Liver transplantation for unresectable hepatocellular carcinoma in normal livers.

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8 cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation < 12 months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ≥ 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC.

A prospective randomized multicenter trial comparing histidine-tryptophane-ketoglutarate versus University of Wisconsin perfusion solution in clinical pancreas transplantation.

We aimed to evaluate early pancreas transplant graft function after histidine-tryptophan-ketoglutarate (HTK) versus University of Wisconsin (UW) perfusion. Prospective randomized multicenter study including 68 pancreas transplantations stratified according to preservation fluid used (27 HTK vs. 41 UW). Primary endpoint was pancreas graft survival at 6 months. Serum alpha-amylase, lipase, C-peptide, HbA1C and exogenous insulin requirement were compared at several time points. Mean pancreas cold ischemia time was 10.8 +/- 3.7 (HTK) vs. 11.8 +/- 3.4 h (UW) (P = 0.247). Simultaneous pancreas-kidney transplantation was performed in 95.6% of the patients, pancreas transplantation alone in 2.9%, and pancreas after kidney transplantation in 1.5%. Six months graft survival was 85.2% (HTK) vs. 90.2% (UW) (P = 0.703). Serum amylase and lipase values did not differ between both the groups during the observation period. C-peptide levels were elevated in both the groups without significant differences at each time point. Higher exogenous insulin requirement early after transplantation in the UW group had resolved at 3 months. Six month patient survival was 96.3% (HTK) vs. 100% (UW) (P = 0.397). With a mean cold ischemia time of 10 h in this study, HTK and UW solutions appear to be equally suitable for perfusion and organ preservation in clinical pancreas transplantation.

Carcinoma of the distal and middle bile duct: surgical results, prognostic factors, and long-term follow-up.

BACKGROUND/PURPOSE: Carcinoma of the distal bile duct is associated with poor prognosis. Surgical resection remains the only potentially curative treatment. We conducted a retrospective study to identify prognostic factors determining longterm survival. METHODS: From 1990 to 2006, 95 patients with distal and/or middle bile duct carcinoma had resections. Fifty-four patients underwent pylorus-preserving pancreaticoduodenectomy (57%) and 41 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (43%). Nine patients underwent pancreaticoduodenectomy including portal vein resection (9%). RESULTS: Overall 1-, 3-, and 5-year survival rates were 60%, 36%, and 29%, respectively. Five-year survival after R0 resection was 34%, and after R1 resection it was 0%. Four patients died during their hospital stay (4%). Multivariate analysis showed negative resection margins (P = 0.040), lymphatic vessel invasion (P = 0.036), and portal vein infiltration (P = 0.027) as strong predictors for survival, whereas the location of the tumor (distal bile duct vs middle bile duct) and lymph node status were not identified as independent prognostic factors. CONCLUSIONS: Five-year survival depends strongly on negative resection margins, independent of nodal status. Portal vein resections in patients with portal vein involvement fail to ameliorate long-term survival. Primary tumor site--middle bile duct or distal bile duct--did not determine prognosis.

Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study.

BACKGROUND/PURPOSE: Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping. METHODS: Twenty patients who underwent hepatic resection were randomized into two groups: a steroid group (n = 10), in which patients were given 30 mg/kg per body weight (BW) methylprednisolone intravenously, and a control group (n = 10), in which patients received a placebo (sodium chloride) infusion. The main outcome parameter to assess systemic stress was the serum plasma level of interleukin-6 (IL-6). To evaluate cell-mediated immune function, human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes and lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release by peripheral monocytes was measured. Other investigated serum parameters included C-reactive protein (CRP), total bilirubin, alanine aminotransferase (ALT), prothrombin time (PT)-INR, and cytokines such as IL-8 and IL-10 and TNF-alpha. Postoperative convalescence, complication rate, and length of hospital stay were compared between the groups. RESULTS: Postoperative plasma concentrations of IL-6 (days 1 and 2), IL-8 (days 2 and 3), and CRP (days 1-4) were significantly lower in the steroid than in the control group. The total bilirubin concentration was significantly lower on day 6 in the steroid than in the control group. Four hours after surgery, LPS-induced TNF-alpha secretion was significantly reduced in the steroid group, but it increased rapidly during the following days. HLA-DR, ALT, and PT-INR levels were not different between the two groups. The postoperative hospital stay in the steroid group was significantly lower compared to that in the control group (mean, 10.5 days versus 14.8 days; P < 0.05). No differences were found in the convalescence score or postoperative complication rate. CONCLUSIONS: Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release. No adverse effect on immunity was noted due to the methylprednisolone. We found no significant difference in the convalescence score, but a significantly shorter hospital stay in the steroid group. Further studies with more patients are needed to elucidate the clinical impact of preoperative steroid bolus therapy in liver surgery.

