Abstract: PURPOSE: The aim of this study was to analyze the impact of hepatic arterial infusion (HAI) of oxaliplatin with systemic 5-Fluorouracil and leucovorin on patients with isolated unresectable liver metastases. PATIENTS AND METHODS: A total of 87 patients treated in our hospital with HAI of oxaliplatin with systemic 5-Fluorouracil and leucovorin for isolated unresectable colorectal liver metastases from May 1999 to May 2007 were extracted from a prospective database and analyzed. The resectability rate, perioperative findings, postoperative outcomes, and long-term follow-up were evaluated. RESULTS: HAI was delivered after failure of previous systemic chemotherapy in 69 patients (79%). The main criterion for unresectability was massive liver involvement (86% of patients). Most patients had synchronous (85%), bilateral metastases (89%). The median number of HAI courses was 8 (0-25). About 31 patients experienced technical catheter-related problems, which were responsible for withdrawal of HAI in only 7 patients (8%). Finally, a total of 23 patients (26%) were operated on, and resection or radiofrequency ablation was performed in 21 patients (24%). No postoperative mortality was observed and the morbidity rate was 35%. Five-year overall survival was 56% in the surgery group versus none in the nonsurgery group (P < 0.0001). After a median follow-up of 63 months, intrahepatic recurrence occurred in 10 patients among the 23 operated patients. CONCLUSIONS: HAI of oxaliplatin with systemic 5-Fluorouracil and leucovorin offers a second chance to remove initially unresectable isolated colorectal liver metastases in 24% of patients, and appears to be more efficient when performed as first-line therapy. Long-term overall survival can be obtained with this approach.
Abstract: INTRODUCTION: The aims of this study were to examine the trends in performance of open and laparoscopic appendicectomy at a district general hospital, and to compare the diagnostic outcomes in the two patient groups. PATIENTS AND METHODS: Data were collected prospectively from patients undergoing an open or laparoscopic procedure for suspected appendicitis in an 8-year period between January 2000 and December 2007. RESULTS: A total of 1700 patients (873 women, 827 men) with a median age of 24 years underwent surgery for suspected appendicitis in the study period. There were 1357 patients (group A) who underwent an open procedure for presumed appendicitis (610 women and 747 men [F:M ratio, 1:1.2]). There were 343 patients (group B) who underwent laparoscopy with or without laparoscopic appendicectomy (82 men and 261 women [F:M ratio, 1:0.31]). Over the study period, there was an increasing trend towards the performance of laparoscopic procedures for suspected appendicitis, increasing from 4% to 39% of the total per year. In group A, 1172 (86%) patients had appendicular pathology, while the appendix was normal histologically in 178 (13%). Other pathologies were diagnosed intra-operatively in 1%. In group B, 193 patients (56%) had appendicular pathology while in 150 (44%) the appendix was normal. In the subgroup with a normal appendix, 56 patients (37%) had another cause for their symptoms identified. CONCLUSIONS: Laparoscopic appendicectomy is increasingly being performed. Laparoscopy is often used as a diagnostic tool in general surgical patients, particularly women, with lower abdominal pain. In effect, these patients are undergoing diagnostic laparoscopy, with or without appendicectomy. This has resulted in a lower positive appendicectomy rate, but a higher yield of diagnoses other than appendicitis, in the laparoscopic group. Overall appendicectomy rates, however, have remained unchanged.
Abstract: OBJECTIVE: We describe a new ultrasound guided conservative procedure for patients with liver tumors invading the middle hepatic vein (MHV) at its caval confluence. SUMMARY BACKGROUND DATA: Morbidity and mortality for major hepatectomies are not negligible. However, when tumors invade the MHV at the caval confluence, major surgery is usually recommended. METHODS: Patients included in this study were those with tumors invading the MHV at its hepato-caval confluence (within 4 cm). Minimum follow-up was established at 6-months from surgery. Among 284 consecutive hepatectomies, 17 (6%) met the inclusion criteria. Partial sparing of segments 4, 5, and 8 was established intraoperatively, based on color-Doppler IOUS findings (NCT00600522 on ClinicalTrials.gov). RESULTS: In all the 17 patients at least one of the color-Doppler IOUS criteria was disclosed, and limited resections of just segments 4sup and 8 were always feasible. The MHV tract involved was always resected. Seven patients had single tumor removed and 10 multiple: total number of resected tumors was 58 (median: 2; range: 1-18). There were no postoperative mortality and major morbidity. Overall morbidity occurred in 3 (18%) patients. Median blood loss was 250 (range: 50-1000). One patient (6%) received blood transfusion. No local recurrences were observed (median follow-up: 26 months). CONCLUSIONS: IOUS assistance systematically allows conservative resection of liver tumor invading the MHV at caval confluence. This drastically limits the need for larger resections, and further broadens the role of IOUS in optimizing the surgical strategy.
Abstract: CONTEXT: Preoperative neck ultrasonography may yield false-negative findings in more than one-third of medullary thyroid cancer (MTC) patients. If not cleared promptly, cervical lymph node metastases may emerge subsequently. Reoperations entail an excess risk of surgical morbidity and may be avoidable. OBJECTIVE: This comprehensive investigation aimed to evaluate in a head-to-head comparison the clinical utility of pretherapeutic biomarker serum levels (basal calcitonin; stimulated calcitonin; carcinoembryonic antigen) for indicating extent of disease and providing biochemical stratification of pretherapeutic MTC risk. DESIGN: This was a retrospective analysis. SETTING: The setting was a tertiary referral center. PATIENTS: Included were 300 consecutive patients with previously untreated MTC. INTERVENTIONS: The intervention was compartment-oriented surgery. MAIN OUTCOME MEASURE: Stratified biomarker levels were correlated with histopathologic extent of disease. RESULTS: Higher biomarker levels reflected larger primary tumors and more lymph node metastases. Stratified basal calcitonin serum levels correlated better (r = 0.59) with the number of lymph node metastases than carcinoembryonic antigen (r = 0.47) or pentagastrin-stimulated calcitonin (r = 0.40) levels. Lymph node metastases were present in the ipsilateral central and lateral neck, contralateral central neck, contralateral lateral neck, and upper mediastinum, respectively, beyond basal calcitonin thresholds of 20, 50, 200, and 500 pg/ml. Bilateral compartment-oriented neck surgery achieved biochemical cure in at least half the patients with pretherapeutic basal calcitonin levels of 1,000 pg/ml or less but not in patients with levels greater than 10,000 pg/ml. CONCLUSIONS: Most newly diagnosed MTC patients, i.e. those with pretherapeutic basal calcitonin levels greater than 200 pg/ml, may need bilateral compartment-oriented neck surgery to reduce the number of reoperations.
Abstract: BACKGROUND: Some series have suggested that laparoscopy is beneficial for resection of hepatocellular carcinoma. This has to be confirmed in larger series. The aim of this study was to analyze the results of 3 European surgical centers on laparoscopic liver resections for hepatocellular carcinoma. STUDY DESIGN: Prospective databases of 3 European centers involved in the development of laparoscopic liver surgery were combined. Between 1998 and 2008, 163 liver resections for hepatocellular carcinoma were performed. Liver parenchyma was cirrhotic in 120 (73.6%) patients. Liver resection was anatomic in 107 (65.6%) patients and was a major resection (>or=3 segments) in 16 (9.8%). A totally laparoscopic approach was used in 155 (95.1%) patients. RESULTS: Median surgical duration was 180 minutes. Median operative blood loss was 250 mL, and 16 (9.8%) patients received blood transfusion. Conversion to open surgery was required in 15 (9.2%) patients. Median tumor size was 3.6 cm and median surgical margin was 12 mm. Liver-specific and general complications occurred in 19 (11.6%) and 17 (10.4%) patients, respectively. Hospital length of stay was 7 days. A further analysis of early (n = 75) and recent (n = 88) experiences showed improved results in the latter group. Overall and recurrence-free survival rates at 1, 3, and 5 years were 92.6%, 68.7%, 64.9%, and 77.5%, 47.1%, 32.2%, respectively. CONCLUSIONS: This study demonstrates that laparoscopic resection for hepatocellular carcinoma is feasible in selected patients, with good operative and oncologic results. Laparoscopy should be routinely considered in centers experienced in liver surgery and advanced laparoscopy.
Abstract: BACKGROUND: Complications of blind feeding tube (FT) placement include pneumothorax, pneumonia, empyema, and death. A safe and effective method of FT placement is desired. The Davis FT is a novel device that detachably couples to an ultrathin transnasal gastroscope. The objective of this study was to evaluate the safety and efficacy of Davis FT placement. METHODS: Fifty consecutive patients requiring transpyloric enteral tube feeding underwent placement of the Davis FT. Placement efficacy was evaluated with postplacement radiographs. Patient demographics, route of tube placement, use of sedation, and complications were abstracted. RESULTS: The Davis FT was placed successfully in 50 patients. The mean age of the cohort was 52 (+/- 18) years. Sixty-two percent (31/50) were men. The success rate of nonpulmonary placement was 100% (50/50), and the postpyloric success rate was 96% (48/50). IV sedation was used in 72% (36/50) of placements. Eighty-six percent (43/50) of tubes were placed transnasally. The majority (62%) of esophagogastroduodenoscopies and Davis FT placements was performed by a pulmonologist. Forty-four percent (22/50) of patients had an endotracheal tube, 20% (10/50) had a tracheotomy, and 36% (18/50) had no breathing tube at the time of Davis FT placement. There were no complications. CONCLUSIONS: Transpyloric placement of the Davis FT is safe (100%) and effective (96%). The tube can be placed transorally or transnasally with or without sedation. The data suggest that postplacement radiographs are not necessary to confirm placement. Pulmonologists were successful in performing EGD and Davis FT placement.
Abstract: BACKGROUND: Anastomotic leakage represents a major complication after anterior resection of the rectum. The incidence of anastomotic leakage varies considerably among clinical studies in part owing to the lack of a standardized definition of this complication. The aim of the present article was to propose a definition and severity grading of anastomotic leakage after anterior rectal resection. METHODS: After a literature review a consensus definition and severity grading of anastomotic leakage was developed within the International Study Group of Rectal Cancer. RESULTS: Anastomotic leakage should be defined as a defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments. Severity of anastomotic leakage should be graded according to the impact on clinical management. Grade A anastomotic leakage results in no change in patients' management, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy. CONCLUSION: The proposed definition and clinical grading is applicable easily in the setting of clinical studies. It should be applied in future reports to facilitate valid comparison of the results of different studies.
Abstract: OBJECTIVE: The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms. SUMMARY BACKGROUND DATA: Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression. METHODS: We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5'-end [gamma-P] ATP-labeled polymerase chain reaction methods. RESULTS: PAR-1 -506 ins/del (adjusted P value=0.011) and EGF +61 A>G (adjusted P value=0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 -506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value<0.001). CONCLUSION: This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.
Abstract: Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson's disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE+BZ), LD+BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD+BZ or MPE+BZ at high (6mg/kg) and medium (4mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD+BZ at low doses (2mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE+BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12mg/kg and 20mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD+BZ or MPE+BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD+BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug discoveries and novel treatment strategies in PD.
Abstract: BACKGROUND: There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression-free survival, the trial was extended to the phase 3 trial reported here. METHODS: We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival. RESULTS: After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52 to 0.80; P<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (P<0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, P=0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups. CONCLUSIONS: As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. (ClinicalTrials.gov number, NCT00262769.)
Abstract: BACKGROUND AND OBJECTIVE: Despite numerous publications on the epidemiology of inflammatory bowel diseases (IBD) there is a lack of systematic investigations on live-threatening complications of IBD and their causes. This study evaluates risk factors, course and outcome in intensive-care patients which were related to complications of IBD. PATIENTS AND METHODS: Among 6071 admissions to the intensive-care unit (ICU) of a gastroenterological department (university hospital with IBD-outpatient unit) between 1.1.1991 and 31.1.2008 36 ICU admissions of 28 patients with IBD were documented and prospectively analysed from 1996 onwards, using a structured questionnaire on causes for ICU admission as well as risk factors regarding death, organ failure and length of ICU stay. RESULTS: ICU admissions of IBD patients mainly resulted from three causes: complications specific to IBD (44 %), including acute flare-up, perforation and electrolyte imbalance, septic complications (22 %) and thromboembolic complications (17 %). Five patients died, all from septic complications related to immunosuppression including candida sepsis, varicella pneumonia during treatment with infliximab, and pneumocystis pneumonia related to treatment with azathioprine. The most important risk factors according to uni- and multivariate analyses were old age on ICU-admission and first diagnosis of IBD, previous surgery related to IBD and Crohn's disease. CONCLUSIONS: Complications of both IBD and immunosuppressive therapy may be live-threatening in patients with IBD. Better characterization of patients with a high probability of improved outcome by immunosuppressive and/or antibody-therapy seems to be preferable to noncritical early use of these drugs.
Abstract: BACKGROUND: To perform focused or minimally invasive surgery for hyperparathyroidism (HPT) exact preoperative localization is mandatory. Computed tomography-(99m)Tc-sestamibi-single photon emission computed tomography image fusion (CT-MIBI-SPECT) serves this difficult task in single gland HPT to a large extent. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT alone and CT alone in detecting abnormal parathyroid tissue in patients with multiglandular disease. PATIENTS AND METHODS: CT-MIBI-SPECT image fusion for preoperative localization was performed in 30 patients with multiglandular disease. There were six patients with primary hyperparathyroidism (four MEN I syndromes and two double adenomas; one of these patients has HRPT2 gene mutation), 14 with secondary, and eight with tertiary HPT, further one patient each suffering from persistent primary and persistent secondary hyperparathyroidism. In both persistent patients only one remaining gland was left from primary surgery. The results of MIBI-SPECT, CT, and CT-MIBI-SPECT image fusion were compared in these patients. The outcome and the exact predicted positions were correlated with intraoperative findings. RESULTS: In five out of six patients with multiglandular primary hyperparathyroidism more than one gland was detected, thus multiglandular disease could be suspected preoperatively. Overall CT-MIBI-SPECT image fusion was able to predict the exact position of all abnormal glands per patient in 14 of 30 (46.7%) cases, whereas CT alone was successful in 11 (36.7%), and MIBI-SPECT alone just in four (13.3%) of 30 patients. CONCLUSION: Multiglandular disease in primary hyperparathyroidism can be suspected preoperatively in a high percentage of patients. Additionally, this study shows that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone in preoperative localization of all pathologic glands in patients suffering from multiglandular disease.
Abstract: BACKGROUND:: Portal vein embolization (PVE) increases the resectability of initially unresectable colorectal liver metastases (CLM). This study evaluated long-term survival in patients with CLM who underwent hepatectomy following PVE. METHODS:: In a retrospective analysis patients treated by PVE before major hepatectomy were compared with those who did not have PVE, and with those who had PVE without resection. RESULTS:: Of 364 patients who underwent hepatectomy, 67 had PVE beforehand and 297 did not. Those who had PVE more often had more than three liver metastases (68 versus 40.9 per cent; P < 0.001) that were more frequently bilobar (78 versus 55.2 per cent; P < 0.001), and a higher proportion underwent extended hepatectomy (63 versus 18.1 per cent; P < 0.001). Postoperative morbidity rates were 55 and 41.1 per cent respectively (P = 0.035), and overall 3-year survival rates were 44 and 61.0 per cent (P = 0.001). Thirty-two other patients who were treated by PVE but did not undergo resection all died within 3 years. CONCLUSION:: PVE increased the resectability rate of initially unresectable CLM. Among patients who had PVE, long-term survival was better in those who had resection than in those who did not. PVE is of importance in the multimodal treatment of advanced CLM. Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Abstract: Resection is a means of improving survival in patients with gallbladder cancer. A more aggressive surgical approach, including resection of the gallbladder, liver, and regional lymph nodes, is advisable for patients with T1b to T4 tumors. Aggressive resection is necessary because a patient's gallbladder cancer stage determines the outcome, not the surgery itself. Therefore, major resections should be offered to appropriately selected patients. Patients with advanced tumors or metastatic disease are not candidates for radical resection and thus should be directed to more suitable palliation.
Abstract: BACKGROUND: Primary hyperaldosteronism (PHA) is potentially curable by laparoscopic unilateral adrenalectomy (LUA). Pre-operative assessment rarely differentiates adrenal adenoma from hyperplasia. This study aimed to evaluate the results of LUA for PHA according to pathologic findings when an adrenal mass was identified unequivocally on a CT scan. METHODS: A retrospective analysis of LUA for PHA from July 1997 to May 2008 was performed. The minimal follow-up was 6 months. We considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM). Improvement was defined by a decrease of AM. RESULTS: Fifty-seven patients were included. Thirty-six patients (63%) had an adrenal adenoma and 21 (37%) a hyperplasia. The median follow-up was 6.4 years. Hypokalemia was cured in all patients, 33 patients (58%) were cured of their hypertension, and 23 (96% of the 24 noncured patients) were improved with a reduction of the number of AM. Predictive factors for a cure were: gender, age, BMI, duration of hypertension, number of pre-operative AMs, pre-operative arterial systolic blood pressure, creatinin and plasma renin activity. Postoperative predictive factors were pathology, size of the mass, and systolic and diastolic arterial pressures. In the multivariate analysis the only remaining factor was pathology. CONCLUSION: LUA for PHA cured all patients from their hypokalemia and cured or improved hypertension in 98%. Pre-operative diagnosis of adenoma or hyperplasia is not mandatory but it is important to warn patients that hypertension can persist after adrenalectomy, especially in case of adrenal hyperplasia, although this hypertension is easier to control.
Abstract: BACKGROUND: The introduction of limited explorations (LE) for parathyroidectomy broadened the management possibilities for hyperparathyroidism. We sought to document this evolution of change in parathyroid surgery. STUDY DESIGN: Members of the American Association of Endocrine Surgeons and the American College of Surgeons were sent a 49-question survey, and 256 surgeons, accounting for 46% of parathyroid operations nationwide, responded. Associations derived from questionnaire data were tested for significance using chi-square and Kruskal-Wallis methods. RESULTS: Currently, 10% of surgeons practice bilateral neck exploration, 68% practice LE, and 22% have a mixed practice. Five years ago, these percentages were, respectively, 26%, 43%, and 31%; and 10 years ago they were 74%, 11%, and 15%. Shift to LE was greatest among endocrine surgeons, high-volume surgeons, and surgeons trained by mentors who practiced LE. A focal, single-gland examination under general anesthesia and 23-hour observation are preferred by most surgeons. Half of all general surgeons, in contrast to fewer than 10% of endocrine surgeons, never monitor parathyroid hormone intraoperatively, even with LE. Dramatic differences were apparent among subsets of surgeons in operative volumes, indications for bilateral neck exploration, followup care, expertise with ultrasound and sestamibi, and perceptions of cure and complication rates. Evidence-based literature and guidance from surgical societies had the greatest influence on the decision to practice LE. CONCLUSIONS: This survey formally documents the evolution of practice patterns in parathyroid surgery over the last decade. Although LE has achieved wide acceptance, surgical management of hyperparathyroidism has become increasingly disparate. This trend may highlight a need to define best-practice guidelines.
Abstract: About 6% of patients with thyroid cancer present with life-threatening tumor invasion of the trachea and/or esophagus. The extent of resection depends on tumor diagnosis and stage (indication only in differentiated and perhaps medullary thyroid cancer without extrapulmonary metastases), extent of aerodigestive invasion, and general health state of the patient. After complete tumor resection, 5-year and 10-year survival rates of 40-75% can be achieved. Incomplete tumor resection however has a negative effect on prognosis. Tangential tumor resection (shaving) is indicated if no transmural invasion of trachea/esophagus has occurred. Tracheal resection can be subdivided into six standard procedures--types 1 and 2: laryngotracheal or tracheal window resection; types 3 and 4: circular resection with primary reconstruction infraglottic or tracheal; and types 5 and 6: laryngectomy and cervical evisceration.
Abstract: OBJECTIVE: Imaging in patients with primary hyperparathyroidism has been proven difficult. During the last decade, sestamibi scintigraphy and ultrasound (US) have been used with various success. The importance of these procedures has risen since minimal invasive parathyroid (MIP) surgery also has developed, and it is claimed that preoperative localization usually is needed before embarking on such a procedure. METHODS: We have scanned the most recent literature in this matter in order to identify evidence, using commonly accepted grading, and also concluded a number of recommendations. RESULTS AND CONCLUSIONS: We found evidence at level III leading to recommendations at grade B, that sestamibi scintigraphy is a recommended first test, but that US by an experienced investigator may be an alternative. MIP may be performed when both tests are concordant, and in case of only one test being positive, unilateral exploration and use of intraoperative PTH measurements are recommended. Bilateral neck exploration is used when both tests are negative. For reoperative procedures, repeat investigations are recommended, but also to use US-guided fine needle aspiration and PTH measurements as well as venous sampling. However, for reoperative procedures, the level of evidence is weaker-level IV, but recommendations still at grade B.
Abstract: BACKGROUND: The only cure for primary hyperparathyroidism (pHPT) is operative resection of the parathyroid gland(s) responsible for the disease. The 1990 National Institute of Health's (NIH) consensus development conference on asymptomatic pHPT and its subsequent workshop in 2001 established which clinical criteria warranted parathyroidectomy (PTx) versus observation. While there is no debate that these NIH criteria capture a group of patients likely to benefit from PTx, there is concern that these guidelines miss a significant percentage of pHPT patients who actually are symptomatic. Unfortunately, these additional symptoms are often subtle, nonspecific, not traditionally measured, frequently not assessed or considered in this patient population, and are usually attributed to other diagnoses or simply advanced age. METHODS: An evidence-based literature review was performed assessing symptoms and clinical conditions associated with bone, neuropsychiatry, cognition, quality of life, and the neuromuscular system. The level of evidence and grade of recommendations were assigned to key studies to help determine recommendations regarding indications and potential benefits of parathyroidectomy (PTx). RESULTS: Symptoms ranging from decreased bone mineral density, increased fracture risk, neuropsychiatric symptoms and cognitive changes, lower quality of life, and neuromuscular symptoms were found to be associated with pHPT. The effects of PTx on these symptoms was addressed in a variety of studies that varied in quality. CONCLUSION: Although there are few Level I randomized clinical trials addressing the benefit of PTx in patients with pHPT, there are supportive data to suggest that most patients with pHPT would benefit from operative cure.
Abstract: CONTEXT: Calcitonin (CT) is the main medullary thyroid carcinoma (MTC) tumor marker. However, it has several limitations, including a concentration-dependent biphasic half-life, sensitivity to rapid in vitro degradation, and the presence of different isoforms/fragments. Procalcitonin (PCT), the prohormone of calcitonin, is free of these limitations but is currently used only as a sepsis marker. OBJECTIVES: The objective of the study was to determine whether PCT is suited as a MTC tumor marker by comparing the diagnostic performance of PCT with that of CT in MTC. DESIGN: PCT and CT were measured in a total of 835 subjects, including normal volunteers (n = 197) and patients with active-MTC (n = 91), cured-MTC (n = 42), neuroendocrine tumors (n = 225), mastocytosis (n = 48), follicular cell-derived thyroid carcinoma (cured = 120, persistent/recurrent = 55), and benign thyroid disease (n = 57). RESULTS: PCT levels were significantly higher in the active-MTC patients (mean 126.4 ng/ml) than the cured-MTC patients (mean <0.1 ng/ml). The overall concordance between the two markers was 95.7% (kappa = 0.81). Receiver-operating characteristic curve analysis showed no significant difference in diagnostic performance between CT and PCT. PCT's diagnostic sensitivity and specificity were 91 and 96%, respectively. The corresponding values for CT were 99 and 98%. Analyte stability studies showed that CT is very unstable in vitro with a decrease of 35-50% from the original value 24 h after the blood draw, whereas PCT levels did not significantly change during this time. CONCLUSIONS: A strong correlation was observed between PCT and CT levels in patients with MCT. Given PCT's greater analytical stability, we conclude that it represents a promising complementary MTC tumor marker.
Abstract: PURPOSE: The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. PATIENTS AND METHODS: By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. RESULTS: Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. CONCLUSION: Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.
Abstract: BACKGROUND/PURPOSE: Liver transplantation (LT) is the best theoretical treatment of hepatocellular carcinoma (HCC) fulfilling the Milan criteria (TNM stages 1-2). However, LT is limited by organ availability and tumor progression on the waiting list. Liver resection (LR) may represent an alternative in these patients. The aim of this study is to report the results of LR in transplantable patients. PATIENTS: From 1990 to 2007, 274 patients underwent liver resection for HCC. Sixty-seven (24%) met the Milan criteria on pathologic study of the specimen. Ten were TNM stage 1 and 57 stage 2 and all had chronic liver disease. There were 56 men and 11 women with a mean age of 63. LR included 12 major hepatectomies, 14 bisegmentectomies, 14 segmentectomies, and 27 nonanatomic resections. Thirty-seven resections were performed through a laparoscopic approach and there were only 8 open resections since 1998. RESULTS: Three patients died postoperatively (4.5%), none after laparoscopic resection. Morbidity rate was 34%. After a mean follow-up of 4.8 years, 36 patients (54%) developed intrahepatic tumor recurrence. Twenty-eight (77%) were again transplantable of which 16 (44%) were transplanted. Two additional patients underwent pre-emptive LT (ie before recurrence). When considering 44 patients <65 years at the time of resection (ie upper age limit for LT), the rates of recurrence, transplantable recurrence, and intention to treat salvage transplantation (patients with transplantable recurrence actually transplanted) were 59%, 80%, and 61%, respectively. Overall and disease free 5-year survival rates were 72% and 44%, respectively. Survival was not influenced by TNM stage 1 or 2, AFP level, tumor differentiation, or the presence microscopic vascular invasion. Survival after salvage LT was 70% and 87% when calculated from the date of LT and LR, respectively. CONCLUSION: LR for small solitary HCC in compensated cirrhosis yields an overall survival rate comparable to upfront LT. Despite a significant recurrence rate, close imaging monitoring after resection allows salvage LT in 61% of patients with recurrence on intention to treat analysis.
