Massive venous thrombosis of inferior vena cava as primary manifestation of renal Ewing's sarcoma.

We report an extraordinarily rare case of a 17-year-old male with an extraskeletal Ewing's sarcoma (ESS) of the kidney and a massive thrombosis involving the inferior vena cava (IVC), from the iliac axis to the right atrium. This onset resembled renal cell carcinoma (RCC), although histological examination revealed it was an extraskeletal Ewing's sarcoma/peripheral neuro-ectodermal tumor (EES/PNET). EES/PNET should benefit from neoadjuvant chemotherapy to reduce the risk of metastasis and of recurrent disease due to delay in suitable treatment. Therefore, in the presence of a renal mass with tumor extension of IVC, it is reasonable to bear in mind that other tumors, apart from RCC, could occur. In such cases, a US or CT-scan guided biopsy could be useful.

Significant improvement in patient survival after renal transplantation in the last decade.

INTRODUCTION: The extremely good results of renal transplantation have favored the use of pre-emptive procedures for treatment of patients with end-stage renal disease before entering dialysis, but still some concerns exist about patient survival. The aim of this study was to analyze the evolution of death rates and the causes of mortality among recipients of procedures performed between 1970 and 2007. METHODS: We examined the outcomes at 1, 5, 10, and 15 years follow-up of 793 adults who underwent primary or repeat renal transplantation from living or deceased donors between January 1, 1970 and December 31, 2007. To evaluate the impact of immunosuppressive regimens on patient survivals, we considered 3 time intervals: the precyclosporine era, the cyclosporine era, and the postcyclosporine era. RESULTS: During follow-up 115/793 (14.5%) renal transplant recipients died. There was a significant decrease in the overall mortality rate over the years. Patients who underwent transplantation more recently in the postcyclosporine era (1997-2007) showed a mortality rate of 1.8% (7/394) at 1 year and 3.3% (13/394) at 5 years, significantly lower than in previous periods. There was no significant change in the most frequent causes of death: cardiovascular diseases and sepsis. CONCLUSION: Our data indicated a significant improvement in patient survival after renal transplantation over the last decade. These data are significantly better than those reported for dialysis treatment thus supporting the strategy of pre-emptive transplantation for end-stage renal disease.

High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats.

AIMS/HYPOTHESIS: Incretins are hormones released by enteroendocrine cells in response to meals, depending upon absorption of nutrients. The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP). METHODS: Forty male Wistar rats, 4 months old, were randomised into two groups; one group received a chow diet and the other one received a purified tripalmitin-based HFD ad libitum. An OGTT was performed every 10 days and histological and immunofluorescence evaluations of the duodenum were obtained at 60 days from the beginning of the diets. Plasma glucose, insulin, GIP and glucagon-like peptide-1 (GLP-1) levels were measured. Immunofluorescence analysis of duodenal sections for pancreatic duodenal homeobox-1 (PDX-1), KI67, GLP-1, GIP and insulin were performed. RESULTS: Compared with chow diet, HFD induced a progressive significant increase of the glucose, insulin and GIP responses to OGTT, whereas GLP-1 circulating levels were reduced over time. After 60 days of HFD, cellular agglomerates of KI67 and PDX-1 positive cells, negative for insulin and GLP-1 but positive for GIP staining, were found inside the duodenal mucosa, and apoptosis was significantly increased. CONCLUSIONS/INTERPRETATION: With the limitation that we could not establish a causal relationship between events, our study shows that HFD stimulates duodenal proliferation of endocrine cells differentiating towards K cells and oversecreting GIP. The progressive increment of GIP levels might represent the stimulus for insulin hypersecretion and insulin resistance.

Study of the effects of transoral gastroplasty on insulin sensitivity and secretion in obese subjects.

