A late unusual complication after an open cholecystectomy: Amputation neuroma of the CBD causing obstructive jaundice.

INTRODUCTION: Cholecystectomy is one of the most frequently done procedures in general surgery. There are few reports of amputation neuromas following this procedure. This presentation describes a case of obstructive jaundice due to amputation neuroma in a patient with a history of cholecystectomy. CASE PRESENTATION: We report about a 53 y o lady who presented with obstructive jaundice, 8 years following open cholecystectomy. Paraclinical investigations were in favor of cholangicarcinoma, however the final pathology revealed an amputation neuroma of the CBD. DISCUSSION: Amputation neuromas are rarely seen in the era of laparoscopic cholecystectomy. They are benign reparative lesions of the CBD following surgery or manipulation of the extra hepatic biliary tree. It is very difficult to diagnose them pre-operatively. Surgical resection is the first choice of treatment. CONCLUSION: Traumatic neuromas should always be among the differential diagnosis, when assessing a CBD mass in patients with a previous history of open cholecystectomy or surgery to the gastrointestinal tract.

Bowel obstruction secondary to an ectopic pancreas in the small bowels: About 2 cases.

INTRODUCTION: Ectopic pancreas is most commonly found in the jejunum and stomach. Most patients remain asymptomatic, and the diagnosis is usually made at autopsy or incidentally. We report here 2 cases of intestinal occlusion, secondary to an ectopic pancreatic tissue. Both cases were managed successfully by laparoscopy and laparotomy with subsequent segmental intestinal resection. CASE PRESENTATIONS: Case 1 - An elderly patient presented to the ER because of intestinal occlusion. Paraclinical investigations were consistent with occlusion, with ileal suffering signs on CT-scan. After laparotomy and segmental intestinal resection were done, histopathalogy showed evidence of ectopic pancreas obstructing the intestinal lumen. Case 2 - A young man presented to the ER with acute onset of epigastric pain. signs of peritoneal irritation. Ct-scan showed evidence of small bowel intussusception. Exploratory laparoscopy was done, and confirmed the diagnosis. The intussusceptum was at the level of the proximal jejunum. The suffering intestinal part was exteriorized and then resected. Histopathology was consistent with an ectopic pancreas. DISCUSSION: Symptomatic ectopic pancreas is extremely rare. Symptoms may include, bleeding, intestinal occlusion and intussusception. Few similar cases have been reported in the literature, and the current ones are to be added. CONCLUSION: As mentioned above, ectopic pancreatic tissue rarely causes symptoms. We presented 2 cases that presented 2 possible complications secondary to this pathology. Both cases were managed successfully.

International Multi-Specialty Delphi Survey: Identification of Diagnostic Criteria for Hepatic and Renal Cyst Infection.

BACKGROUND: Cyst infection is one of the complications of autosomal dominant polycystic kidney disease and polycystic liver disease. The diagnosis is typically made on a mix of clinical, laboratory and imaging abnormalities but the importance of individual items is uncertain. We aimed to perform a Delphi survey amongst physicians to achieve consensus on diagnostic criteria. METHODS: We retrieved diagnostic items from the literature and conducted physician and patient interviews. All items were combined to create the online questionnaire. Participants rated each item during 3 consecutive rounds. Items were rated for diagnostic helpfulness for hepatic and renal cyst infection on a 9-point scale with anchors, from extremely unimportant (n = 1) to extremely important (n = 9). We determined consensus with the disagreement index. The median rating of each item was calculated and categorized into inappropriate (≤3.4), uncertain (3.5-6.4) or appropriate (≥6.5). By combining all items that reached an appropriate consensus rating, we developed a diagnostic algorithm based on expert consensus. RESULTS: We invited 58 physicians to participate in the survey. In total, 35 (60%) responded to round 1 of which 91% (n = 32) and 86% (n = 30) responded to round 2 and 3, respectively. The final panel included 23 nephrologists, 5 hepatologists, a nuclear medicine specialist and an infectious disease physician from 11 countries (male 67%, mean age 47 ± 11 years, median clinical experience 21 years). The panel rated the diagnostic helpfulness of 59 potential items. Ultimately, 22 hepatic and 26 renal items were rated appropriate, including positive blood cultures and fluorodeoxyglucose positron-emission CT imaging. Ultrasonography and absence of intracystic bleeding were amongst those deemed uncertain or inappropriate. Subsequently, by combining items rated appropriate, we developed a clinical tool to diagnose hepatic and renal cyst infection. CONCLUSIONS: We identified diagnostic items for hepatic and renal cyst infection and developed an expert-based diagnostic algorithm, which may aid physicians in the diagnostic work-up. A prospective study is necessary to validate this algorithm.