Abstract: OBJECTIVE: To summarize the current world position on laparoscopic liver surgery. SUMMARY BACKGROUND DATA: Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver resections have been performed with efficacy and safety equaling open surgery in highly specialized centers. Although the field has begun to expand rapidly, no consensus meeting has been convened to discuss the evolving field of laparoscopic liver surgery. METHODS: On November 7 to 8, 2008, 45 experts in hepatobiliary surgery were invited to participate in a consensus conference convened in Louisville, KY, US. In addition, over 300 attendees were present from 5 continents. The conference was divided into sessions, with 2 moderators assigned to each, so as to stimulate discussion and highlight controversies. The format of the meeting varied from formal presentation of experiential data to expert opinion debates. Written and video records of the presentations were produced. Specific areas of discussion included indications for surgery, patient selection, surgical techniques, complications, patient safety, and surgeon training. RESULTS: The consensus conference used the terms pure laparoscopy, hand-assisted laparoscopy, and the hybrid technique to define laparoscopic liver procedures. Currently acceptable indications for laparoscopic liver resection are patients with solitary lesions, 5 cm or less, located in liver segments 2 to 6. The laparoscopic approach to left lateral sectionectomy should be considered standard practice. Although all types of liver resection can be performed laparoscopically, major liver resections (eg, right or left hepatectomies) should be reserved for experienced surgeons facile with more advanced laparoscopic hepatic resections. Conversion should be performed for difficult resections requiring extended operating times, and for patient safety, and should be considered prudent surgical practice rather than failure. In emergent situations, efforts should be made to control bleeding before converting to a formal open approach. Utilization of a hand assist or hybrid technique may be faster, safer, and more efficacious. Indications for surgery for benign hepatic lesions should not be widened simply because the surgery can be done laparoscopically. Although data presented on colorectal metastases did not reveal an adverse effect of the laparoscopic approach on oncological outcomes in terms of margins or survival, adequacy of margins and ability to detect occult lesions are concerns. The pure laparoscopic technique of left lateral sectionectomy was used for adult to child donation while the hybrid approach has been the only one reported to date in the case of adult to adult right lobe donation. Laparoscopic liver surgery has not been tested by controlled trials for efficacy or safety. A prospective randomized trial appears to be logistically prohibitive; however, an international registry should be initiated to document the role and safety of laparoscopic liver resection. CONCLUSIONS: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery. National and international societies, as well as governing boards, should become involved in the goal of establishing training standards and credentialing, to ensure consistent standards and clinical outcomes.
Abstract: Cancer of the low rectum provides a challenge for both preoperative staging and optimum operative management. Current outcomes for patients with low rectal cancer are poor, particularly for those treated by abdominoperineal excision. It has been suggested that this poor outcome is due to an inherent oncological inferiority of the traditional abdominoperineal excision procedure, which might be explained by the unique anatomical features of the low rectum and the lack of clearly defined anatomical excision planes. In this Personal View, we discuss the anatomical and surgical planes available for the management of low rectal cancer, and describe the two-plane approach to low rectal cancer using the mesorectal plane and the extralevator plane.
Abstract: BACKGROUND: Ischemia of the gastric conduit remains an important complication of esophagectomy and is associated with an increased risk of anastomotic leak and sepsis. We report a group of patients with multiple comorbid conditions and an ischemic gastric conduit that was successfully managed by a delayed esophagogastrostomy. STUDY DESIGN: Between 2000 and 2007, esophagectomy with gastric pullup was performed in 554 patients. In 37 patients (7%), the combination of an ischemic graft and substantial comorbid conditions prompted delayed reconstruction to avoid an immediate esophagogastrostomy. In these patients, the gastric conduit was brought up and secured in the neck, and a cervical esophagostomy was constructed. Subsequently, a delayed esophagogastrostomy was performed through neck incision. Outcomes were analyzed at a median of 22 months (interquartile range [IQR], 13 to 30 months). RESULTS: There were 29 male and 8 female patients, with a median age of 65 years (IQR, 58 to 75 years). Thirty-one patients had malignant disease; 12 received neoadjuvant therapy. All 37 patients recovered from their esophagectomy without evidence of ischemic necrosis or fistula from their gastric conduit. In 35 patients, a delayed esophagogastrostomy was performed at a median of 98 days (IQR, 89 to 110 days). At the time of reconstruction, all had well-perfused gastric conduits, and the anastomoses healed without leak, wound infection, or sepsis. A stricture developed in three patients and was treated with dilation. Delayed esophagogastrostomy was never performed in two patients because of development of recurrent malignant disease. CONCLUSIONS: Delayed esophagogastrostomy is a safe strategy for management of patients with comorbidities and an ischemic gastric conduit at the time of esophagectomy.
Abstract: BACKGROUND: Patients undergoing liver transplantation for hepatocellular carcinoma within the Milan criteria (single tumour </=5 cm in size or </=3 tumours each </=3 cm in size, and no macrovascular invasion) have an excellent outcome. However, survival for patients with cancers that exceed these criteria remains unpredictable and access to transplantation is a balance of maximising patients' chances of cure and organ availability. The aim of this study was to explore the survival of patients with tumours that exceed the Milan criteria, to assess whether the criteria could be less restrictive, enabling more patients to qualify as transplant candidates, and to derive a prognostic model based on objective tumour characteristics, to see whether the Milan criteria could be expanded. METHODS: Data on patients who underwent transplantation for hepatocellular carcinoma despite exceeding Milan criteria at different centres were recorded via a web-based survey completed by specialists from each centre. The survival of these patients was correlated retrospectively with the size of the largest tumour nodule, number of nodules, and presence or absence of microvascular invasion detected at pathology. Contoured multivariable regression Cox models produced survival estimates by means of different combinations of the covariates. The primary aim of this study was to derive a prognostic model of overall survival based on tumour characteristics, according to the main parameters used in the Tumour Node Metastasis classification. The secondary aim was the identification of a subgroup of patients with hepatocellular carcinoma exceeding the Milan criteria, who achieved a 5-year overall survival of at least 70%-ie, similar to the outcome expected for patients who meet the Milan criteria. FINDINGS: Over a 10-month period, between June 25, 2006, and April 3, 2007, data for 1556 patients who underwent transplantation for hepatocellular carcinoma were entered on the database by 36 centres. 1112 patients had hepatocellular carcinoma exceeding Milan criteria and 444 patients had hepatocellular carcinoma shown not to exceed Milan criteria at post-transplant pathology review. In the group of patients with hepatocellular carcinomas exceeding the criteria, the median size of the largest nodule was 40 mm (range 4-200) and the median number of nodules was four (1-20). 454 of 1112 patients (41%) had microvascular invasion and, for those transplanted outside the Milan criteria, 5-year overall survival was 53.6% (95% CI 50.1-57.0), compared with 73.3% (68.2-77.7) for those that met the criteria. Hazard ratios (HR) associated with increasing values of size and number were 1.34 (1.25-1.44) and 1.51 (1.21-1.88), respectively. The effect was linear for size, whereas for number of tumours, the effect tended to plateau above three tumours. The effect of tumour size and number on survival was mediated by recurrence (b=0.08, SE=0.12, p=0.476). The presence of microvascular invasion doubled HRs in all scenarios. The 283 patients without microvascular invasion, but who fell within the Up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumour [in cm] and the number of tumours) achieved a 5-year overall survival of 71.2% (64.3-77.0). INTERPRETATION: More patients with hepatocellular carcinoma could be candidates for transplantation if the current dual (yes/no) approach to candidacy, based on the strict Milan criteria, were replaced with a more precise estimation of survival contouring individual tumour characteristics and use of the up-to-seven criteria.
Abstract: BACKGROUND: Persistent secondary or tertiary hyperparathyroidism (HPT) results from failure to remove enough hyperfunctioning parathyroid tissue. Ectopically situated parathyroid glands and supernumerary glands make failure more likely. Recurrent HPT after subtotal Ptx is usually due to regrowth of the remaining parathyroid tissue. Recurrence may also develop from a hyperplastic supernumerary gland or rarely from parathyromatosis. Recurrent HPT after total Ptx with autotransplantation is usually due to overgrowth of the autograft or for the previously mentioned reasons. METHODS: Since 1995, 464 patients with SHPT or THPT were treated surgically; intraoperative parathormone (PTH) was measured in 277 patients. Sixty-eight patients also had a preoperative MIBI scan. We compared the preoperative MIBI scan results with intraoperative findings, parathyroid gland weight and histology. We questioned whether MIBI uptake corresponded to parathyroid gland size and weight. We also correlated the number of Ki67 nuclear positive cells with MIBI uptake. For SHPT in group I with 145 patients, neither intraoperative PTH (IO-PTH) assay nor MIBI scanning was done. In group II with 163 patients IO-PTH was used and in group III with 48 patients both IO-PTH and MIBI scanning was used. For THPT in group I with 42 patients, neither IO-PTH assay nor MIBI scanning was done. In group II with 46 patients IO-PTH was used and in group III with 20 patients both IO-PTH and MIBI scanning was used. RESULTS: Parathyroid weight correlated directly with MIBI uptake. No correlation, however, occurred between MIBI uptake and parathyroid histology or between Ki67 staining and MIBI scanning. For SHPT in group I the persistence rate was 6.2% and recurrence rate 11%; in group II the persistence rate was 4.9% and recurrence rate 4.9%; in group III the persistence rate was 2%, and recurrence 4.2% (P < 0.05 between group I and III for persistence and recurrence). We obtained similar results in THPT, but recurrence was 0 in groups II and III, also when only 3 glands were removed, probably due to asymmetric hyperplasia commonly seen in this particular population (P < 0.05 regarding recurrence between group I and II-III, no difference between group II and III). CONCLUSION: In conclusion our findings support that the surgeon experience is a very important factor for good results in patients with SHPT and THPT. Preoperative MIBI scanning and IO-PTH are helpful but not essential except in reoperations.
Abstract: HYPOTHESIS: Laryngeal dysfunction after thyroidectomy is a common complication. However, few data are available to differentiate whether these complications result from injury to the recurrent nerve or to the vocal folds from intubation. SETTING: University medical center. PATIENTS: Seven hundred sixty-one patients who underwent surgery to the thyroid gland from 1990 to 2002. Of these patients, 8.4% underwent a revision thyroidectomy. INTERVENTION: Preoperative and postoperative laryngostroboscopic examination. MAIN OUTCOME MEASURE: Laryngostroboscopic evaluation of laryngeal complications. RESULTS: The overall rate of laryngeal complications was 42.0% (320 patients). Complications from an injury to the vocal folds occurred in 31.3% of patients. Weakness or paresis of the recurrent nerve was initially present in 6.6% and was related to the nerves at risk. This rate was higher in revision thyroidectomies than in primary surgical interventions (6.2% vs 11.6%; P = .04). The rate of laryngeal injuries was higher in patients older than 65 years (39.8% vs 30.8%; P = .03). CONCLUSIONS: These data suggest that laryngeal complications after thyroidectomies are primarily caused by injury to the vocal folds from intubation and to a lesser extent by injury to the laryngeal nerve. We recommend documentation of informed consent, especially for patients who use their voice professionally, such as singers, actors, or teachers.
Abstract: Resection of the caudate lobe (segment I- dorsal sector, segment IX- right paracaval region, or both) is often technically difficult due to the lobe's location deep in the hepatic parenchyma and because it is adjacent to the major hepatic vessels (e.g., the left and middle hepatic veins). A literature search was conducted using Ovid MEDLINE for the terms "caudate lobectomy" and "anterior hepatic transection" (AHT) covering 1992 to 2007. AHT was used in 110 caudate lobectomies that are discussed in this review. Isolated caudate lobectomy was performed on 28 (25.4%) patients, with 11 case (11%) associated with hepatectomy, while 1 (0.9%) was associated with anterior segmentectomy. Complete caudate lobectomy was performed on 82 (74.5%) patients. Hepatocellular carcinoma was observed in 106 (96.3%) patients, while 1 (0.9%) had hemangioma and 3 (2.7%) had metastatic caudate tumors. AHT was used in 108 (98.1%) caudate resections, while AHT associated with a right-sided approach was performed in 2 (1.8%) cases. AHT is recommended for tumors located in the paracaval portion of the caudate lobe (segment IX). AHT is usually a safe and potentially curative surgical option.
Abstract: Abstract Objective: A review of the literature was undertaken to provide an overview of the surgical management of locally recurrent rectal cancer (LRRC) after the introduction of total mesorectal excision (TME). Method: A systematic literature search was undertaken using PubMed, Embase, Web of Science and Cochrane databases. Only studies on patients having surgery for their primary tumour after 1995, or if more than half of the patients were operated on after 1995, were considered for analysis. Studies concerning only palliative treatments were excluded. Results: A total of nineteen studies fulfilled the inclusion criteria. LRRC still occurs in 5-10% of the patients and is a major clinical problem, due to severe symptoms and poor survival. In most studies 40% to 50% of all patients with LRRC can be expected to undergo surgery with a curative intent and of those 30% to 45% will have R0 resection. Thus, only 20-30% of all patients with LRRC will have a potentially curative operation. The postoperative complication rate varies considerably from 15% to 68%. The rate of re-recurrence varies from 4% to 54% after curative surgery. The five year overall survival varied between 9% and 39% and the median survival between 21 months and 55 months. Conclusion: Compared to previous studies the proportion of potentially curative resections seems to have increased, probably due to improved staging, neoadjuvant treatment and increased surgical experience in dedicated centres, which has resulted in a tendency to improved survival.
Abstract: BACKGROUND: Routine oral calcium and vitamin D supplementation may prevent hypocalcemic crisis, but its efficacy has not been studied in patients undergoing thyroidectomy plus central neck dissection (CND). The authors therefore prospectively evaluated the clinical usefulness of routine oral calcium and vitamin D supplementation for prevention of hypocalcemia after total thyroidectomy and CND. METHODS: Of 197 patients with differentiated papillary thyroid carcinoma, 49 underwent total thyroidectomy alone, and 148 underwent total thyroidectomy plus CND. The latter were randomized to oral calcium (3 g/day) plus vitamin D (1 mg/day) (Group A, n=49), calcium alone (Group B, n=49), or no supplements (Group C, n=50). Hypocalcemic symptoms, serum calcium, and parathyroid hormone (PTH) levels were compared among the groups. RESULTS: Group C had significantly higher incidences of symptomatic (26.0% vs 6.1%; P<.015) and laboratory (44.0% vs 14.3%; P<.015) hypocalcemia than the group without CND. The incidences of symptomatic and laboratory hypocalcemia were significantly decreased in Groups A (2.0% and 8.2%, respectively) and B (12.2% and 24.5%, respectively) (P<.05). Serum calcium levels decreased in most patients after surgery, but recovered earliest in Group A. Hypercalcemia and PTH inhibition did not occur in gs A and B. CONCLUSIONS: Compared with total thyroidectomy alone, CND significantly increases the rate of postoperative hypocalcemia, which can be prevented by routine postoperative supplementation with oral calcium and vitamin D.
Abstract: The aim of the study was to evaluate our institutional experience with monotherapies for hepatocellular carcinoma (HCC) in the setting of cirrhosis. A retrospective cohort study was carried out at the tertiary care academic referral center and involved 185 consecutive HCC patients with cirrhosis and no previous treatment who underwent resection (n = 61), transarterial chemoembolization (TACE) (n = 64), or liver transplantation (LT) (n = 60). Long-term survival and survival according to the Milan criteria were the main outcomes measured. Median survival after resection, TACE, and LT was 11, 14, and 23 months, respectively. Five-year cumulative survival after resection, TACE, and LT was 23, 10, and 59%, respectively (P = 0.001). Five-year cumulative disease-free survival after resection and LT was 15% and 77%, respectively (P = 0.002). The presence of complications in the resection group (P = 0.004), MELD score (P = 0.0003), and maximum tumor diameter (P = 0.05) in the TACE group, and tumor grade (P = 0.01) and complications (P = 0.004) in the LT group were found to be independent predictors of survival. Five-year survival for patients within the Milan criteria after resection, TACE, and LT was 26, 37, and 66%, respectively. Five-year survival for patients outside the Milan criteria for patients undergoing LT was 53%. The results suggest that LT represents the best oncological treatment option for patients with HCC in the setting of cirrhosis, even for those beyond the Milan criteria. Considering the scarcity of available organs, liver resection remains the best alternative option. TACE remains a potential therapy in patients within the Milan criteria, where it may be more beneficial than resection.
Abstract: PURPOSE: Comparisons of open and laparoscopic colon cancer resection have shown that laparoscopy offers an oncologically safe option. However, there are no data on long-term influence of converted resection, despite conversion rates of up to 30% and the general observation that short-term outcome is significantly worsened. The aim was to compare the long-term results of primary open resection (OR), purely laparoscopic resection (LR-p) and converted resection (LR-c). METHODS: In a prospective study at 282 German hospitals demographic, tumor- and treatment-related data and disease-free survival were compared in the three groups. RESULTS: 8015 of 8307 patients with OR, 280 of 290 patients with LR-p and 55 of 56 patients with LR-c were followed for 39.5 months (median). Overall, no statistically significant differences were seen for five-year DFS (74.8%, 81.3% and 65.6%). However, for patients in stage II with conversion, the five-year DFS was significantly poorer (43.3%) than for OR (80.5%; p=0.003) and LR-p patients (92.5%; p=0.001). For stages I and III no differences were observed. CONCLUSION: Conversion of laparoscopic colon cancer resection worsens DFS in locally advanced stage II carcinoma. There is a need to reduce the conversion rate by adequate patient selection for laparoscopic resection by experienced surgeons.
Abstract: BACKGROUND: Current literature shows no consensus for the technique of laparoscopic total mesorectal excision (LTME). This study aimed to assess the current practice of LTME. METHODS: From January to March 2008, members of the European Association for Endoscopic Surgery (EAES), the Indian Association of Gastrointestinal Endo-Surgeons (IAGES), and the Society of Laparoscopic Surgeons (SLS), together with renowned surgeons in the field of LTME, were invited to fill out an online questionnaire concerning aspects of LTME. RESULTS: The 368 questionnaires showed that 77% of the study participants performed 1-20 LTMEs per year (low volume) and that 33% performed more than 20 LTMEs per year (high volume). Preoperative bowel preparation (PBP), Trendelenburg position, periumbilical insertion of a 30 masculine laparoscope, medial-to-lateral dissection, ultrasonic hemostasis, high-tie ligation, splenic flexure mobilization, left ureteral identification, partial sigmoid resection, extraction of the specimen by a new minilaparotomy and wound protector, end-to-end stapled anastomosis using a 28- to 29-mm anvil with 3.5-mm staples, abdominal lavage, pelvic drainage, and diverting ileostoma were performed by a majority of the surgeons. Less consistency was observed in identification of the right ureter, dissection of Denonvilliers' fascia, location of the minilaparotomy, and construction of a colonic pouch. There were significant differences between high and low volume and between American and European surgeons. Significantly more low-volume surgeons indicated a preference for an open TME depending on the age and gender of the patient, the presence of comorbidity, previous laparotomy, and locally advanced tumor. More low-volume surgeons applied PBP (83.4% vs. 71.8%; p = 0.017). On the average, high-volume surgeons identified more autonomic pelvic nerves during dissection (2.6 vs. 1.8 nerves). The right ureter was identified by 66% of the American and 31.2% of the European surgeons. In the United States 91.5% and in Europe 61.2% created an end-to-end anastomosis. Pouches were created by 32% of the European and 6.8% of the American surgeons. CONCLUSION: The respondents showed an apparent preference for several aspects of LTME. Differences were related to expertise and still more to continent.
Abstract: BACKGROUND: Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. METHODS: Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842. FINDINGS: During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]). INTERPRETATION: Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.
Abstract: PURPOSE: To review the current management options in inflammatory pseudotumours via analysis of ten cases from this unit the largest experience of this pathology in a Western series. To assess the medical and operative options available for this condition and the varying outcomes and the lessons learned in this unit over the time period. RESULTS: Data from the ten cases were analysed and a comprehensive review of the published literature to date has detailed 128 case reports with 215 cases of inflammatory pseudotumour of the liver. Data analysed included patient demographics, diagnostic modalities, details of treatment and eventual outcome. The data was tabulated using an Excel spreadsheet (Microsoft Excel 2004 for Mac 2004.Version 11.0). Categorical variables were compared using Pearson's chi(2) test and p values <0.05 were defined as statistically significant. Statistical analysis was performed using SPSS for Windows (Version 9.0, SPSS Inc., Chicago, IL). CONCLUSION: Emphasis is placed on a preferred medical management initially for this tumour with a good prognosis coupled with regular follow up. There may be a need for surgical resection cases where diagnosis is unclear or the patient is not responding to medical treatment with progression of disease or symptoms.
Abstract: OBJECTIVE: To evaluate a multicenter, international series on minimally invasive liver resection for colorectal carcinoma (CRC) metastasis. SUMMARY BACKGROUND DATA: Multiple single series have been reported on laparoscopic liver resection for CRC metastasis. We report the first collaborative multicenter, international series to evaluate the safety, feasibility, and oncologic integrity of laparoscopic liver resection for CRC metastasis. METHODS: We retrospectively reviewed all patients who underwent minimally invasive liver resection for CRC metastasis from February 2000 to September 2008 from multiple medical centers from the United States and Europe. The multicenter series of patients were accumulated into a single database. Patient demographics, preoperative, operative, and postoperative characteristics were analyzed. Actuarial overall survival was calculated with Kaplan-Meier analysis. RESULTS: A total of 109 patients underwent minimally invasive liver resection for CRC metastasis. The median age was 63 years (range, 32-88 years) with 51% females. The most common sites of primary colon cancer were sigmoid/rectum (51%), right colon (25%), and left colon (13%). Synchronous liver lesions were present in 11% of patients. For those with metachronous lesions liver lesions, the median time interval from primary colon cancer surgery to liver metastasectomy was 12 months. Preoperative chemotherapy was administered in 68% of cases prior to liver resection. The majority of patients underwent prior abdominal operations (95%). Minimally invasive approaches included totally laparoscopic (56%) and hand-assisted laparoscopic (41%), the latter of which was employed more frequently in the US medical centers (85%) compared with European centers (13%) (P = 0.001). There were 4 conversions to open surgery (3.7%), all due to bleeding. Extents of resection include wedge/segmentectomy (34%), left lateral sectionectomy (27%), right hepatectomy (28%), left hepatectomy (9%), extended right hepatectomy (0.9%), and caudate lobectomy (0.9%). Major liver resections (> or =3 segments) were performed in 45% of patients. Median OR time was 234 minutes (range, 60-555 minutes) and blood loss was 200 mL (range, 20-2500 mL) with 10% receiving a blood transfusion. There were no reported perioperative deaths and a 12% complication rate. Median length of hospital stay for the entire series was 4 days (range, 1-22 days) with a shorter stay in medical centers in the United States (3 days) versus that seen in Europe (6 days) (P = 0.001). Negative margins were achieved in 94.4% of patients. Actuarial overall survivals at 1-, 3-, and 5-year for the entire series were 88%, 69%, and 50%, respectively. Disease-free survivals at 1-, 3-, and 5-year were 65%, 43%, and 43%, respectively. CONCLUSIONS: Minimally invasive liver resection for colorectal metastasis is safe, feasible, and oncologically comparable to open liver resection for both minor and major liver resections, even with prior intra-abdominal operations, in selected patients and when performed by experienced surgeons.
Abstract: INTRODUCTION: Pancreaticoduodenectomy (PD) is the standard operation for cancer of the pancreatic head. To achieve complete tumor resection and, thus, improve long-term survival, venous resection of the portal or superior mesenteric vein with reconstruction has become routine for advanced pancreatic adenocarcinoma (PDAC). However, its clinical benefit still remains controversial. The aim of this study was to investigate morbidity, mortality, and survival of patients with advanced PDAC following PD with venous resection and to identify significant survival determinants. MATERIAL AND METHODS: From October 2001 to December 2007, 488 patients with PDAC of the pancreatic head underwent PD at our department. Venous resection was performed in 110 patients (22.5%). Clinical data, surgical techniques, perioperative parameters, and histopathologic data were analyzed on a prospective database. RESULTS: Major venous reconstruction was accomplished through primary lateral venorrhaphy in 18 patients (16.3%), polytetrafluoroethylene grafting (n = 14, 12.7%), primary end-to-end anastomosis (n = 72, 65.5%), an autologous saphenous venous graft patch (n = 4, 4.6%) or a Goretex(R) patch (n = 2, 2.3%). In 78.1% histopathologic examination revealed cancer invasion of the vein, whereas the remainder had peritumoral inflammation extending to the vessel wall. Perioperative morbidity rate was 41.8%; and the mortality rate 3.6%. The 1-, 2-, and 3-year survival rates were 55.2%, 23.1%, and 14.4%, respectively. Operating time (>420 min) and advanced age (>70 years) were the only prognostic variables, which significantly diminished survival on multivariate analysis. CONCLUSION: Resection of the superior mesenteric or portal vein to achieve macroscopic tumor clearance can be performed safely with acceptable operative morbidity and mortality. However, improved local clearance in these patients cannot achieve a favorable long-term survival for all patients because distant metastases or local recurrence is frequent.
