Abstract: OBJECTIVE: The aim of this study was to evaluate the results of pancreatic resection in pancreatic endocrine neoplasias (PENs) in patients affected by multiple endocrine neoplasia type 1 (MEN1) syndrome. BACKGROUND: Since these tumors often show an indolent course, the role of diagnostic procedures and type of surgical approach are controversial. Experience with new diagnostic approaches and more aggressive surgery is still limited. METHODS: Sixteen MEN1 patients were referred to our Surgical Unit (1992-2003) and were operated on for the indications of hypergastrinism, hypoglycemia, and/or pancreatic endocrine neoplasias larger than 1 cm. Zollinger-Ellison syndrome (ZES) was present in 13 patients, 2 of whom experienced a recurrence after previous surgery. Preoperative tumor localization was carried out using ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), somatostatin receptor scintigraphy (SSRS), or selective arterial secretin injection (SASI). Rapid intraoperative gastrin measurement (IGM) was carried out in 8 patients, and 1 patient also underwent an intraoperative secretin provocative test. RESULTS: Either pancreatoduodenectomy (PD) or total pancreatectomy (TP) or distal pancreatectomy was performed. There was no postoperative mortality; 37% complications included pancreatic (27%) and biliary (6%) fistulas, abdominal collection (6%), and acute pancreatitis (6%). EUS and SSRS were the most sensitive preoperative imaging techniques. At follow-up, 10 of 13 hypergastrinemic patients (77%) are currently eugastrinemic with negative secretin provocative test, while 3 are showing a recurrence of the disease. All patients affected by insulinoma were cured. CONCLUSIONS: MEN1 tumors should be considered surgically curable diseases. IGM may be of value in the assessment of surgical cure. Our experience suggests that PD is superior to less radical surgical approaches in providing cure with limited morbidity in MEN1 gastrinomas and pancreatic neoplasias.
Abstract: Primary carcinoid tumors of the extrahepatic biliary tree are exceedingly rare, accounting for 0.2-2% of all digestive carcinoids. The authors in this study describe a case of biliary duct primary well-differentiated endocrine tumor in a 30-year-old man with symptoms of biliary obstruction and watery diarrhoea. Abdominal ultrasound showed a 2-cm solid lesion in the head of the pancreas, compressing the distal common bile duct. A computed tomography scan confirmed these findings, revealing the hypervascular pattern of the tumor. Gastrointestinal hormonal screening demonstrated an increase in plasma serotonin. The patient underwent standard pylorus-preserving pancreatoduodenectomy. Pathological examination showed a neuroendocrine tumor of the distal common bile duct measuring 1.8 cm in greatest dimension. The tumor cells were immunopositive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, serotonin, and cytokeratin. Stains for gastrin and somatostatin were negative. Seven years later, the patient is well, with no evidence of disease. Given the site of these tumors and the difficulty in differentiating them from periampullary lesions, decisions as to the appropriate surgical approach may be problematic. After an exhaustive review of the literature, the authors conclude that pancreatoduodenectomy is the treatment of choice.
Abstract: BACKGROUND: Control of blood outflow from the liver has become mandatory to reduce back-bleeding and prevent air emboli in difficult liver resections when dealing with the hepatic veins. Selective control of the major hepatic veins rather than unselective vena cava clamping is preferable in most of these cases. Extrahepatic isolation of the left-middle hepatic veins has been considered for a long time to be a hazardous maneuver, and there is no general agreement about the technique that should be used. HYPOTHESIS: The purpose of this article is to describe a technique used by us for the isolation of the left-middle hepatic veins so that total or selective (hemihepatic) vascular exclusion of the liver can be performed without vena cava clamping. METHODS: The inferior approach is easily accomplished soon after the exposure of some anatomical landmarks, and a triangle is described in which a clamp is inserted or, alternatively, when one uses a superior approach, when the instrument tip exits to enable the veins' looping. CONCLUSION: Compared with other techniques, this approach is easier and safer to perform in nearly all cases, providing that there is no tumor located close to the vena cava or hepatic vein junction that contraindicates this maneuver.