BACKGROUND AND AIMS: Transoral gastroplasty (TOGA) recently emerged as a new, feasible and relatively safe technique for the surgical treatment of obesity. However, so far there are no data on the effects on insulin sensitivity in the literature. Our aim is to evaluate the effect of TOGA on insulin sensitivity and secretion. METHODS AND RESULTS: Nine glucose normo-tolerant obese subjects (age:41+/-6 years; BMI:42.49+/-1.03 kg/m(2)) were studied. Fat-free mass (FM) and fat mass (FM) were assessed by bioelectrical impedance; plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT) before and 3 months after the operation. Insulin sensitivity was calculated using the oral-glucose insulin-sensitivity index, and insulin secretion by C-peptide deconvolution. Three months after surgery, a significant (P=0.008) reduction of BMI to 35.65+/-0.65 kg/m(2), with a decrease of FM and FFM from 57.22+/-2.19 to 41.46+/-3.02 kg (P=0.008) and from 59.52+/-1.36 to 56.67+/-1.10 kg (P=0.048) respectively, was observed. Insulinemia was significantly reduced at fast and at 120 min after OGTT; in contrast, no significant change in glucose concentration was observed. Insulin sensitivity significantly increased (348.45+/-20.08 vs. 421.18+/-20.84 ml/min/m(2), P=0.038) and the incremental area of insulin secretion rate (total ISR) significantly decreased (from 235.05+/-27.50 to 124.77+/-14.50 nmol/min/m(2), P=0.021). Total ISR correlated with weight, BMI and FM (r=0.522, P=0.028; r=0.541, P=0.020; r=0.463, P=0.049, respectively). BMI represented the most powerful predictor of ISR decrease (R(2)=0.541, P=0.020). CONCLUSION: Transoral gastroplasty allows a significant weight loss 3 months after the intervention as well as an amelioration of insulin sensitivity with subsequent reduction of the insulin secretion.

Bariatric surgery: unstressing or boosting the beta-cell?

Bariatric surgery is the most effective therapy for severe obesity in terms of reduction of morbidity and mortality and quality of life improvement. Different bariatric procedures distinctly differ with regard to their effectiveness to reduce body weight and to improve morbidities, such as type 2 diabetes. In this regard, the most effective procedures are bilio-pancreatic diversion (BPD) and duodenal switch procedure curing 98.9% of the diabetes patients, followed by Roux-en-Y gastric bypass (RYGB) with 83.7% success rate, by gastroplasty with 71.6% and by gastric banding with 47.9%. Interestingly, a net improvement up to resolution of type 2 diabetes has been consistently reported few days after RYGB and BPD. RYGB promotes incretin secretion which, in turn, stimulates insulin secretion while insulin sensitivity is slightly improved. Rarely, the long-term effect of incretin hypersecretion might result in hypertrophy and hyperplasia of the islets of Langerhans, otherwise known as nesidioblastosis, associated with hyperinsulinaemia and severe postprandial hypoglycaemia. In contrast, BDP improves insulin resistance to a greater extent and results, in the long run, in supra-normal values of insulin sensitivity with subsequent reduction of insulin secretion. The mechanism allowing diabetes resolution after surgical intestinal manipulation is extremely interesting but only partially understood.

Prospective clinical trial comparing two immunosuppressive regimens, tacrolimus and mycophenolate mofetil versus everolimus and low-dose cyclosporine, in de novo renal transplant recipients: results at 6 months follow-up.

OBJECTIVE: The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus. PATIENTS AND METHODS: Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids. RESULTS: At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 +/- 38 vs EVL 250 +/- 55 mg/dL; P < .003). CONCLUSIONS: This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.

Cardiovascular risk profile in kidney transplant recipients treated with two immunosuppressive regimens: tacrolimus and mycophenolate mofetil versus everolimus and low-dose cyclosporine.