Abstract: BACKGROUND: We assessed the activity of gemcitabine (G) and cisplatin/gemcitabine (C/G) in patients with locally advanced (LA) or metastatic (M) (advanced) biliary cancers (ABC) for whom there is no standard chemotherapy. METHODS: Patients, aged > or =18 years, with pathologically confirmed ABC, Karnofsky performance (KP) > or =60, and adequate haematological, hepatic and renal function were randomised to G 1000 mg m(-2) on D1, 8, 15 q28d (Arm A) or C 25 mg m(-2) followed by G 1000 mg m(-2) D1, 8 q21d (Arm B) for up to 6 months or disease progression. RESULTS: In total, 86 patients (A/B, n=44/42) were randomised between February 2002 and May 2004. Median age (64/62.5 years), KP, primary tumour site, earlier surgery, indwelling biliary stent and disease stage (LA: 25/38%) are comparable between treatment arms. Grade 3-4 toxicity included (A/B, % patients) anaemia (4.5/2.4), leukopenia (6.8/4.8), neutropenia (13.6/14.3), thrombocytopenia (9.1/11.9), lethargy (9.1/28.6), nausea/vomiting (0/7.1) and anorexia (2.3/4.8). Responses (WHO criteria, % of evaluable patients: A n=31 vs B n=36): no CRs; PR 22.6 vs 27.8%; SD 35.5 vs 47.1% for a tumour control rate (CR+PR+SD) of 58.0 vs 75.0%. The median TTP and 6-month progression-free survival (PFS) (the primary end point) were greater in the C/G arm (4.0 vs 8.0 months and 45.5 vs 57.1% in arms A and B, respectively). CONCLUSION: Both regimens seem active in ABC. C/G is associated with an improved tumour control rate, TTP and 6-month PFS. The study has been extended (ABC-02 study) and powered to determine the effect on overall survival and the quality of life.
Abstract: OBJECTIVE: To evaluate the "learning curve" effect on feasibility and reproducibility of laparoscopic liver resection (LLR). SUMMARY BACKGROUND DATA: LLR is currently limited to few centers and to few procedures. Its reproducibility is still debated. METHODS:: Patients undergoing LLR between 1996 and 2008 were included. Indications and type of hepatectomies were compared with those of open resections performed in the same period, considering 3 periods (1996-1999, 2000-2003, and 2004-2008). LLRs were divided into 3 equal groups of 58 cases and technical data and outcomes were compared. Risk-adjusted Cumulative Sum model was used for determining the learning curve based on the need for conversion. RESULTS: Of 782, 174 (22.3%) patients underwent LLR. Proportion of LLR progressively increased (17.5%, 22.4%, and 24.2%), such as hepatocellular carcinoma (17.6%, 25.6%, and 39.4%, P < 0.05), colorectal metastases (0%, 6.5%, and 13.1%, P < 0.05), major hepatectomies (1.1%, 9.1%, 8.5%, P < 0.05), and right hepatectomies (0%, 13.2%, and 13.1%, P < 0.05). Comparing groups, results of LLR significantly improved in terms of conversion rate (15.5%, 10.3%, and 3.4%, P < 0.05), operative time (210, 180, and 150 minutes, P < 0.05), blood loss (300, 200, and 200 mL, P < 0.05), and morbidity (17.2%, 22.4%, and 3.4%, P < 0.05). Pedicle clamping was less used over time (77.6%, 62.1%, and 17.2%, P < 0.05) and for shorter durations (45, 30, and 20 minutes, P < 0.05). Having adjusted for case-mix, the Cumulative Sum analysis demonstrated a learning curve for laparoscopic hepatectomies of 60 cases. CONCLUSION: A slow but constant evolution of LLR occurred: indications and magnitude of procedures increased and technical outcomes improved. The learning curve demonstrated in this study suggests that LLR is reproducible in liver units but specific training to advanced laparoscopy is required.
Abstract: BACKGROUND: Randomized trials in low-risk populations have failed to show any benefit for laparoscopic compared with open colorectal resection in terms of morbidity. Furthermore, it is not known whether laparoscopic colorectal resection would yield advantages if randomization were revealed during surgery after a diagnostic laparoscopy. METHODS: Patients with cancer of the colon or upper rectum were randomly assigned to laparoscopic or open resection. All patients underwent diagnostic laparoscopy to assess whether laparoscopic resection was feasible and the result of randomization was then revealed to the surgeon. Main endpoints were overall, general and surgical morbidity, and mortality. RESULTS: Some 679 patients underwent diagnostic laparoscopy which led to the exclusion of 207; 250 patients were allocated to laparoscopic and 222 to open resection. Conversion to laparotomy occurred in 28 patients (11.2 per cent). There were no differences in morbidity (overall 25.2 versus 23.9 per cent) or mortality (1.2 versus 0.9 per cent) between laparoscopic and open groups. Postoperative hospital stay was shorter after laparoscopic resection (median (range) 10 (1-123) versus 12 (4-109) days; P = 0.032). CONCLUSION: Laparoscopic resection of colorectal cancer is associated with increased operating time but does not decrease morbidity even in a moderate-risk population.
Abstract: BACKGROUND: In patients with hilar cholangiocarcinoma, ipsilateral en bloc hepatic resection improves survival but is associated with increased morbidity. Preoperative biliary drainage of the future liver remnant (FLR) and contralateral portal vein embolization (PVE) may improve perioperative outcome, but their routine use is controversial. This study analyses the impact of FLR volume and preoperative biliary drainage on postoperative hepatic insufficiency and mortality rates. METHODS: Patients who underwent hepatic resection and for whom adequate imaging data for FLR calculation were available were identified retrospectively. Patient demographic, operative and perioperative data were recorded and analysed. The volume of the FLR was calculated based on the total liver volume and the volume of the resection that was actually performed using semi-automated contouring of the liver on preoperative helical acquired scans. In patients subjected to preoperative biliary drainage, the preoperative imaging was reviewed to determine if the FLR had been decompressed. Hepatic insufficiency was defined as a postoperative rise in bilirubin of 5 mg/dl above the preoperative level that persisted for >5 days postoperatively. Operative mortality was defined as death related to the operation, whenever it occurred. RESULTS: Sixty patients were identified who underwent hepatic resection between 1997 and 2007 and for whom imaging data were available for analysis. During this period, preoperative biliary drainage of the FLR was used selectively and PVE was used in only one patient. The mean age of the patients was 64 +/- 11.6 years and 68% were male. The median length of stay was 14 days and the overall morbidity and mortality were 53% and 10%, respectively. Preoperative FLR volume was a predictor of hepatic insufficiency and death (P= 0.03). A total of 65% of patients had an FLR volume >/=30% (39/60) of the total volume. No patient in this group had hepatic insufficiency, but there were two operative deaths (5%), both occurring in patients who underwent preoperative biliary drainage. By contrast, in the group with FLR < 30% (21/60, 35%), hepatic insufficiency was seen in five patients and operative mortality in four patients, and were strongly associated with lack of preoperative biliary drainage of the FLR (P= 0.009). Patients with an FLR >/= 30% were more likely to have radiographic evidence of ipsilateral lobar atrophy and hypertrophy of the FLR (46.2% vs. 9.5% in patients with FLR < 30%; P= 0.004). CONCLUSIONS: In patients undergoing liver resection for hilar cholangiocarcinoma, FLR volume of < 30% of total liver volume is associated with increased risk for hepatic insufficiency and death. Preoperative biliary drainage of the FLR appears to improve outcome if the predicted volume is < 30%. However, in patients with FLR >/= 30%, preoperative biliary drainage does not appear to improve perioperative outcome and, as many of these patients have hypertrophy of the FLR, PVE is likely to offer little benefit.
Abstract: BACKGROUND: Postoperative bile leak secondary to a fistula is a known complication of hepatic surgery. Four different biliary fistula sub-types have been described: type A refers to minor leakage from the bile duct stump; type B to major leakage caused by insufficient closure of the bile duct stump; type C to major leakage caused by injury to the bile duct, and type D (the rarest) to the division and exclusion of a bile duct. This complication results from functional liver parenchyma in which bile drainage is excluded from the main duct. METHODS: A retrospective review of the database for 163 patients diagnosed with post-hepatic surgery bile leak from April 1992 to June 2007 was performed. RESULTS: Three patients were found to have type D biliary fistula, with durations of 3-21 months. The bile leak developed after a right hepatectomy in two patients and a right hepatectomy extending to segment IV in one patient. All three patients were rescheduled for surgical exploration, following failure of medical treatment. The procedure consisted of repeat resection of the independent liver parenchyma containing the fistula. One patient developed a postoperative leak from a hepaticojejunal anastomosis (treated conservatively) and the other two patients had an uneventful recovery. No recurrence of bile leak was encountered during their follow-up. CONCLUSIONS: Our experience indicates that conservative treatment is deceptive and not efficacious. For this condition, surgical intervention is the treatment of choice because it is very effective and is associated with a low morbidity.
Abstract: CONTEXT: Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia. OBJECTIVE: The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT. DESIGN: This was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk. SETTING: The study was conducted at 23 centers in Europe, the United States, and Canada. PATIENTS: The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter). INTERVENTION: During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted. MAIN OUTCOME MEASURE: The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase. RESULTS: Mean +/- sd baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias. CONCLUSIONS: In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need.
Abstract: OBJECTIVE: To analyze the results of 6 international surgical centers performing laparoscopic major liver resections. SUMMARY BACKGROUND DATA: The safety and feasibility of laparoscopy for minor liver resections has been previously demonstrated. Major anatomic liver resections, initially considered to be unsuitable for laparoscopy, are increasingly reported by several centers worldwide. METHODS: Prospective databases of 3 European, 2 U.S., and 1 Australian centers were combined. Between 1997 and 2008, 210 major liver resections were performed: 136 right and 74 left hepatectomies. Results and differences in surgical techniques between the 6 centers are outlined. RESULTS: Surgical duration was 250 minutes (range: 90-655 minutes). Operative blood loss was 300 mL (range: 20-2500 mL). Thirty patients (14.3%) received blood transfusion. Conversion to open surgery was required in 26 patients (12.4%). Portal triad clamping was performed in 24 patients (11.4%). Median tumor size was 5.4 cm (range: 1-25 cm) and surgical margin was 10.5 mm (range: 0-70 mm). Two patients died during the postoperative period from pulmonary embolism and urosepsis. Liver-specific and general complications occurred in 17 (8.1%) and 29 patients (13.8%), respectively. Hospital length of stay was 6 days (range: 1-34 days). A further analysis of early (n = 90) and late (n = 120) experience showed improved surgical and postoperative results in the latter group. CONCLUSIONS: This multicenter study demonstrates that laparoscopic major liver resections are feasible in selected patients and results improve with experience. However, proficiency in both open liver surgery and advanced laparoscopy is compulsory and surgeons must begin with minor laparoscopic resections.
Abstract: OBJECTIVE: The Siewert classification system differentiates between adenocarcinoma of the gastroesophageal junction and that of the distal esophagus. The purpose of this study was to evaluate whether there were differences in the location and prevalence of lymph node metastases, type of recurrence, and survival with these tumors that warrant distinguishing between them in clinical practice. METHODS: Records of all patients who underwent resection for adenocarcinoma of the distal esophagus or gastroesophageal junction from 1987 to 2007 were retrospectively reviewed. Based on the endoscopic location of the epicenter of the tumor in relation to the gastroesophageal junction, tumors were categorized in 301 patients as being of the distal esophagus and in 208 as being of the gastroesophageal junction. RESULTS: There were no significant differences in age, sex, or body mass index between patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Patients with adenocarcinoma of the distal esophagus were more likely to have reflux symptoms (75% vs 53%, P < .0001) and peritumoral intestinal metaplasia (73% vs 51%, P < .0001) and be in a surveillance program (54% vs 9%, P = .0005) compared with patients with adenocarcinoma of the gastroesophageal junction. However, the prevalence and location of nodal metastases was similar, and in node-positive patients mediastinal node involvement was present in more than 40% of the patients in each group (distal esophageal adenocarcinoma, 47%; gastroesophageal junction adenocarcinoma, 41%). Survival was similar (5 years: distal esophageal adenocarcinoma, 45%; gastroesophageal junction adenocarcinoma, 38%; P = .14), as was the prevalence and type of recurrence. CONCLUSION: The prevalence and distribution of lymph node metastases in patients with adenocarcinoma of the distal esophagus and gastroesophageal junction were similar, and after esophagectomy, there was no difference in overall survival or recurrence. Efforts to differentiate between these tumors are unnecessary, and both are effectively treated with esophagectomy.
Abstract: BACKGROUND: In papillary thyroid cancer, quantitative relationships may exist between central and lateral neck lymph node metastases, which may be of clinical usefulness. METHODS: This comparative analysis of central and lateral neck lymph node metastases was undertaken in 88 patients with untreated papillary thyroid cancer who underwent compartment-oriented lymph node dissection in the central and ipsilateral lateral neck. In 32 of these patients, the contralateral lateral neck was dissected in addition. RESULTS: Central lymph node metastases were categorized in increments of 0 (22 patients), 1-5 (29 patients), 6-10 (12 patients), and more than 10 positive nodes (25 patients). With more than 5 positive nodes, the rates and numbers of lateral lymph node metastases increased from between 45% and 69% to 100% and from a mean of between 2 and 3 to between 6 and 8 lymph node metastases (all P < .001) in the ipsilateral neck; and from between 0% and 33% to between 60% and 71% (P = .009) and from a mean of between 0 and 1 to between 3 and 7 lymph node metastases (P = .003) in the contralateral neck. Lateral lymph node metastases in the contralateral neck always coexisted with metastases in both the central and the opposite lateral neck. When only patients with positive lateral nodes were considered, the successive increase in the number of lateral lymph node metastases was still present. Altogether, the ipsilateral neck harbored more often lateral lymph node metastasis with more positive lateral nodes than the contralateral neck. CONCLUSION: These histopathologic associations may provide a foundation for more evidence-based decisions regarding lymph node dissection of the lateral neck compartments in patients with node-positive papillary thyroid cancer.
Abstract: Unilateral exploration based upon preoperative imaging has become increasingly applied in the management of patients with primary hyperparathyroidism. Unilateral surgical exploration purportedly has high rates of disease control, limited morbidity, and shortened operative time. Unfortunately, significant cohorts of patients with primary hyperparathyroidism are unable to have abnormal glands localized on preoperative imaging evaluation. AIM: The aim of our study was to evaluate the efficacy of Tc(99m) sestamibi preoperative imaging, intraoperative Tc(99m) sestamibi with gamma probe, and intraoperative parathyroid hormone (IOPTH) assessment in a large cohort of patients with primary hyperparathyroidism. RESULTS: A total of 427 patients were prospectively evaluated who were deemed surgical candidates for the treatment of primary hyperparathyroidism. Of these patients, 240 (56%) presented with positive Tc(99m) sestamibi imaging. Another 105 (25%) presented with equivocal Tc(99m) sestamibi imaging. Finally, 82 (19%) presented with negative Tc(99m) sestamibi imaging. Intraoperative rapid assessment of parathyroid hormone was performed at the time of surgical exploration in all patients with negative and equivocal preoperative imaging. All 240 patients with positive preoperative imaging underwent unilateral surgical exploration utilizing intraoperative Tc(99m) sestamibi with gamma probe. The most common finding in the positive Tc(99m) sestamibi scan group was single adenoma in 235 (98%). Normocalcemia was achieved in 233 (97%) of these patients, although in 25 (10%) this was normocalcemia with a persistent elevation in parathyroid hormone (PTH). The most common surgical finding in the equivocal Tc(99m) sestamibi scan group was single adenoma in 85 (81%). Additionally 85 (81%) of these equivocal patients were able to undergo unilateral exploration limited by IOPTH assessment. Normocalcemia was achieved in 101/105 (96%) of patients; although, 10 patients were normocalcemic with persistently elevated PTH and 2 patients had normocalcemia with low PTH. All patients with negative Tc(99m) sestamibi scan underwent bilateral cervical exploration plus IOPTH; 52/82 (63%) were found to have a single adenoma which was the most common surgical finding. Normocalcemia was achieved in 77/82 (94%) of the negative Tc(99m) sestamibi cohort; although 5 patients had normocalcemia with persistently elevated PTH and 2 had normocalcemia with low PTH. Only 3 (0.7%) overall recurrent laryngeal nerve injuries were encountered, and only 1 (0.2%) was permanent. Wound complication rates are reported in detail and were low and comparable for all three Tc(99m) sestamibi imaging based cohorts. CONCLUSIONS: Tc(99m) sestamibi preoperative imaging, intraoperative Tc(99m) sestamibi with gamma probe, IOPTH, and combinations of these strategies allow for excellent opportunities for targeted excision of pathologic parathyroid tissue with the least dissection necessary while achieving excellent long-term calcium control and low rates of complication.
Abstract: INTRODUCTION: Normocalcemic hyperparathyrinemia, i.e. elevated parathyroid hormone (PTH) levels after parathyroidectomy in patients with primary hyperparathyroidism (pHPT) may occur in the course of postoperative recovery without the development of persistence or relapse. MATERIALS, METHODS AND RESULTS: Intraoperative and long-term (7 year) postoperative PTH and calcium levels after curative parathyroidectomy are demonstrated on the basis of a case report of a 62-year-old female patient with severe pHPT and pronounced osseous and renal manifestations. The intraoperative PTH gradient displayed a decrease from 1072 pg/ml to 13 pg/ml (normal range 11-67 pg/ml) followed by an increase of up to 287pg/ml. The hyperparathyoid values decline to subnormal levels on administration of calcium and vitamin D and increase again after tapering these medications. The inverse calcium/PTH correlation in the course of the 7-year observation period suggests an intact feed-back mechanism. Preoperative PTH screening was performed in 316 consecutive normocalcemic thyroid patients to evaluate the rate of incidental hyperparathyroidism in patients with normal serum calcium levels. Of these patients 31 (9.8%) with normocalcemia (average 2.28 mmol/l, normal range 2.1-2.7 mmol/l) exhibited increased PTH levels averaging 84.2 pg/ml. A parathyroid adenoma was found intraoperatively as the cause for normocalcemic pHPT in only 1 of these 31 patients. DISCUSSION AND CONCLUSIONS: A review of the literature revealed that late postoperative elevated parathyroid hormone levels after successful pHPT surgery occur in 21.5%. Multiple causes are discussed, e.g. reactive hyperparathyroidism in cases of relative hypocalcemia, hungry bone syndrome, vitamin D deficiency, renal dysfunction and ethnic or lifestyle differences. In mild cases of postoperative hyperparathyrinemia observation of the patient may be sufficient. In cases of reactive hyperparathyroidism due to hypocalcemia, administration of calcium is indicated, in symptomatic patients, additional administration of vitamin D or calcitriol is necessary. Vitamin D deficiency per se needs adequate substitution. In cases of ongoing hyperparathyrinemia an interdisciplinary diagnostic and therapeutic approach is required.
Abstract: BACKGROUND: Leakage from the pancreaticojejunostomy is the major cause of septic complications after partial pancreaticoduodenectomy. This study evaluated a new transpancreatic U-suture technique (Blumgart anastomosis, BA), which aims to avoid shear forces during knot-tying. METHODS: Using a before-after study design, BA was compared with a modified Cattell-Warren anastomosis (CWA). Two patient cohorts (CWA, 90; BA, 92), which were similar with respect to primary diagnosis, age, sex and American Society of Anesthesiologists score, were compared retrospectively. Dependent variables were surgical and overall morbidity and mortality after partial pancreaticoduodenectomy. RESULTS: Duration of operation (354 versus 328 min for CWA versus BA; P = 0.002), pancreatic leakage rate (13 versus 4 per cent; P = 0.032), postoperative haemorrhage (11 versus 3 per cent; P = 0.040), total surgical complications (31 versus 15 per cent; P = 0.011), general complications (36 versus 17 per cent; P = 0.005) and length of intensive care unit stay (median 5.4 versus 2.8 days; P = 0.015) were significantly reduced after BA. These effects were not related merely to an improvement over time. CONCLUSION: BA appears to be a fast, simple and safe technique for pancreaticojejunostomy. It might reduce leakage rates and surgical complications after partial pancreaticoduodenectomy.
Abstract: BACKGROUND: Parastomal hernia is a major clinical problem. In a randomized, clinical trial, a prosthetic mesh in a sublay position at the index operation reduced the rate of parastomal hernia at 12-month follow-up, without any increase in the rate of complications. This study was designed to evaluate the rate of complications after 5 years. METHODS: Between January 2001 and April 2003, 54 patients who had a permanent ostomy were randomized to a conventional stoma or to a stoma with the addition of a mesh in a sublay position. A large-pore, lightweight mesh with a reduced polypropylene content and a high proportion of absorbable material was used. RESULTS: After 5 years, 21 patients with a conventional stoma were alive and parastomal herniation was recorded in 17 patients, of whom repair had been demanded in 5. In 15 patients operated on with the addition of a mesh herniation, that did not require repair, was present in 2 (P<0.001). No fistulas or strictures developed. No mesh infection was noted and no mesh was removed during the study period. CONCLUSIONS: At stoma formation, a prophylactic low-weight mesh in a sublay position is a safe procedure that reduces the rate of parastomal hernia.
Abstract: BACKGROUND: Physical restraints are regularly applied in German nursing homes. Their frequency varies substantially between centres. Beneficial effects of physical restraints have not been proven, however, observational studies and case reports suggest various adverse effects. We developed an evidence-based guidance on this topic. The present study evaluates the clinical efficacy and safety of an intervention programme based on this guidance aimed to reduce physical restraints and minimise centre variations. METHODS/DESIGN: Cluster-randomised controlled trial with nursing homes randomised either to the intervention group or to the control group with standard information. The intervention comprises a structured information programme for nursing staff, information materials for legal guardians and residents' relatives and a one-day training workshop for nominated nurses. A total of 36 nursing home clusters including approximately 3000 residents will be recruited. Each cluster has to fulfil the inclusion criteria of at least 20% prevalence of physical restraints at baseline. The primary endpoint is the number of residents with at least one physical restraint at six months. Secondary outcome measures are the number of falls and fall-related fractures. DISCUSSION: If successful, the intervention should be implemented throughout Germany. In case the intervention does not succeed, a three-month pre-post-study with an optimised intervention programme within the control group will follow the randomised trial. TRIAL REGISTRATION: ISRCTN34974819.
Abstract: BACKGROUND: The management of small pancreatic cystic lesions presents a clinical challenge. METHODS: We reviewed our experience with 78 patients who presented with a cystic pancreatic lesion who underwent operative management between 1995 and 2005. Data on cyst characteristics were analyzed in the context of pathologic findings following resection. RESULTS: Among 78 patients, there were 55 (71%) females; median age 63 years. Patients presented with: an incidental finding (48%), pain (40%), acute pancreatitis (4%), other (8%). Operations were distal pancreatectomy (n = 47), pancreaticoduodenectomy (n = 16), and other (n = 15). Most patients had a non-malignant lesion (n = 65, 83%) (mucinous cystadenoma (n = 29), serous cystadenoma (n = 15), IPMN without invasion (n = 8), pseudocyst (n = 8), other benign (n = 5)). Malignant lesions (adenocarcinoma, neuroendocrine tumor, and other) were found in 13 patients (17%). The risk of malignancy increased with size: <3 cm (n = 25), 4%; 3-5 cm (n = 23), 13%; and >5 cm (n = 30), 30%. Pre-operative cyst fluid cytology was performed in 41 patients. The negative predictive value (NPV) of cytology for malignancy was 88% and the positive predictive value (PPV) was 80%. The NPV of CA 19-9 for malignancy was 90%; the PPV was 50%. CONCLUSIONS: Initial conservative management of small cystic pancreatic lesions may be indicated in selected patients.
Abstract: Men and women differ in thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult medullary thyroid cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult medullary thyroid cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted medullary thyroid cancer better than unisex thresholds. At lower (<or=50 pg/ml basally; <or=500 pg/ml after stimulation), but not higher, calcitonin serum levels, women revealed medullary thyroid cancer four to eight times more often than men. Most discriminatory between C-cell hyperplasia and medullary thyroid cancer was a basal calcitonin threshold of 15 pg/ml (corrected 20 pg/ml) for women and 80 pg/ml (corrected 100 pg/ml) for men, based on the greatest accuracy at the lowest possible calcitonin level. The respective gender-specific stimulated peak calcitonin thresholds were 80 pg/ml (corrected 100 pg/ml) and 500 pg/ml. Corresponding positive predictive values for medullary thyroid cancer at these calcitonin thresholds were 89 and 90% for women, as opposed to 100% for men. To increase the positive predictive value for women to 100%, the respective calcitonin thresholds would have to be raised to 40 pg/ml (corrected 50 pg/ml) and 250 pg/ml. These findings indicate that gender-specific calcitonin thresholds predict sporadic occult medullary thyroid cancer better than unisex thresholds.