Long-term Outcome of Kidney Recipients Transplanted for Aristolochic Acid Nephropathy.

BACKGROUND: Aristolochic acids (AA) are nephrotoxic and carcinogenic. The aim of this study was to assess the long-term outcome of patients with AA nephropathy (AAN) after kidney transplantation. METHODS: Observational study. Patients' characteristics, long-term surveillance and follow-up data, patient and graft survival, as well as outcomes with respect to rejection, cardiovascular complications, infections, and cancers with a focus on urothelial carcinomas, are reported. RESULTS: Twenty patients transplanted for AAN were included. All were submitted to prophylactic bilateral ureteronephrectomy and annual surveillance of the bladder. Median duration of posttransplant follow-up was 12.5 (3-19) years. Time from diagnosis of AAN to renal replacement therapy was relatively short (1 [0-15] years). Immunosuppression consisted of a triple therapy in the majority of patients. Nineteen patients had upper urinary tract multifocal atypia. Eleven patients presented with urothelial carcinomas of the upper tract; 2 of them with additional bladder urothelial carcinomas. Of these 2 patients, one required radical cystectomy. One patient developed a hepatocarcinoma. Patient survival was 100% in AAN patients at 5, 10, and 15 years after transplantation. Graft survival at 5, 10, and 15 years was 95%, 83%, and 75%. CONCLUSIONS: Despite a high prevalence of urothelial carcinoma and the risk of bladder carcinoma, the long-term patient and kidney graft survival is excellent in patients with AAN, provided that prophylactic bilateral ureteronephrectomy and lifelong surveillance of the bladder are performed.

Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study.

BACKGROUND: Tivantinib (ARQ 197), a selective oral inhibitor of MET, has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. We aimed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma. METHODS: In this completed, multicentre, randomised, placebo-controlled, double-blind, phase 2 study, we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy. We randomly allocated patients 2:1 to receive tivantinib (360 mg twice-daily) or placebo until disease progression. The tivantinib dose was amended to 240 mg twice-daily because of high incidence of treatment-emergent grade 3 or worse neutropenia. Randomisation was done centrally by an interactive voice-response system, stratified by Eastern Cooperative Oncology Group performance status and vascular invasion. The primary endpoint was time to progression, according to independent radiological review in the intention-to-treat population. We assessed tumour samples for MET expression with immunohistochemistry (high expression was regarded as ≥2+ in ≥50% of tumour cells). This study is registered with ClinicalTrials.gov, number NCT00988741. FINDINGS: 71 patients were randomly assigned to receive tivantinib (38 at 360 mg twice-daily and 33 at 240 mg twice-daily); 36 patients were randomly assigned to receive placebo. At the time of analysis, 46 (65%) patients in the tivantinib group and 26 (72%) of those in the placebo group had progressive disease. Time to progression was longer for patients treated with tivantinib (1·6 months [95% CI 1·4-2·8]) than placebo (1·4 months [1·4-1·5]; hazard ratio [HR] 0·64, 90% CI 0·43-0·94; p=0·04). For patients with MET-high tumours, median time to progression was longer with tivantinib than for those on placebo (2·7 months [95% CI 1·4-8·5] for 22 MET-high patients on tivantinib vs 1·4 months [1·4-1·6] for 15 MET-high patients on placebo; HR 0·43, 95% CI 0·19-0·97; p=0·03). The most common grade 3 or worse adverse events in the tivantinib group were neutropenia (ten patients [14%] vs none in the placebo group) and anaemia (eight [11%] vs none in the placebo group). Eight patients (21%) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two (6%) patients in the 240 mg group. Four deaths related to tivantinib occurred from severe neutropenia. 24 (34%) patients in the tivantinib group and 14 (39%) patients in the placebo group had serious adverse events. INTERPRETATION: Tivantinib could provide an option for second-line treatment of patients with advanced hepatocellular carcinoma and well-compensated liver cirrhosis, particularly for patients with MET-high tumours. Confirmation in a phase 3 trial is needed, with a starting dose of tivantinib 240 mg twice-daily. FUNDING: ArQule, Daiichi Sankyo (Daiichi Sankyo Group).

Diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease: attributes and limitations of the current modalities.

Cyst infection is a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD) because of the lack of specific manifestations and limitations of conventional imaging procedures. Still, recent clinical observations and series have highlighted common criteria for this condition. Cyst infection is diagnosed if confirmed by cyst fluid analysis showing bacteria and neutrophils, and as a probable diagnosis if all four of the following criteria are concomitantly met: temperature of >38°C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dL and no evidence for intracystic bleeding on computed tomography (CT). In addition, the elevation of serum carbohydrate antigen 19-9 (CA19-9) has been proposed as a biomarker for hepatic cyst infection. Positron-emission tomography after intravenous injection of 18-fluorodeoxyglucose, combined with CT, proved superior to radiological imaging techniques for the identification and localization of kidney and liver pyocyst. This review summarizes the attributes and limitations of these recent clinical, biological and imaging advances in the diagnosis of cyst infection in patients with ADPKD.

Significant rate of hepatitis B reactivation following kidney transplantation in patients with resolved infection.

BACKGROUND: Limited data is available on the risk of hepatitis B virus (HBV) reactivation in patients with resolved infection undergoing kidney transplantation. It is generally thought that this risk is negligible. OBJECTIVES: To evaluate the incidence of HBV reactivation in such patients, and the potential risk factors for reactivation. STUDY DESIGN: Retrospective cohort study including 93 patients transplanted with a kidney between 1995 and 2007 who had evidence of resolved HBV infection (HBsAg negative, anti-HBc positive, anti-HBs positive or negative, and normal liver enzymes). HBV reactivation was defined as HBsAg reversion with HBV DNA>2000 IU/mL. RESULTS: Six patients experienced HBsAg reversion followed by HBV reactivation, 3 within the first post-transplant year. Immunosuppression regimen was similar in patients with and without reactivation. Among patients with reactivation only one was positive for anti-HBs antibodies at time of transplantation; these were progressively lost before reactivation. The odds ratio for reactivation in patients without anti-HBs antibodies at transplantation compared to those with anti-HBs antibodies was 26 (95% CI [2.8-240.5], p=0.0012). In patients with anti-HBs antibody titer above 100 IU/L, no reactivation was observed. CONCLUSIONS: Reactivation rate of resolved hepatitis B is not negligible in patients without anti-HBs antibodies at transplantation. We suggest monitoring of liver tests and HBV serology including HBsAg and anti-HBs antibodies after transplantation as well as vaccination pre- and post-transplantation in all patients, including those with resolved hepatitis B, aiming at maintaining anti-HBs antibody level above 100 IU/L.

Positron-emission computed tomography in cyst infection diagnosis in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Cyst infection remains a challenging issue in patients with autosomal dominant polycystic kidney disease (ADPKD). In most patients, conventional imaging techniques are inconclusive. Isolated observations suggest that (18)fluorodeoxyglucose (¹8FDG) positron-emission computed tomography (PET/CT) might help detect cyst infection in ADPKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Comparative assessment of administrative databases from January 2005 to December 2009 identified 27 PET/CT scans performed in 24 ADPKD patients for suspicion of abdominal infection. Cyst infection was definite if confirmed by cyst fluid analysis. Cyst infection was probable if all four of the following criteria were met: temperature of >38°C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dl, and no CT evidence for intracystic bleeding. Episodes with only two or three criteria were grouped as "fever of unknown origin". RESULTS: Thirteen infectious events in 11 patients met all criteria for kidney (n = 3) or liver (n = 10) cyst infection. CT was contributive in only one patient, whereas PET/CT proved cyst infection in 11 patients (84.6%). In addition, 14 episodes of "fever of unknown origin" in 13 patients were recorded. PET/CT identified the source of infection in nine patients (64.3%), including 2 renal cyst infections. Conversely, PET/CT showed no abnormal ¹8FDG uptake in 5 patients, including 2 intracystic bleeding. The median delay between the onset of symptoms and PET/CT procedure was 9 days. CONCLUSIONS: This retrospective series underscores the usefulness of PET/CT to confirm and locate cyst infection and identify alternative sources of abdominal infection in ADPKD patients.

