milan criteria in the active tumors after the down-staging procedures. The outcome of patients down-staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention-to-treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down-staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow-up of 2.5 years after transplantation, the 1 and 3 years' disease-free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down-staging. The actuarial intention-to-treat survival was 27/48 patients (56.3%) in the down-staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down-staging criteria provide a comparable outcome to the conventional criteria.
Abstract: BACKGROUND/AIMS: Patients with hepatocellular carcinoma on the waiting list for liver transplantation are excluded due to causes related to liver failure and tumor progression. We analyze the various factors to suggest a new liver transplant priority. METHODOLOGY: We evaluated the outcome on the list of 309 patients with hepatocellular carcinoma and causes of drop-out from the list were divided as death, "too sick" and tumor progression. The impact of model for end stage liver disease score, tumor stage and waiting time on the causes of drop-outs was evaluated. RESULTS: During the study period, 197 patients had a liver transplantation, 50 were still on the list and the remaining 62 were removed from the list (28 deaths, 30 tumor progressions, and 4 "too sick"). The receiver operating characteristic curves analysis showed that the model for end stage liver disease score predicted the rate of deaths on the list at 1-year (p<0.001). The waiting time and the tumor stage predicted the rate of drop-outs for tumor progression at 1-year on the list (p<0.05). CONCLUSIONS: Patients with hepatocellular carcinoma on the waiting list should have priority based on their model for end stage liver disease score, waiting time with tumor and tumor stage.
Abstract: BACKGROUND: Patients with adhesive small intestine obstruction (ASIO) are difficult to evaluate and to manage and their treatment is still controversial. The diagnostic and therapeutic role of water-soluble contrast medium (Gastrografin) in ASIO is still debated. This study was designed to determine the therapeutic role of Gastrografin in patients with ASIO. METHODS: The study was a multicenter, prospective, randomized, controlled investigation. The primary end points were the evaluation of the operative rate reduction and shortening the hospital stay after the use of Gastrografin. A total of 76 patients were randomized into two groups: the control group received traditional treatment (TT), whereas the study group (GG) received in addition a Gastrografin meal and follow-through study immediately. Patients with Gastrografin in the colon within 36 hours were considered to be partially obstructed and submitted to nonoperative management. If after 36 hours, the Gastrografin had not entered the colon, the subjects were submitted to laparotomy. RESULTS: No significant differences were found in age, sex, intravenous administration of prokinetics, incidence and characteristics of the previous procedures in surgical history of the patients, previous episodes of ASIO and surgery for adhesiolysis, or duration of symptoms before admission. In the GG group obstruction resolved subsequently in 31 of 38 cases (81.5%) after a mean time of 6.4 hours. The remaining seven patients were submitted to surgery, and one of them needed bowel resection for strangulation. In the control group, 21 patients were not submitted to surgery (55%), whereas 17 showed persistent untreatable obstruction and required laparotomy: 2 of them underwent bowel resection for strangulation. The difference in the operative rate between the two treatment groups reached statistical significance (p = 0.013). The time from the hospital admission for obstruction to resolution of symptoms was significantly lower in the GG group (6.4 vs. 43 hours; p < 0.01). The length of hospital stay revealed a significant reduction in the GG group (4.7 vs. 7.8 days; p < 0.05). This reduction was more evident in the subset of patients who did not require surgery (3 vs. 5.1 days; p < 0.01). No GG-related complications or significant differences in major complications and the relapse rate were found (relapse rate, 34.2% after a mean time to relapse of 6.3 months in the GG group vs. 42.1% after 7.6 months in the TT; p = not significant). CONCLUSIONS: Data showed that the use of Gastrografin in ASIO is safe and reduces the operative rate and the time to resolution of obstruction, as well as the hospital stay.
Abstract: Small bowel transplantation can be associated with large fluid shifts due to massive blood loss, dehydration, vascular clamping, long ischemia times, intraoperative visceral exposure, intestinal denervation, ischemic damage, and lymphatic interruption. Fluid management is the major intra- and postoperative problem after small bowel and multiple organ transplantation, because of the highly variable fluid and electrolyte needs of the transplant recipient. Third-space fluid requirements can be massive; inadequate replacement leads to end-organ dysfunction, particularly renal failure. Several liters of fluid may be required in the initial 24 to 48 hours postoperatively to simply maintain an adequate central pressure to provide a satisfactory urine output. During this time patients may develop extensive peripheral edema, which dissipates over the next few days as the fluids are mobilized and requirements stabilize. Based on our experience in 29 cases of intestinal transplantation and 4 cases of multivisceral transplantation, we have herein described the intraoperative fluid management and hemodynamic changes. Our study confirmed a large quantity of fluid administration during and after small bowel transplantation that required adequate volume monitoring.
Abstract: BACKGROUND: The use of the Model for End-stage Liver Disease (MELD) score to prioritize patients on liver waiting lists and to share organs among centers was effective according to US data, but few reports are available in Europe. MATERIALS AND METHODS: We evaluated the outcome of 887 patients listed between April 2004 and July 2006 in a common list by two transplant centers (University of Bologna [BO] and University of Modena [MO] ordered according to the MELD system. Patients with hepatocellular carcinoma had a score calculated according to their real MELD, tumor stage, and waiting time. RESULTS: Five hundred eighty-six (67%) patients were listed from BO and 291 (33%) from MO. The clinical features of recipients (sex, age, blood group, and real MELD) were comparable between centers. The number of liver transplantations performed was 307, and 273 (89%) recipients had a calculated MELD >or=20. Liver transplantations were equally distributed according to the number of patients listed: 215 out of 586 (36.7%) for BO and 92 out of 291 (31.6%) for MO. The median real MELD of patients transplanted was 20, and 246 out of 307 (80.1%) grafts transplanted were functioning. The dropouts from the list were 124 (14%), and 87 (70%) of these patients had a calculated MELD >or=20. CONCLUSION: The MELD system was effective to share livers among the two Italian centers. According to this policy, livers were allocated to the recipients with the highest probability of dropout and who had a satisfactory survival after liver transplantation.
Abstract: ABSTRACT: BACKGROUND: In some randomized trials successful laparoscopic cholecystectomy for cholecystitis is associated with an earlier recovery and shorter hospital stay when compared with open cholecystectomy. Other studies did not confirm these results and showed that the potential advantages of laparoscopic cholecystectomy for cholecystitis can be offset by a high conversion rate to open surgery. Moreover in these studies a similar postoperative programme to optimize recovery comparing laparoscopic and open approaches was not standardized. These studies also do not report all eligible patients and are not double blinded. DESIGN: The present study project is a prospective, randomized investigation. The study will be performed in the Department of General, Emergency and Transplant Surgery St Orsola-Malpighi University Hospital (Bologna, Italy), a large teaching institutions, with the participation of all surgeons who accept to be involved in (and together with other selected centers). The patients will be divided in two groups: in the first group the patient will be submitted to laparoscopic cholecystectomy within 72 hours after the diagnosis while in the second group will be submitted to laparotomic cholecystectomy within 72 hours after the diagnosis. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER ISRCTN27929536 - The ACTIVE (Acute Cholecystitis Trial Invasive Versus Endoscopic) study. A multicentre randomised, double-blind, controlled trial of laparoscopic versus open surgery for acute cholecystitis in adults.
Abstract: BACKGROUND: Marginal organs not suitable for single kidney transplantation are considered for double kidney transplantation (DKT). Herein we have reviewed short and long-term outcomes of DKT over a 7-year experience. PATIENTS AND METHODS: Between 2001 and 2007, 80 DKT were performed in the transplant centers of Bologna, Parma, and Modena, Italy. Recipient mean age was 61+/-5 years. The main indications were glomerular nephropathy (n=33) and hypertensive nephroangiosclerosis (n=14). Mean HLA A, B, and DR mismatches were 3.1+/-1.2. Donor mean age was 69+/-8 years and mean creatinine clearance was 75+/-27 mL/min. Almost all kidneys were perfused with Celsior solution. Mean cold ischemia time was 17+/-4 hours and mean warm ischemia time was 41+/-17 minutes. Mean biopsy score was 4.4. Immunosuppression was based on tacrolimus (n=52) or cyclosporine (n=26). RESULTS: Fifty (62.5%) patients displayed good postoperative renal function. Thirty (37.5%) experienced acute tubular necrosis and required postoperative dialysis treatment; 8 acute rejections occurred. Urinary complications were 13.7% with 8/11 requiring surgical revision. There were 6 surgical reexplorations: intestinal perforation (n=2), bleeding (n=3), and lymphocele (n=1). Two patients lost both grafts due to vascular and infectious complications at 7 or 58 days after transplantation. Two patients underwent intraoperative transplantectomy due to massive vascular thrombosis. Four (5%) patients underwent transplantectomy of a single graft due to vascular complications (n=2), bleeding (n=1), or infectious complications (n=1). Graft and patient survivals were 95% and 100% versus 93% and 97% at 3 versus 36 months, respectively. CONCLUSIONS: DKT is a safe approach for organ shortage. The score used in this study is useful to determine whether a kidney should be refused or accepted.
Abstract: This study reports major gastrointestinal (GI) complications among a group of 1611 patients following kidney transplantation. The immunosuppressive regimen changed somewhat during the course of the study but included azathioprine, prednisolone, antilymphocyte globulin, cyclosporine, tacrolimus, mycophenolate mofetil, and sirolimus. Perforations occurred in the colon (n=21), small bowel (n=15), duodenum (n=6), and stomach (n=4). Nearly 50% of the complications occurred while patients were being given high-dose immunosuppression to manage either the early postoperative period or acute rejection episodes. Of the 46 patients affected, 11 (24%) died as a direct result of the GI complication. This high mortality appeared to be related to the effects of the immunosuppression and the associated response to sepsis. Reduction of these complications may be achieved by improved surgical management, preventive measures, prompt diagnosis, and a reduced immunosuppressive protocol.
Abstract: Acute cellular rejection (ACR) episodes in intestinal transplant recipients are diagnosed by histologic and clinical findings. We have applied zoom video endoscopy and the use of serologic markers granzyme B (GrB) and perforin (PrF) to monitor rejection together with conventional tools. Seven hundred eighty-two blood samples (obtained at the time of the biopsy) collected from 34 recipients for GrB/PrF upregulation were positive among 64.9% of ACRs during a 3-year follow-up. Considering only the first year results posttransplantation, it reached 73.1% of rejection events. Zoom videoendoscopy was used by our group in 29 recipients of isolated intestine (n = 24) or multivisceral transplantations (n = 5) to enable observation of villi and crypt areas. From more than 270 procedures, 84% of the zoom findings agreed with the histologic results, namely, a specificity of 95%. In fact, during ongoing ACR, villi were altered in 80% of cases. Both procedures were helpful to support conventional histologic findings and clinical symptoms of ACR in intestinal transplant recipients.
Abstract: PURPOSE: Although at present nonabsorbable meshes are the preferred material for tension-free hernioplasty, some problems with their use have yet to be addressed (i.e., chronic pain and infections). In order to address these disadvantages, a collagen-based material, the porcine small-intestinal submucosa mesh (Surgisis Inguinal Hernia Matrix, Cook Surgical, Bloomington, IN, USA), has recently been developed for hernia repair. METHODS: With the aim of investigating the clinical safety and effectiveness of Surgisis IHM inguinal hernia repair, we report our experience of 45 consecutive hernioplasties with a medium-term follow-up. The surgical technique for the use of this material in hernioplasty is described in detail. RESULTS: Although some local (i.e., seromas) and general (i.e., hyperpyrexia), complications appeared in the immediate postoperative period (all of them disappeared spontaneously), no rejection or infection was observed after operations. At the 2-year follow-up, a low degree of pain and discomfort and no recurrences were observed. CONCLUSIONS: We conclude that the Surgisis IHM hernioplasty is feasible with promising results and, from a clinical perspective, seems safe and effective.
Abstract: BACKGROUND: Due to the shortage of available cadaveric organs, living donor liver transplantation (LDLT) has been recently applied extensively in adults. The use of the left lobe should be encouraged because of donor safety, but frequently the metabolic requirements of severely cirrhotic patients are great and subsequent graft dysfunction is encountered after transplantation. The importance of increased portal inflow to the graft in previously severely cirrhotic patients and other hemodynamic changes in LDLT using left lobes are still under debate, as are the surgical modulations to correct them. In this study, we have reported an initial series of adult-to-adult LDLT using left lobes, underlining the hemodynamic changes encountered during the transplant and the surgical modulations we applied to correct them. METHODS: Eight adult recipients underwent left lobe liver transplantation from living donors. Portal vein pressure and central venous pressure were measured before and after surgical modulation. RESULTS: We encountered four cases of small-for-size syndrome. Two patients were retransplanted; the other two died. Seventy-five percent of our recipients survived and 50% did not require further surgery. CONCLUSION: Surgical portal inflow modulation should be considered in cases of left lobe liver transplantation between adults.
Abstract: BACKGROUND/AIMS: Induction with rabbit antithymocyte globulin (RATG) has been reported to be effective in cadaveric liver transplantation. The aim of this study was to compare two immunosuppressive protocols in adult living-related liver transplantation (LRLT). METHODOLOGY: From May 2001 through May 2003, 34 LRLT were performed. The first 17 patients (group 1) were treated with tacrolimus (TAC) and steroids. The next 17 patients (group 2) were treated with a steroid-sparing protocol using RATG. RESULTS: The one-year patient and graft survival was respectively 76.5% and 64.7% for group 1 and 88.2 and 76.5% for group 2 (p = 0.037 and p = NS, respectively). Incidence of acute cellular rejection was 41.2% in group 1 compared to 47% in group 2 (p = NS). Mean daily TAC dose at 6 months was 6.5 +/- 1.1 mg/day in group 1 and 3.2 +/- 0.9 mg/day in group 2 (p < 0.001). In group 1, 41.1% experienced CMV infection compared to 11.7% in group 2 (p = NS). CONCLUSIONS: These results suggest that this approach of RATG induction followed by postoperative, steroid-free, and low-dose TAC is safe and provides for adequate immunosuppression and similar outcome when compared to controls treated with standard TAC and steroid immunosuppression.
Abstract: PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors have been recently introduced in clinical practice after intestinal transplantation. We focused on Sirolimus (Rapamycin) to examine effects on rejection and graft survival following intestinal transplantation. PATIENTS AND METHODS: Twenty isolated intestinal recipients and 5 multivisceral patients (2 with liver) in our series were divided into 3 groups: patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who continued therapy longer than 3 months (n = 11); patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who received therapy less than 3 months because of side effects (n = 4); and a control group, who never received rapamycin (n = 10). RESULTS: During prolonged treatment combined with Tacrolimus (Prograf), both Sirolimus groups showed a decreased number of acute cellular rejections (P < .01). Cumulative 3-year graft and patient survival rates were 81% in the Sirolimus greater than 3 months group, 100% in the Sirolimus less than 3 months group, and 80% and 90% in the control group, respectively (P = .63 and P = .62). CONCLUSION: In our experience, the use of mTOR-inhibitors in combination with calcineurin-inhibitors seemed to be more effective than monotherapy to reduce the number of rejections. Side effects can limit its use as maintenance therapy.
Abstract: We report a unique association of ruptured hepatocellular adenoma, focal nodular hyperplasia and granulomatous hepatitis in a young woman taking oral contraceptives. Diffuse granulomatous hepatitis was found in the liver parenchyma, which was associated with a large granulomatous mass of the left lobe and loco-regional granulomatous lymphadenitis. We cannot give a full explanation of the situation, which represented a challenge in the diagnosis and in the treatment of this patient.
Abstract: PATIENTS AND METHODS: Between December 2000 and November 2006, 28 isolated intestinal transplants and nine multivisceral transplants (five with liver) from cadaveric donors have been performed for short gut syndrome (n = 15), chronic intestinal pseudo-obstruction (n = 10), Gardner's syndrome (n = 9), radiation enteritis (n = 1), intestinal atresia (n = 1), and massive intestinal angiomatosis (n = 1). Indications for transplantations were: loss of venous access, recurrent sepsis due to central line infection, and/or major electrolyte and fluid imbalance. Liver dysfunction was present in 19 cases. All patients were adults of median age at transplant of 34.7 years and mean weight 59.6 kg. All recipients were on total parenteral nutrition for a mean time of 38.8 months. Mean donor/recipient body weight ratio was 1.1. RESULTS: The mean follow-up was 892 +/- 699 days. Twenty-five patients were alive (67.5%) with 3-year patient survivals of 70% for isolated intestinal transplantations and 41% for the multivisceral transplantations (P = .01). The mortality rate was 32.5% with losses due to sepsis (63%) or rejection. Our 3-year graft survival rates were 70% for isolated intestinal transplantations and 41% for multivisceral transplantations (P = .02); graftectomy rate was 16%. These were 88% of grafts working properly with patients on regular diet with no need for parenteral nutrition. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the doses of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis, mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe acute chronic rejections.