Abstract: BACKGROUND: Disruptions in cognitive function have been described in the constellation of symptoms associated with "asymptomatic" primary hyperparathyroidism (PHPT). The aim of this study was to determine the impact of parathyroidectomy (PTX) on brain function and sleep in "asymptomatic" PHPT patients. METHODS: We conducted a prospective, randomized trial comparing immediate PTX with observation in patients with asymptomatic PHPT. We performed functional magnetic resonance imaging (fMRI) of the brain, sleep assessment, and validated neuropsychological battery at baseline, 6 weeks, and 6 months. Wilcoxon rank-sum and Pearson and Spearman correlations were used. RESULTS: A total of 18 patients were randomized. Subjective sleepiness correlated with worse performance on executive function tests during fMRI at 6 weeks (Pearson, -0.473; P = .047) and 6 months (Pearson, -0.673; P = .002). Total sleep time correlated with PTH levels at both 6 weeks (Pearson, 0.518; P = .048) and 6 months (Pearson, 0.567; P = .018). At 6 weeks, hypersomnolence as measured subjectively was decreased in the PTX group, but increased in those observed (-2.56 vs 2.22; P = .03) CONCLUSION: This prospective, randomized trial for asymptomatic PHPT patients demonstrated an association of sleep with brain function. Sleep seemed to be an indicator of brain activation in the anterior cingulate gyrus and precentral cortex. Subjective sleepiness was associated with executive function. The results of this pilot study suggest that decreased serum PTH levels correlate with improved sleep and that PTX decreases sleepiness in patients with asymptomatic PHPT.
Abstract: PURPOSE: Current adjuvant therapies for pancreatic cancer (PC) are inconsistently used and only modestly effective. Because a high proportion of patients who undergo resection for PC likely harbor occult metastatic disease, any adjuvant trials assessing therapies such as radiotherapy directed at locoregional disease are significantly underpowered. Stratification based on the probability (and volume) of residual locoregional disease could play an important role in the design of future clinical trials assessing adjuvant radiotherapy. PATIENTS AND METHODS: We assessed the relationships between margin involvement, the proximity to operative resection margins and outcome in a cohort of 365 patients who underwent operative resection for PC. RESULTS: Microscopic involvement of a resection margin by tumor was associated with a poor prognosis. Stratifying the minimum clearance of resection margins by 0.5-mm increments demonstrated that although median survival was no different to clear margins based on these definitions, it was not until the resection margin was clear by more than 1.5 mm that optimal long-term survival was achieved. CONCLUSION: These data demonstrate that a margin clearance of more than 1.5 mm is important for long-term survival in a subgroup of patients. More aggressive therapeutic approaches that target locoregional disease such as radiotherapy may be beneficial in patients with close surgical margins. Stratification of patients for entry onto future clinical trials based on this criterion may identify those patients who benefit from adjuvant radiotherapy.
Abstract: PURPOSE: The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma. METHODS: A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed. RESULTS: Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3-64.2% was reported (median, 26.5%). Of the operated patients, 57.1-100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0-8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6-13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months. CONCLUSIONS: The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.
Abstract: INTRODUCTION: The feasibility and safety of pancreaticoduodenectomy (PD) combined with long segmental mesentericoportal vein (MPV; >5 cm) resection and end-to-end anastomosis without graft has rarely been demonstrated. MATERIALS AND METHODS: Eight patients with pancreatic head adenocarcinoma underwent PD combined with long MPV resection between August 2006 and May 2008 in Peking University School of Oncology. RESULTS: By liver mobilization and Cattell-Braasch maneuver, direct and tension-free end-to-end anastomosis was easily performed even when the resected segment of the MPV was longer than 5 cm. All the eight patients experienced uneventful recovery without severe complications. CONCLUSIONS: PD with long MPV resection and direct end-to-end anastomoses is safe and effective.
Abstract: BACKGROUND: The aim of this study was to evaluate the safety of performing a pancreaticojejunostomy with a duct-to-mucosa anastomosis without a stenting tube. METHODS: One hundred twenty-one patients with pancreaticojejunostomy, classified into 2 groups of those with duct-to-mucosa anastomoses with stenting tubes (group A; n = 49) and without stenting tubes (group B; n = 72), were investigated. Outcomes, including complications and survival rates, are reported. RESULTS: In group A, morbidity was 32.7%, 6.7% had pancreatic fistulas, 14.3% had delayed gastric emptying, 6.1% had remnant pancreatitis, 2% had intra-abdominal abscesses, 2% had intra-abdominal bleeding, and mortality was 2%. In group B, morbidity (15.3%) and delayed gastric emptying (2.8%) showed significant differences from group A. Other results were nonsignificant. In the normal soft pancreas, pancreatic fistulas in group B (3.3%) were less frequent than in group A (12.5%). CONCLUSION: Pancreaticojejunostomy of a duct-to-mucosa anastomosis could be performed more safely without than with a stenting tube to obtain a definitive anastomosis and transection of the pancreas.
Abstract: BACKGROUND: The purpose of this study was to evaluate the operative risk and the prognostic implications of pancreatectomy plus resection and reconstruction of peripancreatic vessels (PPV) in patients with pancreatic adenocarcinoma. METHODS: One hundred ten patients who underwent pancreatectomy with PPV resection and reconstruction (Study Group; SG) were retrospectively compared with 62 patients without distant metastasis who were palliated, (Control Group 1; CG-1), as well as 197 patients who underwent "conventional"pancreatectomy (Control Group 2; CG-2). RESULTS: Postoperative morbidity and mortality were similar in SG (33% and 3%), in CG-1 (26% and 3%), and in CG-2 (40% and 6%) patients. Median survival time (MST) of SG patients (15 months) was longer than that of CG-1 patients (6 months; P < .0001) and similar to that of CG-2 patients (18 months). Patients undergoing isolated venous resection (n = 84) had the best outcome (MST: 15 months) ( P < .0001 vs CG-1 patients), while patients undergoing resection of multiple PPV (n = 14) had the worst outcome (MST: 8 months). PPV infiltration, histologically proven in 64 patients (65%), was associated with decreased MST only if the tunica intima was infiltrated (26%) (11 months; P < .001). Multivariate analysis showed that no adjuvant therapy, intimal invasion, and poorly differentiated histology were associated with a higher hazard of death by 2.2, 2.2, and 2.5-fold, respectively. CONCLUSION: In properly selected patients, pancreatectomy plus resection and reconstruction of PPV was performed as safely as palliation or "conventional" pancreatectomy and was associated with better survival when compared to palliation.
Abstract: Hepatocellular cancer (HCC) has always been considered a therapeutic challenge, given the cytoxic drug resistant nature of the cancer and associated disorder in liver function, reducing the safety of many conventional chemotherapy agents. The Multikinase inhibitor sorafenib has been found to prolong survival in patients with advanced HCC, by around 3months compared to placebo, but novel treatments need to be explored. Current experimental therapeutic approaches encompass a broad range of science, ranging from intrahepatic irradiation to virus directed immunotherapy. This chapter presents a horizon scan of novel treatments which are currently at early stages of trial development.
Abstract: OBJECTIVES: Although intensified therapy has contributed to improved outcomes for patients with head and neck cancer, acute toxicity has increased as well. To lessen the severity of nutritional compromise in these patients, our institutional protocol has been to routinely place feeding tubes before the initiation of therapy. This investigation details the toxicities associated with feeding tube placement and predictors for duration of tube dependence. MATERIALS AND METHODS: The records of the Radiation Oncology Department at Emory Clinic were reviewed for patients receiving definitive radiotherapy between 6/1/2003 and 6/1/2006. The records of the subset of patients with feeding tube placement before the initiation of therapy were then reviewed for toxicities as well as length of time of tube dependence. RESULTS: There were 102 eligible patients. Radiotherapy was delivered with concomitant chemotherapy in all. Median time with feeding tube in place for all patients was 4.4 months (range, 0.2-28.9 months). For 82 patients with eventual tube removal, the median time of tube dependence was 3.8 months (range, 1.4-28.9 months). Risk factors for prolonged tube dependence are analyzed; on multivariate analysis, patient age, T stage, and nodal status remained significant. The most common complication was tube replacement, with 11.8% of all tubes requiring replacement. Infection and pain occurred in 8.8% and 5.9% of patients, respectively. CONCLUSION: Feeding tubes are required for more than 2 months after combined modality treatment of head and neck cancer. They are generally well tolerated, but toxicities are not trivial: more than 10% require replacement and more than 8% of patients develop infection at the insertion site. We are assessing their routine placement in light of these data.
Abstract: The liver is the primary metastatic site in patients with colorectal cancer, and the only hope for a cure or prolonged survival in patients with liver metastases is provided by surgical resection. Advances obtained in non-resectable metastatic disease using new chemotherapeutic agents raise important questions about the use of neoadjuvant and adjuvant chemotherapy in patients with resectable liver metastases. Two major randomized studies have yielded positive results. First, a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen demonstrated a relapse-free survival benefit when compared to systemic 5-fluorouracil-leucovorin therapy alone. This approach is still restricted to specialized centres, however, due to technical limitations and locoregional toxicities. Secondly, an EORTC trial demonstrated the superiority of peri-operative FOLFOX-4 chemotherapy in comparison to surgery alone. Oxaliplatin and irinotecan can induce substantial liver damage, especially steatohepatitis and vascular lesions, but the impact of these lesions on postoperative morbidity and survival remains unclear. Ongoing and planned trials will assess the addition of anti-angiogenic and anti-epidermal growth factor receptor agents to chemotherapy regimens.
Abstract: OBJECTIVE: This study sought to define the need for lymph node dissection in Rearranged during Transfection (RET) carriers at risk for hereditary medullary thyroid cancer. SUMMARY BACKGROUND DATA: Controversy surrounds the need for lymph node dissection to complement thyroidectomy in RET carriers. METHODS: Integration of molecular, biochemical, histopathologic, and clinical information from 308 RET carriers referred for (re-)operation to a specialist surgical center. RESULTS: The carriers differed significantly in age at thyroidectomy when stratified by histopathology (tumor-free thyroid, node-negative, and node-positive medullary thyroid cancer) and mutated codon (611, 618, 620, 634, 768, 790, 804, 891, and 918). The wide overlap among the 3 histopathologic groups compromised individual predictions based on age alone. There was a significant relationship between the presence of lymph node metastases and increased pretherapeutic basal calcitonin levels. All 46 carriers with node-positive medullary thyroid cancer, who harbored 1 to 68 positive nodes, exhibited increased pretherapeutic basal calcitonin levels (91.4 pg/mL or higher). Conversely, 74 (44%) of 168 carriers with normal thyroids, C-cell hyperplasia, or node-negative medullary thyroid cancer displayed normal pretherapeutic basal calcitonin levels (negative predictive value 100%). Prediction of lymph node metastasis was better in carriers of codon 918 mutations (positive predictive value, PPV, 80%-100%) and those older than 20 years of age (PPV, 50%). DISCUSSION: In the absence of clinical evidence to the contrary, RET carriers with normal pretherapeutic basal calcitonin levels may forgo lymph node dissection. The usefulness of calcitonin thresholds to break down the block of carriers with increased calcitonin levels should be explored further.
Abstract: PURPOSE: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but nonmetastatic pancreatic carcinoma (LAPC). The French program Standards, Options, and Recommendations was promoted to conduct a qualitative systematic review to evaluate the role of radiotherapy in patients with LAPC. METHODS: A search to identify eligible studies was undertaken using the MEDLINE database. All phase III randomized trials and systematic reviews evaluating the role of radiotherapy in LAPC were included, together with some noncontrolled studies if no phase III trials were retrieved. The quality and clinical relevance of the studies were evaluated using validated checklists, which allowed associating each result with a level of evidence. RESULTS: Twenty-one studies were included, as follows: two meta-analyses, 13 randomized trials, and six nonrandomized trials. Chemoradiotherapy increases overall survival when compared with best supportive care (level of evidence C) or with exclusive radiotherapy (level B1), but is more toxic (level B1). Chemoradiotherapy is not superior to chemotherapy in terms of survival (level B1) and increases toxicity (level A). Recent data favor limited irradiation to the tumor volume (level C). Fluorouracil is still the reference chemotherapy in association with radiotherapy (level B1). Induction chemotherapy before chemoradiotherapy improves survival (level C). CONCLUSION: No standard treatment exists, but there are two options for treatment of LAPC; these are gemcitabine-based chemotherapy and chemoradiotherapy. Induction chemotherapy followed by a chemoradiotherapy is a promising strategy for selection of patients without early metastatic/progressing disease.
Abstract: This article summarizes the expert discussion on the management of hepatocellular carcinoma (HCC), which took place during the 10th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, June 2008. A multidisciplinary approach to a patient with HCC is essential, to guarantee optimal diagnosis and staging, planning of surgical options and selection of embolisation strategies or systemic therapies. In many patients, the underlying cirrhosis represents a challenge and determines therapeutic options. There is now robust evidence in favour of systemic therapy with sorafenib in patients with advanced HCC with preserved liver function. Those involved in the care for patients with HCC should be encouraged to participate in well-designed clinical trials, to increase evidence-based knowledge and to make further progress.
Abstract: OBJECTIVE: We report the outcome of the care of 209 patients with hepatocellular carcinoma with a focus on relevant scoring systems for predicting overall survival and time to progression and on changes in presentation status and outcome from 1991 to 2006. MATERIALS AND METHODS: Hepatic arterial chemoembolization was performed on 209 patients in 375 sessions. Disease status was evaluated with the Child-Pugh, Okuda, Cancer of the Liver Italian Program, and American Joint Committee on Cancer (AJCC) systems. Changes in status at presentation from 1991 to 2006 and change in overall survival period and time to progression were analyzed. RESULTS: Median and mean overall survival periods for the entire group were 376 and 574 +/- 61 days. Median and mean times to progression were 267 and 409 +/- 54 days. Forty-nine patients underwent liver transplantation a median of 143 days after chemoembolization. The median and mean overall survival times among patients not undergoing transplantations were 466 and 574 +/- 61 days. Okuda score (p < 0.0001) and AJCC stage (p = 0.014) were the best predictors of overall survival and time to progression, respectively. Patients with disease with an Okuda I score and in AJCC stage I or II had median and mean overall survival periods of 667 and 992 +/- 176 days and times to progression of 378 and 589 +/- 110 days. Clinical status at presentation, overall survival period (p = 0.64), and time to progression (p = 0.44) were unchanged from 1991 to 2006. The 30-day mortality was 3.2%. CONCLUSION: Patients treated with hepatic arterial chemoembolization for HCC in Okuda score I and AJCC stage I or II have more durable survival than previously reported in a U.S. population.
Abstract: BACKGROUND: We used a novel combination of induction chemotherapy with gemcitabine (GEM) and cisplatin (CDDP), followed by concurrent chemoradiotherapy (CCRT) with the same agents in patients with locoregionally advanced pancreatic cancer. Surgery or additional chemotherapy followed on the basis of response. METHODS: Patients with borderline resectable or locally advanced pancreatic cancer received induction weekly with GEM (1000 mg/m(2)) or CDDP (30 g/m(2)). Patients without progression of disease then underwent surgery or CCRT, including four cohorts of escalating GEM/CDDP doses combined with full-dose radiotherapy. After CCRT, patients deemed resectable underwent surgery; patients with disease that remained unresectable and that did not progress received additional GEM/CDDP for 2 months. RESULTS: A mean 76% of intended GEM dose and 75% of CDDP dose was delivered during induction (n = 26). There were three incidences of grade 4 toxicity (fever or neutropenia). After induction, five patients progressed and one patient underwent resection. Eighteen patients received CCRT, and three patients underwent resection. After CCRT, disease of 10 patients progressed, and in 5 patients, it remained unresectable without progression, and the patient received additional GEM/CDDP. Dose-limiting toxicity was at dose level IV (thrombocytopenia). Median overall and disease-specific survival was 13 months. CONCLUSION: GEM/CDDP induction chemotherapy followed by CCRT is well tolerated and rendered the disease of 4 of 26 patients resectable in this study. The recommended phase II dose for GEM and CDDP in combination with full-dose radiotherapy (5040 cGy) is 300 mg/m(2) and 10 mg/m(2) weekly for 5 weeks. Median survival in this group was 13 months. This neoadjuvant combined modality approach is both feasible and active; further studies are warranted.
Abstract: Imaging studies play a crucial role in the diagnosis and management of patients with pancreatic adenocarcinoma. Computed tomography (CT) is the most widely available and best-validated modality for imaging patients with pancreatic adenocarcinoma. To maximize the diagnostic efficacy of CT, use of a pancreas protocol is mandatory. The sensitivity of CT for diagnosis of pancreatic adenocarcinoma (89%-97%) and its positive predictive value for predicting unresectability (89%-100%) are high. The positive predictive value of CT for predicting resectability (45%-79%) is low because the diagnostic criteria for diagnosing vascular invasion by tumor favors specificity over sensitivity to avoid denying surgery to patients with potentially resectable tumor. Furthermore, the sensitivity of CT for small hepatic and peritoneal metastases is limited. Magnetic resonance imaging has not been shown to perform better than CT for the diagnosis and staging of pancreatic adenocarcinoma, but can be helpful as an adjunct to CT, particularly for evaluation of small hepatic lesions that cannot be fully characterized by CT. Ultrasound is often the first study obtained in patients with obstructive jaundice or unexplained abdominal pain, but its utility for diagnosis and staging of patients with pancreatic adenocarcinoma is limited. Positron emission tomography/CT combines the functional information provided by positron emission tomography with the anatomic information provided by CT and is a promising modality for imaging of patients with pancreatic adenocarcinoma, but its utility has not been established. Endoscopic ultrasound is generally considered superior to CT for the diagnosis and local staging of pancreatic cancer, but is limited by availability and inability to assess for distant metastases.
Abstract: PURPOSE: The primary goal of this study was to evaluate whether pathologic response to chemotherapy predicts patient survival after preoperative chemotherapy and resection of colorectal liver metastases (CLM). The secondary goal of the study was to identify the clinical predictors of pathologic response. PATIENTS AND METHODS: A retrospective review was performed of 305 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by resection of CLM. Pathologic response was systematically evaluated and reported as the mean of the percentage of cancer cells remaining within each tumor. Univariate and multivariate analyses were performed to identify the predictors of pathologic response and survival. RESULTS: Cumulative 5-year overall survival rates by pathologic response status were as follows: 75% complete response (no residual cancer cells), 56% major response (1% to 49% residual cancer cells), and 33% minor response (> or = 50% residual cancer cells; complete v major response, P = .037; major v minor response, P = .028). Multivariate analysis revealed that only surgical margin status (P = .050; hazard ratio [HR], 1.77) and pathologic response (major response: P = .034; HR, 4.80; minor response: P = .007; HR, 6.93) were independent predictors of survival. Multivariate analysis of the predictors of pathologic response revealed that carcinoembryonic antigen level < or = 5 ng/mL, tumor size < or = 3 cm, and chemotherapy with fluoropyrimidine plus oxaliplatin and bevacizumab were independent predictors of pathologic response. CONCLUSION: Pathologic response predicts survival after preoperative chemotherapy and resection of CLM. Degree of pathologic response represents a new outcome end point for prognosis after resection of CLM.
Abstract: Resection of liver metastases for locally resectable pancreatic cancer has rarely been performed. Recently, promising results regarding morbidity and mortality as well as long-term survival have been shown. Thus, we conducted a systematic review of the literature on pancreatic cancer resection with associated liver metastasis resection. There are 3 case reports and 18 studies including less than 10 patients. Only three studies are larger series with 10 or more patients in whom pancreatic resections and hepatic metastasectomies were performed. Here, morbidity and mortality ranged from 24.1 to 26% and from 0 to 4.3%, respectively. Median survival was reported to be between 5.8 and 11.4 months. In total, all identified studies included 103 patients in whom a metastasis resection was performed. Liver metastasis resection for locally resectable pancreatic cancer can be performed in selected cases with low morbidity and mortality. Overall survival in cases with one or few liver metastases which are concomitantly resected seems to be comparable to cases without evidence of metastasis. Therefore, randomized controlled clinical trials will have to be initiated to determine the value of such resections and to identify factors which will allow for selection of patients in whom the extension of the resectability criteria might confer a survival benefit.
Abstract: CONTEXT: Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer. OBJECTIVE: The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer. DESIGN: This was a retrospective study. SETTING: The investigation took place at a tertiary referral center. PATIENTS: Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer. MAIN OUTCOME MEASURE: Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases. RESULTS: There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41-54 vs. 4-27%; P = 0.001) and number (means of 3.0-10.8 vs. 0-1.1 positive nodes, P < 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14-27 vs. 0-7%; P = 0.027), distant metastasis (9-23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40-55 vs. 53-82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels. CONCLUSIONS: Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.
Abstract: BACKGROUND: The aim of this study was to report the results of preoperative contralateral portal vein embolization (PVE) performed in a single institution. METHODS: Between January 1997 and March 2006, 146 patients requiring a right or extended right hepatectomy for primary or secondary liver tumors underwent contralateral PVE when the future remnant liver volume (FRL) was less than 30% of total liver. Liver volumes and hepatic function were evaluated before and after PVE. RESULTS: Contralateral PVE was performed successfully in 145 patients. In one patient, the catheterization of the left portal branch failed. Complications occurred in 14 patients (10%) including a transitory fever (n = 9), a parenchymal hematoma (n = 1), a mild hemoperitoneum (n = 1), a mesenterico-portal venous thrombosis (n = 1), a pulmonary embolism (n = 1) and a systemic sepsis (n = 1). The prothrombin ratio and the platelet count were significantly lower 3 days after PVE. Insufficient hypertrophy of the FRL was observed in 8 patients, malignant disease progression in 15, and both insufficient hypertrophy and disease progression in 4. The hypertrophy rate of the FRL 4 to 8 weeks after PVE was 47.7 +/- 31.9%. Pathological type of the liver tumor, cirrhosis, diabetes mellitus, and chemotherapy did not affect the volume of the left liver hypertrophy. However, the time required to achieve an adequate liver hypertrophy was significantly shorter in patients with normal liver. One-hundred and fourteen patients (78.6%) subsequently underwent hepatic resection. CONCLUSIONS: The results suggest that contralateral PVE is a safe and efficient procedure inducing adequate hypertrophy of the FRL before major liver resection.
Abstract: In murine models, resection of a primary tumor leads to increased vascularization and accelerated growth of metastases that previously had remained microscopic. To study such a potentially inhibitory effect of primary tumors on the outgrowth of distant metastases in humans, we assessed the metabolic activity of liver metastases by 18F-FDG PET before and after resection of primary colorectal tumors. METHODS: Group A consisted of 8 patients with synchronous colorectal liver metastases who were scheduled for resection of their primary tumor. These patients underwent an (18)F-FDG PET scan shortly before resection and 2-3 wk after resection of the primary tumor. The patients in a control group (group B, n = 9) underwent an 18F-FDG PET scan at the time of diagnosis of the liver metastases and a second scan several weeks later, before initiating treatment. There was no surgical intervention between the two 18F-FDG PET scans in this group. RESULTS: In group A, the maximum and mean standardized uptake values of the liver metastases clearly increased after resection of the primary tumor, by 38% +/- 55% and 42% +/- 52%, respectively, as compared with the first 18F-FDG PET scan. In group B, the maximum and mean standardized uptake values of the second 18F-FDG PET scan were not significantly higher than those of the first 18F-FDG PET scan; -11% +/- 23% and 1% +/- 29%, respectively. The difference in standardized uptake value increase between the 2 groups was statistically significant (P < 0.05). CONCLUSION: Our data cannot differentiate between the immunologic sequels caused by the surgical trauma itself and those caused by removal of the primary tumor. The observation itself, however, of increased metabolic activity after surgical resection of the primary tumor may have direct clinical applications and suggests the administration of antiangiogenic therapy after surgery of the primary tumor.
Abstract: PURPOSE: Abdominoperineal excision (APE) of the rectum and anus for rectal cancer continues to have greater local recurrence and poorer survival than that seen following anterior resection. Changing to an extended prone perineal dissection results in a more cylindrical specimen and should improve outcomes. PATIENTS AND METHODS: One hundred twenty-eight specimens from patients who underwent APE that was performed for potentially curable primary rectal adenocarcinoma were dissected according to standard protocol in Leeds and Stockholm between 1997 and 2007 and were studied. Tissue morphometry was performed on the cross sectional photographs of 93 patient cases. RESULTS: The cylindrical technique removed more tissue in the distal rectum and in all slices that contained tumor compared with the standard operation (both P < .0001). Greater distance was observed from the muscularis propria or internal sphincter to the anterior, posterior, and lateral resection margins (all P < .0001). This was associated with lower circumferential resection margin (CRM) involvement (14.8% v 40.6%; P = .013) and intraoperative perforations (3.7% v 22.8%; P = .0255). An increase in the amount of tissue removed in the distal rectum (P < .0001) was demonstrated by a single surgeon who changed from the standard to the cylindrical technique during the study period; the change was associated with a reduction in CRM positivity (from 36.2% to 12.5%) and in perforations (from 12.8% to 0.0%). CONCLUSION: Cylindrical APE performed in the prone position for low rectal cancer removes more tissue around the tumor that leads to a reduction in CRM involvement and intraoperative perforations, which should reduce local disease recurrence. The cylindrical technique has the potential to improve patient outcomes substantially if appropriate surgical education programs are developed.