Liver transplantation and neuroendocrine tumors: lessons from a single centre experience and from the literature review.

Neuroendocrine tumor (NET) metastases represent at this moment the only accepted indication of liver transplantation (LT) for liver secondaries. Between 1984-2007, nine (1.1%) of 824 adult LTs were performed because of NET. There were five well differentiated functioning NETs (four carcinoids and one gastrinoma), three well differentiated non functioning NETs and one poorly differentiated NET. Indications for LT were an invalidating unresectable tumor (4x), and/or a diffuse tumor localization (3x) and/or a refractory hormonal syndrome (5x). Median post-LT patient survival is 60.9 months (range 4.8-119). One-, 3- and 5-year actuarial survival rates are 88%, 77% and 33%; 1, 3 and 5 years disease free survival rates are 67%, 33% and 11%. Due to a more rigorous selection procedure, results improved since 2000; three out of five patients are alive disease-free at 78, 84 and 96 months. Review of these series together with a review of the literature reveals that results of LT for this oncological condition can be improved using better selection criteria, adapted immunosuppression and neo- and adjuvant surgical as well as medical treatment. LT should be considered earlier in the therapeutic algorithm of selected NET patients as it is the only therapy that can offer a cure.

Carbohydrate antigen 19-9 as a diagnostic marker for hepatic cyst infection in autosomal dominant polycystic kidney disease.

The diagnosis of hepatic cyst infection is difficult in patients with autosomal dominant polycystic kidney disease (ADPKD). We hypothesized that carbohydrate antigen 19-9 (CA 19-9), secreted by the biliary epithelium lining the cysts, is overproduced in the case of cyst infection. In this report, we describe 3 patients with ADPKD with hepatic cyst infection, all with functioning kidney transplants, who had markedly increased serum CA 19-9 levels. Furthermore, CA 19-9 level was extremely increased in cystic fluid obtained in 2 of these individuals. Corresponding with clinical improvement, there was a marked decrease in serum CA 19-9 level in all 3 patients. To assess the potential applicability of these findings, serum CA 19-9 was measured in asymptomatic patients with ADPKD with known liver cysts and in controls without ADPKD. Although serum CA 19-9 levels were significantly higher in asymptomatic patients with ADPKD than in controls, they were markedly increased in patients with cyst infection compared with either asymptomatic ADPKD patients or controls. Immunostaining for CA 19-9 showed strong positivity in biliary tree epithelia and cysts of polycystic livers from patients with ADPKD that appeared more intense than in normal livers. Although further study is necessary, these data suggest that serum CA 19-9 level is markedly increased during liver cyst infection in kidney transplant recipients with ADPKD and has potential utility as a diagnostic marker.

Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis.

Fatigue is a common debilitating complication of primary biliary cirrhosis (PBC), the pathophysiologic mechanism of which is poorly understood. Recently, the neuroactive steroid dehydroepinadrosterone sulfate (DHEAS) was reported to be implicated in Chronic Fatigue Syndrome in the absence of liver disease. The present study was undertaken to analyse fatigue scores and their relationship with disease severity and circulating levels of DHEAS as well as its precursors DHEA and pregnenolone in PBC patients with (n=15) or without fatigue (n=10) compared to control subjects (n=11). Fatigue was assessed using the fatigue impact scale (FIS) including cognitive, physical and psychosocial subclasses. Steroids were measured by radioimmunoassay or gas chromatography/mass spectrometry. Plasma concentrations of DHEAS were significantly reduced in PBC patients with fatigue as compared to controls, while those of its precursors DHEA and pregnenolone remained within the control range. Plasma levels of DHEAS in PBC patients were significantly correlated with fatigue severity as reflected by total FIS scores including total (rp=-0.42; p=0.018), as well as the cognitive (rp=-0.37; p=0.03), physical (rp=-0.48; p=0.006) and psychosocial (rp=-0.35; p=0.04) subclasses of fatigue scores. No correlation of fatigue scores was observed with indices of liver function. These findings suggest that reduced levels of the neurosteroid DHEAS may contribute to fatigue in patients with PBC; substitutive therapy using DHEAS or its precursor DHEA could be beneficial in the management of fatigue in patients with low levels of DHEAS.