Laparoscopic-assisted placement of peritoneal dialysis catheters: implantation technique and results.

BACKGROUND: Peritoneal dialysis is a generally accepted method for the treatment of patients with end-stage renal failure. The laparoscopic placement of peritoneal dialysis catheters is a well-established technique and offers some advantages, such as a safer placement of the catheter, less post-operative complications, and a longer functional survival, compared to the conventional open technique. The aim of this study was to describe our implantation technique and to determine the results of our approach. PATIENTS AND METHODS: Between January 2000 and February 2006, 47 patients with end-stage chronic renal failure underwent a laparoscopic peritoneal dialysis catheter insertion procedure. Perioperative and follow-up data were collected prospectively. RESULTS: The mean operating time was 35 minutes (range, 16-100). There was no perioperative morbidity. Nine (19.1%) patients experienced 10 mechanical complications: fluid leakage in 6 (12.8%) patients, acute hydrothorax in 1 (2.1%), catheter tip migration in 2 (4.3%), and catheter obstruction in 1 (2.1%) patient. Episodes of peritonitis were observed in 5 (10.6%) patients. One (2.1%) patient developed a catheter infection. In 3 (6.4%) patients, a port site hernia occurred that required surgical repair, 5 (10.6%) patients underwent laparoscopic revisions owing to mechanical complications, 9 (19.1%) patients underwent renal transplantation, and 6 (12.8%) patients died during the later follow-up. After a mean follow-up time of 17 months (range, 2-76), 30 (63.8%) catheters are still in use for dialysis. CONCLUSIONS: The functional outcome of the dialysis catheters was satisfactory in the majority of patients in this study. The described technique for catheter implantation is simple and safe, and in our opinion, the laparoscopic technique should be considered as the method of choice in patients with end-stage chronic renal failure.

Short-term anti-CD4 plus anti-TNF-alpha receptor treatment in allogeneic small bowel transplantation results in long-term survival.

BACKGROUND: Despite improved immunosuppression, intestinal transplantation is still complicated by severe rejection episodes. To further improve immunosuppressive concepts, we evaluated an anti-CD4 antibody and an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody for their immunosuppressive efficacy in the standard rat model of intestinal transplantation. METHODS: Intestinal transplantation was performed in the DA to Lewis combination, and recipients were treated perioperatively with either the anti-CD4 antibody RIB5/2 (day -1, 0, postoperative days 1, 2, 4, 7, 10, 14, 17, and 21), the anti-TNF antibody etanercept (60 min before reperfusion, postoperative days 3, 6, and 9) or a combination of both. Survival, histology and expression of immunologic mediator genes on days 3 and 4 after transplantation were investigated. RESULTS: Treatment with anti-CD4 antibody alone (19.71+/-5.94) and the antibody combination (171.58+/-122.76) prolonged survival. The chemokine MIP-1alpha was significantly decreased in both anti-CD4 antibody treatment groups, possibly indicating an additional effect of the TNF-alpha blockade on the immune modulation by RIB5/2. CONCLUSIONS: Our study demonstrated long-term graft survival in short-term treatment with a combination of an anti-CD4 antibody and a TNF-alpha antibody in more than 50% of the recipients of intestinal grafts. Such a combined approach could also be useful in clinical small bowel transplantation.

Influence of donor histology on outcome in patients undergoing transplantation for hepatitis C.

BACKGROUND: Risk factors for graft loss and recipient death in liver transplantation for hepatitis C virus (HCV) have been extensively investigated. Donor age was defined as one of the most important predictors of outcome in these patients; however, the mechanism leading to more severe recurrent hepatitis has not yet been investigated. METHOD: In a retrospective analysis, histological findings of 79 donor liver grafts were assessed according to criteria inflammation, fibrosis, fatty degeneration, and necrosis. These findings were correlated with the histological and clinical course of HCV-positive liver graft recipients. RESULTS: The overall 1-, 5- and 10-year graft survival figures were 85%, 77%, and 60%, respectively. We could not identify any correlation between outcome, fat content, and necrosis in the donor liver. However, stage 3 and 4 fibrosis 1 year after liver transplantation was significantly increased in the group of patients receiving a graft from a donor with portal inflammation (P<0.05). Additionally, the occurrence of intrahepatic inflammation was significantly increased in older donors (P<0.05) and donors with prolonged intensive care hospitalization (P<0.05). CONCLUSION: A number of risk factors for detrimental outcome in HCV-positive patients after liver transplantation have been identified. In particular, older donor age significantly impaired outcome in recent analysis, but due to donor shortage it is not possible to provide young grafts for all HCV-positive patients. Our data show that donor histology is helpful in identifying patients with more severe recurrent hepatitis prior to transplantation, and that especially in older donors, prolonged intensive care hospitalization should be avoided.