Abstract: BACKGROUND: The liver surgeon's decision to operate is based on imaging studies. However, no clear practical guidelines are available enabling surgeons to safely predict tumor-free margins after a partial hepatectomy. The aim of this retrospective study is to provide surgeons with simple and easily applicable practical guidelines. METHODS: We retrospectively stringently selected 42 anatomical right or left hepatectomies whose main characteristic was to pass along the median hepatic vein, which was preserved. This vein is an easily visualized anatomical landmark on preoperative imaging and is never transgressed by the surgeon. We compared the minimum distance between the tumor and this vein measured on preoperative imaging, and the minimum tumor-free excision margin measured on the specimen by the pathologist. RESULTS: The median tumor-free excision margin was 5 mm at pathological analysis, significantly different (P < .0001) from the tumor-free margin measured on preoperative imaging (15 mm). The mean difference between these two measurements was 10 +/- 4 mm (median, 9 mm). This difference was partly the result of the transection and partly the result of technical deviations in relation to the ideal resection line. CONCLUSIONS: The liver surgeon must consider that roughly a 5 to 8 mm tumor-free margin will disappear during hepatectomy when comparing measurements on the basis of preoperative imaging versus tumor-free specimen margins. If the histologically assessed minimum 2-mm tumor-free margin is added, the surgeon must plan to have a 7 to 10 mm tumor-free margin on preoperative imaging. However, few technical solutions exist that would enable the surgeon to increase the safety margin in borderline cases.
Abstract: BACKGROUND: In medullary thyroid cancer (MTC), there is a concordance between central and lateral neck involvement, but this relationship has not been assessed quantitatively. METHODS: After compartment-oriented lymphadenectomy for untreated MTC, the numbers of central lymph node metastases with ipsilateral (195 patients) and contralateral (185 of 195 patients) lateral lymph node metastases were analysed retrospectively. RESULTS: With one to three positive central lymph nodes, involvement of the ipsilateral lateral neck increased from 10.1 per cent (with no central node involvement) to 77 per cent, and from a mean of 0.6 to 3.7 nodal metastases (P < 0.001). With four or more central nodes, the rate was 98 per cent, with 10.7 nodal metastases (P = 0.001). A weaker increase was observed in the contralateral lateral neck: with one to nine positive central nodes, contralateral lateral neck involvement increased from 4.9 to 38 per cent, and from a mean of 0.6 to 2.3 nodal metastases (P = 0.011). With ten or more positive central nodes, the rate rose to 77 per cent, with 6.2 nodal metastases (P = 0.009). With one exception, contralateral lateral nodal metastases coexisted with metastases in the central and ipsilateral lateral neck. CONCLUSION: These data may lay the groundwork for more informed decision-making regarding dissection of the lateral neck compartments.
Abstract: OBJECTIVE: It was the aim of this study to evaluate a new infiltration score to determine the resectability of pancreatic carcinomas in preoperative planning. MATERIALS AND METHODS: Eighty patients with suspected pancreatic tumor were examined prospectively using 16-row spiral CT. The scans were evaluated for the presence of pancreatic carcinoma, peripancreatic tumor extension and vascular invasion using a standardized questionnaire. Invasion of the surgically relevant vessels was evaluated using a new invasion score. The operative and histological findings and the clinical follow-up served as the gold standard. RESULTS: Forty patients had a pancreatic carcinoma, 5 had metastasis of a different primary tumor, and in 35 patients, there was no malignant pancreatic disease. The sensitivity for tumor detection was 100%, with a specificity of 88% for differentiating between malignant and benign pancreatic tumors. Invasion of the surrounding vessels was evaluated correctly using the invasion score, with a sensitivity of 89% and a specificity of 99%. In evaluation of resectability, a sensitivity of 94% and a specificity of 89% were achieved. CONCLUSION: Using 16-row spiral CT, the invasion score is a valid tool for correctly assessing invasion in relevant vessels in cases of pancreatic carcinoma and for determining resectability.
Abstract: PURPOSE: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. METHODS AND MATERIALS: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. RESULTS: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. CONCLUSIONS: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients.
Abstract: BACKGROUND/PURPOSE: The majority of surgeons agree that ampullary adenocarcinoma should be removed by partial pancreatoduodenectomy. Favoring extended resection, based on the uncertainty of the preoperative diagnosis and the higher probability of clear resection margins, we aimed to disclose the results of this surgical procedure in terms of postoperative morbidity and mortality, and to identify prognosticators of long-term survival. METHODS: We documented, prospectively, 25 consecutive patients with adenocarcinoma of the papilla of Vater in whom pylorus-preserving pancreatoduodenectomy was performed. Clinical data, pathology reports, International Union Against Cancer (UICC) tumor stage, postoperative morbidity, mortality, and long-term follow-up results were evaluated. The Kaplan-Meier method and log-rank test were applied for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. RESULTS: Postoperative mortality was 4%, overall morbidity was 32%, and pancreas-associated morbidity was 8%. Mean survival time was 53.8 months. Tumor size, N status, UICC stage, lymphatic invasion, blood vessel infiltration, R0 resection, and age of patient at the cutoff of 70 years were independent predictors of survival on univariate analysis. Multivariate analysis, however, disclosed no independent predictors of prognosis. CONCLUSIONS: Pancreatoduodenectomy for ampullary carcinoma is reasonable in terms of postoperative morbidity and mortality. Tumor-related factors, R0 resection, and advanced age appeared as the main predictors of survival.
Abstract: BACKGROUND: Most patients with medullary thyroid carcinoma (MTC) have persistent disease after primary surgery, as evidenced by calcitonin elevation. Previous reports showed that reoperation on selected patients yields immediate calcitonin normalization in one-third of patients. Long-term follow-up data are needed to assess the outcome in such patients. This report aims to provide 8- to 10-year follow-up on reoperations for persistent or recurrent MTC. METHODS: An Internal Review Board (IRB) approved database on patients treated for MTC has been prospectively maintained. This database was reviewed to report follow-up data on calcitonin levels and survival. RESULTS: Between 1992 and 2006, 148 patients underwent reoperations for recurrent or persistent MTC (55 patients had 59 reoperations for palliation, and 93 patients had 105 reoperations for cure). Of the 93 patients operated on for cure (44 with hereditary MTC, 49 with the sporadic form), 8-10-year follow-up data were available on 56. Four patients died of disease (4.3% of 93). Two died of unrelated causes, and were excluded from calcitonin outcome analysis. Fourteen patients of 54 (26.0%) have unstimulated calcitonin levels of <10 pg/ml at 8-10 years. Eleven additional patients (20.4%) have levels<100 pg/ml. None of these 25 patients (46.4%) have radiologic recurrence. CONCLUSIONS: Previous reports demonstrated the low morbidity of reoperation for MTC in experienced hands, and success was determined by lowering of calcitonin levels. Follow-up data demonstrate that at least one third of such patients have long-term eradication of their disease following reoperation, as evidenced by biochemical and imaging studies.
Abstract: Background. The surgical treatment of perihilar cholangiocellular carcinoma (CCC) is challenging due to the adjacency of the tumor to the hilar vessels, major hepatic veins, bile ducts, and the inferior vena cava. Additionally, the tumour frequently infiltrates the parenchyma of the caudate lobe or/and invades its bile ducts. Consensus statements. Negative margin caudate hepatectomy is rarely feasible. Isolated partial or complete caudate lobe resection is an oncologically inadequate procedure. Extended hepatectomies in combination with caudate lobectomy can provide prolonged survival, even in patients with advanced CCC. Mesohepatectomy is an oncologically adequate procedure for selected patients with CCC and compromised liver function. The procedure is technically demanding; however, it lowers the risk of postoperative liver failure.
Abstract: BACKGROUND: Bleeding is the most relevant operative risk during mesohepatectomy because of the wideness of the resection surfaces and the exposure of main intrahepatic vascular structures. Preliminary extraparenchymal exposure of the main hepatic veins, with the possibility of clamping them in association with the Pringle maneuver, and the maintenance of a low central venous pressure during mesohepatectomy, can contribute to substantially reducing operative bleeding. STUDY DESIGN: We report the results obtained in 18 mesohepatectomies, performed for liver metastases (13 patients) and for hepatocellular carcinoma (5 patients). Liver resection was performed without preliminary exposure of the main hepatic veins in nine patients (group A) and with preliminary looping of the main hepatic veins in nine patients (group B), without complications related to the maneuver. RESULTS: Intermittent pedicle clamping was used in all patients; in six patients in group B (66.7%), clamping of the main hepatic veins was also performed (mean duration, 37 minutes; range 16 to 68 minutes). Intraoperative blood transfusions were needed in 5 patients (5 of 18, 27.8%): 4 belonged to group A (44.4%) and 1 to group B (11.1%). Mortality was nil and morbidity was 33.3%, involving four patients in group A and two in group B (none related to the exposure, looping, and clamping of the main hepatic veins). CONCLUSIONS: Preliminary control of the main hepatic veins is a safe maneuver. During mesohepatectomy, clamping of these veins, associated with pedicle clamping, is effective in reducing operative bleeding. In our patients, this resulted in a low blood transfusion rate, similar to that of classic major hepatectomies, despite the higher complexity of mesohepatectomy.
Abstract: BACKGROUND: The definition of what is unresectable in liver surgery is controversial. Problems that many believe render patients unresectable can currently be resected using advanced techniques of liver surgery. This study assesses liver resection in patients who were unresectable with standard liver resection but were potentially resectable using an aggressive approach to liver surgery. STUDY DESIGN: From 1997 to 2007, 830 adult patients undergoing hepatectomy were reviewed. Patients were categorized as having unresectable disease by standard resection if the disease could not be resected without resection of the IVC, hepatic vasculature, or because of tumor extent. RESULTS: One hundred sixteen patients were initially believed to have unresectable disease but went on to laparotomy. Eighteen patients were unresectable at operation, although 98 patients were resected. Seventy-eight trisectionectomies; 18 lobectomies; 1 mesohepatectomy; and 1 segment 5, 6 resection, combined with pancreaticoduodenectomy, nephrectomy, and colectomy, were performed. Fourteen patients also had pancreatic resections. Vascular reconstructions were performed on the IVC (n = 35), hepatic veins (n = 21), portal vein (n = 34), and hepatic artery (n = 5). Hypothermic perfusion of the liver was used in 12 patients (4 ex vivo, 8 in situ cold perfusion). Patients undergoing resection had 6% mortality with a morbidity of 35%. Median survival was 37 months (95% CI, 34-42 months). Five-year actuarial survival was 32%. CONCLUSIONS: Patients with liver tumors considered "unresectable" by standard liver resection should be considered for resection with an aggressive approach to liver surgery. Five-year survival of approximately one-third of patients can be expected.
Abstract: Although pancreaticoduodenectomy has become a safe and effective procedure for benign and malignant pancreatic diseases in recent years, leakage of pancreaticoenteric anastomosis still remains a major cause of morbidity and even mortality. Various methods have been used to prevent pancreatic fistula with either pharmacologic or technical approaches. Based on meta-analysis of results from European and American trials, prophylactic use of octreotide to inhibit pancreatic secretion cannot be recommended for routine use in pancreaticoduodenectomy. Further randomized trials are required to clarify the role of selective use of octreotide in patients at high risk for pancreatic leakage. Technical improvement by surgeons is probably the most important approach to reduce pancreatic anastomotic leakage rate. Various technical modifications for pancreaticoenteric anastomosis have been suggested; some have been tested in randomized controlled trials, but data from randomized trials are generally scarce. Use of PG instead of PJ anastomosis, internal stenting of PJ anastomosis, pancreatic duct occlusion, and fibrin glue have not been shown to be effective in reducing pancreatic leakage rate after pancreaticoduodenectomy. One randomized trial recently showed significant reduction of pancreatic leakage rate using an external diverting stent after PJ anastomosis, and another randomized trial showed significant reduction in PJ anastomosis leakage using the binding PJ anastomosis technique. Nonetheless, further high-quality randomized controlled trials are needed to evaluate the benefit of these technical modifications in decreasing the pancreatic leakage rate after pancreaticoduodenectomy.
Abstract: Survival from differentiated thyroid carcinoma is generally good, but postoperative management plays an important role in minimizing the likelihood of disease recurrence. Postoperative management is generally performed by endocrinologists and nuclear medicine physicians, who exploit thyroid cells' inherent iodineavidity and sensitivity to hormonal manipulation in a unique cancer management paradigm. Endocrinologists manage thyroid hormone replacement/thyroid stimulating hormone suppression and coordinate surveillance. Nuclear physicians administer targeted therapy with radioactive iodine and perform imaging studies to assess disease status. This article provides an overview of the postoperative assessment, treatment, and follow-up of patients who have thyroid carcinoma.
Abstract: Aim. Multiorgan dysfunction is often encountered in jaundiced patients and may compromise the postoperative outcome after liver resection for cholangiocarcinoma (CCA). The aim of the present study was to elucidate evidence-based medicine regarding the benefit of the available preoperative treatments currently used for the preparation of patients before surgery for hilar CCA. Material and methods. An electronic search using the Medline database was performed to identify relevant articles relating to renal dysfunction, bacterial translocation, hemostasis impairment, malnutrition, liver failure, and postoperative outcome in jaundiced patients undergoing liver resection for CCA. Results. There is grade B evidence to expand the extracellular water volume and to administer oral synbiotic supplements. Intravenous vitamin K administration is an effective treatment. Perioperative nutritional support should be administered preferably by the enteral route in severely malnourished patients with compromised liver function undergoing extended liver resection (grade A evidence). There is only grade C evidence to recommend a portal vein embolization in patients with CCA when the future remnant liver volume is <40%. Conclusions. A simplified scheme that might be useful in the management of patients presenting with obstructive jaundice was presented. Despite surgical technique improvements, preparation of patients for surgery will continue to be one of the major determinants for the postoperative prognosis of jaundiced patients.
Abstract: PURPOSE: Complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy is of limited predictive value for complete pathologic response (CPR) and cure of the disease. The objective of this study was to determine predictive factors of CPR as well as its impact on survival. PATIENTS AND METHODS: From January 1985 to July 2006, 767 consecutive patients with CLM underwent liver resection after systemic chemotherapy. Patients with CPR were compared with patients without CPR. RESULTS: Twenty-nine of 767 (4%) patients had CPR, and none of these 29 patients had CCR. Patients with CPR (mean age, 54 years) had a mean number of 3.3 metastases at diagnosis (mean size, 29.3 mm). Objective response and stable disease were observed in 79% and 21% of cases, respectively. Postoperative mortality rate was 0%. After a median follow-up of 52.2 months (range, 1.1 to 193.0 months), overall 5-year survival was 76% for patients with CPR compared with 45% for patients without CPR (P = .004). Independent predictive factors for CPR were: age <or= 60 years, size of metastases <or= 3 cm at diagnosis, carcinoembryonic antigen (CEA) level at diagnosis <or= 30 ng/mL, and objective response following chemotherapy. The probability of CPR ranged from 0.2% when all factors were absent to 30.9% when all were present. CONCLUSION: CPR was observed in 4% of patients with CLM treated with preoperative chemotherapy. However, CPR may occur in almost one-third of objective responders age <or= 60 years with metastases <or= 3 cm and low CEA values. CPR is associated with uncommon high survival rates.
Abstract: Medullary thyroid carcinoma (MTC) is responsible for 13.4% of the total deaths attributable to thyroid cancer in human beings and research on MTC over the last 40 years has identified the RET proto-oncogene as a very relevant component of development of both sporadic and hereditary MTC. An activating germline RET proto-oncogene mutation responsible for a multiple endocrine neoplasia syndrome type 2 (MEN2) or a familial hereditary MTC syndrome is carried by 25% to 35% of patients with MTC. The recognition of RET proto-oncogene mutations by genetic sequencing has allowed us to differentiate hereditary from sporadic MTC, so that it is now possible to identify and treat children at risk for this disease before development of metastasis. Thanks to this discovery, we can now establish the association of MTC with other tumors in the context of MEN2 syndrome; determine adequate follow-up, prognosis, and treatment for patients with hereditary disease; and use this information to develop new therapies against both sporadic and hereditary MTCs.
Abstract: BACKGROUND: Pleural or peritoneal effusions (ascites) are frequent in terminal stage malignancies. Medical management may be hazardous. METHODS: A 60-year-old man with metastatic malignant melanoma presented refractory ascites as well as bilateral pleural effusions. After failure of the medical treatment, bilateral pleural aspiration and paracentesis became necessary two to three times a week. A multi perforated 15F silicone catheter connected with a subcutaneous port was implanted in peritoneal and both pleural cavities surgically under general anesthesia. Leakage around the catheter is prevented by subcutaneous tunneling. Surgical technique is described and illustrated in a video. RESULTS: Implanted systems were immediately operational. Follow up period was 41 days. Each port was accessed 10 times and a total of 65'200 ml of fluid was drained. By the end of the forth week, pleural effusions diminished, systems were controlled for permeability and chest x-rays confirmed absence of effusion. CONCLUSION: Implanted port systems for refractory ascites and pleural effusions avoid morbidity and the patient's anxiety related to repeated puncture-aspiration. Large catheter diameter allows an easy and fast drainage of large volumes. Compared to chronic indwelling catheters, subcutaneous location of port system allows an entire integration, giving the patient a total liberty in daily life between two sessions of drainage. Drainage can be performed in an outpatient basis as an ambulatory procedure. This patient-friendly technique may be a treatment option in case of failure of other techniques.
Abstract: CASE: A 76-year-old gentleman presented with painless jaundice, weight loss, and anorexia. Computed tomography imaging revealed fullness of the pancreatic head and multiple enlarged retroperitoneal lymph nodes. Cholangiogram revealed a distal common bile duct stricture. Due to concerns of malignancy, the patient underwent operative exploration. Several enlarged lymph nodes in the aortocaval region and a firm hard mass in the pancreatic head were found. Frozen section from one of the lymph nodes was suspicious for low-grade lymphoma. A pancreaticoduodenectomy was performed. Histologic analysis of the pancreatic head revealed a lymphoplasmacytic infiltrate with stromal fibrosis consistent with autoimmune pancreatitis. The retroperitoneal lymph nodes were involved by small lymphocytic lymphoma. DISCUSSION: Autoimmune pancreatitis is the most common benign diagnosis after pancreatic resection for presumed malignancy. It has a well-documented association with autoimmune conditions, such as Sjögren's syndrome, inflammatory bowel disease, and sclerosing cholangitis. Additionally, chronic lymphocytic leukemia-small lymphocytic lymphoma is often associated with autoimmune phenomena, most notably autoimmune hemolytic anemia. However, an association between autoimmune pancreatitis and small lymphocytic lymphoma has not been previously described. To our knowledge, this is the first reported case of a patient with concurrent autoimmune pancreatitis and small lymphocytic lymphoma.
Abstract: Gastric gastrointestinal stromal tumors (GIST) commonly present as an incidental finding on upper gastrointestinal endoscopy. Advances in endoscopic technology have allowed some to perform attempted excision of these lesions endoscopically. The oncologic implications of such an approach remain unclear. A-74-year-old man initially presented with an incidental finding of a 1.6 x 1.8-cm c-kit-positive gastrointestinal stromal tumor with low mitotic activity in the gastric fundus. The patient underwent an attempted endoscopic resection of this mass resulting in incomplete excision and gastric perforation. There was immediate conversion to a celiotomy and the patient underwent partial gastrectomy; there was no evidence of metastatic GIST. Three years later, the patient was noted to have an asymptomatic large pelvic mass (4 x 7 cm) on CT scan and was referred for evaluation. Subsequent surgical exploration revealed a single mass adherent to the pelvic sidewall that was resected. Subsequent pathology demonstrated a c-kit-positive GIST consistent with metastatic disease. Eighteen months later, the patient remains free of disease. Complications from endoscopic resection of gastric GIST may be associated with peritoneal dissemination of disease. This should be considered when formulating a strategy for management of gastric GIST. Complete transperitoneal excision (either open or laparoscopic) with clear margins and without tumor rupture remains the gold standard for management of gastric GIST.
Abstract: BACKGROUND: To assess in-hospital complication rates and survival duration after en bloc vascular resection (VR) for infiltration of pancreatic malignancies in major vessels. METHODS: Between 1994 and 2005, 585 patients underwent potentially curative pancreatic resection without adjuvant chemotherapy. Four hundred forty-nine patients (77%) underwent standard oncologic resection (VR-), whereas 136 (23%) received VR (VR+). For calculation of in-hospital morbidity and mortality rates, all 136 patients who underwent VR were considered. In contrast, for survival analysis, only pancreatic adenocarcinoma patients (n = 100) were included. RESULTS: One hundred twenty-eight VR+ patients underwent portal or superior mesenteric vein resection and 13 hepatic artery (HA) or superior mesenteric artery (SMA) resection. In 5 patients, synchronous VR addressing both the mesenterico-portal axis and either the HA or SMA was performed. In-hospital morbidity and mortality rates of VR- patients (39.7%/4.0%) nearly equaled that of VR+ patients (40.3%/3.7%). From the 100 patients with pancreatic adenocarcinoma, histopathology confirmed "true" vascular invasion in 77 patients. Twenty-three patients had peritumoral inflammation, mimicking tumor invasion. Median survival was 15 months (11.2-18.8) in patients with histopathologic proven vascular invasion and 16 months (14.0-17.9) in those without (P = 0.86). Two-year survival probabilities were 36% (without) versus 34% (with vascular invasion; P = 0.9). Among VR+ patients with histopathologically evidenced vascular invasion, 19 survived longer than 30 months, and 6 were still alive 5 years after surgery. Multivariate modeling identified nodal involvement (N1) and poor grading (G3) as the only predictors of decreased survival. Evidence of vascular invasion had no adverse impact on survival. CONCLUSION: Postoperative morbidity and mortality rates after en bloc VR are comparable with "standard" pancreatectomy procedures. Median survival of 15 months in patients with vascular invasion is superior to that of patients who undergo palliative therapy and nearly equals that of patients who are not in need for VR.
Abstract: BACKGROUND: Medullary thyroid carcinoma (MTC) is a well-differentiated thyroid tumor that maintains the typical features of C cells. An advanced stage and the presence of lymph node metastases at diagnosis have been demonstrated to be the most important bad prognostic factors. Somatic RET mutations have been found in 40-50% of MTCs. Although a relationship between somatic mutations and bad prognosis has been described, data are controversial and have been performed in small series with short-term follow ups. The aim of this study was to verify the prognostic value of somatic RET mutations in a large series of MTCs with a long follow up. METHODS: We studied 100 sporadic MTC patients with a 10.2 yr mean follow-up. RET gene exons 10-11 and 13-16 were analyzed. The correlation between the presence/absence of a somatic RET mutation, clinical/pathological features, and outcome of MTC patients was evaluated. RESULTS: A somatic RET mutation was found in 43 of 100 (43%) sporadic MTCs. The most frequent mutation (34 of 43, 79%) was M918T. RET mutation occurrence was more frequent in larger tumors (P=0.03), and in MTC with node and distant metastases (P<0.0001 and P=0.02, respectively), thus, a significant correlation was found with a more advanced stage at diagnosis (P=0.004). A worse outcome was also significantly correlated with the presence of a somatic RET mutation (P=0.002). Among all prognostic factors found to be correlated with a worse outcome, at multivariate analysis only the advanced stage at diagnosis and the presence of a RET mutation showed an independent correlation (P<0.0001 and P=0.01, respectively). Finally, the survival curves of MTC patients showed a significantly lower percentage of surviving patients in the group with RET mutations (P=0.006). CONCLUSIONS: We demonstrated that the presence of a somatic RET mutation correlates with a worse outcome of MTC patients, not only for the highest probability to have persistence of the disease, but also for a lower survival rate in a long-term follow up. More interestingly, the presence of a somatic RET mutation correlates with the presence of lymph node metastases at diagnosis, which is a known bad prognostic factor for the definitive cure of MTC patients.
Abstract: BACKGROUND: Resection of the caudate lobe (involving segments I [dorsal sector] and/or IX [right paracaval region]) often presents a technical challenge. It is difficult to perform because of its deep location and adjacency to the major hepatic vessels (ie, the left and middle hepatic veins). METHODS: A literature review was performed based on a Medline search to identify articles on caudate lobectomy published from 1990 to 2005. This article describes the right and left-sided approaches to the liver for caudate resection according to caudate lobe tumor location and topographic classification. RESULTS: The results of 377 lobectomies were analyzed in this review. The left-sided approach to the liver was used in 55 (14.58%), the right-sided approach in 24 (6.36%), and both approaches in 298 (79.04%) caudate lobectomies. Primary benign and malign liver tumors, as well as secondary liver tumors, were resected. CONCLUSIONS: Access to and resection of the caudate lobe should be determined on the basis of tumor location and hepatic function. The left or right approach to the caudate lobe can be recommended for local resection of tumor located at Spiegel's portion or process portion. Approaches to caudate lobectomy are therefore largely dependent on size and location of the lesion, type of associated resection, and presence of scarring from previous resection.
Abstract: BACKGROUND: Patients with borderline resectable pancreatic adenocarcinoma (PA) include those with localized disease who have tumor or patient characteristics that preclude immediate surgery. There is no optimal treatment schema for this distinct stage of disease, so the role of surgery is undefined. STUDY DESIGN: We defined patients with borderline resectable PA as fitting into one of three distinct groups. Group A comprised patients with tumor abutment of the visceral arteries or short-segment occlusion of the Superior Mesenteric Vein. In group B, patients had findings suggestive but not diagnostic of metastasis. Group C patients were of marginal performance status. Patients were treated initially with chemotherapy, chemoradiation, or both; those of sufficient performance status who completed preoperative therapy without disease progression were considered for surgery. RESULTS: Between October 1999 and August 2006, 160 (7%) of 2,454 patients with PA were classified as borderline resectable. Of these, 125 (78%) completed preoperative therapy and restaging, and 66 (41%) underwent pancreatectomy. Vascular resection was required in 18 (27%) of 66 patients, and 62 (94%) underwent a margin-negative pancreatectomy. A partial pathologic response to induction therapy (< 50% viable tumor) was seen in 37 (56%) of 66 patients. Median survival was 40 months for the 66 patients who completed all therapy and 13 months for the 94 patients who did not undergo pancreatectomy (p < 0.001). CONCLUSIONS: This is the first large report of borderline resectable PA and includes objective definitions for this stage of disease. Our neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.