OBJECTIVE: The aim of this prospective study was to compare the cardiovascular risk (CVR) profile in patients treated with 2 different immunosuppressive regimens: tacrolimus and mycophenolate mofetil (TAC) compared with everolimus and low-dose cyclosporine (EVL). PATIENTS AND METHODS: Sixty consecutive renal transplant recipients prospectively assigned to TAC (n = 30) or to EVL (n = 30) were followed for 6 months. TAC group immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil (MMF), and steroid. EVL group immunosuppression consisted of basiliximab, everolimus, and low doses of cyclosporine and steroid. Main CVR factors analyzed were: hypertension, dyslipidemia, posttransplant diabetes mellitus, and weight gain. RESULTS: Six months posttransplantation, patients in the EVL group showed significantly higher mean serum cholesterol (P < .003) and serum triglyceride levels (P < .027), as well as a greater number of patients were receiving statin treatment (P < .05). Mean systolic blood pressure, mean diastolic blood pressure, number of patients treated for hypertension, number of antihypertensive medications prescribed per patient, posttransplant weight gain, and posttransplant diabetes mellitus were not significantly different among the EVL and TAC groups after 1, 3, and 6 months posttransplantation. CONCLUSIONS: This study showed that at 6 months posttransplantation, patients on EVL displayed significantly greater dyslipidemia with respect to the TAC group. A longer follow-up will be necessary to discover whether the presence of everolimus in the immunosuppressive regimen provides significant benefits for the CVR of renal transplant recipients.

Long-term clinical impact of vesicoureteral reflux in kidney transplantation.

INTRODUCTION: It is unclear whether the presence of vesicoureteral reflux (VUR) after renal transplantation compromises long-term graft function. The aim of this study in renal allograft recipients with a history of late recurrent urinary tract infections (UTI) was to determine whether the presence of VUR conferred an increased risk of long-term graft dysfunction. METHODS: We included 37 renal allograft recipients, who were at least 2 years after transplantation and had a history of at least 1 recurrent UTI per year underwent voiding cystourethrograms (VCUG). The presence and severity of VUR were graded with severity scores ranging from G1 to G5. RESULTS: Of the 37 patients, 15 (41%) showed low grades of reflux (G1-3) on VCUG. Patient and graft survivals were not significantly different in the VUR group (n = 15) compared with the no VUR group (n = 22) at 1, 3, or 5 years. Renal function assessment by means of serum creatinine (Cr) concentration also demonstrated similar results in both groups at 1, 3, and 5 years: 5 y mean Cr: VUR 1.5 +/- 0.6 mg/dL versus no VUR 1.8 +/- 1.1 mg/dL (P = NS). No difference was also observed in the 2 groups in the number of UTI episodes for each patient per year. CONCLUSIONS: In patients with late UTIs, the presence of low-grade VUR did not affect long-term graft function. There was no indication for a operative repair of low-grade VUR.

The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI <35 kg/m2.

AIMS/HYPOTHESIS: To aim of the study was to investigate the effect of bilio-pancreatic diversion (BPD) on type 2 diabetes in patients with BMI <35 kg/m(2). METHODS: OGTTs were performed and anthropometric data were compared between five diabetes patients (BMI 27-33 kg/m(2)) following BPD and seven diabetes patients after a low-energy diet. Insulin secretion was computed by C-peptide deconvolution. A euglycaemic-hyperinsulinaemic clamp was performed only in the BPD group and the M value measured. RESULTS: One month after BPD, fasting and 2 h post-OGTT glycaemia decreased from 15.22 +/- 3.22 to 6.22 +/- 0.51 mmol/l (p = 0.043), while insulin sensitivity increased significantly. No significant changes were observed in the low-energy diet group. Insulin secretion did not differ significantly after either intervention. Diabetes amelioration (change in HbA(1c) level) was observed up to 18 months after BPD without pharmacological therapy. CONCLUSIONS/INTERPRETATION: BPD can achieve adequate control of type 2 diabetes also in patients with BMI <35 kg/m(2). The rapid postoperative remission of diabetes is primarily related to an improvement in insulin sensitivity.

Donor risk index and organ patient index as predictors of graft survival after liver transplantation.