Abstract: BACKGROUND: Pancreato-enteric reconstruction after pancreatoduodenectomy (PD) is still a source of debate because of the high incidence of complications. Among the various types of pancreato-jejunostomies we don't know yet which is the best in terms of anastomotic failure and related complications rates. Wirsung-jejunal duct-to-mucosa anastomosis (WJ) and "dunking" pancreato-jejunal anastomosis (DPJ) are the two most used ones worldwide but conflicting results are reported. To determine which is the safer anastomosis and to define when an anastomosis should be preferred, we retrospectively reviewed two groups of patients who underwent WJ or DPJ. METHODS: Twenty-three patients underwent PD with WJ (n = 17) with dilated (WJD) (n = 9) or not-dilated Wirsung's duct (WJND) (n = 8) or with a DPJ (n = 6) over a 3-year period at a single institution. RESULTS: The complications rate was high in all groups of patients (33.3% in WJD, 37.5% in WJND and 66.7% in DPJ). A pancreatic fistula developed in one patient in each group (11.1% in WJD, 12.5% in WJND and 16.7% in DPJ). All these patients were managed conservatively. Anastomotic disruption took place in the WJ patients especially in the WJND group (n = 2) compared to the WJD (n = 1) (25% vs. 11.1%) or DPJ groups (0%): these three patients required a re-operation. Overall, the anastomotic defects were higher in patients who underwent WJND (37.5%), compared to WJD (22.2%) and to DPJ (16.7%). However, no statistical differences were found among the groups. Delayed gastric emptying (DGE) and total parenteral nutrition (TPN) along with anastomotic defects were responsible for a prolonged hospital stay. CONCLUSIONS: Our results were not able to demonstrate any statistical difference between the two different techniques in preventing anastomotic failure. WJ can represent a valid choice in case of a dilated duct and a firm, fibrotic enlarged gland that could not be properly invaginated in a small jejunal loop. DGE may occur in those patients who experienced an anastomotic failure and required a TPN regimen with a prolonged hospital stay.
Abstract: BACKGROUND : Functional outcome after sphincter-saving operations can be improved by colonic pouch compared to the straight procedure. However, it is not clear whether the colonic pouch has a different behavior in patients treated by low anterior resection with colorectal (LAR) or coloanal anastomosis (CAA). METHODS : We evaluated the 1-year results of 75 patients who underwent a sphincter-saving operation for rectal carcinoma or villous tumor of the middle or lower third of the rectum: 18 patients underwent coloanal anastomosis (CAA), in 13 patients we performed a coloanal anastomosis with a colonic pouch (PCAA), 20 patients had low anterior resection (LAR) and 24 had LAR with pouch construction (PLAR). The two groups of patients were similar in terms of age and gender. Anorectal function was assessed 12 months after the initial operation by an interview and anorectal manometry. RESULTS : One year after surgery, the daily mean number of defecations was significantly higher in the LAR group than in the other groups (2.0+/-1.5 in CAA group, 2.2+/-1.0 in PCAA, 2.3+/-1.8 in PLAR, 4.1+/-0.7 in LAR; p<0.05). Frequent soiling was observed in all the groups except PLAR. A lower degree of incontinence and a lower frequency of urgency were found in PCAA than in CAA. There were no differences in anal resting pressure and squeeze pressure among the various groups. Greater distensibility and compliance of the neorectum were observed in CAA, PCAA and PLAR compared to LAR, respectively 8.5+/-7.0 ml air/mmHg for CAA, 8.7+/-5.0 ml air/mmHg for PCAA, 6.3+/-4.0 ml air/mmHg for PLAR and 3.1+/-2.7 ml air/mmHg for LAR. A significant inverse linear correlation was present between the mean daily number of defecations and compliance. No difference in sense of incomplete evacuation was observed among the groups of patients. CONCLUSIONS : Colonic J-pouch provides an advantage over straight anastomosis in sphincter-saving operations by reducing the daily number of defecations, and the frequencies of fecal soiling and urgency. The role of the pouch seems to be different in LAR compared to CAA. In fact, in LAR the pouch increases compliance and consequently decreases the daily number of defecations. In CAA, the pouch does not reduce the number of defecations or the compliance, but reduces the frequency of fecal soiling and urgency.
Abstract: At the present, surgical treatment still represents the only chance of cure for liver metastases from colorectal cancer. Moreover in the last years the new chemotherapic adjuvant and neoadjuvant regimens and the use of radioablative techniques as radiofrequency have improved resectability and even survival. Besides, iterative surgery seems to show more and more encouraging results in terms of disease-free and overall survival, sometimes even in patients already resected for extrahepatic disease. The golden rule is in fact to try to perform every time an R0 resection, with no macro- and possibly microresidual disease.
Abstract: Hepatocellular carcinoma mainly develops in a cirrhotic liver; in the majority of the patients chronic hepatitis or cirrhosis are virus-related and/or postalcoholic. Liver resection is the gold standard treatment when there is no multifocality of the tumor and liver disease is not advanced (patients with Child-Pugh A score, or B in selected cases). In our experience the presence of vascular invasion and satellite nodules is clearly related to a decreased rate of disease-free survival and a higher percentage of intrahepatic recurrence.