Abstract: BACKGROUND: In patients with asymptomatic colorectal cancer with irresectable metastatic disease, the optimal treatment strategy remains controversial. Resection of the primary tumor followed by chemotherapy when possible versus systemic chemotherapy followed by resection of the primary tumor when necessary are compared in this systematic review. PATIENTS AND METHODS: Seven studies reported series of patients with asymptomatic stage IV colorectal cancer and compared first-line chemotherapy with surgery for the primary tumor (n = 850 patients). Primary outcome measure was the complication rate related to the primary tumor in situ in patients receiving first-line systemic chemotherapy. RESULTS: When leaving the primary tumor in situ, the mean complications were intestinal obstruction in 13.9% [95% confidence interval (CI) 9.6% to 18.8%] and hemorrhage in only 3.0% (95% CI 0.95% to 6.0%) of the patients. After resection, the overall postoperative morbidity ranged from 18.8% to 47.0%. CONCLUSIONS: For patients with stage IV colorectal cancer, resection of the asymptomatic primary tumor provides only minimal palliative benefit, can give rise to major morbidity and mortality and therefore potentially delays beneficial systemic chemotherapy. When presenting with asymptomatic disease, initial chemotherapy should be started and resection of the primary tumor should be reserved for the small portion of patients who develop major complications from the primary tumor.
Abstract: INTRODUCTION: Even after potentially curative esophagectomy, the majority of patients with adenocarcinoma of the esophagus or gastroesophageal junction die due to cancer recurrence. To predict individual disease-specific survival, a nomogram has been developed in a high-volume center in the Netherlands. The validity of this nomogram was externally tested in patients treated in another country at a different high-volume institution. METHODS: Clinicopathological data from patients who underwent a macroscopically radical resection in a high-volume center in Leuven, Belgium, were used to validate the original nomogram based on a Cox regression model. Moreover, it was examined whether adjusting the value of the original coefficients of the predictors or adding new predictors would improve the fit of the nomogram in the validation cohort. Calibration was evaluated by comparing the observed survival with the expected survival as predicted by the original nomogram across patients with different risk profiles. The discriminatory ability of the nomogram was determined in the validation cohort, using the concordance index and compared with the original estimate. RESULTS: A total of 382 patients were used in the validation study. The median esophageal cancer-specific survival was 38 months. None of the coefficients re-estimated in the validation cohort differed significantly from the values of the original nomogram. Observed and expected survival curves showed good calibration. Discrimination of the original nomogram was preserved in the validation cohort: the concordance index hardly decreased from 0.77 in the original cohort to 0.76 in the validation cohort. CONCLUSIONS: The nomogram model that was originally developed in a Dutch institute had good individual discriminatory properties and good overall calibration when applied to an independent series of patients. The nomogram was updated using the data from both cohorts to provide even more robust estimates of survival for individual patients. This tool is clinically helpful to supply more reliable prognostic information, to offer tailored follow-up schedules and/or novel therapeutic strategies in subgroups of patients with higher risk of recurrence.
Abstract: AIM: The aim of this study was to compare transrectal ultra-sound (TRUS), hydro-computed tomography (hydro-CT), and endorectal magnetic resonance imaging (MRI) in the preoperative staging of rectal cancer. PATIENTS AND METHODS: 23 patients with rectal adenocarcinoma underwent TRUS, hydro-CT, and MRI (1 Tesla) with endorectal coil. The results were correlated with the histopathological findings based on the TNM classification. RESULTS: T staging with TRUS, hydro-CT, and endorectal MRI correlated with the histopa-thological findings in 83% of patients (19/23). Tumors were overestimated by TRUS in 2/23 patients, by CT in 3/23, and by MRI in 3/23 patients. Tumor size was underestimated by TRUS in 2 patients, by CT and MRI in 1 case each. Local lymphatic node involvement was correctly diagnosed with CT and MRI in 87% and 83%, respectively. Using TRUS, false-negative results in the staging of lymph node involvement were seen in 3/23 patients, whereas 1 patient was over-staged. Using hydro-CT as well as endorectal MRI, overstaging of the local lymph nodes took place in 2/23 patients. CONCLUSION: All methods are limited because peritumoral inflammation cannot be precisely distinguished from infiltration by the tumor. Correct lymph node staging is hampered in advanced disease using TRUS. In these patients, further cross-sectional imaging may be required.
Abstract: BACKGROUND: Hepatectomy for resectable colorectal liver metastases provides a survival advantage but is usually reserved for patients without extrahepatic disease. Metastases to perihepatic lymph nodes (LN) occur with controversial significance. This study uses standard pathologic analysis and immunohistochemistry (IHC) to determine the impact of occult metastatic disease to perihepatic LN in patients with colorectal cancer undergoing hepatectomy. METHODS: Fifty-nine patients with liver metastases from colon or rectal primary cancer were studied prospectively. Perihepatic LN were sampled from the portocaval, pancreaticoduodenal, and common hepatic artery regions. All LN were analyzed using hematoxylin and eosin (H&E), and those negative by H&E were analyzed using IHC for cytokeratin. Recurrence and survival were compared amongst LN groups. RESULTS: Median follow-up was 42 months for survivors. There were eight patients with metastatic disease to at least one perihepatic LN identified by H&E and fourteen patients with metastases identified by IHC only. Forty-one patients (70%) recurred after resection, and patients with LN metastases, regardless of detection method, had a shorter recurrence-free survival compared to node negative patients. However, patterns of recurrence differed by LN group. Compared to H&E-positive patients, IHC-positive patients had a better overall survival and were more likely to recur at a single site amenable to salvage resection. CONCLUSIONS: In patients with hepatic colorectal metastases, IHC analysis of perihepatic LN adds prognostic value regarding the timing and burden of recurrence after resection. Routine IHC assessment of perihepatic LN is reasonable since the information garnered would potentially influence postresection chemotherapy recommendations.
Abstract: The aim of this study was to correlate the status of the KLF6 tumour suppressor gene including loss of heterozygosity (LOH), mutation and alternative splicing in human pancreatic cancer with tumour grade and survival. Whereas neither KLF6 loss nor mutation was identified, expression of the KLF6 alternative splice forms was significantly increased in pancreatic tumour samples and cell lines. These cancers demonstrated marked cytoplasmic KLF6 expression, consistent with over-expression and accumulation of KLF6 splice form(s), which lack a nuclear localisation signal. In addition, KLF6 splicing correlated significantly with tumour stage and survival. In summary, pancreatic cancer displays a novel pattern of KLF6 dysregulation through selectively increased expression of KLF6 splice variants. Therefore, determination of KLF6 mRNA splicing levels may represent a novel biomarker predicting prognosis.
Abstract: BACKGROUND: In children with Wilms' tumor, the 5-year overall survival rate is over 90% in the SIOP/GPOH study group. However, a small group of patients have tumor lesions in the liver at the time of initial diagnosis or as a recurrence. This group seems to have a worse prognosis in terms of survival. The treatment and outcome of patients with a hepatic recurrence were analyzed compared to previously published data of patients with primary hepatic metastases. PATIENTS AND METHODS: We reviewed the records of 45 out of 1365 patients enrolled in the SIOP 93-01/GPOH study and the SIOP 2001/GPOH study between April 1, 1994 and September 30, 2004. Median age at diagnosis was 6.49 years (1.37-34.16 years) in 29 patients who were initially presented with hepatic metastases (group I) with 9 males and 20 females. In 16 children who had a recurrence of a nephroblastoma in the liver (group II), median age at diagnosis was 4.62 years (1.84-31.08 years) with 9 males and 7 females. RESULTS: In group I out of 29 patients, 11 died at a median of 13.07 months. Overall survival in group I was 62.58%. In group II, 9 patients died at a median 52 months. Overall survival in group II was 54.7%. CONCLUSION: This report suggests that when complicated by metastases of the liver, Wilms' tumor has a less favorable outcome. Chemotherapy and radiotherapy play a definitive role in the treatment of these children. The importance of complete resection of hepatic lesions in both groups should be emphasized.
Abstract: OBJECTIVE: To compare long-term outcome of R0 (negative margins) and R1 (positive margins) liver resections for colorectal liver metastases (CLM) treated by an aggressive approach combining chemotherapy and repeat surgery. SUMMARY BACKGROUND DATA: Complete macroscopic resection with negative margins is the gold standard recommendation in the surgical treatment of CLM. However, due to vascular proximity or multinodularity, complete macroscopic resection can sometimes only be performed through R1 resection. Increasingly efficient chemotherapy may have changed long-term outcome after R1 resection. METHODS: All resected CLM patients (R0 or R1) at our institution between 1990 and 2006 were prospectively evaluated. Exclusion criteria were: macroscopic incomplete (R2) resection, use of local treatment modalities, and presence of extrahepatic disease. We aimed to resect all identified metastases with negative margins. However, when safe margins could not be obtained, resection was still performed provided complete macroscopic tumor removal. Overall survival (OS) and disease-free survival were compared between groups, and prognostic factors were identified. RESULTS: Of 840 patients, 436 (52%) were eligible for the study, 234 (28%) of whom underwent R0 resection, and 202 (24%) underwent R1 resection. Number and size of CLM were higher, and distribution was more often bilateral in the R1 group. After a mean follow-up of 40 months, 5-year OS was 61% and 57% for R0 and R1 patients (P = 0.27). Five-year disease-free survival was 29% in the R0 group versus 20% in the R1 group (P = 0.12). In the R1 group, intrahepatic (but not surgical margin) recurrences were more often observed (28% vs. 17%; P = 0.004). Preoperative carcinoembryonic antigen level > or =10 ng/mL and major hepatectomy, but not R1 resection, were independent predictors of poor OS. Size > or =30 mm, bilateral distribution, and intraoperative blood transfusions independently predicted positive surgical margins. CONCLUSIONS: Despite a higher recurrence rate, the contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar to that of R0 resection.
Abstract: INTRODUCTION: In selected patients with isolated colorectal lung or liver metastases resection can provide an increase in overall survival and even cure. Here, we evaluate whether also patients with combined or sequential metastatic disease to liver and lung may still be candidates for surgical resection. METHODS: From 1997 till 2006 39 patients underwent pulmonary metastasectomy. Two subgroups were identified: resection of pulmonary metastases only (PM) and resection of hepatic and later pulmonary metastases (LPM). RESULTS: Patient characteristics were identical in both groups. Median follow-up in group PM was 35 months and 38 months in group LPM. Two-year survival in group PM was 61%, and in group LPM 81% (p=NS). Five-year survival was 30% and 20% in PM and LPM groups, respectively (p=NS). The median disease free survival was 12 months in the PM group and 13 months in the LPM group. The extent of pulmonary resection had no impact on survival. Complications occurred in seven patients in the PM group and two patients in the LPM group. Complication rate and severity were related to the extent of pulmonary resection. A small group of patients underwent repeated pulmonary resection without serious complications. CONCLUSION: Resection of pulmonary colorectal metastases may improve survival, even in patients who underwent hepatic resection for colorectal liver metastases at an earlier stage.
Abstract: BACKGROUND: Duodenal adenomatosis is a premalignant condition often not treatable by local resection or endoscopy. An option for treatment is a pylorus-preserving (pp)-Whipple resection. Since the introduction of pancreas-preserving total duodenectomy (PPTD), the question has arisen whether a pp-Whipple resection is still needed to treat duodenal adenomatosis. PATIENTS AND METHODS: In a 5-year period 23 PPTDs were performed for duodenal adenomatosis. In a matched-pairs analysis the outcome following PPTD (16 patients with a follow-up longer than 12 months) was compared with pp-Whipple. RESULTS: Hospital mortality in all 23 patients was 4.3% and total morbidity 30% after PPTD. Operation time, intensive care and hospital stay, morbidity, and mortality were comparable between the matched paired groups (16 patients). Patients with PPTD had significantly lower intraoperative blood loss. No PPTD patient required pancreatic enzyme substitution, compared with 12 patients after pp-Whipple. Quality-of-life analysis in PPTD patients revealed no difference compared to a normal control population and the pp-Whipple group. CONCLUSIONS: PPTD is a safe surgical procedure for duodenal adenomatosis that avoids pancreatic head resection, provides high quality of life, and shows advantages over the pp-Whipple procedure.
Abstract: OBJECTIVE: The progression of medullary thyroid cancer is difficult to assess with imaging modalities; we studied the interest of calcitonin and carcinoembryonic antigen (CEA) doubling times and of Ki-67 labeling and mitotic index (MI). PATIENTS AND METHODS: Fifty-five consecutive medullary thyroid carcinoma (MTC) patients with elevated calcitonin levels underwent repeated imaging studies in order to assess tumor burden and progression status. We looked for relationships between tumor burden and levels of calcitonin and CEA and between progression status according to the response evaluation criteria in solid tumors (RECIST) and calcitonin and CEA doubling times, and Ki-67 labeling and MI. RESULTS: The calcitonin and CEA levels were correlated with tumor burden. Ten patients with calcitonin levels below 816 pg/ml had no imaged tumor foci. Among the 45 patients with imaged tumor foci, 19 had stable disease and 26 had progressive disease, according to the RECIST. The calcitonin and CEA doubling times were strongly related to disease progression, with very few overlaps: 94% of patients with doubling times shorter than 25 months had progressive disease and 86% of patients with doubling times longer than 24 months had stable disease. Ki-67 labeling and MI were not significantly associated with disease progression. CONCLUSION: For MTC patients, the doubling times of both calcitonin and CEA are efficient tools for assessing tumor progression.
Abstract: BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a notoriously aggressive malignancy associated with a highly lethal clinical course despite therapeutic intervention. Our present study attempts to identify factors that could potentially improve therapeutic strategies by analyzing the clinicopathological features, treatment and outcome of ATC patients managed over the past four decades at our institution. METHODS: Fifty patients with biopsy-proven ATC during the period 1966 to 2006 were studied. All patients were managed with surgery, radiotherapy, chemotherapy and/or chemoradiation. Survival was calculated by the Kaplan-Meier method. Potential factors affecting survival were compared by the log rank test. RESULTS: Most patients (88%) presented with a neck mass; 17 patients (34%) also had cervical lymphadenopathy. Distant metastases were clinically present in 9 (18%). Median survival was 97 days, whereas the 1- and 3-year survival was 14% and 8%, respectively. On univariate analysis, patients aged </=65 years (P = .04), absence of metastatic disease at presentation (P < .01), surgical resection (P < .01), and postoperative radiotherapy (P < .01) were associated with longer survival. The adoption of cytotoxic chemotherapy was not associated with better survival (P = .4). Moreover, there was no improvement in survival rate over the last four decades despite the adoption of multimodal treatment (P = .5). CONCLUSION: ATC remains a deadly disease despite technical advances in surgical technique and adoption of multidisciplinary treatment strategies over the last four decades. However, younger patients with localized ATC might benefit from an aggressive multidisciplinary approach.
Abstract: BACKGROUND: Predicting the severity of complications after esophagectomy may supply important information for both patient and surgeon. The aim of the present study was to develop a nomogram based on preoperative risk factors to predict the severity of complications in patients who undergo esophagectomy for cancer. METHODS: A consecutive series of 663 patients who underwent esophagectomy between January 1993 and August 2005 was used to develop a prognostic model. The model was validated in a second group of patients who were operated between August 2005 and November 2006. Ordinal logistic regression analysis was performed to predict the severity of complications. Diverse simple and conventional preoperative risk factors were evaluated. A nomogram was developed to enhance clinical applicability. RESULTS: Patients were divided into three complication categories: those who suffered from no complications (n = 197); minor complications (n = 354); and major complications (n = 112). The following predictors remained in the model after multivariate analysis: higher age (p = 0.014); cerebrovascular accident/transient ischemic attack (CVA/TIA) (p = 0.009) or myocardial infarction in the medical history (p = 0.066); lower forced expiratory volume in the first second of expiration (FEV(1)) (p = 0.030); presence of electrocardiogram-changes (p = 0.008); and more extensive surgery (p < 0.001). A nomogram based on these variables was constructed. Overall agreement between the predicted probabilities and the observed frequencies was good in the development and the validation set. CONCLUSIONS: The nomogram predicts the severity of complications for individual patients and may help in informing the patient before undergoing esophagectomy for cancer and in choosing the optimal extent of surgery. When externally validated, the nomogram may play a role in risk-adjusted audit of morbidity after esophagectomy.
Abstract: BACKGROUND: Intraoperative tumour perforation, positive tumour margins, wound complications and local recurrence are frequent difficulties with conventional abdominoperineal resection (APR) for rectal cancer. An alternative technique is the extended posterior perineal approach with gluteus maximus flap reconstruction of the pelvic floor. The aim of this study was to report the technique and early experience of extended APR in a select cohort of patients. METHODS: The principles of operation are that the mesorectum is not dissected off the levator muscles, the perineal dissection is done in the prone position and the levator muscles are resected en bloc with the anus and lower rectum. The perineal defect is reconstructed with a gluteus maximus flap. Between 2001 and 2005, 28 patients with low rectal cancer were treated accordingly at the Karolinska Hospital. RESULTS: Two patients had ypT0 tumours, 20 ypT3 and six ypT4 tumours. Bowel perforation occurred in one, the circumferential resection margin (CRM) was positive in two, and four patients had local perineal wound complications. Two patients developed local recurrence after a median follow-up of 16 months. CONCLUSION: The extended posterior perineal approach with gluteus maximus flap reconstruction in APR has a low risk of bowel perforation, CRM involvement and local perineal wound complications. The rate of local recurrence may be lower than with conventional APR.
Abstract: BACKGROUND: The current study was conducted to determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). METHODS: Between December 1993 and July 2005, 323 consecutive patients with LAPC were treated at the authors' institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine chemotherapy. Two hundred forty-seven patients received CR as initial treatment, and 76 patients received a median of 2.5 months of gemcitabine-based induction chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in 10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine (39%), or capecitabine (20%). RESULTS: The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. CONCLUSIONS: The results from this analysis indicated that, by excluding patients with rapid distant progression, induction chemotherapy may select patients with LAPC for optimal benefit from consolidative CR. The authors believe that this strategy of enriching the population of patients who receive a locoregional treatment modality merits prospective randomized evaluation.
Abstract: BACKGROUND: Dramatic responses to chemotherapy are occurring more and more frequently in patients with multiple colorectal liver metastases (LMs), leading to resection. In a few patients, some LMs vanish on imaging studies, remain undetected during hepatectomy, and are left in place, which defines the "missing LMs." The aim of our study was to assess the long-term outcome of such "missing LMs." PATIENTS: Between January 1999 and June 2004, among 228 patients treated for colorectal LMs, missing LMs were observed in 16 patients. All the patients were operated within 4 weeks of imaging. Hepatic arterial infusion (HAI) with oxaliplatin was administrated in 12 patients (75%): seven before hepatectomy and five after. RESULTS: Overall, 69 missing LMs were diagnosed and left in place. Among the persistent LMs resected, a complete pathological response was significantly more often observed in the group with preoperative HAI (6 of 7), than in the group without (2 of 9, P < .02). With a mean follow-up of 51 months (24-90), missing LMs did not reappear in 10 patients (62%). Adjuvant HAI was significantly correlated with the definitive eradication of missing LMs (P < .01), as it was not a complete pathological response. The overall 3-year survival rate of these highly selected 16 patients was 94%. CONCLUSION: Colorectal LMs under chemotherapy that vanish on high-quality imaging studies, remain undetected during hepatectomy, and are left in place, are definitively cured in 62% of cases. This excellent result seems to be due to the administration of adjuvant hepatic arterial infusion of chemotherapy and should stimulate new investigations.
Abstract: This article summarizes the clinical features and molecular pathogenesis of medullary thyroid cancer (MTC) and focuses on the current use of molecular, biochemical, and imaging disease markers as a basis for selection of appropriate therapy. Clinicians treating patients who have MTC face the following challenges: (1) distinguishing MTC as early as possible from benign nodular disease and differentiated thyroid cancer to choose the appropriate initial surgery, (2) managing low-level residual cancer in otherwise asymptomatic individuals, and (3) treating progressive metastatic disease. Early clinical trials using small molecules targeting Ret or vascular endothelial growth factor receptors suggest that such approaches could be effective and well tolerated. This article highlights early progress in targeted therapy of MTC and significant challenges in disease monitoring to appropriately select and evaluate patients being treated with these therapies.
Abstract: Medullary thyroid carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs in hereditary (25% of cases) and sporadic (75%) forms. Sporadic MTCs frequently metastasize to cervical lymph nodes. Thorough surgical extirpation of the primary tumor and nodal metastases by compartment-oriented resection has been the mainstay of treatment (level IV evidence). Surgical resection of residual and recurrent disease is effective in reducing calcitonin levels and controlling complications of central neck disease (level IV evidence). Radioactive iodine, external beam radiation therapy, and conventional chemotherapy have not been effective. Newer systemic treatments, with agents that target abnormal RET proteins hold promise and are being tested in clinical trials for patients with metastatic disease.
Abstract: OBJECTIVE: Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy. External drainage of pancreatic duct with a stent has been shown to reduce pancreatic fistula rate of pancreaticojejunostomy in a few retrospective or prospective nonrandomized studies, but no randomized controlled trial has been reported thus far. This single-center prospective randomized trial compared the results of pancreaticoduodenectomy with external drainage stent versus no stent for pancreaticojejunal anastomosis. METHODS: A total of 120 patients undergoing pancreaticoduodenectomy with end-to-side pancreaticojejunal anastomosis were randomized to have either an external stent inserted across the anastomosis to drain the pancreatic duct (n = 60) or no stent (n = 60). Duct-to-mucosa anastomosis was performed in all cases. RESULTS: The 2 groups were comparable in demographic data, underlying pathologies, pancreatic consistency, and duct diameter. Stented group had a significantly lower pancreatic fistula rate compared with nonstented group (6.7% vs. 20%, P = 0.032). Radiologic or surgical intervention for pancreatic fistula was required in 1 patient in the stented group and 4 patients in the nonstented group. There were no significant differences in overall morbidity (31.7% vs. 38.3%, P = 0.444) and hospital mortality (1.7% vs. 5%, P = 0.309). Two patients in the nonstented group and none in the stented group died of pancreatic fistula. Hospital stay was significantly shorter in the stented group (mean 17 vs. 23 days, P = 0.039). On multivariate analysis, no stenting and pancreatic duct diameter <3 mm were significant risk factors of pancreatic fistula. CONCLUSION: External drainage of pancreatic duct with a stent reduced leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy.
Abstract: Dramatic responses are being observed in colorectal cancer liver metastases treated with newer chemotherapeutic regimens. These have been associated with normalization of [(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake (complete metabolic response) on follow-up Positron Emission Tomography with [(18)F]fluoro-2-deoxy-D-glucose (FDG-PET) scans in some patients. It is unclear how often complete metabolic response is indicative of complete tumor destruction. We analyzed a subset of patients who had neoadjuvant chemotherapy for hepatic metastases from colorectal adenocarcinoma. Inclusion criteria were: (1) FDG-avid hepatic lesions before initiation of chemotherapy; (2) complete metabolic response of the same lesions after chemotherapy; and (3) histopathologic examination of hepatic lesions. Complete pathologic response was defined as no histologically identifiable viable tumor. Fourteen patients fit the inclusion criteria. All had synchronous, hepatic-only colorectal metastases. On microscopic examination, complete pathologic response to the neoadjuvant regimen was found in only 5 of 34 lesions (15%) and in only 3 of the 14 patients (21%). Seven lesions had complete metabolic response and disappeared on computed tomography (CT); of these, six still contained viable tumor. We conclude that complete metabolic response on FDG-PET after neoadjuvant chemotherapy is an unreliable indicator of complete pathologic response. Therefore, currently, curative resection of liver metastases in these patients should not be deferred on the basis of FDG-PET findings.
Abstract: A pancreatic fistula is an uncommon and challenging problem for the general surgeon. Protean in presentation, the underlying pathophysiology of a pancreatic duct disruption is consistent. Several basic principles, when followed, simplify management. These tenets include medical stabilization and nutritional optimization, definition of the underlying duct disorder, and, finally, definitive management with or without surgery. With appropriate prompt care, patients can achieve good outcomes.
Abstract: BACKGROUND: The decrease of calcitonin levels after curative operation in patients with medullary thyroid cancer is characterized by individual variation; therefore, intraoperative calcitonin measurements to evaluate the completeness of the resection seem to not be feasible. The aim of this study was to evaluate whether an intraoperative pentagastrin test after thyroidectomy and central neck dissection is useful to predict lymph node involvement of the lateral neck. METHODS: A group of 30 consecutive patients underwent primary surgery. After thyroidectomy and dissection of the central lymph node compartment, an intraoperative pentagastrin test was performed. Biochemical and histologic data were compared retrospectively. RESULTS: Of the group, 20 patients (67%) showed no, or only central neck lymph node, involvement and no increase in calcitonin after intraoperative stimulation. Lymph node involvement was documented histologically in the lateral neck of 10 patients (33%), and 8 patients showed an increase of calcitonin as an indication of lymph node involvement. In two patients, each with 1 single micrometastasis in the lateral neck, the intraoperative pentagastrin test was negative. CONCLUSIONS: Intraoperative calcitonin monitoring after pentagastrin stimulation seems promising in predicting lymph node involvement of the lateral neck to aid selection of patients for lateral lymph node dissection. The development of a highly sensitive, quick calcitonin assay is imperative.