Abstract: The psychological construct of coping has been studied extensively in other medical populations and has more recently been applied in the field of transplant psychology. Coping can be defined as all abilities used by people to face problematical and stressful situations, as the data in literature describe the experience of transplantation. The purpose of this study was to describe the coping styles used by 25 intestinal transplant recipients. To assess the coping strategies, we used the Italian version of Coping Orientation to Problems Experienced (COPE) by Sica, Novara, Dorz, and Sanavio (1997). The authors divided these strategies into three classes: problem-focused, emotion-focused, and potentially disadaptive strategies. This questionnaire is usually used in a medical setting. Even if the long process of psychological-clinical adaptation required by intestinal transplantation put patients in a passive acceptance of their situation and their incapacity to face it, our patients showed high levels of problem-focused strategies, indicators of positive outcomes for this intervention. Anyway, this is a slow and gradual path that goes with the psychological distress and the need for a peculiar psychological support of problem-focused strategies. The result suggested that assessment of coping strategies should be explored in intestinal transplant to encourage the use of action-oriented methods and discourage those with possible negative effects.
Abstract: BACKGROUND/AIMS: To assess the effect of long-term maintenance of steroids on HCV recurrence after liver transplantation (LT), that is still controversial, a prospective multicentre trial was conducted at the centres of Bologna and Padua, Italy. METHODS: From September 2002, 47 eligible HCV positive LT recipients were randomized to receive 2 different steroid schedules in association with tacrolimus: group A: rapid tapering and withdrawal 91 days after LT group B: slow tapering and withdrawal 25 months after LT. Thirty-nine patients were assessable: 23 in group A and 16 in group B. Donor and recipient characteristics were similar in the two groups. Median follow-up was 841 days (130-1376). One hundred liver biopsies were performed, and every patient had a biopsy at month 12. RESULTS: Twenty-two out of 23 (95, 65%) patients in group A and 15 out of 16 (93, 75%) in group B had histologically-confirmed HCV recurrence. Twelve-month histology showed advanced fibrosis (score 3 or 4) in 42.1% of the patients in group A versus 7.6% in group B (P=0.03). One-and 2-year advanced fibrosis-free survival were 65.2 and 60.8 in group A and 93.7% in group B (P=0.03 and =0.02, respectively). CONCLUSIONS: Slow tapering of steroids reduced the progression of recurrent hepatitis C after LT.
Abstract: Surgisis IHM is an acellular biomaterial derived from porcine small intestinal submucosa (SIS) that induces site-specific remodeling in the organ or tissue into which it is placed. Previous animal studies have shown that the graft recipient mounts a helper T type 2-restricted immune response to the SIS xenograft without signs of rejection. The aims of this study were to evaluate the immune response to the SIS implant in a small series of humans and to examine the long-term clinical acceptance of the xenograft in these patients. Five consecutive male patients (mean age 56 years, range 34-68) who underwent inguinal hernioplasty with Surgisis IHM were assessed at 2 weeks, 6 weeks, and 6 months after implant for SIS-specific, alpha-1,3-galactose (alpha-gal) epitope and type I collagen specific antibodies. All five patients were also clinically assessed up to 2 years for signs of clinical rejection, hernia recurrence, and other complications. All 5 patients implanted with Surgisis IHM produced antibodies specific for SIS and alpha -gal with a peak between 2 and 6 weeks after implantation. By 6 months, all patients showed decreasing levels of anti-SIS antibodies. Two patients developed a transient, mild local seroma that resolved spontaneously. None of the patients showed any clinical signs of rejection, wound infection, hernia recurrence, or other complications in the follow-up out to 2 years. Thus, this study showed that in a small series of patients the SIS elicits an antibody response without clinical rejection of the xenograft and minimal postoperative complications.
Abstract: BACKGROUND: Analysis of intraoperative changes of metabolic, hemodynamic, and coagulative parameters is useful to detect early ischemia-reperfusion damage after intestinal transplant. METHODS: The objective of our study is to correlate the histological damage at the end of transplant in relation to the intraoperative changes after reperfusion. The histological aspect was graded according to Park's classification at the end of the surgical procedure with biopsies of the graft. Patients were divided into two groups according to the presence or absence of histological damage of the small bowel wall: group A (normal mucosa/minimal damage: Park's grades 0-1) and group B (mucosal damage: Park's grades 2-8). RESULTS: Significant hemodynamic, metabolic, and coagulative disorders were observed in group B. Consequently, these disorders are thought to be early indicators of graft damage. CONCLUSIONS: Actual monitoring procedures used for postoperative graft surveillance remain paramount in detecting postoperative intestinal dysfunction, but the indicators described in this paper could represent a further help in intraoperative and postoperative management.
Abstract: The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.
Abstract: OBJECTIVE: To examine modifications of acid-base balance of cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Acid-base disorders are frequently observed in cirrhotics; however, modifications during hepatectomy and their impact on prognosis have never been investigated. METHODS: Two hundred and two hepatectomies for HCC on cirrhosis were reviewed. Arterial blood samples were collected immediately before and at the end of resection. Preresection and postresection acid-base parameters were compared and related to patient characteristics and postoperative course. The accuracy of acid-base parameters in predicting postoperative liver failure, defined as an impairment of liver function after surgery that led to patient death or required transplantation, was assessed using receiver operating characteristic analysis (ROC). RESULTS: All patients showed a significant reduction in pH, bicarbonate, and base excess at the end of hepatectomy (P < 0.001 in all cases), worsened by intraoperative blood loss (P < 0.010) and preoperative Model for end-stage liver disease score > or =11 (P < 0.010). ROC curve analysis identifies patients with postresection bicarbonate <19.4 mmol/L at high risk for liver failure (50.0%) whereas levels >22.1 mmol/L did not lead to the event (0%; P < 0.001). Postoperative prolongation of prothrombin time and increases in bilirubin, creatinine, and morbidity were also more frequent in patients with lower postresection bicarbonate, resulting in a longer in-hospital stay. CONCLUSION: In cirrhotic patients, a trend toward a relative acidosis can be expected during surgery and is worsened by the severity of the underlying liver disease and intraoperative blood loss. Postresection bicarbonate level lower than 19.4 mmol/L is an adverse prognostic factor.
Abstract: Impaired hepatic function and histology have been observed in experimental models of diversion of the portal vein blood inflow from the liver and among patients with intestinal failure. Survival after total enterectomy, pancreatectomy, and portal vein ligation, and the effect of such a condition on liver function have never been reported in humans. Herein a 32-year-old woman with familial adenomatous polyposis and multiple desmoid tumors involving the mesentery and the retroperitoneum underwent total enterectomy and pancreatectomy followed by en bloc transplantation of the stomach, small bowel, and pancreas. Due to early graft failure, the patient underwent graftectomy, ligation of the portal vein, and external drainage of the common bile duct. Liver function tests were checked daily and a liver biopsy performed 15 days after graftectomy. The patient died of a ruptured mycotic aneurysm of the abdominal aorta at 27 days after the graftectomy. Liver function tests remained normal throughout the postoperative period; liver biopsy showed normal hepatic architecture with mild portal inflammation and cholestasis and spotty necrosis. Total enterectomy with pancreatectomy and ligation of the portal vein are compatible with survival in humans (at least in the short term), allowing normal hepatic function with minimal histological alterations to the liver.
Abstract: Ductal adenocarcinoma of pancreas represents one of the most aggressive tumor as demonstrated by 3- and 5-year survival rates. Involvement of mesenteric pedicle affects both the possibility to perform a tumor-free margin resection and accounts for most exploratory laparotomy for locally advanced disease. The ex vivo resection of the tumor (autotransplantation) after total exenteration and perfusion of the intestine might have a role to overcome some technical obstacles. So far, only 5 patients have been reported to have undergone small-bowel autotransplantation for tumor involving the mesenteric root. We describe 2 cases of adenocarcinoma of pancreas involving mesenteric root treated by small-bowel autotransplantation. Both patients survived from the procedure and were discharged home on postoperative days 16 and 29, respectively. The tumor was resected with free surgical margins, and both patients underwent adjuvant treatment. Intestinal autotransplantation can represent a significant technical advance for increasing the resectability rate and, ultimately, the survival rate for advanced adenocarcinoma of the pancreas in highly selected patients.
Abstract: INTRODUCTION: Induction therapy has been recently adopted for intestinal transplant. PATIENTS AND METHODS: We compared during first 30 days post-transplantation 29 recipients, allocated in two groups, treated with Daclizumab (Zenapax) or Alemtuzumab (Campath-1H). RESULTS: During first month, 45% of Daclizumab recipients experienced six acute cellular rejections (ACRs) of mild degree, while 63% of them developed an infection requiring treatment. We found three acute cellular rejections in 17.6% of Alemtuzumab recipients, two with moderate degree; 64.7% of them required treatment for infection. DISCUSSION AND CONCLUSIONS: Graft and patient 3-years cumulative survival rate were not significantly different between groups. Alemtuzumab seems to offer a better immunosuppression during first month.
Abstract: BACKGROUND: Complicated hernias often involve contaminating surgical procedures in which the use of polypropylene meshes can be hazardous. Prostheses made of porcine dermal collagen (PDC) have recently been proposed as a means to offset the disadvantages of polypropylene meshes and have since been used in humans for hernia repairs. The aim of our study was to evaluate the safety and efficacy of incisional hernia repair using PDC as a mesh in complicated cases involving contamination. METHODS: A prospective study of hernia repair of complicated incisional hernias with contamination using PDC grafts was carried out at the Department of General, Emergency and Transplant Surgery of St Orsola-Malpighi University Hospital. RESULTS: From January 2004 up to the writing of this article, seven patients were treated for complicated incisional hernias with a PDC prosthesis. In six out of seven patients a bowel resection was carried out. There were not surgical complications. Morbidity was 14.2%. No recurrences and wound infections were observed. CONCLUSIONS: Incisional hernioplasty using PDC grafts is a potentially safe and efficient approach in complicated cases with contamination.
Abstract: BACKGROUND: Despite its accuracy, the model for end-stage liver disease (MELD), currently adopted to determine the prognosis of patients with liver cirrhosis, guide referral to transplant programmes and prioritise the allocation of donor organs, fails to predict mortality in a considerable proportion of patients. AIMS: To evaluate the possibility to better predict 3-month liver disease-related mortality of patients awaiting liver transplantation using an artificial neural network (ANN). PATIENTS AND METHODS: The ANN was constructed using data from 251 consecutive people with cirrhosis listed for liver transplantation at the Liver Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival on 188 patients, tested on the remaining 63 (internal validation group) unknown by the system and finally on 137 patients listed for liver transplantation at the King's College Hospital, London, UK (external cohort). Predictions of survival obtained with ANN and MELD on the same datasets were compared using areas under receiver-operating characteristic (ROC) curves (AUC). RESULTS: The ANN performed significantly better than MELD both in the internal validation group (AUC = 0.95 v 0.85; p = 0.032) and in the external cohort (AUC = 0.96 v 0.86; p = 0.044). CONCLUSIONS: The ANN measured the mortality risk of patients with cirrhosis more accurately than MELD and could better prioritise liver transplant candidates, thus reducing mortality in the waiting list.
Abstract: PATIENTS AND METHODS: Between December 2000 and December 2005, 25 isolated intestinal transplants from cadaveric donors have been performed for short gut syndrome (short bowel syndrome, 52%), chronic intestinal pseudo-obstruction (24%), Gardner syndrome (16%), radiation enteritis (4%) and massive intestinal angiomatosis (4%). Indications for transplantation were: loss of venous access, recurrent sepsis due to central line infection, major electrolyte and fluid imbalance. Liver dysfunction was present in 13 cases. All patients were adult; median age was 36.3 yr and mean weight at transplantation 61.6 kg. All recipients were on life-threatening parenteral nutrition for a mean time of 23.7 months. Mean donor/recipient body weight ratio was 1.08. Rejection monitoring was accomplished by graft ileoendoscopies and intestinal biopsies through the temporary ileostomy. Our immunosuppressive regimen was based on induction therapy with three different protocols: daclizumab for induction, tacrolimus and steroids as maintenance therapy; alemtuzumab for induction and low-dose tacrolimus as maintenance; thymoglobulin for induction and maintenance based on low-dose tacrolimus. Closure of the abdomen at the end of transplantation represented a technical problem with several options performed: graft reduction, only skin closure, prothesic meshes, abdominal closure in two steps, cutaneous flaps and abdominal wall transplant in one case. RESULTS: The mean hospital stay was 37 days. The mean follow-up 27 months. Twenty patients are alive (80%) with two- and five-yr patient survival rate of 80% and 66%; mortality rate was 20% due to sepsis in all cases. Our two- and five-yr graft survival rate is 76% and 64%, graftectomy rate was 16%. Sixteen grafts are working properly, with no need of parenteral nutrition. We diagnosed 35 mild acute cellular rejection (ACRs), seven moderate ACRs and three severe ACRs (two needed graftectomy). We experienced two episodes of chronic rejection biopsy-proven. Rapamicine was added in case of renal failure or biopsy-proven intestinal rejection. Graft-vs.-host disease was not seen in our series while post-transplant lymphoproliferative disease in two cases. After discharge, the most common indication for medical support was dehydration. The abdominal wall transplant did not experience any rejection. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the amount of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis and the mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe ACR.
Abstract: BACKGROUND: Recently, new immunosuppressive protocols after intestinal transplantation have been proposed to avoid steroids use and their adverse effects. We evaluated the impact of steroids on survival and post-transplant complications in our experience. PATIENT AND METHODS: In our retrospective study we considered the mean daily dosage of steroids received by 25 patients after intestinal/multivisceral transplantation (minimal follow-up was six months). We analyzed graft and patient survival rates, correlation with rejection and infectious episodes and steroids side effects. RESULTS: After a mean follow-up of three yr, we did not find any significant difference in steroid doses between our immunosuppressive protocols. Patients with a mean dosage of prednisone higher than 20 mg/d experienced a lower graft (p = 0.009) and patient (p = 0.02) survival rate. The side effects of steroids after transplant were similar. Infections were more frequent during steroids administration (p = 0.04). Discussion and conclusion: Steroids therapy may be useful to treat acute rejection, but in our experience high steroids regimen did not improve graft and patient survival, increasing infectious rate. We assumed that high dose of steroids can be avoided as maintenance therapy, except in selected cases.
Abstract: BACKGROUND: The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account. METHODS: We evaluated the outcome of 418 patients listed during 1 year whose MELD score was computed by two laboratories (lab 1 and lab 2). The two labs had different normality ranges for bilirubin (maximal normal value [Vmax]: 1.1 for lab 1 and 1.2 for lab 2) and creatinine (Vmax: 1.2 for lab 1 and 1.4 for lab 2). The outcome during the waiting time was evaluated by considering the liver transplantations and the dropouts, which included deaths on the list, tumor progression, and patients who were too sick. RESULTS: Although the clinical features of patients were similar between the two laboratories, 36 (13.1%) out of 275 were dropped from the list in lab 1, compared to 5 (3.5%) out of 143 in lab 2 (P<0.01). The differences were mainly due to the deaths on the list (8% lab 1 vs. 2.1% lab 2, P<0.05). The competing risk analysis confirmed the different risk of dropout between the two labs independently of the MELD score, blood group, and preoperative diagnosis. The bias on MELD calculation was considered and bilirubin and creatinine values were "normalized" to Vmax of lab 1 (corrected value=measured value x Vmax lab 1/Vmax lab 2). By comparing receiver operating characteristic curves, the ability of MELD to predict the 6-month dropouts significantly increased from an area under the curve of 0.703 to 0.716 after "normalization" (P<0.05). CONCLUSIONS: Normalization of MELD is a correct and good compromise to avoid systematic bias due to different laboratory methods.
Abstract: To ascertain whether postoperative antiplatelet therapy could reduce the incidence of hepatic artery thrombosis (HAT) after liver transplantation (LT), 838 consecutive adult whole-graft LTs performed from April 1986 to August 2005 that survived beyond the first postoperative month were reviewed. Antiplatelet prophylaxis with aspirin (100 mg per day) was given following 236 LTs; the median starting time was 8 postoperative days (range, 1 to 29 days). Early HAT was observed in 29 cases. The median time of presentation was 5 postoperative days (range, 1-28 days), and the effect of aspirin on this type of complication was therefore not assessable. A total of 14 cases of late HAT were observed (1.67 %). The median time of presentation was 500.5 days (range, 50-2,405 days). Late HAT occurred in 1 out of 236 (0.4 %) patients who were maintained under antiplatelet prophylaxis and in 13 out of 592 (2.2 %) who did not receive prophylaxis (P = 0.049). Risk factors for late HAT (grafts retrieved from donors who died of cerebrovascular accident and/or use of iliac conduit at transplantation) were present in 498 LTs: in this group the incidence of late HAT was significantly higher among cases who did not receive prophylaxis (12/338 vs 1/160; p = 0.037). There were no hemorrhagic complications associated with the use of aspirin. In conclusion,antiplatelet prophylaxis can effectively reduce the incidence of late HAT after LT, particularly in those patients at risk for this complication.
Abstract: Many patients undergoing intestinal or multivisceral transplantation have a past history of complete midgut removal with the loss of the domain of the abdominal compartment or have severely damaged abdominal walls from repeated laparotomies, tumours or enterocutaneous fistulae. These patients may encounter severe abdominal wall closure problems at the end of transplantation, resulting in increased morbidity and mortality. It is, therefore, of paramount importance to properly cover transplanted organs in order to reduce postoperative complications. Abdominal wall transplantation was recently proposed for closure of patients undergoing both small-bowel and multivisceral transplantation: the results are encouraging. However, the technical procedure proposed requires the procurement of long segments of iliac vessels as far as the vena cava and the aorta. Since donor multiorgan procurement involves many surgical teams, the removal of these vessels, with the abdominal graft, led to their unavailability for vascular surgeons. Here we present three consecutive cases of abdominal wall transplantation in which, by taking advantage of microsurgical experience, we were able to carry out a transplantation of the abdominal wall by direct anastomosis of the epigastric vessels, obtaining a very good outcome.
