Screening for head and neck cancer in liver transplant candidates: a review of 11 years of experience at the University of Pittsburgh.

OBJECTIVES/HYPOTHESIS: At our institution, any liver transplant candidate with a recent history of smoking combined with daily use of alcohol prior to a 6-month sobriety period warrants formal evaluation by otolaryngology. Given the significant resource consumption and lack of evidence in support of this strategy, we sought to determine the effectiveness of these guidelines in detecting head and neck cancer. STUDY DESIGN: Retrospective review of clinical database and patient billing records. METHODS: Under an institutional review board-approved protocol, a search was performed for patients seen at our institution's otolaryngology office from 1999 to 2010. This patient list was cross-matched with the patients evaluated for transplant at the University of Pittsburgh Starzl Transplantation Institute during the same timeframe. A search for the diagnosis of head and neck squamous cell carcinoma of the head and neck (HNC) among these patients was carried out through both a National Cancer Institute-affiliated clinical research registry and ICD-9 codes from billing records. Otolaryngology attending physicians were also asked to recall detection of HNC upon screening of this patient population. RESULTS: Of 581 patient evaluations performed by the otolaryngologist for HNC screening prior to liver transplantation from 1999 to 2009, one (0.17% of evaluations) case of HNC was detected. CONCLUSIONS: Given the consumption of resources required for this screening strategy and the limited yield, it appears that current screening guidelines are ineffective and need to be reconsidered.

Combined heart and liver transplantation in a patient with situs ambiguous.

We report the case of 21-year-old man with Fontan circulation failure and end-stage liver cirrhosis, along with situs ambiguous. Combined simultaneous heart and liver transplantation was successfully performed with technical modifications, including rotated implantation and bilateral venous reconstruction.

Hepatitis C recurrence is not adversely affected by the use of donation after cardiac death liver allografts.

Many factors can worsen a recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). We sought to determine whether the use of donation after cardiac death (DCD) livers affects HCV recurrence. From January 2000 to June 2008, 37 HCV patients underwent LT with DCD allografts. The outcomes and severity of HCV recurrence were analyzed along with those for 74 matched control patients with HCV who received donation after brain death (DBD) livers. The 2 groups had similar donor and recipient characteristics, immunosuppression regimens, rates of acute cellular rejection (ACR), and HCV profiles. DCD patients had a higher incidence of primary nonfunction (19% versus 3%, P = 0.006) and significantly higher peak aspartate aminotransferase levels in comparison with DBD subjects, suggesting a greater degree of ischemia/reperfusion injury. Although the survival rates were not significantly different, DCD recipients had lower 1- and 5-year patient survival rates (83% and 69% versus 84% and 78%, respectively, P = 0.75) and graft survival rates (70% and 61% versus 82% and 74%, respectively, P = 0.24). Three hundred fourteen protocol and clinically indicated liver biopsy procedures were performed within 6 years after transplantation, and mixed modeling analysis showed that fibrosis progression rates were similar for the 2 groups (0.6 fibrosis units/year according to the Ishak modified staging system). The rates of severe HCV recurrence (retransplantation or death due to recurrent hepatitis C and/or the development of stage 4/6 fibrosis or worse within 2 years) were similar [3 DCD patients (8%) versus 11 DBD patients (15%), P = 0.38], and cytomegalovirus infection (hazard ratio = 7.9, P = 0.002, 95% confidence interval = 2.1-28.9) and ACR (hazard ratio = 6.2, P = 0.002, 95% confidence interval = 2.0-19.7) were the only independent risk factors for severe recurrence. In summary, although there was a trend of poorer overall outcomes in DCD patients, the use of DCD livers did not appear to adversely affect HCV recurrence after LT.

Simultaneous pancreatectomy and liver transplantation: a single-institution experience.