Abstract: BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and occlusion). To further investigate these assumptions, we retrospectively reviewed the results of partial porta-caval shunts performed at different stages of liver disease. METHODS: Twenty-nine cirrhotic patients underwent a partial porta-caval shunt with a ringed polytetrafluoroethylene interposition prosthesis of 8-mm (20 patients) or 10-mm (9 patients) in diameter. Pre and post-shunt porta-caval pressure was measured in all patients. Twelve patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%). Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively. Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval pressure gradient, reduced significantly using either 8- or 10-mm prosthesis. The overall early mortality and morbidity were 13.8% and 48% respectively. The early mortality and morbidity were different between patients of Child A and B when compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No patient re-bled early from varices. The overall late mortality and morbidity were 40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8% of the two groups of patients respectively; variceal re-bleeding occurred in 4 patients (16%). Encephalopathy occurred postoperatively in 5 patients (20%), acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at 3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate that partial porta-caval shunt with a small diameter interposition H-graft is an effective procedure for the treatment of variceal bleeding, as well as for the prevention of re-bleeding in patients of Child A and those of Child B, as an elective or emergency/urgency procedure, with a low rate of complications and encephalopathy. This technique could be used safely in patients with good liver function but they should be monitored closely because of the risk of shunt occlusion.
Abstract: BACKGROUND AND AIMS: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied. METHODS: Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype. RESULTS: In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8(+) T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor kappaB, resulting in induction of proinflammatory genes. CONCLUSIONS: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.
Abstract: BACKGROUND & AIMS: Proliferation and migration of hepatic stellate cells (HSCs) and expression of chemokines are involved in the pathogenesis of liver inflammation and fibrogenesis. Peroxisome proliferator-activated receptor (PPAR)-gamma is a receptor transcription factor that controls growth and differentiation in different tissues. We explored the effects of PPAR-gamma agonists on the biological actions of cultured human HSCs. METHODS: HSCs were isolated from normal human liver tissue and used in their myofibroblast-like phenotype or immediately after isolation. Activation of PPAR-gamma was induced with 15-deoxy-Delta(12, 14)-prostaglandin J(2) or with troglitazone. RESULTS: PPAR-gamma agonists dose-dependently inhibited HSC proliferation and chemotaxis induced by platelet-derived growth factor. This effect was independent of changes in postreceptor signaling or expression of c-fos and c-myc and was associated with inhibition of cell cycle progression beyond the G(1) phase. Activation of PPAR-gamma also resulted in a complete inhibition of the expression of monocyte chemotactic protein 1 at the gene and protein levels. Comparison of quiescent and culture-activated HSCs revealed a marked decrease in PPAR-gamma expression in activated cells. CONCLUSIONS: Activation of PPAR-gamma modulates profibrogenic and proinflammatory actions in HSCs. Reduced PPAR-gamma expression may contribute to confer an activated phenotype to HSCs.
Abstract: An alternative technique of restorative proctocolectomy, by means of straight ileoanal anastomosis with multiple myotomies (SIAM) of the terminal ileum in 15 patients, nine with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) is reported. SURGICAL TECHNIQUE: Eight to ten longitudinal myotomies (3-4 cm long, on three different circumferential sites) were performed on the terminal ileum for a total length of 12-14 cm. CLINICAL RESULTS: At a mean follow up of 44 months (range 3-84 months) from the closure of the ileostomy, daytime continence was achieved in all the patients; stool frequency per 24 hours (+/- SD) was 4.1 +/- 1.8 for FAP patients and 5.8 +/- 1.7 for UC patients; nocturnal defecation was 1.0 +/- 0.5 and 1.2 +/- 0.8 for FAP and UC patients respectively; frequent nocturnal soiling was present in 2/5 of UC patients, and in 3/9 of FAP patients. SIAM failed in one UC patient that was converted to an ileoanal reservoir because of poor functional result. Signs of ileal mucosal inflammation were never observed at endoscopic examination. Histopathological assessment showed no evidence of acute terminal ileitis. MANOMETRIC FINDINGS: A significant postoperative reduction in anal resting pressure was observed after SIAM. Neither the absence of anal inhibitory reflex nor the presence of high pressure waves generated in the terminal ileum during air insufflation were related to the presence of soiling. The closure of the loop ileostomy was followed by an increased capacity and distensibility of the terminal ileum. Values of neorectal compliance were similar in FAP and UC patients although FAP patients were able to reach higher values of maximum tolerated volume and pressure. CONCLUSIONS: 1) SIAM can be an alternative to pelvic pouch in patients who have undergone restorative proctocolectomy when the construction of the pouch is not feasible. 2) The functional result observed after SIAM has been shown to be similar to that observed after pouch construction.