Abstract: Although at present nonabsorbable meshes are the preferred material for tension-free hernioplasty, some problems with their use are still to be addressed (i.e., chronic pain and infections). To address these disadvantages, a collagen-based material, the porcine small intestinal submucosa mesh, has recently been developed for hernia repair. The technique to use this material in performing an hernioplasty is described. A preshaped Surgisis(R) Inguinal Hernia Matrix (IHM)trade mark is fashioned as appropriate, with a slit 2 cm from its inferior edge to accommodate the spermatic cord, placed for at least 10 min into a dish with room-temperature normosaline to be rehydrated and then transferred to the already prepared and dissected inguinal region. After drawing its tails around the cord, the mesh is sutured to the inguinal ligament with a continuous suture of PDS II 2/0, starting from the pubic tubercle laterally up to the deep orifice. The fixation of the mesh to the internal oblique abdominal muscle and the rectus sheath is accomplished with interrupted stitches. An extra stitch is placed between the two tails to close the new deep orifice. We conclude that an hernioplasty using Surgisis(R) IHMtrade mark is feasible with promising results.
Abstract: BACKGROUND: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. METHODS: 9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. RESULTS: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a "probable autoimmune hepatitis" (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). CONCLUSIONS: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.
Abstract: The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes >/=50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with alpha-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment.
Abstract: Experimental evidence indicates that chronic mechanical sub-occlusion of the intestine may damage the enteric nervous system (ENS), although data in humans are lacking. We here describe the first case of enteric degenerative neuropathy related to a congenital obstruction of the gut. A 3-year and 9-mo old girl began to complain of vomiting, abdominal distension, constipation with air-fluid levels at plane abdominal radiology. Her subsequent medical history was characterized by 3 operations: the first showed dilated duodeno-jejunal loops in the absence of occlusive lesions; the second (2 years later) was performed to obtain full-thickness biopsies of the dilated intestinal loops and revealed hyperganglionosis at histopathology; the third (9 years after the hyperganglionosis was identified) disclosed a Ladd's band which was removed and the associated gut malrotation was corrected. Repeated intraoperative full-thickness biopsies showed enteric degenerative neuropathy along with reduced interstitial cells of Cajal network in dilated loops above the obstruction and a normal neuromuscular layer below the Ladd's band. One year after the latest surgery the patient tolerated oral feeding and did well, suggesting that congenital (partial) mechanical obstruction of the small bowel in humans can evoke progressive adaptive changes of the ENS which are similar to those found in animal models of intestinal mechanical occlusion. Such ENS changes mimic neuronal abnormalities observed in intestinal pseudo-obstruction.
Abstract: BACKGROUND: Mild and moderate vascular alterations in intestinal biopsies after isolated small bowel transplantation (SBT) have uncertain clinical significance. METHODS: We retrospectively investigated the incidence, association with acute cellular rejection (ACR), treatment, and outcome of mild and moderate vascular changes in 15 adult SBTs performed between December 2000 and October 2003. The semiquantitative Ruiz score for vascular changes in intestinal mucosa was used. RESULTS: A total of 332 biopsies were analyzed. All patients had at least one sample showing mild or moderate vascular injury, which was globally found in 117 biopsies (35% of the total; 29% mild and 6% moderate). No cases of severe vascular injury were observed. First appearance of vascular alterations occurred 2 to 36 days after SBT (median: 6). Patients with vascular injury had a higher incidence of associated ACR than patients without this feature (16% vs 5%, P = .001). Patients with moderate vascular injury were also more likely to have moderate-to-severe ACR than patients showing no or mild vascular changes (14% vs 2%; P = .015). Treatment of rejection was more frequently administered with simultaneous diagnosis of ACR than in cases of isolated vascular alterations (84% vs 26%; P < .0001). Only one graft (7%) was lost due to severe ACR. DISCUSSION: Mild and moderate vascular changes are common findings in early post-SBT biopsies. They are frequently associated with ACR and parallel its severity. The clinical impact of mild or moderate vascular injury appears to be of little relevance.
Abstract: AIM: We compared the health related quality of life (HRQOL) of stable patients on home parenteral nutrition (HPN) and of patients who underwent successful intestinal transplantation (ITx). METHODS: HRQOL was evaluated by the non-disease-specific Short Form 36 instrument, which examines eight specific domains and scores them on a scale of 0% to 100%. Patient scores were standardized for the sex-matched and age-matched group scores of the healthy population by calculating the Z-score (reduced value: Z-score < -1). RESULTS: Eighteen patients on HPN and 12 patients who underwent ITx were studied. The two groups did not differ for primary intestinal disease, cause of intestinal failure, presence of a stoma, body mass index, and employment and marital status. HPN Z-scores were physical functioning -2.3, physical role -1.5, body pain -1.0, general health -1.2, vitality -0.5, social functioning -0.9, emotional role -0.7, and mental health 0.0. ITx Z-scores were physical functioning -1.7, physical role -0.8, body pain 0.0, general health -0.4, vitality 0.0, social functioning -0.4, emotional role -0.3, and mental health 0.0. Only the body pain Z-scores differed significantly (P = .012). CONCLUSIONS: The value of the physical components of the SF-36 was reduced in all the components in the HPN patients and in the physical functioning component in the ITx patients. The mental health components were normal in both. Successful ITx showed a better subjective physical health feeling than stable HPN.
Abstract: PURPOSE: We report our experience with intestinal and multivisceral transplantation in Italy. METHODS: We performed 23 adult isolated intestinal transplants and seven multivisceral ones, three with liver, between December 2000 and June 2005. Indications for transplantation were loss of venous access (n = 14), recurrent sepsis (n = 10), and electrolyte-fluid imbalance (n = 6), 14 of whom also presented with total parenteral nutrition (TPN)-related liver dysfunction. Immunosuppression was based on induction agents like daclizumab (followed by tacrolimus and steroids) in the first period; alemtuzumab or thymoglobulin (with tacrolimus) in a second period after 2002. RESULTS: The mean follow-up was 742 +/- 550 days. Three-year patient actuarial survival rate was 88% for intestinal transplants and 42% for multivisceral (P = .015). Three-year graft actuarial survival rate was 73% for intestinal patients and 42.8% for multivisceral (P = .1). Graft loss was mainly due to rejection (57%). Complications were mainly represented by bacterial infections (92% of patients), relaparotomies (82%), and rejections (72%). Full bowel function without any parenteral nutrition or intravenous fluid support was achieved in 60% of recipients with functioning bowel including 95% on a regular diet. One patient underwent abdominal wall transplantation as well. DISCUSSION AND CONCLUSION: Intestinal transplantation has achieved high rates of patient and graft survival with even longer follow-up. Early referral of patients, especially in cases of TPN-liver disease, is mandatory to obtain good outcomes and avoid high mortality rates on the transplant waiting list. Immunosuppressive management remains the key factor to increase the success rate.
Abstract: Granzyme B (GrB) and perforin are promising immunological markers to predict acute rejection of transplanted organs. Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up.
Abstract: Transthyretin-related hereditary amyloidosis (ATTR) is genotypically/phenotypically heterogeneous. We investigated myocardial involvement in ATTR in a cohort of patients with a wide range of mutations. Clinical/echocardiographic follow-up of 41 consecutive symptomatic ATTR patients from a single referral center was analyzed according to TTR mutation. Diagnosis was based on histology, immunohistochemistry and genotyping. Median follow up was 40 months (range 8-120). Among the 12 different mutations identified, Val30Met was found in 10 patients and Glu89Gln in seven. Compared with Val30Met, Glu89Gln was associated with higher LV mass index, lower left ventricular ejection fraction and shorter E-wave deceleration time. All Glu89Gln carriers had cardiomyopathy, which was more severe (for left ventricular thickness, left ventricular mass and restrictive pathophysiology) than in the six affected Val30Met patients. Glu89Gln was independently associated with higher risk of major cardiovascular events among cardiomyopathy patients. This follow-up study of ATTR patients carrying a wide range of mutations indicates that (1) cardiac involvement is a very important component of phenotypic expression; and (2) genotype is an important source of heterogeneity in myocardial involvement, with Glu89Gln being associated with a severe, heart-driven prognosis. We think that combined heart-liver transplantation could be considered for Glu89Gln carriers with established, morphologically severe cardiomyopathy.
Abstract: The use of sirolimus as the main immunosuppressant in a calcineurin inhibitor-free regimen in the early postoperative period of liver transplantation (LT), when the incidence of rejection is the highest, has seldom been reported. We report six patients who received sirolimus in association with steroids only, at a median time of 10 days after LT (range 3-23). Tacrolimus, initially given as the standard immunosuppressant, was discontinued because of nephrotoxicity in three of these patients and neurotoxicity in the other three. Resolution of the neurological symptoms was observed in all cases and a marked improvement of the renal function in two of three patients. Two patients died, one of sepsis and the other of recurrent hepatitis C virus hepatitis, after 47 and 143 days respectively. Three patients developed acute rejection which responded to intravenous steroids. In this cohort of patients, the use of sirolimus appeared safe and provided an adequate prophylaxis against rejection, even though the drug was administered in the immediate postoperative period after LT.
Abstract: PURPOSE: We sought to evaluate liver function recovery after isolated intestinal transplantation in adults with irreversible intestinal failure. PATIENTS AND METHODS: Over a 5-year period, we transplanted 34 adult patients, 25 of whom received an isolated intestinal graft, 4 a multivisceral graft without a liver, and 5, a multivisceral graft with a liver. Among the group of patients transplanted with the isolated graft we selected 14 recipients with pretransplant liver dysfunction, namely, a serum bilirubin >2 mg/dL (normal value: 1.2) and/or transaminases >100 IU/mL (NV, 37/40). Other inclusion criteria were total parenteral nutrition, period > 3 months, no diagnosis of portal hypertension or cirrhosis. Two patients had biopsy-proven liver fibrosis. RESULTS: At discharge, all patients recovered liver function to normal values: mean bilirubin blood level was 0.9 +/- 0.96 mg/dL (range: 0.3-1.6) and mean transaminases were 26 +/- 9 and 31 +/- 18 IU/mL (range: 10-44/27-65). After a mean follow-up of 2 years, only one patient has an elevated alanine aminotransferase level without clinical signs of liver disease. Type of pretransplant liver disease did not impact on survival rates. CONCLUSION: In selected cases, an isolated intestinal or a multivisceral graft without a liver can represent a "liver salvage therapy" for an early failing liver in patients with irreversible intestinal failure. Pretransplant liver disease is not a negative prognostic factor.
Abstract: Liver resections are usually considered the treatment of choice for colorectal and neuroendocrine metastases. Recently, the morbidity and mortality rates for liver surgery have dramatically decreased. Therefore, hepatic resection has been applied in selected cases of non-colorectal, non-neuroendocrine hepatic metastases. We report our experience with three cases of liver metastases from lung carcinoma and review the literature, to evaluate the role of liver surgery for this indication.
Abstract: AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.
Abstract: BACKGROUND/AIMS: Evaluation of the short- and long-term outcome of liver resections for HCC in cirrhotic patients. METHODOLOGY: A retrospective analysis was performed on 106 consecutive cirrhotic patients with HCC resected between June 1974 and September 2002. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. RESULTS: Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumor recurrence appeared in 25 patients (23.5%). The 1-, 3-, and 5-year overall survival rates were 86.6%, 70.3%, and 60.6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86.3%, 58.1%, and 40.7%. Univariate analysis showed that viral etiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) are related to a worse long-term survival. Multivariate analysis showed that only the viral etiology of cirrhosis and the presence of multiple nodules were significant independent prognostic factors. CONCLUSIONS: Results after hepatic resection for HCC in cirrhotic patients can be improved by using a limited surgical approach. The viral etiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.
Abstract: BACKGROUND: Hepatectomy for hepatocellular carcinoma in cirrhosis is followed by an impairment of liver function that can lead to patient death. The model for end-stage liver disease (MELD) is considered an index of hepatic functional reserve, and its assessment on postoperative course may properly identify individuals at risk of liver failure. STUDY DESIGN: Two hundred hepatectomies for hepatocellular carcinoma in cirrhosis were reviewed. Irreversible postoperative liver failure was defined as an impairment of liver function after hepatectomy that led to patient death or required transplantation. The MELD scores at postoperative days (POD) 1, 3, 5, and 7 were calculated and kinetics of changes investigated with t-test; logistic regression was applied to identify predictive variables of postoperative liver failure. RESULTS: Kinetics of postoperative MELD score showed an impairment of liver function between PODs 1 and 3; 185 patients in whom postoperative liver failure did not develop showed a considerable decrease in MELD score between PODs 3 and 5 (11.9+/-2.8 and 10.6+/-2.4, respectively, p<0.001). On the contrary, 15 patients, who experienced the event, showed an increase in MELD score between PODs 3 and 5 (18.2+/-3.9 and 18.3+/-3.6, respectively; p=0.845). Multivariate analysis showed preoperative MELD score (p<0.001), major hepatectomy (p=0.028), and MELD score increase between PODs 3 and 5 (p=0.011) as independent predictors of irreversible postoperative liver failure. Scores are reported as mean+/-SD. CONCLUSIONS: Recovery from liver impairment after hepatectomy for hepatocellular carcinoma in cirrhosis starts from POD 3; MELD scores increasing between PODs 3 and 5 may identify patients at risk of liver failure and represents the trigger for beginning intensive treatment or evaluating salvage transplantation.
Abstract: BACKGROUND/AIMS: An aggressive surgical approach in the management of gallbladder cancer (GBC) has improved survival significantly in recent years. The aim of this retrospective study is to evaluate the long-term results of surgical treatment of GBC reassessed following the TNM staging system of the AJCC-2002. METHODOLOGY: The present series considers 118 patients with GBC treated between 1982 and 2003. Seventy-four cases (63%) were females and 44 (37%) males; overall age was 63 years (range 38-91). RESULTS: Among the 118 patients with GBC, 35 (36%) underwent radical surgery: 3 pTNM IA [3 cholecystectomy (CT)], 10 IB [3CT, 3 CT + hepatic resection (HR), 4 HR], 3 IIA (3 HR), 7 IIB (3 CT+HR+ bile duct resection (BDR), 3 HR, 1 hepatopancreatoduodenectomy +CT), 10 III [4 CT+HR, 5 extensive HR (eHR), 1 HR+right colectomy+BDR+total gastrectomy], 2 IV (2 eHR). Overall 1-, 3-, 5-year survival was 67%, 46%, 34% respectively for stage IA-IB; 63%,12%, 12% for IIA-IIB; 50%, 30%, 30% for III-IV (p=ns); in particular, 1-, 3-, 5-year survival was 100%, 100%, 100% for T1a; 50%, 50%, 50% for T1b; 70%, 46%, 35% for T2; 50%, 12%, 12% for T3; 54%, 32%, 32% for T4 (p=ns); 1-, 3-, 5-year survival for patients without lymph node involvement was 58%, 44%, 37% and 60%, 15%, 15% for patients with lymph node metastases (p=ns), respectively. CONCLUSIONS: CT seems to be sufficient in T1a GBC patients but inadequate in T1b (stage IA), which requires a more aggressive approach. In stage IIB, III and IV, the presence of lymph-node metastasis is not a contraindication to aggressive surgery.
Abstract: OBJECTIVES: Interest in developing noninvasive markers of liver fibrosis continues to increase, especially in recurrent hepatitis C virus infection after liver transplantation. Recently, a model for predicting significant fibrosis (bridging fibrosis and cirrhosis) on the basis of logistic regression and routine laboratory data has been proposed (logit model). The aim of the present study was to evaluate the accuracy of an artificial neural network, a technique reported to work better than logit models in complex biological situations, built on those same clinical variables and data set of patients, in predicting significant fibrosis. METHODS: The neural network was constructed on the training set of 414 protocol biopsies, from liver transplant recipients, and then tested on the remaining 96 biopsies, as validation set. Model performances of neural network and logit model were evaluated and compared by means of areas under receiver operating characteristic curves. RESULTS: With a cutoff value of >0.4 to predict significant fibrosis, the neural network provided sensitivity, specificity, positive and negative predictive values, respectively, of 100, 79.5, 60.5 and 100%, in the validation set. The performance of the neural network was significantly better than that of the logit model (in the validation set area under the curve = 0.93 vs. 0.84; P = 0.045). CONCLUSIONS: Artificial neural network provides accurate prediction of the presence or absence of significant fibrosis from clinical variables, allowing theoretically protocol liver biopsy to be avoided in several instances, a result of particular interest, given the lack of other types of reliable noninvasive indexes of fibrosis in the setting of transplantation.