In liver transplantation the identification of risk factors and the risk quantification for each single case represent a field of great interest. There are donor-related and recipient-related risk factors. Donor risk index (DRI) was retrospectively calculated in 223 liver transplant cases. We did not include patients with preoperative diagnosis of hepatocarcinoma and retransplants. The cases were stratified into two classes according to the DRI (low risk, DRI<1.7, and high risk, DRI >or= 1.7). A new index, namely the organ patient index (OPI) was calculated adding the Model for End-stage Liver Disease (MELD) score to the DRI. Patients were stratified into two classes according to the OPI (low risk, OPI 2.85). The cases with low DRI (n=144) showed better survival than the cases with high DRI (n=82; P< .02). The cases with low OPI (n=173) showed better survival than cases with high OPI (n=50; P< .01). The OPI predicted outcomes better than DRI, increasing the gap in the long-term graft survival between the low- and the high-risk class. The inclusion of the MELD in the new index allowed better prediction of graft survival.

Treatment of chronic hepatitis C virus infection with pegylated interferon and ribavirin in cirrhotic patients awaiting liver transplantation.

Successful treatment of chronic hepatitis C virus (HCV) infection can prevent reinfection after orthotopic liver transplantation (OLT). Pegylated interferon (PEG-IFN) may ameliorate virological response (VR), making the risk-to-benefit ratio of therapy favorable in waiting list patients. From January 2001 to April 2006, we treated 15 HCV cirrhotics with PEG-IFN alpha-2b (1.5 microg/kg/week) and ribavirin (RIBA; >or=10.6 mg/kg/d). Their mean age was 51.5 years. There were 9 men. In 6 cases the genotype was 1b. With Child-Pugh scores >or=9 (range 9-12) and Model for End-Stage Liver Disease (MELD) scores >or=14 (range, 14-22). Adverse events occurred in all subjects: thrombocytopenia (<40,000/microL) in 8; neutropenia (<700/microL) in 10; anemia (Hb <8.5 g/dL) in 1; grade III hepatic encephalopathy in 2; pelvic infection in 1; variceal hemorrhage in 1; and hepatocellular carcinoma (HCC) recurrence in 1. Adverse events caused treatment withdrawal in 6 (40.0%) and RIBA and/or PEG-IFN dose reduction in 10 (66.6%). Early VR (EVR) was obtained in 9 subjects (60.0%), end-of-treatment (EOT) VR in 7 (46.6%), and sustained VR (SVR) in 3 (20.0%). Three subjects--2 nonresponder and 1 breakthrough--were transplanted at 25, 23, and 16 months after the EOT, respectively. Three subjects died at 6, 8, and 15 months after the EOT due to HCC, spontaneous bacterial peritonitis, and liver failure. Nine patients are awaiting OLT. The risk-to-benefit ratio is against PEG-INF and RIBA treatment of severely decompensated cirrhotics infected with genotype 1 awaiting OLT, but therapy is probably beneficial in genotype 2 subjects, due to an expected SVR rate of more than 40%. However, one must carefully consider the high risk for severe adverse events.

Acute decompensation and absence of brain and kidney dysfunction predict long-term efficacy of plasma exchange in hyper-bilirubinemic cirrhotic patients awaiting liver transplantation.

Various artificial liver support systems are currently used in patients with decompensated chronic liver disease or acute liver failure as a bridge to recovery or to orthotopic liver transplantation (OLT). Between June 2004 and September 2006, 9 subjects were treated with plasma exchange (PE) for acute decompensation on chronic liver disease or chronic decompensation in end-stage liver disease. All of them were awaiting OLT or were listed at the moment of decompensation. Grade II to III hepatic encephalopathy (HE) was present in 4 patients, significant renal dysfunction in 3 patients, and ascites in 6 patients. Baseline serum total bilirubin was 35.1+/-11.2 mg/dL (mean value+/-SD). The patients underwent a mean of 12.1 2-hour exchanges over 1 to 8 weeks. The 3 who recovered were alive after a mean follow-up of 22.7+/-10.3 months. There were 3 patients who underwent transplantation and 3 who died due to liver failure during treatment. Only subjects with acute decompensation and without HE or significant renal dysfunction survived without OLT. PE did not significantly modify the grade of HE or the renal function. PE seemed to be a safe, long-term, effective therapeutic option for acute decompensation among subjects with chronic liver disease without brain or renal dysfunction.