Abstract: BACKGROUND: Success of chemotherapy and alleviation of pain are frequently less than optimal in pancreatic cancer patients, leading to increasing interest in new pharmacological substances, such as vanilloids. Our study addressed the question of whether vanilloids influence pancreatic cancer cell growth, and if vanilloids could be used for pain treatment via the vanilloid 1 receptor (VR1) in pancreatic cancer patients. METHODS: In vitro, the effect of resiniferatoxin (vanilloid analogue) on apoptosis and cell growth in pancreatic cancer cells--either alone, combined with 5-fluorouracil (5-FU), or combined with gemcitabine--was determined by annexin V staining, FACS analysis, and MTT assay, respectively. VR1 expression was evaluated on RNA and protein level by quantitative polymerase chain reaction and immunohistochemistry in human pancreatic cancer and chronic pancreatitis. Patient characteristics--especially pain levels--were registered in a prospective database and correlated with VR1 expression. RESULTS: Resiniferatoxin induced apoptosis by targeting mitochondrial respiration and decreased cell growth in pancreatic cancer cells without showing synergistic effects with 5-FU or gemcitabine. Expression of VR1 was significantly upregulated in human pancreatic cancer and chronic pancreatitis. VR1 expression was related to the intensity of pain reported by cancer patients but not to the intensity of pain reported by patients with chronic pancreatitis. CONCLUSIONS: Resiniferatoxin induced apoptosis in pancreatic cancer cells indicates that vanilloids may be useful in the treatment of human pancreatic cancer. Furthermore, vanilloid might be a novel and effective treatment option for neurogenic pain in patients with pancreatic cancer.
Abstract: BACKGROUND: Postoperative local water-filtered infrared A (wIRA) irradiation improves tissue oxygen partial pressure, tissue perfusion and tissue temperature, which are important in wound healing. METHODS: The effect of wIRA irradiation on abdominal wound healing following elective gastrointestinal surgery was evaluated. Some 111 patients undergoing moderate to major abdominal surgery were randomized into one of two groups: wIRA and visible light irradiation (wIRA group) or visible light irradiation alone (control group). Uncovered wounds were irradiated twice a day for 20 min from days 2-10 after operation. RESULTS: Irradiation with wIRA improved postoperative wound healing in comparison to visible light irradiation alone. Main variables of interest were: wound healing assessed on a visual analogue scale (VAS) by the surgeon (median 88.6 versus 78.5 respectively; P < 0.001) or patient (median 85.8 versus 81.0; P = 0.040), postoperative pain (median decrease in VAS score during irradiation 13.4 versus 0; P < 0.001), subcutaneous oxygen tension after irradiation (median 41.6 versus 30.2 mmHg; P < 0.001) and subcutaneous temperature after irradiation (median 38.9 versus 36.4 degrees C; P < 0.001). The overall result, in terms of wound healing, pain and cosmesis, measured on a VAS by the surgeon (median 79.0 versus 46.8; P < 0.001) or patient (79.0 versus 50.2; P < 0.001) was better after wIRA irradiation. CONCLUSION: Postoperative irradiation with wIRA can improve normal postoperative wound healing and may reduce costs in gastrointestinal surgery.
Abstract: Medullary thyroid carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs in hereditary (25% of cases) and sporadic forms, and aggressiveness is related to the clinical presentation (hereditary vs. sporadic) and the type of RET mutation present. In hereditary cases, early diagnosis makes preventative surgery possible. In established cases, thorough surgical extirpation of the primary tumor and nodal metastases has been the mainstay of treatment. Radioactive iodine, external beam radiation therapy (EBRT), and conventional chemotherapy have not been effective. Newer systemic treatments, with agents that target abnormal RET proteins, hold promise and are being tested in clinical trials for patients with metastatic disease.
Abstract: BACKGROUND: Neoadjuvant chemoradiotherapy (neo-CRT) is being used with increasing frequency for periampullary tumors, but how it alters the complication rate of pancreaticoduodenectomy (PD) is unclear. METHODS: A retrospective analysis was conducted of 79 patients with periampullary malignancies who received 5-fluorouracil-based neo-CRT followed by PD. RESULTS: There was no difference in mortality between PD after neo-CRT (3.8%) and conventional PD for either malignant (4.5%) or benign (2.2%) disease. Focusing only on patients with malignancy, the neo-CRT group had a significantly lower pancreatic leak rate than the conventional group (10% vs. 43%; P < .001). Intra-abdominal abscesses were less common in the neo-CRT group (8.8% vs. 21%; P = .019), and there was one (1.2%) amylase-rich abscess in neo-CRT group, compared with eight (12%) in the conventional group. In addition, two patients in the conventional group died of leak-associated sepsis, compared with none in the neo-CRT group. Multivariate analysis revealed that neoadjuvant chemoradiation (odds ratio, .15) was the most significant factor associated with a reduced risk of pancreatic leak. CONCLUSIONS: Neo-CRT does not increase the mortality or morbidity of PD. In contrast, neo-CRT was associated with a marked reduction in the incidence of pancreatic leak, as well as leak-associated morbidity and mortality.
Abstract: Accepted management for colorectal cancer (CRC) involves resection of the primary neoplasm and chemotherapy; the debate continues over the most beneficial order of these components. Preoperative chemotherapy aimed at liver metastases may result in complete pathologic response and replacement of the malignancy with scar. The McGill University liver diseases database was retrospectively reviewed. Forty-one patients receiving treatment between December 2003 and August 2004 were identified, their medical records examined, and liver histology reviewed. The histology of the remnants was linked to the appearance of the lesions on preresection imaging and to the primary colorectal neoplasms. Twenty-seven of the 41 patients (66%) received preoperative chemotherapy (oxaliplatin or irinotecan). Features of the primary neoplasm that predicted resolution of the metastases were absence of tumor budding (P = 0.04), absence of a diffusely infiltrative tumor margin (P = 0.02), and loss of expression of the DNA repair gene O6-methylguanine-DNA methyltransferase (P = 0.08). Oxaliplatin and irinotecan demonstrate beneficial effects in treating hepatic colorectal metastases and should be considered in such patients before resection. We propose the acronym RUMP to denote the remnants of uncertain malignant potential remaining. Further investigation is required to determine any correlation between the drug received and the resulting lesion.
Abstract: With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of "borderline resectability." In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180 degrees of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.
Abstract: The majority of lethal complications after pancreatic head resection are due to septic complications after leakage from the pancreatojejunostomy. Especially the smooth pancreatic remnant is prone to develop parenchymal leaks from shear forces applied during tying of the sutures. We developed a new mattress technique that avoids such shear forces, and we compared this method to the standard Cattell (duct-to-mucosa) technique. A total of 113 patients undergoing standard pancreatic head resection were prospectively randomized to receive either the standard Cattell anastomosis (n = 56) or the new mattress technique (n = 57). All patients were evaluated for surgical and medical complications until discharge. Primary diagnosis and further demographic data compared well between the groups. The time to perform the mattress anastomosis was significantly shorter (15 vs. 22 minutes; p < 0.0001). The incidence of complications at the pancreatojejunostomy, and the length of hospital stay and survival were not significantly different between the two groups; however, a trend toward more reoperations was noted in the Cattell group (10 vs. 5; p < 0.097). The new mattress technique is simple, and our data show that the two techniques yield similar incidences of complications. Therefore the mattress technique for pancreatojejunostomy seems to be safe and is, in our opinion, well suitable for training schedules in pancreatic surgery.
Abstract: BACKGROUND: Postoperative chyle leakage is a rare but well-recognized complication after esophageal surgery. The aim of this study was to identify its incidence and potentially predisposing factors and to assess the consequences and management. METHODS: A consecutive series of 536 patients who underwent esophagectomy for malignant disease of the esophagus or gastroesophageal junction was reviewed. RESULTS: There were 20 patients (3.7%) with chyle leakage. After transthoracic esophagectomy the risk for the development of chyle leakage was higher than after transhiatal resection (p = 0.006). Chyle leakage was associated with more positive nodes (p = 0.041). Patients with chyle leakage had significantly more pulmonary complications (p < 0.001) and longer intensive care unit (p = 0.015) and hospital stays (p = 0.001). No patient with chyle leakage died. Conservative management, consisting of no enteral feeding and total parenteral nutrition, was instituted in all patients, but was abandoned in 4 patients (20%) because of persistence of high chyle output through the chest tube. In contrast to patients who were successfully treated with conservative measures, patients who eventually needed a reoperation had a drain output of more than 2 L on the day conservative therapy was started and 1 and 2 days later. CONCLUSIONS: Chyle leakage is seen more often in patients who undergo transthoracic esophagectomy and in patients who have more positive nodes. Patients with chyle leakage have more pulmonary complications. Conservative therapy is often successful, but operative therapy should be seriously considered in patients with a persistently high daily output of more than 2 L after 2 days of optimal conservative therapy.
Abstract: HYPOTHESIS: Antecolic duodenojejunostomy prevents delayed gastric emptying (DGE) after a pylorus-preserving Whipple (ppW) procedure better than retrocolic duodenojejunostomy. DESIGN: A single operation team's experience with antecolic and retrocolic duodenojejunostomy in ppW is analyzed on a prospective database using univariate and multivariate models. SETTING: Tertiary referral center that focuses on pancreatic diseases. PATIENTS AND INTERVENTIONS: One hundred consecutive patients undergoing a ppW procedure with retrocolic reconstruction between January 1, 1996, and December 31, 2001, and 100 consecutive patients undergoing a ppW procedure with antecolic reconstruction between January 1, 2002, and December 31, 2003. Characteristics such as median age, median hospital stay, sex, diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists risk groups, stent implantation, and especially DGE were matched for the comparison groups. MAIN OUTCOME MEASURES: We compared DGE, characteristics, and perioperative variables in patients with antecolic vs retrocolic reconstruction after ppW. RESULTS: The DGE occurred significantly more often in patients with retrocolic reconstruction than in those with antecolic reconstruction (P < .001). The antecolic and retrocolic study groups were comparable in age (P = .25), sex (P = .48), and postoperative surgical (P = .19) and medical (P = .054) complications. The univariate analysis between patients with and without DGE did not show significant differences regarding diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists classification, or stent implantation. In the multivariate analysis, only the type of reconstruction (P = .006) and sex (P = .04) seemed to affect DGE. CONCLUSION: We recommend antecolic duodenjejunostomy in patients undergoing a ppW procedure regardless of their diagnosis.
Abstract: Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.
Abstract: OBJECTIVES: The pancreas is a rare target for metastasis from other primary cancers, but pancreatic metastasis play a role in the diagnostic workup of patients with pancreatic tumors, especially in patients with a history of renal cell carcinoma (RCC). METHODS: Between October 2001 and June 2004 data from 601 patients undergoing pancreatic resection were entered prospectively in a database and were analyzed for metastasis into the pancreas from RCC. RESULTS: Fifteen patients with metastasis to the pancreas from RCC were identified. One patient showed metastatic disease at time of primary diagnosis. In 8 patients, the pancreas was the only site of metastasis, whereas in 7 patients, other organs, such as the thyroid gland, the lung, or the liver, were targets of metastasis, either metachronous or simultaneous at the time of pancreatic metastasis. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 86 months (range, 0-258). Most patients were asymptomatic and diagnosed during standard tumor follow-up. So far, 14 patients remain alive with a median follow-up of 10 months. CONCLUSION: Pancreatic metastasis from RCC is rare but can occur even more than 20 years after primary tumor manifestation. Our results show that pancreatic resections for metastasis can be performed safely with a low rate of complications. Patients with a history of RCC should undergo a long-term follow-up to detect and evaluate for pancreatic metastases as well for metastasis to other organ sites.
Abstract: SUMMARY BACKGROUND DATA: We compare the results of liver resection performed under in situ hypothermic perfusion versus standard total vascular exclusion (TVE) of the liver <60 minutes and > or =60 minutes in terms of liver tolerance, liver and renal functions, postoperative morbidity, and mortality. The safe duration of TVE is still debated. Promising results have been reported following TVE associated with hypothermic perfusion of the liver with durations of up to several hours. The 2 techniques have not been compared so far. METHODS: The study population includes 69 consecutive liver resections under TVE <60 minutes (group TVE<60', 33 patients), > or =60 minutes (group TVE> or =60', 16 patients), and in situ hypothermic perfusion (group TVEHYOPOTH, 20 patients). Liver tolerance (peaks of transaminases), liver and kidney function (peak of bilirubin, minimum prothrombin time, and peak of creatinine), morbidity, and in-hospital mortality were compared within the 3 groups. RESULTS: The postoperative peaks of aspartate aminotransferase (IU/L) and alanine aminotransferase (IU/L) were significantly lower (P[r] < 0.05) in group TVE HYPOTH (450 +/- 298 IU/L and 390 +/- 391 IU/L) compared with the groups TVE<60' (1000 +/- 808; 853 +/- 743) and TVE> or =60' (1519 +/- 962; 1033 +/- 861). In the group TVEHYPOTH, the peaks of bilirubin (micromol/L) (84 +/- 31), creatinine (micromol/L) (75 +/- 22), and the number of complications per patient (1.2 +/- 0.9) were comparable to those of the group TVE<60' (80 +/- 111; 109 +/- 77; and 0.8 +/- 1.1 respectively) and significantly lower to those of the group TVE> or =60' (196 +/- 173; 176 +/- 176, and 2.6 +/- 1.8). In-hospital mortality rates were 1 in 33, 2 in 16, and 0 in 20 for the groups TVE<60', TVE> or =60', and TVEHYOPOTH, respectively, and were comparable. On multivariate analysis, the size of the tumor, portal vein embolization, and a planned vascular reconstruction were significantly predictive of TVE > or =60 minutes. CONCLUSIONS: Compared with standard TVE of any duration, hypothermic perfusion of the liver is associated with a better tolerance to ischemia. In addition, compared with TVE > or =60 minutes, it is associated with better postoperative liver and renal functions and a lower morbidity. Predictive factors for TVE > or =60 minutes may help to indicate hypothermic perfusion of the liver.
Abstract: Pancreatic ductal adenocarcinoma is among the top 10 causes of death from cancer in industrialized countries. In comparison with other gastrointestinal malignancies, pancreatic cancer is one of the tumors most resistant to chemotherapy. An important mechanism of tumor multidrug resistance is increased drug efflux mediated by several transporters of the ABC superfamily. Especially BCRP (ABCG2), MDR1 P-glycoprotein (ABCB1) and members of the MRP (ABCC) family are important in mediating drug resistance. The MRP family consists of 9 members (MRP1-MRP9) with MRP1-MRP6 being best characterized with respect to protein localization and substrate selectivity. Here, we quantified the mRNA expression of BCRP and of all MRP family members in normal human pancreas and pancreatic carcinoma and analyzed the mRNA level of the transporters most abundantly expressed in pancreatic tissue, BCRP, MRP1, MRP3, MRP4 and MRP5, in 37 tissue samples. In addition, we determined the localization of the 4 MRP proteins in normal human pancreas and in pancreatic carcinoma. The expression of BCRP, MRP1 and MRP4 mRNA did not correlate with tumor stage or grading. On the other hand, the expression of MRP3 mRNA was upregulated in pancreatic carcinoma samples and was correlated with tumor grading. The MRP5 mRNA level was significantly higher in pancreatic carcinoma tissue compared to normal pancreatic tissue. These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer.
Abstract: Liver resection combined with the resection and reconstruction of the vena cava represents the only potential curative therapy for malignant hepatic tumors with invasion of the vena cava. We performed a liver resection with segmental replacement of the retrohepatic vena cava by synthetic grafts in 29 patients. In three cases, the additional presence of central involvement of all three hepatic veins required ex situ tumor resection. Four patients underwent a simultaneous exstirpation of the primary tumor (kidney or suprarenals). The remaining hepatic veins were reimplanted into the graft in three cases, and in two cases the renal veins were reimplanted. There was no perioperative mortality. A distal arteriovenous fistula was not applied. Five patients revealed postoperative transient liver insufficiency, requiring temporary dialysis in three cases. Two of these patients developed a transient multiorgan failure with the need of mechanical ventilation. 18 patients died during the course of follow-up, 17 of these cases due to recurrent metastases of the primary disease. Infection or thrombosis of the prosthetic vascular graft have not been observed. Beside tumor exstirpation, extended liver resection and concomitant vena cava replacement may prevent embolism as well as the obstruction of the vena cava with lower extremity swelling and the possibility of developing a Budd Chiari syndrome. We were able to achieve a long-term survival for surgically treated patients even in cases with advanced tumor stages.
Abstract: BACKGROUND: Although laparoscopic resection of colorectal carcinoma improves post-operative recovery, long-term survival and disease control are the determining factors for its application. We aimed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer. METHODS: From Sept 21, 1993, to Oct 21, 2002, 403 patients with rectosigmoid carcinoma were randomised to receive either laparoscopic assisted (n=203) or conventional open (n=200) resection of the tumour. Survival and disease-free interval were the main endpoints. Patients were last followed-up in March, 2003. Perioperative data were recorded and direct cost of operation estimated. Data were analysed by intention to treat. FINDINGS: The demographic data of the two groups were similar. After curative resection, the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1% (SE 3.7%) and 72.9% (4.0%) respectively. The probabilities of being disease free at 5 years were 75.3% (3.7%) and 78.3% (3.7%), respectively. The operative time of the laparoscopic group was significantly longer, whereas postoperative recovery was significantly better than for the open resection group, but these benefits were at the expense of higher direct cost. The distal margin, the number of lymph nodes found in the resected specimen, overall morbidity and operative mortality did not differ between groups. INTERPRETATION: Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients. The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes.
Abstract: Various reconstructive conduits and routes of reconstruction have an impact on operative morbidity and foregut function in patients undergoing oesophagectomy. Advantages of a fundus rotation gastroplasty are the better blood supply and the greater length of the gastric tube and its possible impact on anastomotic complications. For a subgroup of patients with oesophageal carcinoma limited to the lamina propria vagal-sparing oesophagectomy seems to be a good alternative in terms of quality of life to preserve gastric secretory, motor, and reservoir function. Posterior mediastinal reconstruction is usually preferred when complete resection (R0) has been accomplished. Anterior mediastinal reconstruction may secondary prevent dysphagia after incomplete resections due to tumour recurrence (R0, R1). However, for all presently available surgical approaches in the treatment of oesophageal cancer qualified studies (prospective randomised) are needed. In addition, randomized trials are needed to identify the specific subgroups of patients who benefit from neoadjuvant or adjuvant radiochemotherapy.
Abstract: Thus far, there are no studies concerning the radicality of pancreaticoduodenectomy which, in well-performed, randomized-controlled trials employing high standards of evidence-based medicine, show a benefit over extended lymphadenectomy. The results of the only two prospective randomized studies are not comparable and both are underpowered (level of evidence Ib). Therefore, it is still unclear whether extended lymphadenectomy for pancreatic carcinoma improves outcome. Only one study suggests a positive tendency toward increased survival rates in node-positive patients. Extended approaches including additional venous resection can be performed without a rise in the morbidity and mortality rates of patients with pancreatic carcinoma. In the future appropriately powered randomized trials of standard vs. extended resections may show the benefit of extended surgical resections. In addition, well powered trials of postoperative adjuvant therapies or preoperative neoadjuvant strategies together with surgical resections may identify more effective combinations showing a survival benefit in patients with pancreatic carcinoma.
Abstract: BACKGROUND: A dramatic response to chemotherapy in some patients with multiple bilateral and initially unresectable liver metastases (LM) from colorectal cancer sometimes leads to their disappearance from imaging studies. Our study was aimed at assessing the evolution of these metastases when they were also not found during liver surgery. PATIENTS: Among 104 hepatectomized patients for colorectal LM in 4 years, 15 patients were retrospectively eligible. Eligibility criteria were: initially unresectable LM; a dramatic response to chemotherapy; and the complete disappearance of at least one LM on imaging studies (ultrasonography (US), computed tomography, and magnetic resonance) during more than 3 months. In four patients (27%), the disappeared LM could be found and treated at laparotomy. The main selection criterion for the 11 studied patients of this series was the impossibility of finding and treating the disappeared LM sited in the remaining liver after hepatectomy, resulting in "missing LM." RESULTS: After a median follow-up of 31 months (range: 18-55) for the series, eight patients among the eleven (73%) did not present any recurrence of the missing LM. The median follow-up was 31.3 months for these eight patients. The three recurrences occurred respectively at 5, 5, and 8 months after surgery. CONCLUSIONS: The disappearance of LM after chemotherapy on high-quality imaging studies and after intra-operative liver exploration resulted in their definitive cure in approximately 70% of cases. The current dogma stipulating an obligatory resection of the initially affected part of the liver is no longer acceptable.
Abstract: Multiple endocrine neoplasia type 2 (MEN2) is a syndrome characterized by medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma and hyperparathyroidism. Familial MTC (FMTC) is a subvariant of MEN2 in which affected individuals develop MTC without other manifestations of MEN2. The identification of RET proto-oncogene mutations in MEN2 and FMTC have provided a precise method for identifying gene carriers. This review provides a concise discussion of the use of genetic testing in the management of hereditary MTC, discussing the appropriate use of this new technology with an emphasis on early intervention to prevent death or serious morbidity from this disease.
Abstract: OBJECTIVE: To evaluate the influence of the response to preoperative chemotherapy, especially tumor progression, on the outcome following resection of multiple colorectal liver metastases (CRM). SUMMARY BACKGROUND DATA: Hepatic resection is the only treatment that currently offers a chance of long-term survival, although it is associated with a poor outcome in patients with multinodular CRM. Because of its better efficacy, chemotherapy is increasingly proposed as neoadjuvant treatment in such patients to allow or to facilitate the radicality of resection. However, little is known of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of hepatic resection. METHODS: We retrospectively analyzed the course of 131 consecutive patients who underwent liver resection for multiple (> or =4) CRM after systemic chemotherapy between 1993 and 2000, representing 30% of all liver resections performed for CRM in our institution during that period. Chemotherapy included mainly 5-fluorouracil, leucovorin, and either oxaliplatin or irinotecan for a mean of 9.8 courses (median, 9 courses). Patients were divided into 3 groups according to the type of response obtained to preoperative chemotherapy. All liver resections were performed with curative intent. We analyzed patient outcome in relation to response to preoperative chemotherapy. RESULTS: There were 58 patients (44%) who underwent hepatectomy after an objective tumor response (group 1), 39 (30%) after tumor stabilization (group 2), and 34 (26%) after tumor progression (group 3). At the time of diagnosis, mean tumor size and number of metastases were similar in the 3 groups. No differences were observed regarding patient demographics, characteristics of the primary tumor, type of liver resection, and postoperative course. First line treatments were different between groups with a higher proportion of oxaliplatin- and/or irinotecan-based treatments in group 1 (P < 0.01). A higher number of lines of chemotherapy were used in group 2 (P = 0.002). Overall survival was 86%, 41%, and 28% at 1, 3, and 5 years, respectively. Five-year survival was much lower in group 3 compared with groups 1 and 2 (8% vs. 37% and 30%, respectively at 5 years, P < 0.0001). Disease-free survival was 3% compared with 21% and 20%, respectively (P = 0.02). In a multivariate analysis, tumor progression on chemotherapy (P < 0.0001), elevated preoperative serum CA 19-9 (P < 0.0001), number of resected metastases (P < 0.001), and the number of lines of chemotherapy (P < 0.04), but not the type of first line treatment, were independently associated with decreased survival. CONCLUSIONS: Liver resection is able to offer long-term survival to patients with multiple colorectal metastases provided that the metastatic disease is controlled by chemotherapy prior to surgery. Tumor progression before surgery is associated with a poor outcome, even after potentially curative hepatectomy. Tumor control before surgery is crucial to offer a chance of prolonged remission in patients with multiple metastases.
Abstract: Transferrin receptor (TFRC) is a membrane-bound protein expressed in larger amounts in proliferating, e.g., malignant, cells than in quiescent cells. The specific expression of TFRC can represent a diagnostic tool or a therapeutic target in solid tumours expressing this antigen. Whether TFRC is expressed in human pancreatic tumours is unknown. The aim of this study was the investigation of the expression of TFRC and transferrin in human pancreatic cancer and in neuroendocrine tumours of the pancreas. Fifty one specimens of human pancreatic cancer and 14 samples of pancreatic neuroendocrine tumours were obtained after surgery. The expression of TFRC, transferrin and cytokeratin was studied by standard immunohistochemistry. Flow cytometry was used for the investigation of TFRC expression in nine cell lines of ductal pancreatic cancer in vitro. In contrast to normal tissue, 93% of pancreatic tumour cells showed positive (82%) or heterogeneous (11%) expression of TFRC. It was strongly expressed by malignant epithelial cells; normal stromal and endothelial cells were not stained by anti-TFRC antibodies. Primary tumours and metastases showed a similar frequency of TFRC expression. Three neuroendocrine carcinomas showed positive expression of TFRC by malignant tumour cells. The expression of TFRC was negative in benign neuroendocrine tumours of the pancreas. The cell lines of pancreatic cancer were characterised by a low expression of TFRC in vitro. In contrast to normal pancreatic tissue and benign neuroendocrine tumours of the pancreas, pancreatic cancer and neuroendocrine carcinoma are therefore characterised frequently by high expression of TFRC. Hence, TFRC represents a marker of malignant transformation in the pancreas that could be applied as potential diagnostic and therapeutic target.