Abstract: The efficacy of the Meld system to allocate livers has never been investigated in European centers. The outcome of 339 patients with chronic liver disease listed according to their Meld score between 2003 and 2005 (Meld era) was compared to 224 patients listed during the previous 2 years according to their Child score (Child era). During the Meld era, hepatocellular carcinomas (HCCs) had a 'modified' Meld based on their real Meld, waiting time and tumor stage. The dropouts were deaths, tumor progressions and too sick patients. The rate of removals from the list due to deaths and tumor progressions was significantly lower in the Meld than in the Child era: 10% and 1.2% versus 16.1% and 4.9%, p < 0.05. The 1-year patient survival on the list was significantly higher in the Meld era (84% vs. 72%, p < 0.05). The prevalence of transplantation for HCC increased from 20.5% in the Child to 48.9% in the Meld era (p < 0.001), but between HCCs and non-HCCs of this latter era the dropouts were comparable (9.4% vs. 14.9%, p = n.s.) as was the 1-year patient survival on the list (83% vs. 84%, p = n.s.). The Meld allocation system improved the outcome of patients with or without HCC on the list.
Abstract: AIMS: To evaluate short and long-term results in 23 patients resected for hilar cholangiocarcinoma. METHODS: Between January 2001 and December 2003, 23 patients with hilar cholangiocarcinoma were resected and considered for retrospective analysis. Univariate and multivariate analysis were performed on several clinicopathological variables in order to evaluate the short-term results. Median follow-up was 11 months (interquartile range 2-20 months). RESULTS: A major liver resection was performed in 19 out of 23 patients (82%): a right hepatectomy extended to segment 4 in 5 patients and a left hepatectomy in 14 patients. Resection of the caudate lobe was performed in 7 patients (30%). No hospital mortality occurred. Overall morbidity rate was 43%. The 1-year survival rate was 63.2% with a median survival of 19 months. Tumor recurrence appeared in 12 patients (52%). Low preoperative albumin level (P=0.006), presence of positive resection margin (P=0.03) and T-stage (P=0.02) were found to be related to a worse median survival. On multivariate analysis, only the preoperative albumin level and the presence of positive margin were confirmed as independent prognostic factors. CONCLUSION: Aggressive surgical approach remains the only potentially curative therapy for the hilar cholangiocarcinoma. Low preoperative albumin level, presence of positive resection margin and T-stage resulted as factors influencing the prognosis after resection.
Abstract: BACKGROUND AND AIM OF STUDY: The success of intestinal transplantation is affected by the extreme susceptibility of the small bowel to ischemia-reperfusion (I/R) injury. Platelet aggregation decreases after reperfusion in small intestinal ischemia and liver transplantation. Thromboelastography (TEG) is a coagulation test performed whole on blood. The aims of this study were to assess coagulation derangements during bowel transplantation to define appropriate modalities of intraoperative coagulation monitoring. A secondary endpoint was to determine whether measurements of coagulation derangements were useful to estimate small intestinal I/R injury. MATERIALS AND METHODS: We recruited 19 patients who had undergone elective small bowel transplantation for primary short-gut syndrome. We divided our patients into two groups depending on their reperfusion injury as evaluated with a biopsy after reperfusion: group A composed of eight patients who had a reperfusion injury: group B composed of 11 patients who did not experience this problem. We measured five thromboelastogram indicators (r, k, angle, MA, CL30) at defined intervals: dissection phase (T1), vascular anastomoses phase (T2) as well as 30 minutes (T3) and 120 minutes (T4) after reperfusion during the intestinal reconstruction phase. RESULTS: We did not observe any significant difference between intraoperative blood loss, core temperature, or volume of fluid fresh frozen plasma, or platelet administration. Angle and MA were decreased significantly among patients with reperfusion injury. DISCUSSION: Patients showed a hypocoagulation pattern during all the manipulations. This derangement did not depend on the ischemia time. In patients with I/R injury the angle and MA did not change during ischemia, but did change significantly upon reperfusion. Several mechanisms may cause coagulation derangements. During the ischemic period, there may be damage to the vascular bed of the ischemic organ. When arterial blood passes through the damaged vascular bed after reperfusion, platelet activation occurs to varying degrees, resulting in reduced platelet function. CONCLUSION: Further studies are needed to confirm this preliminary work, which was limited by the low number of patients, in order to elucidate relevant mechanisms and develop predictive algorithms.
Abstract: Impact of hepatitis C virus (HCV) recurrence on long-term outcome after orthotopic liver transplantation (OLT) is highly variable, and the role of retransplantation is still debated. From 1996 to 2003, 131 OLT with histologically proven HCV recurrence and 6 months of follow-up were retrospectively reviewed. One and 5-yr overall survivals were 90.7 and 81.3%, respectively. The mean time of HCV recurrence was 10.1 +/- 6.2 months in patients whose donor's age was less than 70 yr old, and 6.6 +/- 4.7 in patients whose donor's age was more than 70 (P < 0.01). The mean time between OLT and HCV recurrence was 10.7 +/- 8.2 months among patients still alive, and 5 +/- 4.2 among the 20 who died (P = 0.02). In 16 (12.2%) patients, retransplantation was required for severe HCV recurrence; 5 are still alive and 11 (68.7%) died. The mean survival time was 16.2 +/- 6 months if re-OLT was performed within 12 months from first OLT, and it was 45.9 +/- 10 months if re-OLT was performed later (P < 0.01). In conclusion, donors older than 70 yr are at high risk of early HCV recurrence; expectancy of life is significantly reduced in case of histologically proven recurrence within 6 months. Outcome is quite dismal in patients with early HCV recurrence requiring retransplantation within 1 yr of first OLT.
Abstract: The Prometheus system is a plasma filtration treatment coupling adsorption and hemodialysis (FPSA) aimed to blood purification in liver failure. After separation through an albumin-permeable membrane, plasma enters a secondary circuit where protein-bound toxic substances are removed by two adsorbers; p01, a neutral resin, and p02, an anion exchanger. Plasma is then returned to the venous line, where a high-flux hemodialyzer removes water-soluble substances. We used the Prometheus system in 12 patients with acute or acute-on-chronic liver insufficiency: eight cirrhosis, one posttransplant dysfunction, and three secondary liver insult (two cardiogenic shock and one rhabdomyolysis). All patients were severely hyperbilirubinemic, hypercholemic, and hyperammonemic. Twenty-eight sessions each lasting 340 +/- 40 minutes were performed (2.5/patient). The mean total bilirubin decreased from 33.6 +/- 20 to 22.2 +/- 13.6 mg/dL (P < .001); the reduction ratios for cholic acid and ammonia were 48.6% and 51.6%, respectively. The pre- to postsession urea reduction was 57.6% +/- 9.5% and creatinine 42.7% +/- 10%. A significant reduction was observed in the circulating levels of soluble interleukin (IL) 2 receptor (pre: 2687.2 +/- 1434.7; post: 1977.1 +/- 602 Ul/ml; P < .001) and in IL 6 (pre: 56.1 +/- 11.1; post: 35.9 +/- 10.3 pg/mL, P = .05). During treatments the hemodynamics were stable. Two patients received liver transplantations. The secondary liver insult was completely overcome in all three patients. The overall survival at 30 days was 41.6% (5/12 patients). Prometheus, based on FPSA, produced high clearance for protein-bound and water soluble markers, which resulted in high treatment efficacy.
Abstract: The objective of this study was to predict postoperative liver failure and morbidity after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis. The model for end-stage liver disease (MELD) score is currently accepted as a disease severity index of cirrhotic patients awaiting liver transplantation; however, its impact on prognosis after resection of HCC on cirrhosis has never been investigated. One hundred fifty-four cirrhotic patients resected in a tertiary care setting for HCC were retrospectively analyzed. For each patient, the MELD score was calculated and related to postoperative liver failure and complications (morbidity). Hospital stay and 1-year survival was also investigated. MELD accuracy in predicting postoperative liver failure and morbidity of cirrhotic patients was assessed using receiver operating characteristic (ROC) analysis. Eleven patients (7.1%) experienced postoperative liver failure leading to death or transplantation. ROC analysis identified cirrhotic patients with a MELD score equal to or above 11 at high risk for postoperative liver failure (area under the curve [AUC] = 0.92, 95% confidence interval [CI] = 0.87-0.96; sensitivity = 82%; specificity = 89%). Forty-six patients (29.9%) developed at least 1 postoperative complication: ROC analysis identified patients with a MELD score equal to or above 9 at major risk for postoperative complications (AUC = 0.85, 95% CI = 0.78-0.89; sensitivity = 87%; specificity = 63%). Cirrhotic patients with MELD score below 9 had no postoperative liver failure and low morbidity (8.1%). In conclusion, the MELD score can accurately predict postoperative liver failure and morbidity of cirrhotic patients referred for resection of HCC and should be used to select the best candidates for hepatectomy.
Abstract: The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC- group, n = 24) IPC (10-min ischemia + 15-min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC- group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC- group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC-, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits.
Abstract: Patients submitted to orthotopic liver transplantation (OLT) show an increased rate of cardiovascular events. OLT subjects have high homocysteine (Hcy) levels, but no data are available on the association of Hcy with cardiovascular events. In a cross-sectional analysis, 230 subjects were studied at least 6 months after OLT (159 on cyclosporine, 71 on tacrolimus). Routine laboratory data and total Hcy were recorded, as well as the history of diabetes, hypertension, dyslipidemia, and overweight. Cardiovascular events occurring in a follow-up of 2-36 months were registered. OLT subjects had higher-than-normal Hcy (median 16.7 micromol/L, range 6.1-171.8) without difference between the 2 immunosuppressive agents. The prevalence of Hcy >15 micromol/L was also similar, and significantly correlated with creatinine levels. A total of 28 arterial events occurred in 25 patients during follow-up (11 in coronary arteries, 10 in peripheral arteries, and 7 in splanchnic arteries). Deep vein thromboses occurred in 2 patients, and splanchnic vein thromboses in 4 patients. Cardiovascular events were frequently associated to high Hcy and hypertension. Cox regression analysis showed that high Hcy was significantly associated with arterial events. The risk of any arterial event, coronary artery or peripheral artery event increased by nearly 10% for any increase in Hcy of 5 micromol/L. In conclusion, high Hcy may be involved in the pathogenesis of cardiovascular events in OLT patients. The usefulness of Hcy-lowering therapy remains to be verified.
Abstract: BACKGROUND: Hepatolithiasis is very common in East Asia but infrequent in Western countries, and few reports have been published in European series. In East Asia, the association between cholangiocarcinoma and hepatolithiasis is well recognized, but, on the contrary, hepatolithiasis is uncommon in Europe and the United States, and the relationship with cholangiocarcinoma is not well established. The goal of this study was to analyze the perioperative and longterm results of surgical therapy for hepatolithiasis. STUDY DESIGN: Record review of 22 patients was done to locate immediate (operative morbidity and mortality) and longterm (stone recurrence and survival) results of patients with hepatolithiasis who underwent surgical treatment. RESULTS: There were 19 (86.4%) hepatic resections and 10 (45.5%) hepatico-jejuno-anastomoses. Operative mortality was absent and morbidity rate was 27.3%. Right hepatectomy was predictive of postoperative complications at multivariate analysis (p = 0.04). One (4.5%) patient had an unknown associated cholangiocarcinoma at time of surgical intervention. Mean followup was 67.59 +/- 65.67 (range 12 to 215) months. None presented recurrent cholangitis during the followup period. CONCLUSIONS: Surgical therapy is a safe and effective management for hepatolithiasis. The possibility of developing cholangiocarcinoma in inveterate hepatolithiasis is real, and hepatic resection removes this risk.
Abstract: BACKGROUND: Policies to decrease dropout during waiting time for liver transplantation (LT) are under debate. METHODS: We evaluated the allocation system from 1996 to 2003, when recipients had priority related to Child-Pugh score and donors >60 years were mainly offered to recipients with hepatocellular carcinoma (HCC). The outcomes of 656 patients with chronic liver disease (142 HCC and 514 non-HCC) listed for LT were prospectively evaluated, considering recipient and donor features. RESULTS: Transplantation and dropout rates were similar between HCC and non-HCC patients: 64.1% vs. 70.6% and 26% vs. 22.6%. Multivariate analysis showed the probability of being transplanted within 3 months was related to Child-Pugh score >10 and to HCC, whereas the probability of being removed from the list within 3 months was only related to Child-Pugh score >10. HCC patients had a lower median waiting time (97 vs. 197 days, P<0.001), a higher rate of donors > 60 years (50.5% vs. 33.5%, P<0.005) and with steatosis (31.6% vs. 14.3%, P<0.01), but a lower Child-Pugh score (9.1+/-2.1 vs. 9.6+/-1.7, P<0.05) than non-HCC patients. The 5-year patient survival was comparable since registration on the list and since LT: 56.9% and 77% in the HCC group vs. 61.4% and 79% in the non-HCC patients. Donors > 60 years affected outcome after LT in the non-HCC group, but not in the HCC patients. CONCLUSION: By allocating donors >60 years mainly to HCC patients, we controlled dropout without affecting their survival and the outcome of non-HCC patients.
Abstract: INTRODUCTION: Experimental evidence has suggested that prostaglandins have positive effects on hepatic perfusion after transplantation. However, randomized clinical trials have failed to show their usefulness to decrease the incidence of primary nonfunction. In order to demonstrate its therapeutic role, we performed a clinical study in which PGE1 was administered only after the appearance of posttransplant liver dysfunction. MATERIALS AND METHODS: Forty patients with macroscopic signs of hypoperfusion or lacking bile production at the end of the operation (n = 24) or with an increase in transaminases and fall in biliary production in the first 24 hours postsurgery (n = 16) were administered alprostadil (PGE1; 0.01 mug/kg/min to the maximum plateau of 0.06 mug/kg/min). We measured the mean values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), activated thromboplastin time-ratio (aPTT-r), international normalized ratio (INR), bilirubin, creatinine and plasma nitrogen, PaO(2)/FiO(2) at the start of the treatment and every 6 hours for 48 hours, and daily diuresis. RESULTS: There appeared to be a significant decrease in AST, INR, aPTT-r, and creatinine clearance (P < .05), while there was a significant rise in the blood urea nitrogen (P < .001). ALT and bilirubin did not show significant variations. The PaO(2)/FiO(2) ratio showed a significant decrease (P < .001) in pulmonary vasodilatation. CONCLUSIONS: Prostaglandins used in the manner in our study showed a significant efficiency to improve liver dysfunction after transplantation.
Abstract: Combined transplants with the liver represent a small number of associated pathologies with little chance of resolving with a single transplant. The small case number prevents us from establishing homogeneous criteria for the procedure. The insertion of the Model for End-Stage Liver Disease in the preoperative evaluation of the patients awaiting liver transplant has definitely increased the number of combined liver-kidney transplants, which have reached more significant numbers. The number of heart-liver transplants is still too low to establish the efficacy of the measure. The multiorgan transplant with the liver represents a rare event entrusted to a series of case reports, each one of which has a history unto itself. Our experience in this field includes 14 combined liver-kidney, six combined heart-liver, and two multiorgan transplants with liver among 36 intestine transplants. We have examined the main pre-, intra-, and postsurgical problems for each one of these transplants, particularly relating to the anesthetic and intensive-care aspects.
Abstract: Surgical approaches to complicated benign intestinal failure are gaining acceptance, especially in the pediatric population. Less international experience has been obtained in adult patients, who are usually treated with total parenteral nutrition (TPN). An intestinal rehabilitation program was started in our institution with comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. Among 38 adult patients referred by our gastroenterologists for bowel rehabilitation and surgically treated in our institution, 92.2% received TPN on admission. After careful evaluation, 71% underwent transplantation. Five patients died, but 18 recipients were completely weaned off TPN at follow-up. Eleven patients underwent surgical resection of the affected bowel and a subsequent program of intestinal rehabilitation: they were all alive and weaned off TPN at discharge. At a 2-year mean follow-up, deaths occurred only in the transplant population. Therefore, intestinal surgical rescue, if successful, is optimal in adult patients.
Abstract: The analysis of intraoperative hemodynamic, metabolic, and coagulation disorders of the recipients in relation to the newly reperfused organ during intestinal transplantation is necessary for an optimal patient management during small bowel transplantation (SBT). The interaction may be minor or may lead to postreperfusion syndrome, producing intense hemodynamic instability, important metabolic changes, and coagulation disorders. This research is based upon experience with 27 patients who underwent SBT. We observed significant decreases in PAM and IRVS after reperfusion in accordance with minor changes of mean pulmonary artery pressure, central venous pressure, and pulmonary capillary wedge pressure. The fall in pH upon revascularization was associated with a concomitant rise in partial carbon dioxide pressure probably due to the increased metabolic activity of the new organ. We found a significant increase in K levels, a rise that may be due to the output of metabolic products by the donor intestine. Patients displayed an hypocoagulative pattern, a derangement that did not seem to depend on ischemia time. It is possible that the same factors supporting the initial TEG pattern endure throughout the surgical procedure. The important and significant maximum amplitude indicator variation between the initial value and that after reperfusion may relate to the release of hypocoagulative factors superimposed on background abnormalities. These interesting metabolic disorders presumably reflected graft function and may provide predictive indices for a good outcome.
Abstract: Mucormycosis is a rare opportunistic infection, usually associated with immunocompromised states. Several conditions such as hematologic malignancy (leukemia, lymphoma, myeloma), solid organ transplantation, diabetes mellitus, corticosteroid therapy, or chemotherapy predispose patients to infection. The aim of this study was to present a single case of mucor infection after 900 consecutive liver transplantations. Rhinomaxillary mucormycosis must be suspected in a transplant recipient showing fever, maxillary swelling, and edema. This condition can be successfully treated with early diagnosis and a combination of aggressive surgery and antifungal therapy.