Abstract: Only recently, in our laboratory of experimental surgery, we started with a protocol for orthotopic liver transplantation (OLT) in a pig model. This was felt as mandatory for experimental purposes as well as for future clinical applications at our center. We report herein our own experience with 41 OLTx. Intraoperative "lethal" complications occurred in up to 32% (14/41) whereas postoperative complications occurred in the remainders at different intervals of time with a maximum survival of 30 days. No attention was paid to prevent rejection-infection episodes. The main cause of death was the primary non-function (PNF) or dis-function (PDF) manifested either intra or postoperatively in 16 out the 41 OLTx (39%). Intraoperative technical errors accounted for up to 9% (4/41 OLTx). Acute hemorrhage gastritis and gastric perforations occurred postoperatively in 6 animals (14%) and represent one of the peculiar aspects of OLT in pig model.
Abstract: PURPOSE: To verify whether short chain fatty acids (SCFA) alter the proliferative and endoscopic pattern of the mucosa in ileal pouches of ulcerative colitis (UC) or familial adenomatous polyposis (FAP) patients. METHODS: We studied patients after proctocolectomy carrying a pelvic ileal pouch for FAP or UC (noncanalized pouches in 10 UC and 4 FAP patients and canalized pouches in 6 UC and 5 FAP patients). Patients with noncanalized pouches were treated twice daily for one week with 30 ml of a SCFA solution (60 mM sodium acetate, 30 mM sodium propionate, 40 mM sodium butyrate, and 22 mM sodium chloride, pH 7); patients with canalized pouches were treated with the same solution twice daily for two weeks. Pouch mucosal biopsies were collected before and after SCFA. Mucosal proliferation was assessed by incorporation of [3H]thymidine in vitro and autoradiography. RESULTS: In UC patients proliferation did not vary in noncanalized pouches but was significantly reduced in canalized pouches after SCFA. In FAP patients SCFA did not alter proliferation. No significant effects of SCFA were observed on daily defecation frequency, endoscopic appearance, or histopathology of the pouches. CONCLUSIONS: SCFA do not control inflammation and clinical functions but reduce cell proliferation in UC patients. On the contrary, FAP patients are refractory to SCFA.
Abstract: Restorative proctocolectomy with ileal-anal anastomosis can induce a duodenal stenosis due to the compression between superior mesenteric artery (SMA) and aorta when the ileum is pulled-down to the anus stretching the SMA. This situation may require prolonged nasogastric intubation or even surgery. In our experience this occurred in 10% of pts. Aiming to avoid this complication we have performed an intestinal derotation just before ileal-anal anastomosis abolishing any possibility of duodenal compression. Comparing this latter group of patients to those who didn't receive intestinal derotation, we observed a significant reduction of nasogastric tube drainage and of the nasogastric intubation time. We think that intestinal derotation could be effective in preventing SMA syndrome after restorative proctocolectomy and ileal-anal anastomosis.
Abstract: Functional results after anterior rectal resections are commonly considered satisfactory but variable percentages of postoperative incontinence are often reported. Continence was evaluated after 20 low anterior resections (LAR) and 13 high anterior resections (HAR) by means of clinical assessment, anorectal manometry, and evacuation proctography. Whereas all HAR patients had perfect continence, 10 patients (50 percent of the LAR group had occasional episodes of soiling from liquid feces, 5 patients (25 percent had frequent soiling or occasional incontinence for solid feces, and 1 patient (5 percent had frequent solid stool loss requiring surgical treatment. Anal canal resting pressure at 3 and 4 cm from the anal verge was significantly lower in the LAR group (P less than 0.02 and P less than 0.05, respectively) than in the HAR group. However, the maximum voluntary contraction did not differ between the two groups. Rectoanal inhibitory reflex was found to be present in 17 of the 20 patients with LAR and in all patients with HAR. The volume at which the anal sphincter is continuously inhibited was significantly reduced in the LAR group (P less than 0.001). Also, the conscious rectal sensibility volumes were found to be significantly reduced for threshold, constant, and maximum tolerated volume. Threshold volume for internal sphincter relaxation was lower than the threshold volume for rectal sensation in some patients with LAR. This could allow postoperative fecal soiling. Rectal compliance was decreased (P less than 0.001) in the LAR group. Evacuation proctography, performed in six LAR patients affected by major soiling or solid stool loss, revealed an abnormal obtuse anorectal angle and pathologic lowering of the perineum at rest and during defecation. The concomitance of internal and sphincter impairment, reduction in rectal compliance, and previous pelvis floor muscle damage are postulated as cause affecting continence in patients who underwent LAR.