Liver transplantation for hepatitis B virus patients: long-term results of three therapeutic approaches.

The indications for liver transplantation among patients with post-hepatitis B virus (HBV)-related cirrhosis have changed over the past 35 years. We reviewed the long-term results of 47 patients treated with liver transplantation for HBV-related cirrhosis. Patients were classified into 3 groups according to the perioperative regimen. In the initial experience, no immunoprophylaxis was adopted (no-IP; n=5). From 1988-1996, an immunoprophylaxis scheme was adopted (HBIg; n=16). From 1997-2007, we adopted the combination of lamivudine and HBIg (LAM-HBIg; n=26). We calculated the prevalence of serological reinfection and patient survival at 1 to 20 years, using the 3 regimens. The recurrence rate was 75% in the group of untreated patients; 30% in the HBIg group; and 9% in the LAM-HBIg group. The overall survival was 67% at 5 years, and 64% at 10 and 20 years. The long-term survival for each of the 3 therapeutic approaches, namely, for the patients who did not receive any treatment, for the HBIg group, and for the LAM-HBIg group, were 20%, 50%, and 84%, respectively. We suggest to use the LAM-HBIg combination.

Donor-recipient MELD-based match in a patient who required three liver grafts in the era of nonstandard donors: case report.

In recent studies, nonstandard donors and high Model for End-stage Liver Disease (MELD) values have been indicated as risk factors for both graft survival and patient survival. A recent debate concerns which donor and recipient match guarantees the best results in terms of early and late survival. To emphasize the role of the donor-recipient match, we have reported herein a complex case of a patient who changed his preoperative risk status, being transplanted three times using donors of different risk levels. At each transplant, the patient moved to a higher MELD class: first transplant MELD=22; second transplant MELD=37; third transplant MELD=38. Only at the third transplant did the patient recover. Besides the liver, almost all his organs (kidneys, heart, lungs) recovered in a few weeks, as well. Unfortunately, severe cortical and subcortical brain damage remained a crucial limiting impairment, leading to death 5 months later, due to pulmonary infection, yet with a perfectly working liver. We underlined the role of donor factors to predict the outcome after liver transplantation in the MELD era.

High saturated-fat diet induces apoptosis in rat enterocytes and blunts GIP and insulin-secretive response to oral glucose load.

Lipoapoptosis has been described in many organs and tissues, but never in enterocytes. We hypothesized that a high saturated-fat diet can induce duodenal enterocyte apoptosis and impair gastric inhibitory polypeptide (GIP) secretion. Forty male Wistar rats, approximately 4 months old, were randomized on standard laboratory or purified tripalmitin-based high-fat diet (59% calories). An oral-glucose tolerance test was performed after 30 and 90 days of diet to measure plasma glucose, insulin and GIP. Duodena were processed for histology and immunohistochemistry by transferase-mediated dUTP nick end-labeling (TUNEL) method. Apoptosis was confirmed by enzyme-linked immunosorbent assay. Glycemic response was significantly higher (P < 0.01 vs controls) in rats after 90 days. Insulin curve was markedly increased at 30 days, while it was blunted at 90 days. GIP area under the curve was 425.6 +/- 67.6 ng ml(-1) at 30 days vs 150.2 +/- 33.4 ng ml(-1) in controls (P < 0.001) and dropped to 53.8 +/- 25.8 ng ml(-1) at 90 days (P < 0.0001). TUNEL-positive nuclei were 66.08+/-26.19 at 30 days 57 (34.58+/-17 in controls, P < 0.05) and 216.99 +/- 129.42 nuclei per mm(3) at 90 days (38.75 +/- 18.36 in controls, P < 0.0001). A high saturated-fat diet stimulates GIP secretion but with time induces apoptosis of duodenal villi epithelium, showing for the first time that enterocytes are also prone to lipoapoptosis. The reduction of circulating GIP levels might contribute to hypoinsulinemia and hyperglycemia.