Abstract: OBJECTIVES: Acute renal failure (ARF) is a severe complication in patients undergoing orthotopic liver transplantation (OLT), which predicts a poor outcome. The aim of this study was to analyze risk factors for the development of ARF, including severity of illness, onset time of ARF prognostic factors of outcome, and mortality in a group of critically patients requiring renal replacement therapy (RRT). METHODS: Retrospective analysis of 240 consecutive liver transplant cases from 1999 to 2001 admitted to the intensive care unit (ICU) was performed to identify risk factors for ARF development after OLT. The analyzed factors were: age, sex, CrS, BUN, diuresis, sepsis, hypovolemia, cardiac failure, nephrotoxic drugs (cyclosporine or FK506, antibiotics), hyperbilirubinemia, associated diseases (DM, CRF), onset time of renal failure and progressiveness, timing of RRT, number of days of RRT, and mortality. We examined variables upon admission to the ICU, before the first RRT, and on the last ICU day before resignation or death. We used Students' t test. Quantitative parameters were expressed as mean values +/- SD. RESULTS: Of the 240 patients, 20 (8.3%) experienced ARF needing renal replacement therapy during the postoperative period. The results of our study suggested that ARF among patients undergoing RRT conferred an excessive risk of in-hospital death: eight patients died (40%). This increased risk cannot be explained solely by a more pronounced severity of illness. CONCLUSION: Our results provide strong evidence that ARF presents a specific, independent risk factor for a poor prognosis.
Abstract: A pretransplant positive cross-match is a contraindication for kidney transplantation, unlike in liver transplantation (OLT). In combined liver kidney transplantation (LKT) it is hypothesized that liver can protect kidney from rejection. We report the case of a 35-year-old woman on renal replacement therapy with gastrointestinal tract compression due to a hematoma following spontaneous liver rupture (May 2004). She was affected by amyloidosis, treated with a bone marrow autotransplantation (2001). The liver rupture was surgically untreatable, so an LKT was proposed. Panel-reactive antibody was 80% to 100% (complement dependent cytotoxicity) with specific anti-HLA antibodies (enzyme-linked immunosorbent assay). A compatible donor was found (July 2004). The cross-match before LKT was positive for B and T cells (score 8): an emergency OLT was performed. Immediately after liver reperfusion the cross-match result was less positive (6) for T cells. After 6 hours it was negative for T and slightly positive for B cells (4): the kidney was transplanted. The immunosuppressive therapy was: alemtuzumab, steroids, and tacrolimus. Renal function immediately recovered. On day 7 a rejection episode was successfully treated by increasing steroids (intravenous bolus). At discharge hepatic and renal function were normal (creatinine 1 mg/dL). They are stable after 1 year. This case showed LKT efficacy even in complex immunological situations. Many immunological mechanisms, still not defined, are hypothesized about the protective role of the liver. This case confirmed experimental data that highlighted that in vivo in humans a cross-match can change from positive to negative after OLT giving highly sensitized patients the possibility for LKT.
Abstract: Combined liver and kidney transplantation (CLKT) has been increasingly used in recent years: 13 of our 19 cases were performed in the last 2 years being 3.2% of our liver transplantation (LT) and kidney transplantation (KT) activity. Only three of them were not on hemodialysis and the scheduling of a CLKT meant being at the top of the waiting list. We accepted only ideal donors and had no case of liver and only one case of kidney delayed graft function. Two deaths occurred during the first postoperative month, due to acute respiratory distress syndrome and multiorgan failure, both in patients with adult polycystic disease who were in poor nutritional condition due to a late indication for CLKT. We had two late deaths, one due to a native kidney tumor at 7 years and one at 8 years due to alcoholic cirrhosis recurrence. The late survival of our patients was 77.3% with all surviving patients showing good liver and kidney function. We planned not to do the KT in the case of a positive preoperative cross-match; but the only positive case became negative 8 hours after LT when we performed the KT. The patient is well after 2 years. The liver does not always protect the kidney if there are preformed antibodies, but we should try every possible technique not to lose the possibility of doing both transplants, because in case of LT alone the patients loses his top position on the CLKT waiting list and often waits years for a kidney.
Abstract: Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).
Abstract: Although advances in immunosuppressive therapy have led to increased survival of solid organ transplantation recipients, it is well established that current protocols have been associated with an increased risk of developing tissue-invasive infections. In particular, cytomegalovirus still represents an important cause of morbidity. We report a case of cytomegalovirus infection involving the graft ileum with documented necrotising enteritis that developed after small bowel transplantation. The patient, a 56-year-old Caucasian female with a postsurgery short bowel syndrome, underwent a small bowel transplantation. Immunosuppression was maintained by combination of tacrolimus, steroids and daclizumab. Both the donor and the recipient were serologically negative for cytomegalovirus IgG. Nevertheless, ganciclovir prophylaxis was given for 21 days after surgery, as standard procedure. On hospital day 174, routine pp65 antigenaemia resulted positive (14/200,000 peripheral blood leukocytes). The patient was asymptomatic and preemptive ganciclovir therapy was instituted. In the following 3 days, due to a cytomegalovirus antigenaemia increase, ganciclovir was changed to foscarnet with subsequent virological response (7/200,000 peripheral blood leukocytes, on day 181). Two days later, the patient complained of acute abdominal pain and she underwent surgery for the diagnosis. Since the intraoperative findings consisted of a diffuse acute purulent peritonitis, the intestinal graft, together with native rectum, was removed. Biopsy specimens showed evidence of tissue-invasive cytomegalovirus infection. Postsurgery, the patient developed septic shock and died on day 198 as a consequence of multiple organ failure.
Abstract: BACKGROUND: Recent reports demonstrate the efficacy of induction immunosuppression with Thymoglobulin, a potent antithymocyte polyclonal antibody, in allowing acquired tolerance by means of a tolerogenic regimen of recipient pretreatment and low-dose postoperative immunosuppression. The effect of this novel approach on recurrence of hepatitis C viral disease after liver transplantation has never been investigated. We report the preliminary results of a retrospective analysis aimed at discovering any relationship between Thymoglobulin immunosuppression and the pattern of recurrence of hepatitis C. METHODS: Thymoglobulin induction plus tacrolimus monotherapy was used in a group of 22 hepatitis C virus (HCV)+ patients receiving liver transplantation; 30 HCV+ patients receiving transplants within the same year received conventional tacrolimus plus steroid immunosuppression and represented the comparison group. RESULTS: Patient survival and acute rejection rate did not differ between the two groups. Significantly lower dosages and levels of tacrolimus were possible with Thymoglobulin, and a progressive weaning of tacrolimus monotherapy was accomplished in most patients, without major rejection complications. The HCV recurrence rate was similar in both groups, although significantly lower HCV RNA loads were obtained with Thymoglobulin pretreatment. The mean time to histologic recurrence was shorter in Thymoglobulin-treated patients; however, no significant difference was observed in mean Ishak's histologic grading and staging of HCV recurrence. CONCLUSIONS: In our preliminary experience, a "prope" tolerogenic regimen with Thymoglobulin pretreatment and low-dose immunosuppression in liver-transplant recipients gave good protection against rejection and permitted lower HCV viral loads, whose significance in the long-term outcome of HCV patients deserves further investigation.
Abstract: BACKGROUND: Cardiac complications represent a cause of morbidity and mortality after liver transplantation among patients with familial amyloid polyneuropathy (FAP), especially for the non-VAL30MET variant types. METHODS: We retrospectively evaluated 11 recipients from a nonendemic area including 90.9% affected by FAP variants. Preoperative cardiovascular symptoms were present in 81% of patients. An intraoperative pacemaker was placed prophylactically in 90.9% of all recipients. Since tacrolimus has been reported in the international literature to display cardiac toxicity, we evaluated the influence of intraoperative prophylactic pacing and rapid postoperative weaning from tacrolimus, mainly allowed by thymoglobulin on the occurrence of posttransplantation cardiac complications. RESULTS: One patient received a combined heart-liver transplant, another, living donor liver transplantation. We did not observe any significant intraoperative cardiac complications. Postoperatively, the pacemaker was removed from all patients but 1. Five patients received tacrolimus and steroids; a subsequent, second group of 6 patients (54.5%) was treated with thymoglobulin followed by tacrolimus. At discharge the mean tacrolimus level was 10.6 ng/mL, whereas after 1 month it was 7.5 ng/mL. We observed a case of acute cellular rejection before discharge, which was successfully treated with intravenous steroids and OKT3. After a mean follow-up of 17.4 months (range, 1-31), 2 patients had died (18.1%): 1 due to sepsis and another, to MI. Two recipients experienced cardiac complications (18.1%), namely, the patient who died due to an myocardial infarction and a second one with a tachyarrhythmia, which was treated successfully with beta-blockers and amiodarone. CONCLUSION: Prophylactic pacing and rapid weaning from immunosuppression are still associated with a significant rate of postoperative cardiac complications.
Abstract: AIM: Isolated small bowel transplantation is becoming the treatment of choice for adult patients with serious parenteral nutrition (PN) related complications: we report our three-year experience (December 2000-December 2003) from a single Italian center (Modena-Italy), with one of the larger European series. METHODS: We transplanted 14 patients, with a previous mean PN course of 27 months and a mean 21-month post-transplantation follow-up (range 3-36 months), obtaining a one-year actuarial survival rate of 92.3% with no intraoperative deaths. RESULTS: We lost 1 patient (7.2%), died for post-transplantation overwhelming sepsis following Cytomegalovirus (CMV) enteritis. Thirteen patients are alive, with one-year actuarial graft survival rate of 85.1%: 1 patient underwent graft removal (7.2%) for intractable severe acute rejection. Our immunosuppressive regimen was based on tacrolimus and 3 induction protocols: daclizumab (8 patients) with steroids, alemtuzumab (4 patients) and thymoglobulin (2 patients) without steroids. In 9 cases, we added sirolimus. Nine recipients experienced 22 episodes of acute cellular rejection (ACR), treated successfully in all cases but one. One patient (7.2%) was treated successfully for Post Transplant Lymphoproliferative Disease (PTLD) and is disease-free after 8 months. CONCLUSIONS: Small bowel transplantation can achieve optimal results depending on appropriate immunosuppressive management and candidate selection, added to shorter ischemia time and careful donor and graft selection.
Abstract: Abdominal wall closure after intestinal transplantation in adult patients can be a difficult procedure. The main possibility offered by international experience is the use of myocutaneous flaps and abdominal wall transplantation. We report our experience in intestinal/multivisceral transplantation, including four difficult cases among 27 adult transplant recipients. Three patients underwent prosthetic mesh alone and one, a myocutaneous flap for abdominal closure after primary mesh positioning. We selected a mesh with a structure that allowed us to close the abdomen without creating adhesions and, at the same time, stimulating tissue repair. Two patients experienced local mesh infection, which has been kept under clinical control by antibiotics and daily medications till neoabdominal wall formation. The mesh was then removed. Another patient underwent mesh substitution for a suspicious fever. The last patient had mesh as a bridge for a subsequent myocutaneous flap from the thigh. All patients are in good health with well-functioning grafts and no need for parenteral nutrition. No enterocutaneous fistulae were detected.
Abstract: BACKGROUND/AIMS: Recurrence of hepatocellular carcinoma (HCC) following surgical resection is influenced by parameters detectable on the resection specimen or through a biopsy. The prognostic significance of HCC doubling time (DT) after surgery has never been investigated. METHODS: We evaluated 62 patients who underwent curative resection of a single HCC on cirrhosis; tumors were assessed before surgery on two subsequent occasions with the same imaging technique allowing the calculation of DT. The influence of tumor DT, clinical and pathological parameters on recurrence-rate and patients survival was assessed with uni- and multivariate analysis. Relationship between DT and pathological features was also analyzed. RESULTS: Three-year recurrence rate was 32.3% (20 patients): this was significantly higher in the presence of DT shorter than 100 days (58 versus 18% when equal to or longer; P=0.008), microvascular invasion (59 versus 17% when absent; P=0.008) or tumor undifferentiation (54 versus 25% when well/moderately differentiated; P=0.015). DT was the only independent predictor of recurrence (P=0.005). Patients survival was affected by Child-Pugh class only. DT was significantly shorter in tumors with microvascular invasion (P=0.007), undifferentiation (P=0.003) and high alpha-fetoprotein levels (P=0.011). CONCLUSIONS: DT is easy to estimate and indicates the prognosis of single HCCs prior to liver resection.
Abstract: BACKGROUND: To evaluate the role of liver resection for noncolorectal, nonneuroendocrine metastases, indications and results were retrospectively reviewed in 142 observed patients. METHODS: A curative liver resection was performed in 83 cases (58.5%), and the remaining 59 patients received palliative treatments. The primary tumor site was gastrointestinal in 18, breast in 21, genitourinary in 15, leiomyosarcoma in 10, and other in 19. The mean number of metastases was 1.4. The mean diameter of the nodules was 5.7 cm. Liver metastases were synchronous in 11 (13.3%) cases and metachronous in the remaining 72 (86.7%). RESULTS: There was no operative mortality. Postoperative morbidity was 20.5%. The median postoperative stay was 9.5 days. The 3- and 5-year actuarial survival rate was 49.5% and 34.3% in resected cases, respectively, whereas there were almost no survivors 3 years after diagnosis in unresected cases (P < .05). The 3- and 5-year disease-free survival was 41.4% and 23.8%, respectively. Among the 83 resected cases, the 3- and 5-year actuarial survival was 17.3% and 8.6% for metastases from gastrointestinal tumors, 53.9% and 24.6% from breast cancer, 63.7% and 36.4% from leiomyosarcoma, 50.4% and 37.8% from genitourinary neoplasms, and 55.6% and 42.4% from other sites, respectively. Fifteen patients (18.1%) survived longer than 5 years. CONCLUSIONS: Liver resection is an effective treatment for noncolorectal, nonneuroendocrine metastases; it allows satisfactory long-term survival with an acceptable operative risk in selected patients. Hepatic metastases from gastrointestinal carcinoma have the worst prognosis; those from genitourinary tumors show a better outcome. Patient selection is the key to achieving encouraging results.
Abstract: To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered.
Abstract: Induction with thymoglobuline, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LTx) has never been investigated. We report here on the outcome in 22 HCV+ patients receiving thymoglobuline pre-treatment and minimal immunosuppression after LTx. Patient survival and acute rejection rates were good, and remarkably low dosages and levels of immunosuppression were achieved with thymoglobuline, without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressor was also possible in the majority of patients without complications. The HCV recurrence rate was similar to what is reported in the literature, although lower HCV-RNA viral loads were obtained with thymoglobuline, with a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobuline is effective in protecting against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.
Abstract: Distinction between recurrent and de novo hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) bears important clinical and therapeutic implications. Techniques for molecular profiling of clinically suspected de novo and recurrent HCC are required since the histological/clinical discrimination of donor vs. recipient tumor origin is difficult. Multiple PCR amplification of 16 highly polymorphic short tandem repeat (STR) DNA sequences (routinely used for paternity and forensic assays) was applied in two patients who developed a second HCC after OLT. In both patients the technique provided reliable evidence that the two second HCC were recurrences of the primary tumor. Multiple STR genetic allelotyping is an effective tool for clear-cut discrimination of donor/recipient origin of a second HCC after OLT. Its application could be of great therapeutic relevance for such OLT patients.
Abstract: BACKGROUND: Adult isolated small bowel transplantation is considered the standard treatment for patients with life-threatening parenteral nutrition-related complications. Here, we report a 3-year experience in a single European centre between December 2000 and December 2003. AIMS: To evaluate and discuss pre-transplant and post-transplant factors that influenced survival rates in our series. PATIENTS: Fourteen patients, with a mean parenteral nutrition course of 27 months, were transplanted. In eight cases they had not experienced any major complication from parenteral nutrition. METHODS: We described pre-transplant evaluation and inclusion criteria, surgical technique and clinical management after transplant. Immunosuppressive therapy was based on induction drugs and Tacrolimus. We reported survival rates, major complications and rejection events. RESULTS: One-year actuarial survival rate was of 92.3% with a mean 21-month follow-up (range 3-36 months). We had no intraoperative deaths. One patient (7.2%) died of sepsis following cytomegalovirus enteritis. One patient underwent graftectomy (7.2%) for intractable severe acute rejection. One-year actuarial graft survival rate of 85.1%. One patient (7.2%) affected by post-transplant lymphoproliferative disease is alive and disease-free after 8 months. CONCLUSION: We believe candidate selection, induction therapy, donor selection and short ischemia time play an important role in survival after small bowel transplantation.
Abstract: BACKGROUND AND AIMS: Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. PATIENTS AND METHODS: We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. RESULTS: Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). CONCLUSIONS: Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.