Neuroendocrine tumor of the pancreas and bilateral adrenal pheochromocytomas. A rare manifestation of von Hippel-Lindau disease in childhood.

BACKGROUND: A 12-year-old girl presenting with intermittent epigastric pains and diarrhea was referred to our clinic. Diagnostic workup revealed nonfunctional bilateral adrenal pheochromocytomas as well as a neuroendocrine tumor of the pancreatic head. This is the first report on the combination of a neuroendocrine pancreatic tumor with adrenal pheochromocytoma in a pediatric patient with von Hippel-Lindau (VHL) disease. METHODS: von Hippel-Lindau disease was confirmed by molecular genetic analysis of peripheral blood lymphocytes, which revealed the mutation VHL c. 695 G > A. The family history showed also VHL disease in the mother who carried the same mutation. RESULTS AND CONCLUSION: Open laparotomy, organ-sparing enucleation of pheochromocytoma, and pylorus-preserving resection of the pancreatic head tumor were successfully performed. After an uneventful postoperative course, the child fully recovered. She was free of further manifestations of VHL disease 30 months after surgery.

Effect of enteral nutrition and synbiotics on bacterial infection rates after pylorus-preserving pancreatoduodenectomy: a randomized, double-blind trial.

OBJECTIVE: Patients undergoing pancreas resection carry several risk factors for nosocomial bacterial infections. Pre- and probiotics (synbiotics) are potentially useful for prevention of these infections. SUMMARY BACKGROUND DATA: First trials in patients following major abdominal surgery including liver transplantation using one Lactobacillus (LAB) and one fiber showed significant reduction of infection rates and reduced length of antibiotic therapy compared with a control group. The present study was designed to analyze whether a combination of different LAB and fibers would further improve outcome. METHODS: A prospective randomized monocentric double-blind trial was undertaken in 80 patients following pylorus-preserving pancreatoduodenectomy (PPPD). All patients received enteral nutrition immediately postoperatively. One group (A) received a composition of 4 LAB and 4 fibers, and another group (B) received placebo (fibers only) starting the day before surgery and continuing for 8 days. Thirty-day infection rate, length of hospital stay, duration of antibiotic therapy, noninfectious complications, and side effects were recorded. RESULTS: The incidence of postoperative bacterial infections was significantly lower with LAB and fibers (12.5%) than with fibers only (40%). In addition, the duration of antibiotic therapy was significantly shorter in the latter group. Fibers and LAB were well tolerated. CONCLUSION: Early enteral nutrition supplemented with a mixture of LAB and fibers reduces bacterial infection rates and antibiotic therapy following PPPD.

Surgical strategies and predictors of outcome for malignant neuroendocrine tumors of the pancreas.

BACKGROUND AND AIM: Neuroendocrine pancreatic carcinomas are rare and little information on factors influencing the clinical course and prognosis is presently available. The aim of this study was to retrospectively review all patients who underwent pancreatic resection for malignant neuroendocrine tumor of the pancreas at the one department from 1989 to 2003. METHODS: Eleven male and eight female patients with a mean age of 51 years (range 13-76 years) underwent surgery for malignant neuroendocrine tumor of the pancreas. The prognostic relevance for long-term survival was investigated for intrapancreatic localization of the primary, histological classification including proliferation index (Ki67), lymph node involvement, surgical treatment and long-term survival after resection. The clinical course after resection was also evaluated. Statistical analysis was performed using multivariate analysis and Kaplan-Meier method. RESULTS: Functional or non-functional tumors occurred in six (32%) and 13 (68%) patients, respectively. The tumors were located in the pancreatic head in 10 patients (53%), body in three (15%) and tail in two (11%). Multilocular tumors were found in five (26%). Surgical procedures performed were six pylorus preserving pancreaticoduodenectomies (32%), four standard pancreaticoduodenectomies (21%), four distal pancreatectomies (21%), three total pancreatectomies (15%) and two segmental resections (11%). Multivariate analysis showed sex (P = 0.018), Ki67 proliferation index (P = 0.023), tumor diameter (P = 0.02) and tumor site (P = 0.011) as significant predictors of outcome. CONCLUSION: Malignant neuroendocrine tumors of the pancreas are associated with poor prognosis. Surgical resection is an appropriate and safe procedure with low morbidity rates. The prognosis seems to be determined by various biological factors. However, with regard to the principles of surgical oncology, tumor-free resection margins are important and radical surgical procedures are justified in selected patients.

Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells.

BACKGROUND AND AIM: Poly (ADP-ribose) polymerase (PARP) inhibitors such as 3-aminobenzamide (3-ABA) enhance the in vitro cytotoxicity of DNA mono-functional alkylating agents such as radiation or chemotherapeutic agents. The aim of this study was to test an approach combining the PARP inhibitor 3-ABA with standard gemcitabine therapy in human pancreatic cancer cells. METHODS: Cell viability was determined by proliferation assay (XTT). Cell-cycle analysis (FACS), ELISA (M30 Apoptosense), Western blot for caspase 8 and PARP, and electron microscopy were used to identify apoptosis. Tumor growth and survival was assessed in nude mice by subcutaneously injected Capan-1 cells. In addition, Ki67 staining was performed on tumors for cell proliferation and in vivo apoptosis induction was measured by TUNEL assay and ELISA. RESULTS: Combination therapy of gemcitabine and 3-ABA suppressed tumor cell growth more than gemcitabine alone in XTT, FACS and ELISA analysis. CONCLUSION: This in vivo study demonstrated a significantly reduced tumor weight and increased survival up to 40 days after cell inoculation with combination therapy compared to animals treated with PBS, gemcitabine or 3-ABA alone. Furthermore, TUNEL assay revealed a significant apoptosis induction and reduced proliferation in the combination group.

Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with colorectal liver metastases: a Phase II-study and historical comparison with the surgical approach.

BACKGROUND: The high complication rates of surgically implanted port catheter systems (SIPCS) represents a major drawback in the treatment of isolated liver neoplasms by hepatic arterial infusion (HAI) of chemotherapy. Interventionally implanted port catheter systems (IIPCS) have evolved into a promising alternative that enable initiation of HAI without laparatomy, but prospective data on this approach are still sparse. Aim of this study was to evaluate the most important technical endpoints associated with the use of IIPCS for the delivery of 5-fluorouracil-based HAI in patients with colorectal liver metastases in a phase 2-study, and to perform a non-randomised comparison with a historical group of patients in which HAI was administered via SIPCS. METHODS: 41 patients with isolated liver metastases of colorectal cancer were enrolled into a phase II-study and provided with IIPCS between 2001 and 2004 (group A). The primary objective of the trial was defined as evaluation of device-related complications and port duration. Results were compared with those observed in a pre-defined historical collective of 40 patients treated with HAI via SIPCS at our institution between 1996 and 2000 (group B). RESULTS: Baseline characteristics were balanced between both groups, except for higher proportions of previous palliative pre-treatment and elevated serum alkaline phosphatase in patients of group A. Implantation of port catheters was successful in all patients of group A, whereas two primary failures were observed in group B. The frequency of device-related complications was similar between both groups, but the secondary failure rate was significantly higher with the use of surgical approach (17% vs. 50%, p < 0.01). Mean port duration was significantly longer in the interventional group (19 vs. 14 months, p = 0.01), with 77 vs. 50% of devices functioning at 12 months (p < 0.01). No unexpected complications were observed in both groups. CONCLUSION: HAI via interventionally implanted port catheters can be safely provided to a collective of patients with colorectal liver metastases, including a relevant proportion of preatreated individuals. It appears to offer technical advantages over the surgical approach.

Fibrosis progression in hepatitis C positive liver recipients after sustained virologic response to antiviral combination therapy (interferon-ribavirin therapy).

The rate of fibrosis progression was analyzed in 28 hepatitis C virus-infected liver graft recipients showing sustained virologic response after treatment with ribavirin plus either standard interferon alpha-2b (n=8), pegylated interferon alpha-2b (n=8), or pegylated interferon alpha-2a (n=12). Protocol biopsies before treatment as well as one, three, and five years after treatment showed no significant increase in mean fibrosis scores within the first three years after treatment (mean score at baseline 1.8 and at one and three years 2.0 and 2.1, respectively). Five years after cessation of treatment, the mean fibrosis score declined to 1.4 (P=0.2). Six of 28 patients (21%) showed an increase in fibrosis, five (18%) a decrease, and 17 (60%) no changes. The yearly fibrosis progression rate was 0.75 before treatment and 0.15 after antiviral treatment. Sustained virologic response is associated with a deceleration of fibrosis progression and might therefore play a major role in prevention of graft cirrhosis in hepatitis C virus-infected liver graft recipients.