Abstract: Surgical manipulation of the gut elicits an inflammatory cascade within the intestinal muscularis that contributes to postoperative bowel dysmotility. A range of cytokines is sequentially released into the peritoneal fluid following abdominal surgery, their concentrations reflecting the magnitude of surgical trauma. The overproduction of inflammatory mediators might have detrimental effects on organ function and contribute to the enhanced risk of anastomotic leakage in the presence of sepsis. Specific cellular immune functions such as the microbicidal activity of peritoneal phagocytes are depressed after elective surgery, imposing a risk of infectious complications. Laparoscopic surgery decreases the local and systemic production of cytokines and acute-phase reactants, and better preserves peritoneal immunity compared with open surgery. As concluded from animal studies, the gas used for the pneumoperitoneum may possess substantial immunomodulatory activity.
Abstract: BackgroundThe laparoscopic approach for liver resections is still limited and controversial. Nevertheless the advantages connected with a mini-invasive approach are significant, especially in cirrhotic patients. In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made endoscopic hepatic surgery feasible and safe. The aim of this study was to report the results of our experience in laparoscopic liver surgery for hepatocellular carcinoma (HCC) in cirrhotic patients.MethodsFrom 2000 to 2003, 16 patients (10 male, 6 female; age 48-69 years; mean age 60.1 years) with HCC and associated severe but well compensated liver cirrhosis underwent laparoscopic hepatic resections at our department. Mean tumour size was 2.9 cm (range 1-3.9). Seven of these lesions were in the left liver and nine in the right lobe. Laparoscopy was performed under CO(2) pneumoperitoneum. The liver was always examined using laparoscopic ultrasound (US) to confirm the extension of the lesions and their relationships to the vasculature. The Pringle manoeuvre was not used. The transection of liver parenchyma was obtained by the use of a harmonic scalpel. The specimens were placed in a plastic bag and removed without contact to the abdominal wall.ResultsThere was one conversion to laparotomy for inadequate exposure. In the remaining 15 patients we performed 13 non-anatomical resections, I segmentectomy and I anatomical left lobectomy. The mean operative time was 152 min (range 80-180). Mean blood loss was 280 ml and none of the patients required blood transfusions. In two patients the resection margin was <1 cm but the capsule was not infiltrated at histology. One patient died on the third postoperative day from a severe respiratory distress syndrome. Major morbidities occurred in two patients who developed moderate postoperative ascites, which resolved successfully with conservative treatment. The mean postoperative hospital stay was 8.8 days. Mean follow-up time has been 18 months, and to date no recurrences at the site of resection or port-site metastases have been observed.DiscussionLimited laparoscopic liver resections in cirrhotic patients are technically feasible with a low complication rate when careful selection criteria are followed (hepatic involvement limited and located in the left or anterior right segments, tumour size smaller than 5 cm, Child-Pugh class A). This approach could be considered the best option for the treatment of small esophitic or subcapsular HCC on well compensated cirrhosis and a useful option when it is necessary to perform a left lateral anatomical resection or non-anatomical resection in well selected patients. In fact the mini-invasive approach can minimise the postoperative morbidity rate, which is still too high in this group of patients. It must be performed in highly specialised units by surgeons assisted by all requested technologies and with extensive experience in hepatobiliary and advanced laparoscopic surgery.
Abstract: Connective tissue growth factor (CTGF), which is regulated by transforming growth factor-ss (TGFss), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46-fold increase in CTGF mRNA expression ( p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFss-induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation ( p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) ( p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFss, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.
Abstract: OBJECTIVE: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. SUMMARY BACKGROUND DATA: Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. METHODS: From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. RESULTS: Seventy-five percent of procedures were major hepatectomies (> or =3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, > or =3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. CONCLUSIONS: Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.
Abstract: Activation of apoptosis in chronic pancreatitis has been demonstrated. The low-affinity neurotrophin receptor p75 (p75NTR) mediates apoptosis in many cell types in vivo and in vitro. The aim of this study was to examine whether p75NTR is involved in the apoptotic process in chronic pancreatitis. The quantity and localization of the receptor was evaluated using northern blot analysis, in situ hybridization, immunohistochemistry, and western blot analysis. Apoptosis was determined by TUNEL assay. By northern blot analysis, p75NTR mRNA levels were increased 40-fold in chronic pancreatitis compared with normal pancreas (P < 0.01). In situ hybridization revealed weak p75NTR mRNA expression in some ductal cells in the normal pancreas. In contrast in chronic pancreatitis moderate p75NTR expression was present in acinar cells next to fibrosis, ductal cells, and cells of ductular structures as well as in some islet cells. Immunostaining of p75NTR in normal pancreas and chronic pancreatitis tissue samples showed a similar intensity and distribution pattern as found by in situ hybridization. Higher p75NTR protein levels could be confirmed by western blot analysis, which revealed an 8.6-fold increase of p75NTR in chronic pancreatitis. TUNEL staining showed, in chronic pancreatitis samples, positivity in some acinar cells next to fibrosis, some ductal cells, and cells of ductular structures. Also some islet cells were positive by TUNEL staining. The presence of p75NTR immunoreactivity was positively correlated (P < 0.05) with the apoptotic index in the exocrine and endocrine pancreas. In conclusion, p75NTR, the low-affinity receptor of neurotrophins which mediates apoptosis, is up-regulated in CP and is involved in the apoptotic process of the exocrine and endocrine pancreas.
Abstract: BACKGROUND: In the past two decades our knowledge of the pathophysiology and surgical treatment options in chronic pancreatitis has improved substantially. Surgical treatment in chronic pancreatitis has evolved from extending to organ-preserving procedures. DISCUSSION: The classical Whipple resection is no longer a standard procedure in chronic pancreatitis, and is continuously being replaced by operations such as the duodenum-preserving pancreatic head resection and pylorus-preserving Whipple. These procedures allow the preservation of exocrine and endocrine pancreatic function, provides pain relief in up to 90% of patients, and contributes to an improvement in life quality. CONCLUSIONS: In addition to presently available results from randomized controlled trials, new studies comparing available surgical approaches in chronic pancreatitis are needed to determine which procedure is the most effective in the treating chronic pancreatitis.
Abstract: INTRODUCTION AND AIMS: Only curative resection for pancreatic adenocarcinoma is related to a favorable prognosis, but the overall survival after surgery still remains poor, and early recurrence is frequently observed. Because recurrence is the limiting factor and the main cause of death after curative resection, the identification of markers that predict early postoperative recurrence is of paramount importance. Angiogenesis is essential for tumor growth and metastases; therefore, we set out to clarify whether vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) correlate with early recurrence and poor prognosis after curative resection. A second goal was to characterize the VEGF-producing cells and the subcellular distribution. METHODOLOGY: Seventy patients with ductal adenocarcinoma of the pancreas were studied after curative resection with a follow-up of at least 2 years. The MVD quantification was performed immunohistochemically with use of a monoclonal antibody to CD34. The VEGF expression was studied with use of polyclonal antibody. To detect the intracellular localization of specific VEGF mRNA sequences, nonisotopic in situ hybridization was performed. The correlations among VEGF expression and MVD, clinicopathologic parameters, and clinical outcome were then statistically analyzed. RESULTS: The VEGF immunoreactivity was 88.6%, and positive mRNA signals were obtained in the cytoplasm of carcinoma and endothelial cells in 81.4%. Furthermore, we observed tumor-associated macrophages close to infiltrating carcinoma cells. All endothelial cells showed positive immunoreactivity to the anti-CD34 antibody, and a median distribution of 85 vessels/x200 field was observed. A significant correlation (p < 0.05) was found between the MVD and the International Union Against Cancer (UICC) stage. Statistical analysis showed a significant correlation between VEGF expression and the height of MVD (p < 0.05). Kaplan-Meier analyses revealed that VEGF expression and MVD had a statistically significant correlation with survival after curative resection (p < 0.05). Furthermore, multivariate analysis indicated that VEGF expression is an independent prognostic marker for cancer recurrence within 8 months after curative surgery (p = 0.003). CONCLUSION: In pancreatic adenocarcinoma, the VEGF expression and the height of MVD are closely correlated, and both-rather than UICC stage and TNM classification (tumor size and nodal involvement)-are markers of prognostic relevance after curative resection. Furthermore, VEGF is a predictor of early recurrence after curative resection. The current study indicates that VEGF may promote the distribution of metastases, leading to early cancer recurrence and poor outcome.
Abstract: BACKGROUND: Laparoscopy has become a popular and widespread surgical technique. An important goal in the treatment of patients with pancreatic cancer is to avoid any unnecessary procedure. Laparoscopy has been suggested as a routine tool for staging in order to prevent unnecessary laparotomies in these patients. METHODS: In this article we present our experience regarding the value of laparoscopic staging and review the literature on this topic. RESULTS AND CONCLUSION: A direct and conclusive comparison of the controversial literature is difficult because of different study designs. Inconsistent use of high-quality CT scans significantly affects the results. However, recent studies reveal that not more than 14% of the patients benefit from diagnostic laparoscopy when a state-of-the-art CT scan has been performed previously. Therefore, we conclude that routine diagnostic laparoscopy is not justified in all patients with pancreatic cancer. Rather, selective use is appropriate, especially in patients in whom ascites is an indirect sign of peritoneal metastases, or if liver metastases cannot be surely excluded preoperatively. This approach is cost-effective and limits diagnostic laparoscopy to a subgroup of patients in whom a laparotomy can be avoided.
Abstract: OBJECTIVE: To find out whether there is any benefit from venous resection during pancreaticoduodenectomy for ductal pancreatic adenocarcinoma. DESIGN: Retrospective study. SETTING: University Hospital Mannheim/Heidelberg, Germany. INTERVENTIONS: 271 patients had resections for ductal adenocarcinoma of the pancreatic head between 1980 and 2001. The outcome of patients who did (n = 68) and who did not (n = 203) have simultaneous resection of major veins (portal vein and/or superior mesenteric vein) were compared. MAIN OUTCOME MEASUREMENT: 5 year survival. RESULTS: The groups differed significantly regarding stage, perineural infiltration, lymphangiosis carcinomatosa, operating time, blood loss, and blood transfusion. However, there was no difference in perioperative morbidity (27% and 22%), mortality (4% and 3%), and long-term survival (at 5 years 23% and 24%). Subgroup analysis of patients with margins free of tumour (R0 resections) showed that those patients who had venous resections in whom histological examination did not show infiltration of tumour had the most favourable outcome. CONCLUSION: There is no reason to exclude patients with suspected venous infiltration from radical pancreaticoduodenectomy including venous resection.
Abstract: BACKGROUND: Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival. METHODS: From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle. FINDINGS: 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively). INTERPRETATION: LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.
Abstract: OBJECTIVES: Despite apparently curative resection adenocarcinomas of the pancreas early recur. Thus, the pathological examination should be enriched by sensitive methods to detect minimal residual disease (MRD). Mutant K-ras is the most promising genetic alteration in ductal adenocarcinoma and may serve to detect malignant cells by polymerase chain reaction (PCR) based techniques. Therefore, we set out to detect K-ras mutations by PCR for evaluation of MRD in patients after curative resection of pancreatic adenocarcinoma. PATIENTS AND METHODS: Tumor tissue and corresponding paraaortic lymph nodes were obtained from 51 patients, who underwent surgery for pancreatic head tumors. The paraaortic lymph nodes were staged as tumor-free by routine histopathology in all cases diagnosed for ductal adenocarcinoma (study group, n = 40) or other tumors (control group, n = 11). Therefore, DNA of both primary tumors and lymph nodes was extracted and analysed by a PCR-based assay with respect to mutated K-ras. As a positive control the human pancreatic cancer cell line PaTu-8902 was used. RESULTS: K-ras mutations were detected in 73 % (29/40) of primary tumors of ductal adenocarcinomas and in 17 % (5/29) in the corresponding paraaortic lymph nodes, which were diagnosed as tumor-free by routine pathology. The identical type of point mutation was found in primary tumors and corresponding lymph nodes by use of sequence specific primers. In the control group no K-ras mutation was detected. CONCLUSION: Tumor cell DNA can be detected sensitively in tumor- and lymph node specimen with the described method. Routinely assessed, this method is able to detect MRD and could enrich the pathological examination, in order to determine prognostic relevant subgroups of patients.
Abstract: BACKGROUND AND STUDY AIMS: Intraluminal stenting of organs with stenoses or fistulae in anatomically difficult locations (for instance cardia, pylorus, large bowel), with a tendency to kinking or increased motility, still carries a high risk of stent dislocation. In the search for a solution, we report on the use of a new thermoplastic stent in animal experiments. MATERIAL AND METHODS: The new stent consists of a plastic-coated wire mesh which can be heated electrically. Once it is warmed up to 55 C, its size and shape can be changed. After being expanded by a dilatation balloon across the stenosed area, the stent can be fitted onto the inner organ surface. This guarantees a low dislocation risk and high stability. In an animal experiment, stents were endoscopically placed in the trachea and the surgically stenosed esophagus of two dogs. The animals were observed for 3 months. RESULTS: The thermostents were implanted easily and without complications. It was possible to mold the thermostent evenly onto the intraluminal wall. No stent dislocation, bleeding or perforation was observed. Upon histologic evaluation, granulation tissue was found to be growing through the wire mesh of the stent. CONCLUSION: It was shown that the stent described here can be implanted without major problems. The greater effort of the implantation procedure, in comparison with self-expanding stents, is compensated by the special mechanical characteristics of the stent. These characteristics may permit implantation in anatomically difficult locations where up to now stenting has been impossible or inadequate.
Abstract: Risk factors for postoperative complications of benign goiter surgery have not been investigated systematically. To this end, a prospective multicenter study (January 1 through December 31, 1998) was conducted involving 7266 patients with surgery for benign goiter from 45 East German hospitals. High-volume providers (>150 operations per year) performed 69% (5042/7266), intermediate-volume providers 27% (50-150), and low-volume providers 4% (258/7266) of operations. Among the hospital groups, the pattern of thyroid disease did not vary significantly, but there was a trend that small-volume providers tended to perform more operations for uninodular goiter and high-volume providers treated more patients with Graves' disease and recurrent goiter. Extent of resection (p < 0.0001) and remnant size (multinodular goiter and recurrent goiter, p < 0.001), differed significantly, with total thyroidectomy being performed more often in hospitals with more than 150 operations compared to hospitals with an operative volume of less than 150 procedures per year. Despite the larger extent of resection and smaller remnant size, rates of recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism were not increased. When the logistic regression analyses were fitted to evaluate the impact of risk factors on transient and permanent RLN palsy and hypoparathyroidism, larger extent of resection [relative risk (RR) 1.5-2.1] and recurrent goiter (RR 1.8-3.4) consistently evolved as independent risk factors. With hypoparathyroidism, additional significant factors included patient gender (RR 2.1-2.4), hospital operative volume (RR 0.8-1.5), and Graves' disease (RR 2.8). Unlike parathyroid gland identification during hypoparathyroidism, RLN identification (RR 1.6) significantly (p = 0.01) reduced permanent RLN palsy rates. The multivariate analyses clearly confirmed the pivotal role of routine RLN identification, independent of the extent of the thyroid resection. These findings might help hospitals with lower operative volumes to identify patients at increased risk whom they might consider for specialist care.
Abstract: CONCLUSIONS: In dogs, 1. Activation of cholecystokinin-receptors is needed for an adequate pancreatic bicarbonate response to secretin; 2. Cholinergic nerve fibers ending on M1-receptors are probably of little or no importance for the bicarbonate response to secretin in the given dose; 3. The bicarbonate response to tryptophan, given with a secretin background, is controlled by cholinergic M1-fibers and by cholecystokinin; 4. M1-fibers mainly mediate the bicarbonate response to low loads of tryptophan, whereas cholecystokinin controls the response to low and high loads of tryptophan; and 5. Both mediators interact in a synergistic manner. METHODS: In six conscious dogs with chronic gastric and duodenal fistulas, we compared the action of the M1-receptor antagonist telenzepine (20.25-81.0 nmol/kg/h), the cholecystokinin-receptor antagonist L-364,718 (0.025-0.1 mg/kg/h), and combinations of both on the pancreatic bicarbonate response to graded loads of intraduodenal tryptophan (0.37-10.0 mmol/h), given against a background of secretin (20.5 pmol/kg/h). RESULTS: Secretin significantly (p < 0.05) stimulated the pancreatic bicarbonate output above basal levels. All doses of L-374,718, but not telenzepine, significantly decreased the bicarbonate response to secretin by up to 64%. Additional administration of telenzepine together with L-364,718 had no further inhibitory effect on the secretin-stimulated bicarbonate output as compared to L-364,718 given alone. All loads of tryptophan significantly increased the bicarbonate output over that seen with secretin alone (= incremental bicarbonate response to tryptophan). Telenzepine significantly decreased the incremental bicarbonate response to the two lower loads (0.37-1.1 mmol/h) of tryptophan (by 82-124%); L-364,718 decreased the incremental bicarbonate response to all loads of tryptophan (by 50-118%). The incremental bicarbonate output, as well as the 180-min integrated bicarbonate response to all loads of tryptophan, were abolished by all combinations of both antagonists.
Abstract: Procalcitonin is a protein which is found in elevated concentrations in the blood circulation during systemic bacterial, fungal or protozoal infection. In contrast to classical acute-phase proteins like C-reactive protein or interleukin-6, it is not elevated after operative trauma. In this paper we present current opinions on the assumed induction mechanisms of the protein by cytokines and endotoxin. Furthermore, the clinical value for early detection of systemic infections in abdominal and transplantation surgery is demonstrated by examples from the literature. Our investigation shows that eight patients with necrotizing pancreatitis had a PCT mean value of 6.9 ng/ml on the day of admission. Seven patients with edematous pancreatitis had only a PCT mean value of 0.69 ng/ml. Despite these differences in the mean values, a significant difference between the normal value and the mean value of the group with necrotizing pancreatitis or edematous pancreatitis was not observed due to the wide range of PCT levels in the group of patients with necrotizing pancreatitis. The fact that only a few of the patients had a superinfected necrosis with systemic evasion of bacterias or their toxins may be the reason for this wide range. We suggest that a discrimination between superinfected necrotizing or sterile pancreatitis and edematous pancreatitis by PCT could be possible but more extensive studies with microbiological examination of the necrotic material are required to recognize the subgroups and to establish the real diagnostic efficiency of PCT in clinical practice, especially in the prediction of the outcome of acute pancreatitis.
Abstract: The technique of Gadolinium-enhanced MR-angiography has become much better over the past year. The quality of the method is equal to conventional angiography. The advantages of MRA in comparison to conventional angiography today are: less strenuous for the patient, faster, CT or ERCP can be saved, MRA can be more economic.
Abstract: In six conscious dogs we compared the action of the M1-receptor antagonist telenzepine (20.25-81.0 nmol.kg-1.h-1), the cholecystokinin (CCK) antagonist L-364,718 (0.025-0.1 mg.kg-1.h-1), and combinations of both on the pancreatic secretory response to intraduodenal tryptophan, given against a secretin background before and after truncal vagotomy. Before vagotomy, the higher doses of telenzepine and of L-364,718 significantly (P < 0.05) decreased the protein response to tryptophan by up to 97%. After vagotomy, all doses of L-364,718 abolished the protein response, whereas telenzepine had no further effect. Before and after vagotomy, all combinations abolished the protein response. The plasma CCK-like immunoreactivity basally, during secretin, and in response to tryptophan was not altered by vagotomy, telenzepine, and/or L-364,718. These findings indicate that in dogs 1) potentiation exists between M1 receptors and CCK for stimulation of the pancreatic enzyme response to intraduodenal tryptophan, 2) the cholinergic fibers of the enteropancreatic reflex activated by tryptophan run within the vagus nerves and end at least in part on M1 receptors, 3) CCK acts in part independently of the vagal nerves, and 4) the CCK release by intestinal tryptophan is not influenced by vagotomy, telenzepine, and/or L-364,718.
Abstract: OBJECTIVE: This study was conducted to determine the criteria for unresectability of major peripancreatic vessels in patients with pancreatic carcinoma as revealed by optimally enhanced, pancreatic-phase thin-section helical CT. SUBJECTS AND METHODS: Twenty-five patients with pancreatic adenocarcinoma who underwent local dissection during curative or palliative surgery also underwent preoperative pancreatic-phase thin-section helical CT (40- to 70-sec delay, 2.5- to 3-mm collimation). Tumor involvement of the portal and superior mesenteric veins and the celiac, hepatic, and superior mesenteric arteries was prospectively graded on a 0-4 scale based on circumferential contiguity of tumor to vessel. Subsequent surgical results were then correlated with the CT grades. RESULTS: At surgery, definitive evaluation was possible for 80 vessels. Forty-eight of 48 vessels graded 0 and three of three vessels graded 1 were resectable. Four of seven vessels graded 2, seven of eight vessels graded 3, and 14 of 14 vessels graded 4 were unresectable. A threshold of between grades 2 and 3, which corresponded to tumor involvement of one-half circumference of the vessel, yielded the lowest number of false-negatives and an acceptable number of false-positives for unresectability. Such a threshold would have yielded a sensitivity of 84%, a specificity of 98%, a positive predictive value of 95%, and a negative predictive value of 93% for unresectability of the vessels studied. CONCLUSION: A grading system for tumor involvement of the major vessels in patients with pancreatic adenocarcinoma can be based on the degree of circumferential contiguity of tumor to vessel. Involvement of vessel to tumor that exceeds one-half circumference of the vessel is highly specific for unresectable tumor.
Abstract: BACKGROUND: The aim of the study was to compare the effects of the cholecystokinin (CCK)-receptor antagonists loxiglumide and L-364, 718 on the endogenously stimulated pancreatic exocrine secretion. METHODS: In six conscious dogs with chronic gastric and pancreatic fistulas we compared the action of different doses of loxiglumide (2.5 to 10.0 mg/kg/h) and L-364, 718 (0.025 to 0.1 mg/kg/h) on the pancreatic secretory response to intraduodenal perfusion of graded loads of tryptophan (0.37-10.0 mmol/ h), given against a background of secretin (20.5 pmol/kg/h intravenously). RESULTS: Both loxiglumide and L-364, 718 inhibited the secretin-stimulated pancreatic bicarbonate output by up to 47% and 48%, respectively. The pancreatic protein output during secretin was significantly inhibited by all doses of L-364,718 (by 65% to 82%) but not by loxiglumide. All doses of loxiglumide and L-364, 718 abolished the 180-min integrated bicarbonate response to tryptophan. The two higher doses of loxiglumide (5.0-10.0 mg/kg/h) and L-364,718 (0.05-0.1 mg/kg/h) significantly decreased the 180-min integrated response to tryptophan by 59% and 79% (loxiglumide) and by 72% and 97% (L-364, 718). The plasma CCK-like immunoreactivity basally and in response to tryptophan was not significantly altered by loxiglumide or L-364, 718. CONCLUSIONS: These findings indicate that in dogs 1) the pancreatic bicarbonate response to secretin is augmented by the hormone CCK; 2) L-364, 718 but not loxiglumide decreases pancreatic protein output during secretin; 3) endogenous released CCK is involved in the pancreatic bicarbonate response and is a major mediator of pancreatic protein response to intraduodenal tryptophan; and 4) the release of CCK by intraduodenal tryptophan is not influenced by loxiglumide and L-364, 718.
Abstract: Between 1972 and 1995, 4434 operations for colorectal carcinoma were performed at the University Clinic of Mannheim. The increasing average age of the patients resulted in a higher lethality rate due to more emergency operations and concomitant failure of other organs. But the prognosis of patients over 70 years old can be compared with younger patients when hospital lethality is not considered. Thus the aim of treatment in older patients is also R0-resection, avoidance of emergency operations, optimum treatment of concomitant failure of other organs and multiple operations in extreme emergency cases.
Abstract: This retrospective study attempted to determine the indications for extended pancreatectomy for locally advanced carcinoma of the pancreas, in terms of postoperative prognosis. An extended pancreatectomy with portal vein or superior mesenteric vein (PV/SMV) resection and regional lymphadenectomy was performed in 35 of 50 consecutive cancers that extended into the retroperitoneal spaces and involved the PV or SMV. Among the many background factors in the 35 resected specimens, the degree of PV/SMV invasion by the cancer was most closely associated with prognosis, despite resection of all involved PV/SMV. This factor generally correlated with the preoperative findings on the portal phase of superior mesenteric arteriograph. In 17 selected patients in whom PV/SMV invasion had been angiographically both semicircular or less and 1.2 cm (1.4 cm on the film) or less in length, the 3-year survival rate was 59%. This survival rate was significantly higher than the 29% 3-year survival rate in all 35 patients (p less than 0.05). Conversely, among the 18 patients in whom invasion was angiographically either beyond semicircular or more than 1.2 cm (1.4 cm on the film) in length, there were no 1.5-year survivors, and this result was even worse than that of 15 nonresectable cases. Based on postoperative survival, the degrees of PV/SMV invasion on preoperative angiography (narrowing pattern and length) are good indicators for aggressive pancreatectomy for locally advanced pancreatic cancer.