Abstract: BACKGROUND: In 2002, the American Joint Committee on Cancer and the International Union Against Cancer redefined the T-classification for hepatocellular carcinoma, shifting the cutoff value for tumor size from 2 to 5 cm and giving more emphasis to vascular invasion. METHODS: A retrospective cohort study was conducted on 223 consecutive patients with hepatocellular carcinoma observed between 1990 and 2002. One hundred twelve were resected and considered for retrospective analysis. Univariate and multivariate analyses were performed on several clinicopathologic variables. After classification according to each staging system, the long-term survival of different stages was compared. The prognostic value of each staging system was further evaluated by entering each stage, in turn, into the Cox regression model with other clinicopathologic variables. The median follow-up was 19 months. RESULTS: On multivariate analysis, the viral etiology of cirrhosis and the presence of multiple nodules were independent prognostic factors. When the new staging system was entered into the multivariate analysis, it was the only independent factor (P = .02). When stratified according to the old tumor-node-metastasis system, there were no significant differences in the survival between stage I and II (P = .14) or between stage IIIA and IVA (P = .33); only the survival of stage II and IIIA was different (P < .01). When stratified according to the new tumor-node-metastasis system, there were significant differences between stage I and II (71.7% vs. 54.7%; P = .02). CONCLUSIONS: The new staging system is a more reliable and objective method for T classification. It is easy to use in clinical practice and is better at stratifying curatively resected patients with respect to prognosis.
Abstract: Molecular detection of monoclonality can play an important role in the diagnosis of posttransplantation lymphoproliferative disorders (PTLD). To permit accurate molecular diagnosis of PTLD even on very small amounts of DNA extracted from routinely embedded histologic material, we adapted a commercially available PCR protocol (for FR-1, -2 and -3 regions), originally designed for use on fresh/frozen samples. We applied this approach on routine biopsy/surgical material of 10 PTLD (from nine patients). All three FR regions were always amplified, indicating that the extracted DNA was of medium quality. All five PTLD morphologically classified as lymphomas were monoclonal in at least one FR region. Thus, using the WHO histologic, immunohistochemical, and clinical criteria as the reference standard, the approach provided 100% sensitivity for detection of monoclonal malignancies, supporting the validity of the method. Of five specimens classified morphologically as polymorphic PTLD, three displayed a solitary IgH gene rearrangement peak, consistent with the presence of a monoclonal B-cell population (ie, monoclonal polymorphic PTLD). This rapid and straightforward procedure, which allows identification of a wide range of IgH rearrangements, could facilitate molecular analysis of PTLD in routine practice, while limiting consumption of valuable diagnostic material.
Abstract: BACKGROUND: In case of anomal hepatic arterial inflow, it can be necessary to perform revascularization of the liver allograft by iliac arterial interposition graft. METHODS: We analyzed retrospectively 613 liver transplants in a 16-yr period. The hepatic artery (HA) graft group (n = 101) consisted of patients with arterial inflow based on recipient infrarenal aorta using donor iliac artery graft tunneled through the transverse mesocolon. The control group (n = 512) consisted of patients who underwent liver transplantation with routine HA reconstruction. RESULTS: Both groups are homogeneous and comparable. In case of retransplantation, arterial conduit with iliac graft was adopted more frequently instead of conventional arterial anastomosis (24.8% vs. 9%, p < 0.0001). The 1-, 3- and 5-yr overall survival was 85.41, 79.42, 76.57% in the control group and 76.21, 73.43, 73.43% in the HA graft group, respectively (p = ns). The 1-, 3- and 5-yr graft survival was better in the control group (81.51, 73.66, 69.22% vs. 71.17, 62.50, 53.42%) (p = 0.01). In case of retransplantation, the 1-, 3- and 5-yr overall (57.81, 53.95, 41.96% vs. 60, 51.95, 49.85%) and graft survival (57.52, 53.68, 41.75% vs. 56, 50.4, 40.3%) was similar in control and HA graft group, respectively (p = ns). Hepatic artery thrombosis (HAT) rate is 21.8% vs. 8.6% (p < 0.0001) in HA graft group and control group, respectively. The only factor independently predictive of early HAT resulted arterial conduit (p = 0.001, OR = 3.13, 95% CI: 1.57-6.21). Retransplant procedure, donor age and arterial iliac conduit were found to be a significant risk factors for late HAT, at univariate analysis. At multivariate analysis, donor age >50 yr old resulted the only factor independently associated with late HAT (p < 0.0001, OR = 1.05, 95% CI: 1.02-1.07). CONCLUSION: Iliac arterial interpositional graft is an alternative solution for arterial revascularization of liver allograft in case of retransplantation when the use of HA is not possible. In case of primary transplantation, is better not to perform arterial conduit if it is possible, for poor graft survival and high incidence of early HAT, especially in case of liver donor aged over 50 yr.
Abstract: BACKGROUND: Infectious complications still represent a major cause of morbidity and mortality in patients with organ transplantation. In particular, small bowel or multivisceral transplantation is complicated to a greater extent than other grafts as a consequence of infectious complications including sepsis. METHODS: This prospective study assessed outcome, incidence, and timing of infections in sequential patients undergoing small bowel or multivisceral transplantation (SB/MVTx) performed at a university transplant center between January 2001 and October 2003. Nineteen patients underwent transplantation during this period, 13 of whom (68%) undergoing isolated SB and 6 (32%) MV grafts with or without liver. RESULTS: The median follow up was 524 days (interquartile range=252-730) with an overall 24.4 person/year of observation. Postoperative mortality rate was 0.1 death/person/year; all patients, except one who died intraoperatively, were alive 6 months postsurgery. There were 100 documented infections including: 59 bacterial (2.4 events/person/year), 35 viral (1.4 events/person/year) and 6 fungal (0.2 events/person/year). Patients developed at least one episode of bacterial infection in 94% of the cases, viral infection in 67%, and fungal infection in 28%. CONCLUSIONS: This cohort describes the very common and complex nature of infectious complications in this challenging group of transplantation patients. Larger cohorts are needed to specifically address infection risk factors and longer term outcomes.
Abstract: cRight lobe living liver transplantation is being performed worldwide with increased frequency. Difficult arterial reconstructions are often encountered because of small diameter or discrepancy between arterial stumps. The risk of arterial thrombosis is reported as high as 26%: microsurgical techniques have reduced this rate below 2%, increasing warm ischemia time. We have developed a new branch patch technique in living related liver transplantation using the donor cystic artery to create an enlarged patch anastomosis that enables increase in the vessel's diameter and therefore greater inflow to the liver. We have followed 8 patients treated with this technique. After more than 1 year (mean follow-up: 636 days) we did not observe any arterial thrombosis by Doppler ultrasound performed every 3 months. The mean resistance index was 0.68 (0.57-0.83-). Three patients died with functional graft without signs of thrombosis. We believe that the cystic artery branch patch technique is feasible in all cases. It is fast (mean time: 6.2 min), it allows a shorter warm ischemia time, and there is no increased risk of thrombosis.
Abstract: Granzyme B (GrB) and perforin are promising markers to predict acute rejection episodes of transplanted organs. Having recently reported that immunohistochemical expression of GrB/perforin correlates with histologically assessed acute cellular rejection (ACR) episodes in intestinal transplantation recipients, herein we have additionally explored the potential of real-time polymerase chain reaction (PCR) assessment of GrB/perforin gene up-regulation in peripheral blood mononuclear cells. Both immunohistochemical evaluation of GrB/perforin expression and real-time PCR assessment of up-regulation, which was defined as a 2-fold increase with respect to "basal" levels during maintenance immunosuppressive protocols, were performed among a population of 23 intestinal transplant recipients under routine surveillance, in addition to histological analysis of ACR. The ACR scores showed direct relationships both with GrB/perforin immunohistochemistry (IHC) scores (P < .001) and with gene up-regulation by real-time PCR (P = .004). Furthermore, real-time PCR upregulation was associated with the IHC score (P < .001). A preliminary analysis of diagnostic accuracy-performed to gain information to plan future studies-indicated that when using histological assessment as the reference technique, our current definition of PCR up-regulation provided good specificity (84%) but insufficient sensitivity (44%) for a noninvasive prediction of ACR. The results of this pilot study suggested that real-time PCR analysis of GrB/perforin upregulation may help therapeutic decision making, and have the potential for detection of presymptomatic rejection. More extensive studies must investigate strategies to improve the sensitivity of the analyses of GrB/perforin up-regulation.
Abstract: Multivisceral transplants are gaining acceptance worldwide for patients with chronic gastrointestinal failure with or without irreversible total parenteral nutrition (TPN)-related liver failure. We describe our experience with nine multivisceral harvests reporting our in vivo technique. Multivisceral grafts included stomach, duodenum, pancreas, small bowel, and part of large intestine with or without the liver. After a careful evaluation of the liver and the bowel, we isolated the superior mesenteric artery origin. Then we identified the distal part of the graft isolating the middle colic vein and stapling the transverse colon to its left. After esophagus isolation and stapling, we mobilized the graft, starting from the spleen to the pancreaticoduodenal block, near the celiac trunk. After cross-clamping and cold perfusion, we created an aortic patch including the superior mesenteric artery and celiac trunk as a multivisceral harvest without the liver. A total hepatectomy is added for a liver multivisceral graft. We harvested four multivisceral grafts without the liver and five multivisceral grafts with the liver. We performed seven multivisceral transplants on adult recipients, four without the liver and three with the liver, as well as two liver and one isolated small bowel transplants. Postreperfusion hemostasis was always satisfactory with a mean ischemia time of 6.5 hours. Four recipients died: there was one intraoperative death due to disseminated intravascular coagulopathy. Another patient underwent graftectomy 1 day after transplantation due to vascular thrombosis. In conclusion, our in vivo technique allows a shorter ischemia time with a minimal postreperfusion bleeding and reduced production of lymphatic ascites, without jeopardizing organ function.
Abstract: Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.
Abstract: INTRODUCTION: Living donation in adult liver transplantation (LDLTx) is an important resource because of the waiting list growth. We started a living donor program to overcome the shortage of cadaveric sources. PATIENTS: From May 2001 to May 2003, 36 patients underwent LDLTx: 27 received a right lobe, 8 received a left lobe, and 1 received segments II and III. RESULTS: The 1-year actuarial survival rate was 77.7%, with a mean follow-up, in survivors, of 754 +/- 248 days. Eleven of 27 (40.7%) right lobe recipients died. Among left graft recipients, 3 patients died (33%). We undertook retransplantation in 4 cases, because of 2 "small for size" syndrome, 1 late hepatic artery thrombosis, and 1 early portal vein thrombosis. After a period of 797 days, all 36 donors returned to a normal social and working life. Two donors, who underwent right lobe donation, experienced major complications: 1 case of biliary stenosis, treated by stenting, and 1 case of biliary leak from the cut surface of the liver, requiring laparotomy and abscess drainage. Left lobe donors developed no complications. CONCLUSIONS: LDLTx has a learning curve for experienced liver transplantation surgeons. Our last 18 cases showed better survivals than the first 18 (9 deaths vs 5), even if, in the latter group, we transplanted 8 left livers. In our experience, LDLTx of a left liver graft has an increased risk of "small for size syndrome," but patients, both donors and recipients, report improved outcomes.
Abstract: OBJECTIVE: The objective of this study was to compare the accuracy of 2 variables: pulmonary artery occlusion pressure (PAOP) and right ventricular end diastolic volume index (RVEDVI) as predictors of the hemodynamic response to fluid challenge as well as definition of the overall correlation between RVEDVI and change in PAOP, right ventricular ejection fraction (RVEF), central venous pressure (CVP), and determination of the right ventricular function during orthotopic liver transplantation. MATERIALS AND METHODS: A modified pulmonary artery catheter equipped with a fast response thermistor was used to determine RVEF, allowing calculation of RVEF end-diastolic volume index (EDVI, as the ratio of stroke index [SI] to EF). The above-mentioned hemodynamic measures were taken in 4 phases: T0, after induction of anesthesia; T1, during anhepatic phase; T2, 30' after graft reperfusion; and T3, at the end of surgery. RESULTS: The variation of the REF value was 36 +/- 4% and 39 +/- 6%. Linear regression analysis showed a significant correlation between RVEDVI (range, 133 +/- 33-145 +/- 40 mL/m(2)) and stroke volume index (SVI) in each phase (r(2) = 0.49, P < .01; r(2) = 0.57, P < .01) at T0 and T1, respectively, and at T2 and T3 (r(2) = 0.51, P < .01; r(2) = 0.44, P < .01), respectively. No significant variations in the linear regression analysis between RVEDVI, PAOP, CVP, and RVEF were observed. No relationship was found between PAOP (range, 10 +/- 2-6 +/- 2 mm Hg) and SVI. CONCLUSION: RVEDVI may be the best clinical estimate of right ventricular preload. In fact, minor changes of RVEF have been recorded, confirming that RV function was not altered during uncomplicated orthotopic liver transplantation.
Abstract: Induction with thymoglobulin, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LT) has never been investigated. We report herein on the outcome of 22 HCV+ patients receiving thymoglobulin pretreatment and minimal immunosuppression after liver transplantation. Patient survival and acute rejection rates were good, with remarkably low dosages and levels of immunosuppression achieved with thymoglobulin, and without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressant was also possible in the majority of patients without complications. The HCV recurrence rate was similar to that reported in the literature, although lower HCV RNA viral loads were obtained with thymoglobulin and a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobulin is effective to protect against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.
Abstract: AIM: Elderly donors are half of the grafts available in our center for liver transplantation. We retrospectively investigated their characteristics, outcomes, and variables related to graft failure. MATERIAL AND METHODS: From 1996 to 2003, 540 (46.4%) of 1163 donors were older than 60 years of age and 236 grafts (43.4%) were transplanted, whereas the others were refused. The clinical investigated variables were examined among this cohort. RESULTS: The median age of donors increased from 37 to 62 years. Donors older than 60 years of age were more often refused than younger ones (66% vs 44%); HCV-positive (9.9% vs 5.4%); HbcAb-positive (18.6% vs 12.6%), and steatotic (35.7% vs 13.9%; P < .01). Among donors older than 60 years, the main parameter to refuse the graft was the grade of steatosis. The variables related to the graft loss from donors older than 60 years were as follows: model for end stage liver disease (MELD) recipient >15 (65% vs 39%), cold ischemia time >10 hours (25% vs 13%), high blood losses (3987 +/- 4764 vs 2664 +/- 2043 mL), and year of liver transplantation after 2000 (26% vs 46%; P < .01). The 1-, 3-, and 5-year graft survival rates were significantly lower among donors older than 60 years than other donors: 75%, 65%, and 62% versus 85%, 83%, and 78%, respectively (P < .001). CONCLUSION: Donors older than 60 years of age provided liver transplants to half of our recipients. The graft survival rate of these organs was lower than that of younger donors and to improve it the other risk variables for poor outcome should be reduced, including MELD score of the recipient and prolonged cold ischemia time.
Abstract: This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab was well tolerated, and a reduction of Epstein-Barr virus (EBV) viral load was documented by quantitive competitive-EBV polymerase chain reaction. Efficacy of therapy needs to be assessed in controlled studies.
Abstract: Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.
Abstract: Even when considering the possibility of organ rejection and the complications of immunosuppression, the risks associated with total parenteral nutrition therapy are life-threatening. Therefore, for patients with end-stage bowel disease small bowel transplantation (SBTx) is the only therapeutic option. The preferred method to procure these organs is debated, especially when, graft retrieval is associated with concurrent abdominal organ procurement of the pancreas, which shares part of the vascular inflow and outflow with the small bowel. While many surgeons procure the graft using the en bloc method, dissecting tissue at the back table, our preference is to use an in vivo technique, which results in shorter cold ischemia times and less bleeding during reperfusion of the pancreas/small bowel as well as decreased ascites production during the postoperative period and less edema and capsular bleeding of the pancreatic grafts. This article presents an analysis of 19 multiorgan cadaveric procurements using the in vivo technique with a focus on the quality of pancreas/small bowel postreperfusion properties during the first 5 to 6 postoperative months.
Abstract: In 2002, the Italian guidelines for eligibility of patients for intestinal transplantation (ITx) were defined as: life-threatening complications of home parenteral nutrition (HPN), lack of venous access for HPN, locally invasive tumors of the abdomen, Chronic intestinal failure (CIF) with a high risk of mortality, primary disease-related poor quality of life (QoL) despite optimal HPN. Our aim was to identify potential candidates for ITx according to these national guidelines among patients managed by a medical referral center for CIF. Records of patients who received HPN were reviewed. CIF was considered reversible or irreversible (energy by HPN <50% or >50% basal energy expenditure). Patients with irreversible CIF were considered eligible for ITx in the absence of a contraindication, as are used for solid organs Tx. From 1986 to 2003 among 64 patients who met the entry criteria 23 showed reversible and 41 irreversible, CIF. Twenty-one patients with irreversible CIF had an indication for ITx, but eight had also contraindications; thus 13 were eligible, including intestinal pseudo-obstruction (n = 6), mesenteric ischemia (n = 3), Crohn's (n = 2), radiation enteritis (n = 1), and desmoid (n = 1). Indications for ITx included HPN liver failure (n = 2), lack of venous access (n = 2), CIF with high risk of mortality (n = 3), very poor QoL (n = 6 including 5 with pseudo-obstruction). According to the Italian guidelines for ITx, 31% of patients with irreversible CIF managed by a medical referral center were eligible for ITx. Primary disease-related poor QoL was the indication in half of them. Studies on the QoL after ITx are required to allow patients to make an educated decision.