A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer.

BACKGROUND: Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. METHODS: A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. RESULTS: Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. CONCLUSION: There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent.

Peroxisome proliferator-activated receptor gamma is highly expressed in pancreatic cancer and is associated with shorter overall survival times.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that has been implicated in carcinogenesis and progression of various solid tumors, including pancreatic carcinoma. We aimed to clarify the expression patterns of PPARgamma in pancreatic ductal carcinomas and to correlate these to clinicopathologic variables, including patient survival. EXPERIMENTAL DESIGN: Array-based expression profiling of 19 microdissected carcinomas and 14 normal ductal epithelia was conducted. Additionally, Western blots of pancreatic cancer cell lines and paraffinized tissue of 129 pancreatic carcinomas were immunostained for PPARgamma. For statistical analysis, Fisher's exact test, chi2 test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied. RESULTS: Expression profiles showed a strong overexpression of PPARgamma mRNA (change fold, 6.9; P=0.04). Immunohistochemically, PPARgamma expression was seen in 71.3% of pancreatic cancer cases. PPARgamma expression correlated positively to higher pT stages and higher tumor grade. Survival analysis showed a significant prognostic value for PPARgamma, which was found to be independent in the clinically important subgroup of node-negative tumors. CONCLUSIONS: PPARgamma is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPARgamma in tumor progression of pancreatic cancer.

Jejunal loop drainage versus direct pancreatic duct drainage after pancreatic head resection.

PURPOSE: Perioperative mortality after pancreatic head resection has fallen to below 5% in high-volume centers, but dehiscence of the pancreatojejunostomy remains a major concern. Despite various methods of protection, insufficiency rates still range from 6% to 19%. External drainage of pancreatic juice from the anastomotic site has shown promising results in the last decade. We compared the morbidity and mortality of two widely used drainage systems. METHODS: The subjects were 143 patients who underwent pancreatic head resection, followed by jejunal loop drainage with the top of the drain being placed between the pancreatojejunostomy and hepaticojejunostomy in 89, and by direct drainage of the pancreatic duct in 54. RESULTS: The median age was similar in both groups. Pancreatic fistula developed in 3 (5%) patients with a pancreatic drain and 6 (7%) with a loop drain. Breakdown of the pancreatojejunostomy occurred in 1 (2%) patient with a pancreatic drain and 2 (2%) with a loop drain. The overall perioperative mortality was 0.7%. The surgical and medical complications and postoperative course were similar in the two groups. CONCLUSION: The choice of drainage system did not impact on the number or severity of postoperative complications or survival, indicating that loop drainage is as safe and effective as direct pancreatic duct drainage.

Transplantation of an eight-organ multivisceral graft in a patient with frozen abdomen after complicated Crohn's disease.

To report an extended multivisceral transplantation (MVTx) including right kidney and ascending colon in a patient with complicated Crohn's disease (CD). A 36-year old female suffering from short bowel syndrome and frozen abdomen due to fistulizing CD after multiple abdominal operations underwent MVTx of eight organs including stomach, pancreatoduodenal complex, liver, intestine, ascending colon, right kidney, right adrenal gland, and greater omentum in November 2003. Immunosuppression consisted of alemtuzumab, tacrolimus and steroids. The patient was off parenteral nutrition by postoperative wk 3. She experienced one episode of pneumonia. The patient recovered completely and discharged 2.5 mo and was doing well 30 mo after MVTx. This is one of the very rare cases in which a complete mulitivisceral graft of eight abdominal organs was transplanted orthotopically.

Long-term results of mycophenolate mofetil as part of immunosuppressive induction therapy after liver transplantation.

BACKGROUND: The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine. METHODS: Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as 'MMF-free' control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated. RESULTS: Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and C(max) of MPA increased in combination with tacrolimus compared with cyclosporine. CONCLUSIONS: Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

Extended surgical resection for xanthogranulomatous cholecystitis mimicking advanced gallbladder carcinoma: A case report and review of literature.

Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography (ERC) showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right lobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.