Dyslipidemia can reduce the immunosuppressive effects of cyclosporine.

AIMS: Dyslipidemia is a significant risk factor for the development of atherosclerotic disease and of chronic allograft rejection. Few data are available on the effects of dyslipidemia on the immunosuppressive action of immunosuppressive agents. We investigate the in vitro effects of lipids solution on the immunosuppressive action of cyclosporine (CsA). METHODS: Peripheral blood mononuclear cells (PBMC) were PHA or OKT3 activated in vitro with/without different concentrations of Intralipid solution (INT, range 0.5% to 15%). CsA inhibition of activation was measured after a 3 day incubation, by adding H3-thimidine. The intracellular concentration of CsA was measured by radioimmunoassay and related to the CsA inhibitory effects. RESULTS: Increasing INT concentration in the medium, CsA inhibition of PBMC activation by PHA or OKT3 was reduced from 72+/-13% to 8+/-2% and from 80+/-10% to 18+/-3%, respectively. A significant reduction of the intracellular CsA concentration was also evident with increasing INT concentrations and was related to the inhibitory activity of CsA. CONCLUSIONS: These results suggest that dyslipidemia may reduce the availability of intracellular CsA concentration to inhibit the immune activation process and may explain the relationship between dyslipidemia and chronic allograft loss.

Higher incidence of acute rejection in renal transplant recipients with low everolimus exposure.

Everolimus (EVL) has shown a potential to reduce nephrotoxicity associated with cyclosporine (CsA) while providing similar protection against rejection. We analyzed the incidence of acute rejection episodes (ARE) among 20 cadaveric renal transplant recipients treated with the combination of EVL + CsA. Immunosuppression consisted of basiliximab induction given pretransplant and on day 4 posttransplant; EVL at a starting dose of 1.5 mg/day followed by concentration control to trough levels of 3 to 8 ng/mL by day 7; CsA at a starting dose of 4 mg/kg per day and then concentration controlled with C2 monitoring (C2 500-700 ng/mL); and steroids in a tapering regimen to reach 5 mg by day 30. The overall incidence of ARE was 25%. On postoperative day 7, patients with ARE showed significantly lower mean EVL trough concentrations compared with those not experiencing ARE (NO ARE: 2.2 +/- 2.1 ng/mL vs 4.8 +/- 2.4 ng/mL) (P = .05). The CsA C2 values were close to the lower end of the target range on day 3 (583 +/- 334 ng/mL). All rejecting grafts were functioning at 3 months posttransplantations, but mean serum creatinine was higher in the ARE group (ARE 2.2 +/- 0.7 mg/dL vs 1.1 +/- 0.2 NO ARE; P = .04). In conclusion, whenever EVL is used in combination with CsA to protect kidney transplant patients against the risk of acute rejection, a threshold of 3 ng/mL must be reached in the first week posttransplantation. We suggest careful monitoring of EVL exposure and increased EVL starting doses.

Posttransplant lymphoproliferative disorders after liver transplantation: analysis of early and late cases in a 255 patient series.

We reviewed the incidence and the impact of posttransplant lymphoproliferative disorders (PTLDs) on patient survival among a consecutive series of 255 patients. Five cases of PTLD were observed in adults: two cases were early (less than 1 year) and three cases, late lymphomas. The EBV positivity and the degree of immunosuppression were the main risk factors. We labeled cases as early or late according to whether the time elapsed from the transplant to the first clinical evidence of PTLD was less than 12 months. The median time from transplant to diagnosis of PTLD was 8 (early) and 108 (late) months. All cases were treated by reduction in immunosuppressive therapy with conventional chemotherapy and rituximab. The early cases with lymphoma located at the hepatic hilum died due to local complications (biliary sepsis and hemobilia), after an initial partial response to chemotherapy. The three patients with late cases are in remission after a mean follow-up of 23 months.