Abstract: BACKGROUND: Graft shortage makes multiorgan procurement mandatory. We describe the results of a simplified method for the en bloc procurement of multiple organs, which permits isolated transplantation of all abdominal grafts, including the pancreas and the small bowel, to different recipients. METHODS: Three hundred forty-three multiorgan procurements were done with a simplified en bloc technique. RESULTS: None of the 1374 grafts that were procured sustained injuries that potentially precluded transplantation. Seventy-two grafts that were procured from 18 donors (5%) who were diagnosed with a neoplasm were discarded. Overall, 339 grafts that were procured from 325 donors were discarded because of specific contraindications, and 963 grafts (74%) were transplanted. Ninety-seven pancreata were transplanted. In 3 instances the pancreas and the small bowel were procured simultaneously and transplanted to different recipients. A total of 287 liver grafts were also transplanted at 13 different institutions. In 42 instances, the liver was not allocated to our center. Forty liver teams (95%) from 11 different institutions agreed to procure their grafts according to the simplified en bloc technique. Our team performed 18 procurements, and a surgeon from the liver transplantation team, who was assisted by one of the members of our team, performed 22 procurements. In all, 576 kidneys were transplanted, either alone or simultaneously, with other abdominal grafts at 15 different institutions. CONCLUSIONS: This procurement method has high yields, allows pancreas and small-bowel procurement, and can be learned readily.
Abstract: Intestinal transplantation (ITx) has become a life-saving procedure for patients with irreversible intestinal failure who can no longer be maintained on parenteral nutrition (PN). This report presents the results of our experience on ITx in patients suffering from chronic intestinal pseudo-obstruction (CIPO). Between December 30, 2000 and May 30, 2003 six adult patients affected by CIPO underwent primary ITx at our Center. Pre-transplant evaluation, indication for ITx and surgical technique are reported. On December 30 2003, the mean follow-up was 25.0 months. No peri-operative deaths occurred in the study population and five out of six patients are alive, with 1-year patient and graft survival of 83.3% and 66.6%. Although our series is limited by the number of patients, our experience suggests that ITx transplantation should be considered in adult patients suffering from CIPO and PN life-threatening complication.
Abstract: BACKGROUND: The purpose of this study was to evaluate the outcome of 19 patients who underwent intestinal transplantation (ITx) for intestinal failure. METHODS: The 19 patients who underwent primary ITx between December 2000 and May 2003 were prescribed three different immunosuppressive protocols that included daclizumab, alemtuzumab, and antithymocyte globulin induction, respectively. A mucosal surveillance protocol for early detection of rejection consisted of zoom video endoscopy and serial biopsies associated with orthogonal polarization spectral imaging. Retrospective review of the clinical records was performed to assess the impact of new modalities of immunosuppression and intestinal mucosal monitoring on patient outcomes. RESULTS: All patients were adults (mean age 35.8 years). Etiology of intestinal failure included chronic intestinal pseudo-obstruction (n = 6), intestinal angiomatosis (n = 1), Gardner syndrome (n = 2), intestinal infarction (n = 8), radiation enteritis (n = 1), and intestinal atresia (n = 1). All patients experienced complications from total parenteral nutrition (TPN). Thirteen patients (68.4%) received isolated small bowel, whereas six (31.6%) received multivisceral grafts with or without the liver. Thirteen of 19 patients experienced at least one episode of rejection (68.4%). Most ACR episodes were treated with steroid boluses and resolved completely within 5 days. The overall 1-year patient survival was 82%. All living patients are in good health with functioning grafts having been weaned off TPN after a mean of 23.7 days post-ITx. DISCUSSION: Advances in immunosuppressive therapy with early detection and prompt treatment of rejection episodes make ITx a valuable treatment option for patients with intestinal failure and TPN-related life-threatening complications.
Abstract: Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10-15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16-49 minutes (mean, 31 +/- 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 +/- 336 U/L) than group 2 (322 +/- 162 U/L; P = 0.03). Mean INR was significantly higher in group 1 (1.8 +/- 0.2) vs. group 2 (1.5 +/- 0.2; P = 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 +/- 2.9 days) than group 2 (6.2 +/- 1.1 days; P = 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy.
Abstract: Postoperative inferior vena cava obstruction is an uncommon complication after liver transplantation. Outflow obstruction, if not rapidly corrected, can lead to graft failure and the patient's death. We report a case in which Doppler ultrasound showed the thrombus inside the vessel, excluding extrahepatic causes of venous outflow obstruction, and permitted early surgical correction of the complication without graft loss.
Abstract: The objective of this study was to assess the timing, incidence, and outcome of infections in patients with small bowel/multivisceral transplants (SB/MV Tx). A 180-day follow-up was obtained on 13 SB/MV patients transplanted from January 2001 to June 2002. Fifty-six documented infections were observed. By Kaplan-Meier analysis for time to infection, most of which were of bacterial origin (more than 86%), revealed most events to have occurred within the first month post-Tx. Viral infections were equally distributed after the 30th postoperative day.
Abstract: Solitary necrotic nodule is a rare benign lesion of the liver of unknown aetiology, which as a result of its radiological features can be misdiagnosed as a necrotic tumour. We believe that surgical exploration with a limited liver resection and an extemporary examination of the specimen is the best strategy for this rare type of lesion.
Abstract: BACKGROUND: The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic finding after liver transplantation, but its correlation with tumor recurrence has never been investigated. METHODS: we retrospectively reviewed the outcome of 54 patients with a single histologically proven HCC after liver transplantation. All cases had a survival of more than 6 months, and patients treated preoperatively had a transarterial chemoembolization (TACE) procedure. Since 1996, our center has applied the Milan criteria. Correlations between tumor recurrences and clinicopathologic variables, including the presence of partial necrosis, were performed. Etiologic factors for HCC partial necrosis were also investigated. RESULTS: Sixteen of 54 (29.6%) HCC nodules presented partial necrosis, and 4 (25%) of them developed HCC recurrence compared with 1 of 38 (2.6%) cases without this histologic finding (P<0.05). Partial necrosis was related to TACE procedure (P<0.05), patient age less than 50 years (P<0.05), and tumor diameter greater than 2 cm (P<0.05). Multivariate analysis showed only TACE as an independent variable. The other variables related to the five (9.3%) tumor recurrences were HCC diameter greater than 2 cm (P<0.05), year of liver transplantation before 1996 (P<0.05), and the presence of satellite nodules (P<0.05). The Cox regression analysis showed the presence of partial necrosis as an independent variable related to tumor recurrence. The analysis of the recurrence-free survival confirmed the results of the recurrence rate. CONCLUSION: Partial necrosis was a risk factor for tumor recurrence after liver transplantation. Patients and procedures should be selected while also bearing in mind the side-effect of incomplete necrosis of the nodules.
Abstract: OBJECTIVE: We retrospectively investigated the efficacy of the MELD score to predict the outcome of liver retransplantation and serve as selection criteria. MATERIALS AND METHODS: From 1987 to 2003, the 765 liver transplantations included 87 patients (11.4%) who received a second graft. In addition to graft and patient survivals, ROC curves were used to establish the best MELD score to select cases with poor outcomes. RESULTS: Indications for retransplantation were: 38 (43.7%) surgical complications; 12 (13.8%) chronic rejections; 15 (17.2%) disease recurrences; and 22 (15.3%) primary graft nonfunction. Overall patient survivals at 1, 3, and 5 years were 62.4%, 50.7%, and 49.1%, respectively. A MELD score of 25, calculated by ROC curves, significantly predicted graft and patient survival (44.2% vs 22.5%, P < .05 and 58.6% vs 27.8%, P < .005). During the first 30 postoperative days, patients with a MELD higher than 25 lost the second graft in 48% of cases compared to 16% in the other group (P < .005). Patients retransplanted for primary graft nonfunction showed significant lower 5-year survival rates than those for other indications (28.6% vs 54.5%, P < .05) and higher mean MELD score (30.7 vs 21.9, P < .05). CONCLUSION: A MELD score of 25 is a valid cut-off to predict the outcome of retransplantations, it may be useful to select patients among those who require a second graft. Cases with primary graft nonfunction displayed lower survival, because of their compromised clinical status as evidenced by their high MELD scores.
Abstract: HYPOTHESIS: To minimize the incidence of ischemic arterial complications, risk factors should be clearly identified. Knowledge of the predisposing factors for such complications would make possible the institution of strict surveillance protocols that could ensure early detection of complications and so prevent the progression of ischemic damage to graft failure. DESIGN: Retrospective univariate and multivariate analysis. SETTING: University hospital. PATIENTS: Six hundred fifty-three adults who underwent 747 orthotopic liver transplantations. MAIN OUTCOME MEASURES: We used univariate and multivariate analyses to retrospectively assess the role of possible risk factors for early and late HA thrombosis (HAT) and stenosis (HAS), including etiology of liver disease, donor and recipient sex and age (aged < or =60 vs >60 years), cause of donor death, preservation solution, cold ischemic time, previous orthotopic liver transplantation, HA back-table reconstruction, direct arterial anastomosis vs interpositional conduit, experience of the surgeon, intraoperative transfusion requirements, acute rejection, and cytomegalovirus infection. RESULTS: We observed 58 ischemic complications, including 26 early HAT, 13 late HAT, and 19 HAS. Independent predictors of early HAT were donor age greater than 60 years and bench reconstruction of anatomical variants of the HA; of late HAT, arterial anastomosis fashioned using an interpositional graft of donor iliac artery (iliac conduit) and donors who died of cerebrovascular accident; and of HAS, previous orthotopic liver transplantation and cytomegalovirus infection. CONCLUSIONS: Predisposing factors for HAT mostly stem from donor and graft features. Use of iliac conduits should be limited, particularly when using old donors. Frequent screening of the arterial flow to the graft with Doppler ultrasonography is advisable in patients at risk.
Abstract: Technical aspects in living-related liver transplantation are still under debate: the main pitfall is the arterial reconstruction due to the small diameter and the discrepancy between stumps, with a subsequent increased risk of arterial thrombosis. The gold standard is the microsurgical technique, that reports the lowest risk of thrombosis, but it is a time consuming procedure requiring a long training. Our method of choice reconstructing hepatic artery in right lobe is the use of the cystic artery as a branch patch with the recipient hepatic artery by loop magnification, saving time and with a low incidence of hepatic artery thrombosis.
Abstract: The risks and benefits of adult-to-adult living donor liver transplantation need to be carefully evaluated. Anesthetic management includes postoperative epidural pain relief; however, even patients with a normal preoperative coagulation profile may suffer transient postoperative coagulation derangement. This study explores the possible causes of postoperative coagulation derangement after donor hepatectomy and the possible implications on epidural analgesia. Thirty donors, American Society of Anesthesiology I, with no history of liver disease were considered suitable for the study. A thoracic epidural catheter was inserted before induction and removed when laboratory values were as follows: prothrombin time (PT) > 60%, activated partial thromboplastin time < 1.24 (sec), and platelet count > 100,000 mmf pound sterling (mm3). Standard blood tests were evaluated before surgery, on admission to the recovery room, and daily until postoperative day (POD) 5. The volumes of blood loss and of intraoperative fluids administered were recorded. Coagulation abnormalities observed immediately after surgery may be related mostly to blood loss and to the diluting effect of the intraoperative infused fluids, although the extent of the resection appears to be the most important factor in the extension of the PT observed from POD 1. In conclusion, significant alterations in PT and platelet values were observed in our patients who underwent uncomplicated major liver resection for living donor liver transplantation. Because the potential benefits of epidural analgesia for liver resection are undefined according to available data, additional prospective randomized studies comparing the effectiveness and safety of intravenous versus epidural analgesia in this patient population should be performed.
Abstract: Small-for-size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year-old patient underwent to LDLT at our institution. During the anhepatic phase a porto-systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post-operative course was characterized by good graft function. Small-for-size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult-to-adult living donor liver transplantation.
Abstract: Aim of the study was to evaluate the surgical strategy for the treatment of the hilar cholangiocarcinoma, focusing on the clinicopathological factors influencing the outcome. Between January 2001 and December 2003 23 patients out of 33 underwent surgery for hilar cholangiocarcinoma. All patients underwent resection of the extrahepatic biliary duct. This was the only treatment in patients with Bismuth-Corlette type I cholangiocarcinoma, or in patients not suitable for hepatic resection. In the other cases, resection of extrahepatic bile duct was associated to right or left hepatectomy. The univariate and multivariate analysis evaluated multiple clinicopathological factors in order to assess long term survival. Major hepatic resection was carried out in 19 (82%) patients. Hepatic resection extended to the segment 4 was performed in 5 patients. Also, left hepatectomy was carried out in 14 patients, while resection of the caudate lobe in 7 (30%) patients. No hospital mortality was recorded, while the overall morbidity was 43%. The 1 year survival rate was 63.2%, and the median survival rate 19 months. Recurrencies showed up in 12 patients (52%). Among the other factors, low level of albumin (p = 0.006), positive resection margins (p = 0.003) and T (p = 0.02) mostly affected the long term survival. Surgery is the gold standard for achieving curative treatment of hilar cholangiocarcinoma. The bile duct resection, along with hepatic resection, the best option to increase long term survival of these patients. The univariate and multivariate analysis showed that low albumin levels, positive resection margins and T are the most important factors influencing long term survival.
Abstract: In human heart and kidney transplantations, granzyme B (GrB) and perforin have both been shown to be predictive markers for acute cellular rejection (ACR). We investigated the tissue expression and possible relationship of GrB and perforin to the clinical outcome, histopathology, and function of intestinal transplants. In 13 consecutive patients undergoing small intestine transplantation, histologic/immunohistochemical rejection monitoring was performed together with GrB and perforin immunostaining (score "0", 0%-10% positive lymphocytes; "1", 10%-25%; "2", 25%-50%; "3", >50%). Eleven patients are currently alive and well. All 11 had at least one episode of ACR: one patient had 6 episodes of severe ACR requiring retransplantation; the remaining 10 experienced only mild or moderate rejection. Both GrB and perforin were always co-expressed. A highly significant correlation was observed between GrB/perforin scores and histological severity of ACR (Pearson's coefficient, R < 0.0009). Interestingly, score 3 GrB/perforin immunostaining was recorded only in the context of severe ACR; all the histologically negative or "indeterminate" biopsies (n = 6) taken from a single affected patient showed GrB/perforin scores of 1 or 2. By contrast, none of the other tested histologically negative/"indeterminate" biopsies (n = 350), including those performed during graft stabilization, had raised GrB or perforin scores. We conclude that in intestinal transplantation recipients, a direct correlation seems to exist between histologically confirmed ACR and raised GrB/perforin immunohistochemical scores. Our findings suggest the need to investigate the possibility of predicting ACR by routine serum polymerase chain reaction (PCR) monitoring, which would reduce discomfort to patients.
Abstract: Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.
Abstract: Five cases of fulminant hepatitis due to herpes simplex virus were identified among patients admitted to the Thomas E. Starzl Transplantation Institute between January 1991 and September 1994. The diagnosis was established in three of the five patients on the basis of transjugular liver biopsy specimen results. These three patients were treated with acyclovir; two survived and one required liver transplantation. Early histologic diagnosis, specific antiviral treatment, and liver transplantation in selected patients may improve the clinical outcome of this almost uniformly fatal disease.
Abstract: Intestinal transplantation has been gradually instituted in the management of intestinal failure. More than 200 cases including isolated intestinal transplant, liver/intestinal transplant, and multivisceral transplant have been performed worldwide,with 1-year graft and patient survival rates of 66% and 54%,respectively. Indications for the procedure include short bowel syndrome and functional abnormalities secondary to a variety of diseases or conditions. Tacrolimus-based immunosuppression regimens have been used universally with improved outcomes. The major contributors to the morbidity and mortality include rejection,infection, and technical complications. Of those, control of rejection remains the most difficult dilemma and it will be the key to improved patient and graft survival.
Abstract: BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP) are locally invasive. Often occurring in the mesentery of the intestine, they sometimes recur after resection. Complications can include intestinal failure and dependence on parenteral nutrition. We describe 9 patients who underwent intestinal transplantation for the treatment of desmoid tumors associated with FAP. METHODS: Records of patients undergoing intestinal transplantation for desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type of graft, procedure date, tumor site, desmoid complications, medications, extracolonic manifestations, status at follow-up, and length of survival. RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One graft lost to severe rejection was replaced with a second intestinal graft. Eleven to 53 months after transplantation, 7 patients were alive, well, independent of parenteral treatment, and leading apparently normal lifestyles. CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral transplantation may help rescue otherwise untreatable patients with complicated desmoid tumors.
Abstract: We report on two recipients of multi-visceral grafts who exhibited sudden onset of acute abdomen discomfort 2 weeks post-transplantation after a fairly uneventful immediate post-operative course. Both patients were shown to have pneumatosis intestinalis and one had air in the portal vein. Both patients underwent exploration, which showed non-viable intestine (terminal ileum and colon in the first patient and the entire small intestine distal to the ligament of Treitz in the second patient). There was no vascular thrombosis. The necrotic intestine was resected in both cases. The first patient developed sepsis and died 15 days later despite the rescue efforts. The second patient was re-transplanted twice and is doing well. The histopathology of the segments involved revealed cryptitis, vasculitis, and features of transmural necrosis. Accordingly, both clinical and pathologic features are diagnostic of necrotizing enterocolitis. To our knowledge this is the first report of this complication following intestinal or multi-visceral transplantation.