Octreotide therapy for advanced hepatocellular carcinoma.

Treatment options for advanced hepatocellular carcinoma (HCC) remain limited. Recently, octreotide has been proposed for therapy, although its efficacy remains controversial. Thus, the aim of this open-label pilot study was to evaluate the response of HCC to long-acting octreotide (Sandostatin LAR). Thirty patients were enrolled for this prospective 2-year trial. Initially, patients were given short acting octreotide to ensure drug tolerability. Thereafter, patients received long-acting octreotide 30 mg IM every 4 to 6 weeks. Measurable disease was assessed at 3-month intervals. Five of 30 patients were unable to tolerate the test dose, and 1 patient was reevaluated and underwent hepatic resection. The remaining 24 patients, who received long-acting octreotide, all had advanced stage of disease with multifocal-massive morphology (67%), vascular thrombosis (63%), or extrahepatic spread (17%), but well compensated liver disease. The treatment was well tolerated, except for diarrhea. Median time to tumor progression was 3.6 months, and median survival was 5.1 months. Seven patients (29%) had stable disease (median duration of 8.0 months) with 2 patients demonstrating disease stability for 24 months. In conclusion, although occasional patients appear to have stable disease on long-acting octreotide therapy, overall the beneficial response in terms of time to tumor progression and survival is limited.

The transjugular intrahepatic portosystemic shunt in the treatment of portal hypertension.

The transjugular intrahepatic portosystemic shunt (TIPS) represents a major advance in the treatment of complications of portal hypertension. It is most commonly used in the management of refractory variceal bleeding, where it can be life-saving. Two other indications have been studied in randomized controlled trials: prevention of variceal rebleeding and refractory cirrhotic ascites. These trials have demonstrated that TIPS is superior to standard therapy but is associated with a higher rate of hepatic encephalopathy and with no improvement in survival. Consequently, TIPS is considered a second-line therapy in these situations. TIPS has also been used successfully in the treatment of hepatic hydrothorax, hepatorenal syndrome, severe portal hypertensive gastropathy, Budd-Chiari syndrome and veno-occlusive disease. Its use in these indications has only been reported in small uncontrolled series. TIPS usefulness is limited by two major problems: shunt dysfunction and hepatic encephalopathy. Shunt dysfunction is frequently responsible for the recurrence of complications of portal hypertension, and requires a surveillance program to monitor shunt patency. The use of polytetrafluoroethylene-covered stents may help prevent this complication.

Centrilobular necrosis after orthotopic liver transplantation: association with acute cellular rejection and impact on outcome.

Several studies have linked centrilobular necrosis (CN) to acute cellular rejection (ACR) following liver transplantation. However, it may be difficult to establish the diagnosis of ACR when the classic portal features are absent. The aim of the present study was to identify specific features that would help to recognize ACR in biopsies with CN. One hundred and forty liver biopsies with CN were identified from 97 patients who underwent liver transplantation. The following histopathologic features were assessed: CN, steatosis, lobular inflammation, cholestasis, endothelialitis, and fibrosis. CN was graded semiquantitatively. A number of clinical and biochemical parameters were also recorded. Biopsies with CN were assessed for the presence or absence of ACR and divided into two groups accordingly. The associations of the biochemical, pathologic, and clinical features with ACR were assessed using a multivariate logistic regression model. The outcomes of patients with and without rejection were compared using the Cox proportional hazards regression model. Seventy-four biopsies (52.9%) showed evidence of ACR, and 52 patients (53.6%) had evidence of ACR at the first biopsy with CN. The multivariate analysis showed the presence of cholestasis, lobular inflammation, the ALT level, and time since liver transplantation to be independent predictors of the presence of ACR in biopsies with CN. Patients with ACR on their first biopsy with CN were significantly more likely to experience graft loss compared with patients without ACR. In conclusion, the presence of cholestasis and lobular inflammation on biopsies with CN appeared helpful in predicting its association with ACR.

Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study.

The hepatorenal syndrome (HRS) is related to vasoconstriction of the renal cortex induced by systemic hypovolemia that follows splanchnic vasodilatation as the primary event in the cascade of hemodynamic changes associated with portal hypertension. We evaluated the effects of octreotide, a splanchnic vasoconstrictor, on HRS in cirrhotic patients. We compared the effects of octreotide infusion (50 microg/h) to placebo using a randomized, double-blind, cross-over design over 2, 4-day periods. Nineteen patients were included, and 14 patients could complete the 2 phases of the study (group 1: placebo first; n = 8 and group 2: octreotide first; n = 6) The end point of the study was to evaluate improvement in renal function as defined by a 20% decrease in serum creatinine value after a 4-day treatment as compared with baseline. In all the patients, a normal central venous pressure was maintained by daily intravenous administration of 2 units of albumin. The 2 groups were similar with regard to demographic data and liver and kidney function parameters at baseline. Improvement in renal function was observed in 2 patients after the placebo and 1 patient after octreotide infusion in group 1 and in 2 patients after octreotide infusion and 1 patient after placebo in group 2 (P = not significant). In addition, treatment with octreotide infusion did not result in significant changes in creatinine clearance, daily urinary sodium, plasma renin activity, plasma aldosterone and glucagon levels, or renal and mesenteric artery resistance indices as measured by Doppler ultrasonography. In conclusion, the present study demonstrates that, under our experimental conditions, octreotide infusion combined with albumin is not effective for the treatment of HRS in cirrhotic patients.

What surgeons should know about viral hepatitis and hepatocellular carcinoma.

Most patients with hepatocellular carcinoma (HCC) have viral hepatitis, either hepatitis C (HCV) or hepatitis B (HBV). HCV is an RNA virus that does not integrate into the host genome but likely induces HCC through viral protein: for example, host protein interactions or via the inflammatory response to the virus. Eradication of HCV with interferon plus riboviron therapy may help prevent cancer recurrence in selected patients. In contrast to HCV, HBV is an DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. HBV is usually classified as replicative (DNA-positive in the serum) or nonreplicative (DNA-negative in the serum). Treatment with nucleoside analogs is indicated in most patients with cirrhotic-stage replicating HBV. Nonreplicative stages of this virus do not merit therapy with these agents.

Assessment of fatigue in patients with chronic hepatitis C using the Fatigue Impact Scale.

The aim of this study was to assess the impact of fatigue on the quality of life of patients with chronic hepatitis C (CHC) and to examine its relationship with various parameters of the disease, including viral load. The Fatigue Impact Scale (FIS), a self-report questionnaire, was applied to 92 patients with CHC, and the results were compared to those of an age-matched cohort of 213 healthy blood donors. Fatigue was frequent and disabling, being present in 67% of CHC patients, and the FIS was significantly increased in CHC patients compared to the healthy controls. Fatigue severity was not correlated with the activity of the disease or with the level of viremia. The FIS proved to be a valuable tool to assess this symptom. It should be of help for better evaluation of the clinical spectrum of the disease and should be included in trials assessing the efficacy of therapeutic interventions.

Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma.

Previous experience with OLT for hilar CCA has been discouraging, and survival was dismal. This study demonstrates that carefully selected patients with unresectable hilar CCA can achieve long-term survival after OLT. The survival rate obtained with this protocol (5-year actuarial survival of 87%) is comparable with the overall survival rate of liver-transplant recipients at the authors' institution. In comparison, the best survival rate after OLT for hilar CCA reported in the literature is 64.8% at 5 years in a subset of nine patients with negative lymph nodes. In the absence of a control group, it is difficult to assess with certainty the role of a combination of chemotherapy and radiotherapy, but in some patients it seems to prevent or slow progression of the disease while waiting for an available organ. Treatment-related morbidity, although significant, is not prohibitive. Nevertheless, a considerable proportion of treated patients ultimately was found to have advanced disease precluding transplantation. This finding confirms the importance of the staging laparotomy as an essential component of the protocol.