Abstract: Hypertrophic obstructive cardiomyopathy (HOCM) associated with the use of tacrolimus is a rare complication of liver and intestinal transplantation seen almost exclusively among pediatric patients. Reduction of tacrolimus dosage or conversion to cyclosporin A (CsA) has been used as an effective treatment in reviewed cases. We present three pediatric transplant recipients who developed hypertrophic obstructive cardiomyopathy while under tacrolimus immunosuppression and were treated with conversion to sirolimus (Rapamycin). The patients (ages 6 yr, 12 yr and 11 months) were transplant recipients (liver, n = 2; liver and intestine, n = 1) who developed significant cardiomyopathy 15 and 96 months post-transplant. One patient died of post-transplant lymphoproliferative disorder 21 days after starting sirolimus. One patient had received two liver transplants and had been on CsA for 12 yr before conversion to tacrolimus at 60 months post-transplant for acute and chronic rejection. The surviving patients were receiving mycophenolate mofetil, tacrolimus and steroids at the time of diagnosis. Dose reduction of tacrolimus and treatment with beta blockers failed to alleviate the hemodynamic changes. The patients were converted to sirolimus 1.6, 37 and 148 months post-transplant and maintained a whole-blood trough level of 15-20 ng/mL 21 days after starting sirolimus. Repeat echocardiograms in the surviving patients showed improvement in cardiomyopathy. One patient had one rejection episode (intestinal biopsy, mild acute cellular rejection) after starting sirolimus that responded to a transient increase in steroids. The early demise of the third patient after sirolimus conversion prevented an adequate assessment of cardiomyopathy. Conversion to sirolimus was associated with a reduction in the cardiomyopathy of the two surviving patients while still providing effective immunosuppression. To our knowledge this observation has not been previously reported.
Abstract: BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a well recognized and prevalent early postoperative complication. The etiology, as well as the effect of this phenomenon on transplant outcome, however, are vague. The aims of this study are to identify factors contributing to thrombocytopenia and to ascertain whether there is any correlation with early rejection and ultimate survival. METHODS: This study examines 541 OLTs (541 grafts in 494 patients) that were transplanted at the University of Miami during the 3-year period from June 1994 to September 1997. The patients with severe postoperative thrombocytopenia (nadir platelet count [PLT] < 20,000/mm3), as well as the whole group of patients, were analyzed. The preoperative PLT, intra-operative platelet transfusion requirements, cross-match, recipient and donor cytomegalovirus (CMV) status, infusion of donor bone marrow cells (DBMC), occurrence of early rejection episodes (in the first posttransplant month), and re-transplantation were factors examined for any association with thrombocytopenia. Total bilirubin (TB) and direct bilirubin (dB), hematocrit, white blood cell count (WBC), aspartate aminotransferase and alanine aminotransferase, determined on the day that platelets reached a nadir (nadir day), were also analyzed. RESULTS: In 90.9% of the cases, there was a 56.5%+/-23.5% fall in platelets in the immediate posttransplant period (first 2 weeks), but the mean PLT exceeded preoperative levels during the 3rd and 4th postoperative weeks. The nadir of the drop in the PLT most commonly occurred on posttransplant day 4. For preoperative PLT, platelet transfusions during the operation, re-transplantation, early rejection, cross-match, and recipient CMV status, there was significant statistical correlation with any degree of postoperative thrombocytopenia. Four of these factors, preoperative PLT, intra-operative platelet transfusions, re-transplantation, and early rejection, were found to be independently associated with thrombocytopenia in general. None of them was found to be independently correlated with severe thrombocytopenia. A statistically significant correlation between bilirubin and WBC on the nadir day and the degree of thrombocytopenia was observed. No correlation was found between infusion of DBMC or donor CMV serology and thrombocytopenia. Both the nadir PLT and the percentage of the platelet fall were independent predictive factors (p<0.01 and 0.005, respectively) of patient and graft survival. CONCLUSIONS: Thrombocytopenia in the immediate posttransplant period is correlated with low preoperative PLT, massive platelet transfusions, and re-transplantation. These factors reflect a poor preoperative condition. There is also a correlation with allograft dysfunction, rejection, and poorer patient and graft survival. A rise in the mean PLT after the 2nd postoperative week reflects proper graft function.
Abstract: Graft-versus-host disease (GvHD) is a multi-organ disease caused by mature donor T cells that are activated by alloantigens expressed by the host antigen-presenting cells. GvHD has been reported after solid organ transplantation with two principal presentations: humoral and cellular. In the cellular type of GvHD after liver transplantation the symptoms are identical to the GvHD after bone marrow transplant, except that the liver is spared because it lacks host antigens. We have described three cases of intestinal GvHD after pediatric liver transplant with an unusual recurrent late presentation in two patients. Two patients were female, and their age at the time of transplant was 8 and 9 months, respectively, and one was an 8-month-old male. They all received reduced liver allografts of identical blood type from three different donors. One patient received two doses of donor bone marrow cell infusion. Two patients received double immunosuppressive therapy constituted by tacrolimus at a dose of 0.05 mg/kg p.o. b.i.d. and steroids 10 mg p.o. daily. One patient received a triple drug immunosuppression with tacrolimus (0.05 mg/kg p.o. b.i.d.), steroids (10 mg p.o. daily) and mycophenolate mofetil (125 mg p.o. b.i.d.). Diagnosis of intestinal GvHD was confirmed histologically on intestinal biopsies performed at the time of presentation of the clinical symptoms or at autopsy.
Abstract: An entire pancreatico-duodenal complex was included in the liver and intestinal graft in eight children who received small-size grafts. This method showed several advantages compared to the traditional approach. They included reducing time for graft preparation by eliminating donor pancreas resection, no necessity of biliary reconstruction and leaving natural tissue support for blood vessels. The method was not associated with an increased risk of complications such as pancreatitis or rejection. It should be considered in pediatric liver and intestinal transplant recipients who require small-size grafts.
Abstract: BACKGROUND: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare autosomal recessive disorder causing a functional neonatal bowel obstruction. Its etiopathogenesis is not fully understood. The prognosis is poor in the majority of cases; most patients die before the age of 6 months. In this report, we describe our experience with three patients with MMIHS in whom multivisceral transplantation was performed. METHODS: Three patients with MMIHS underwent multivisceral transplantation. All patients were females with a history of long-term total parenteral nutrition (TPN) with TPN-related cholestatic liver disease. RESULTS: Patient 1 died 17 months after transplantation because of aspiration after revision of her feeding gastrostomy. At the time of death, the graft was functioning and the patient was completely off TPN. Patient 2 is alive 17 months after transplant. She is a fully functional, active 2-year-old and has also recently begun oral feeding after intensive rehabilitation. Patient 3 died on day 44 of multisystem failure. CONCLUSIONS: This is the first report in the literature of multivisceral transplantation for MMIHS. Although one of the three patients died 44 days after surgery from multiorgan system failure, the other two patients had long-term survival after transplant and both grew well on enteral feeding alone. One patient died 17 months from a non-transplant-related complication, while the other is living at home off of TPN, with almost complete dietary rehabilitation 17 months after transplant. Our case reports suggest that multivisceral transplantation is a valuable therapeutic option for patients affected by MMIHS with TPN-induced liver failure.
Abstract: BACKGROUND: Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. METHODS: Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). RESULTS: Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. CONCLUSION: Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.
Abstract: BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.
Abstract: Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option.
Abstract: Between April 1993 and May 1995, 17 adult orthotopic liver transplant recipients were found to have early hepatic artery thrombosis (HAT) after a median of 7 postoperative days (mean, 11). The HAT was diagnosed in all cases by duplex ultrasound. Thrombectomy was performed with urgent revascularization (UR), using an interposition arterial graft procured from the cadaveric liver donor, and arterial patency was verified with intraoperative angiography. In seven cases, intra-arterial urokinase was administered after the thrombectomy. Fifteen (88%) of the livers remained arterialized throughout the follow-up period (median, 15 months); the remaining two patients developed recurrent HAT after 6 and 8 months. Although there was a high rate of subsequent complications, 11 (65%) of the patients are alive without retransplantation, with a mean follow-up of 17 months. Despite having a patent hepatic artery, the remaining six patients (35%) died from infectious complications that usually were present before the UR. Thus, UR effectively restored arterial inflow in 88% of the patients with early HAT. The ultimate outcome was determined mainly by the presence of intra-abdominal complications at the time of UR. In conclusion, UR, rather than retransplantation, should be considered the prime treatment option for patients who develop early posttransplant HAT.
Abstract: The principal cause of primary non-function in orthotopic liver transplantation is thought to be preservation injury to the microvasculature. We, therefore, evaluated if effluent levels of hyaluronate, whose uptake is an endothelial cell marker, could predict early graft function and ultimate graft outcome in orthotopic liver transplantation. A total of 102 cases were studied in two phases. In the first phase, we attempted to determine if a correlation existed between effluent hyaluronate levels, early graft function and ultimate graft outcome. This phase of the study was also used to determine hypothetical cut-off values for hyaluronate which could discriminate between good and bad livers. Thirty-two livers orthotopically transplanted to randomly selected primary recipients were studied. After varying periods of static cold storage (4 degrees C) in University of Wisconsin solution, the livers were reinfused with cold (4 degrees C) lactated Ringer's solution. The first 50 ml of the reperfusion effluent was collected from the infrahepatic vena cava. Effluent samples were analyzed for hyaluronate. Linear regression analysis demonstrated a significant correlation between effluent hyaluronate levels and post-operative aspartate and alanine aminotransferase levels (p < 0.001 for both). Logistic regression demonstrated a highly significant correlation (p = 0.0056) between effluent hyaluronate levels and ultimate graft outcome. Generation of Receiver Characteristics Curves indicated that a level between 400 and 430 micrograms.l-1 could possibly discriminate between good livers and those at risk of early graft failure. The authenticity of this hyaluronate cut-off level was further confirmed in the second phase of the study where 70 consecutive primary crossmatch-negative transplants were performed. A highly significant difference was observed in peak aspartate and alanine aminotransferase levels in the first week (p < 0.0006 and p < 0.0005, respectively) between livers with effluent hyaluronate levels < or = 400 micrograms.l-1 and livers with hyaluronate levels higher than 400 micrograms.l-1. Logistic regression revealed a highly significant correlation between effluent hyaluronate levels and graft success (p = 0.0001). Since hyaluronate uptake by the microvascular endothelial cell is significantly greater than production, high hyaluronate effluent levels in failed livers would be due to decreased hyaluronate uptake by the injured microvascular endothelial cell. We therefore conclude that effluent hyaluronate levels may prove to be a reliable preoperative test to assess early graft function and outcome in clinical orthotopic liver transplantation.
Abstract: We studied the outcome of hepatitis C virus (HCV) infection in 14 patients with end-stage HCV-related liver disease who received HCV-positive liver allografts. Viral sequences specific for donor and recipient were established by direct sequencing of PCR products from the NS5 region and by single-strand conformation polymorphism. Within a few months after transplantation the donor strain took over the recipient strain in 8 patients while in 6 patients it was the recipient strain which ultimately prevailed. Donor and recipient were infected by identical genotypes in 6 donor/recipient pairs and by different genotypes in the remaining 8 pairs. Subtype 1b and type 1 (1a + 1b) became the predominant strains in all recipient/donor pairs in which they were present. Patients retaining their own strain were found to have significantly more active liver disease than those infected by the donor strain. We show that HCV superinfection and overtake phenomena occur in humans and suggest that genotypes 1b and 1 (1a + 1b) may possess replicative advantages over other genotypes. Furthermore, we provide evidence of the existence of interference preventing simultaneous continuous infection even by the same genotype strains. The development of active liver disease associated with recipient strain infection and mild or no disease associated with infection from the donor suggests various pathogenic abilities of different HCV strains.
Abstract: To determine the differences in outcome in cases of enterococcal bacteremia due to vancomycin-resistant organisms, we compared consecutive patients on a liver transplant service who had clinically significant bacteremia due to vancomycin-resistant Enterococcus faecium (VREF) (n = 54) with a contemporaneous cohort of patients who had vancomycin-susceptible E. faecium (VSEF) bacteremia (n = 48). VREF bacteremia occurred significantly later in the hospitalization than did VSEF bacteremia (43 days vs. 24 days, respectively; P < .01); in addition, VREF was more frequently the sole blood pathogen isolated (91% of patients) than was VSEF (56% of patients) (P = .0002). Invasive interventions for intraabdominal and intrathoracic infection were required more often in the VREF cohort than in the VSEF cohort (34 of 45 patients vs. 20 of 41 patients, respectively; P = .01). Vancomycin resistance more frequently resulted in recurrent bacteremia (22 of 54 patients infected with VREF vs. 7 of 48 patients infected with VSEF; P = .006), persistent isolation of Enterococcus species at the primary site (27 of 33 patients infected with VREF vs. 7 of 18 patients infected with VSEF; P = .005), and endovascular infection (4 patients infected with VREF vs. none infected with VSEF). The decrement in patient survival, as measured from the last bacteremic episode, was greater in the VREF cohort (P = .02). Vancomycin resistance, shock, and liver failure were independent risk factors for Enterococcus-associated mortality. Higher rates of refractory infection, serious morbidity, and attributable death occurred in the VREF cohort and were partially mediated by the lack of effective antimicrobial therapy.
Abstract: Vasoactive intestinal polypeptide was demonstrated in the nerves of the human normal pancreas and in pancreatitis by light microscope immunohistochemical technique. In specimens of normal pancreas, vasoactive intestinal polypeptide-immunoreactive neuronal cells were present in the autonomic ganglia. These ganglia were found to receive an abundant supply of vasoactive intestinal polypeptide-positive fibre plexuses. Immunoreactive nerve fibres were seen to run in the stroma, in association with secretory acini, ducts and blood vessels. Vasoactive intestinal polypeptide-positive fibres were also seen close to the Langerhans' islets, but no vasoactive intestinal polypeptide-like immunoreactivity was observed in the endocrine cells. In specimens from patients affected by pancreatitis, even in lesioned regions, immunoreactive elements were extremely scarce.
Abstract: Hydatidosis is particularly widespread in some geographic areas. Among these Sardinia presents one of the highest incidences. The authors examine the results obtained of 382 patients submitted to surgery between 1973 and 1989. The average age was 38.9 years. Liver involvement was observed in 215 cases, lung involvement in 167 cases, while localizations in other organs were rare. Forty liver cysts and 54 lung cysts were complicated preoperatively. The patients were submitted predominantly to total or subtotal cysto-pericystectomy (270 cases), parenchymal resection (75 cases), simple cystectomy (40 cases). Total postoperative mortality was 2.35%. Postoperative time was significantly shorter after cysto-pericystectomy and after parenchymal resection than after simple cystectomy. Patients suffering from multiple or complicated cysts were given supplementary chemotherapy.
Abstract: Of a total of 77 patients affected by hydatid cysts of the liver observed between 1983 and 1988, we examined a group of 25 patients with cysts that had migrated into the thorax. The main characteristic of these patients was the hydatid hepatic cyst, which was situated in the right hepatic lobe in every patient, involving one or more right hemithoracic structures. In 24 patients, there were different combinations of symptoms, but only ten were thoracic. In those with advanced intrathoracic evolution of the hydatid cyst, we not only found a destruction of the hemidiaphragm, but also the presence of pleural effusion, empyema, atelectasis and multiple pleural hydatidosis caused by the development of a cystic fistula in the pleural cavity. Analysis of these instances allowed us to see that ultrasonograms of the liver and roentgenograms of the thorax are often the most sensitive and reliable diagnostic procedures for showing the intrathoracic evolution of the cyst. We believe that the surgical treatment must be carried out with simultaneous right thoracoabdominal access, which, besides exposing the thoracic lesions, also permits adequate treatment of the hepatic hydatid cyst and the possible associated biliary complications.
Abstract: To determine the advantages and complications of splenectomy in the treatment of beta thalassemia, 221 splenectomies for thalassemia performed upon pediatric patients from 1971 to 1982 are evaluated. There were 125 boys and 96 girls with a mean age of 8.2 +/- 2.5 years at the time of the operation. Sixty-one other patients who underwent splenectomy for other diseases served as the controls. Early and late complications after splenectomy are considered with a follow-up study of ten years. Hemoglobin (Hb) value, transfusional quotients and mean of transfused blood previous to surgical treatment are matched with the same parameters evaluated during the follow-up period. The effect of treatment with salicylates and dipyridamole upon the incidence of early complications after operation is analyzed. The postoperative complications in patients with thalassemia were 43.4 versus 3.2 per cent (p less than 0.01) registered in control patients. Late complications occurred with an incidence of 10.7 per cent and were due principally to sepsis. Six patients died of sepsis during the follow-up period, but the mortality rate for sepsis in the patients we studied was significantly lower than that reported by others in 73 instances of splenectomy for beta thalassemia. Blood consumption dropped from 270 +/- 99 to 155 +/- 31 milliliters per kilogram per year postoperatively (p less than 0.01) and Hb levels rose from 9.7 +/- 1.3 to 11.2 +/- 0.7 grams per milliliter. These results suggest that, even though splenectomy for beta thalassemia causes a relevant incidence of complications and fatalities, surgical treatment permits an improvement in the quality of the lives of patients with beta thalassemia and significantly reduces blood consumption. Prophylactic antibiotic therapy can reduce the incidence of sepsis, as was observed in the patients we studied.