BACKGROUND: There is wide debate among transplant centres regarding the indications for liver transplantation (LT) in malignancy. We report a single-centre experience with simultaneous LT and total pancreatectomy or pancreaticoduodenectomy. METHODS: We performed a retrospective review of a prospectively established database of patients who underwent simultaneous LT and total pancreatectomy or pancreaticoduodenectomy. We analysed demographics, indications, approach and outcomes. RESULTS: Between 1991 and 2006, 11 patients (four male; median age 51 years) underwent simultaneous LT and total pancreatectomy (n = 4) or pancreaticoduodenectomy (n = 7). Indications included metastatic neuroendocrine tumour (n = 5), hepatocellular carcinoma (n = 2), metastatic periampullary adenocarcinoma (n = 1), periampullary adenocarcinoma with end-stage liver disease (ESLD) (n = 2) and intraductal papillary mucinous neoplasm with ESLD (n = 1). The three patients with ESLD had non-alcoholic steatohepatitis, primary sclerosing cholangitis or cryptogenic cirrhosis. Median postoperative length of stay was 31 days (21-110 days). Overall median survival was 101 months (95% confidence interval 70.6-131.4). One-year survival was 91%, 2-year 90%, 5-year 67% and 10-year 33%. Postoperative complications included: re-operation (n = 4); anastamotic leak (n = 2); abdominal abscess (n = 3), and organ rejection (n = 1). CONCLUSIONS: We report a series of pancreatectomy or pancreaticoduodenectomy and simultaneous LT in patients with extensive malignancy or impending liver failure that prevented pancreatectomy. This series provides evidence that combined pancreatic resection and LT can be a strategy in both radical resections and cases with ESLD that would otherwise preclude operative intervention.

Extrahepatic portal vein aneurysm--report of six patients and review of the literature.

Extrahepatic portal vein aneurysm is a rare condition. We report six patients with extrahepatic portal vein aneurysm, four of whom were surgically treated. In addition, a review of the literature was performed to examine natural history, management, and outcomes regarding portal vein aneurysm. Patients seen at our institution with extrahepatic portal vein aneurysm greater than 1.9 cm in diameter were reviewed (1998 to 2006). There were five females and one male; median age was 66.5 (30-77). Computed tomography (CT) scan was utilized for diagnosis in all cases. The median diameter of the aneurysm was 4.7 cm (2.7-6.0). Indications for surgery included gallstone pancreatitis, mass effect on the adjacent duodenum, a peripancreatic mass, and liver cirrhosis. Three patients underwent aneurysm resection, and one patient had an orthotropic liver transplant. Two patients were managed with observation. The median follow-up from first presentation and surgery was 50 months (9-181) and 5 months (2-73), respectively. At last follow-up, five patients were alive with radiologically proven portal vein patency. One patient died 2 months after liver transplantation. There was no case of aneurysmal rupture. One patient had intramural thrombus at presentation that resolved with conservative treatment. This report suggests that symptomatic aneurysms can be safely resected with excellent patency.

Rituximab (chimeric anti-CD20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center.

BACKGROUND: Occurrence of posttransplant lymphoproliferative disorder (PTLD) after transplantation is known. Drastic reduction or withdrawal of immunosuppression with anti-viral therapy for Ebstein-Barr virus (EBV) is the primary treatment for all PTLD. Many PTLD are B cell in origin have CD20 antigen on the cell surface. Rituximab is a chimeric anti CD20 antibody, which has been used to treat PTLD with variable success. This study aims to report long-term experience with rituximab for PTLD from a single center. METHODS: Seventeen patients (13 male, 4 female, mean age 51.2 years) received rituximab to treat PTLD. Five patients received rituximab with drastic reduction in immunosuppression (primary). Nine patients received rituximab after failure of primary therapy (rescue) and three patients received it after resolution of PTLD (prophylactic). Mean follow-up period was 60 months. RESULTS: Overall 1-, 3-, and 5-year patient survivals were 64.7%, 47.1% and 35.3%, respectively. In the primary group, three patients had complete and one had partial response; however, only two (40%) patients are currently alive. In the rescue group, none of the patients had a complete response, four patients had partial response, and only two (22%) patients are currently alive. In the prophylactic group, two patients died at 28 and 41 months due to recurrence and graft failure, respectively. CONCLUSION: Sixty percent (3 of 5) of patients who received rituximab as primary therapy had complete resolution, and 44% (4 of 9) of patients who received it as rescue therapy had partial response. Overall 5-year patient survival was a disappointing 35%.

Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years.

BACKGROUND: Chronic liver disease often leads to amenorrhea in women of childbearing age. There are several reports of successful pregnancy after liver transplantation (LTx) with cyclosporine A immunosuppression. Tacrolimus has been increasingly used in solid-organ transplantation, and the effect of the drug on pregnancy is still of interest to clinicians. This study updates our single-center experience. METHODS: All pregnancies after LTx with tacrolimus immunosuppression were followed prospectively. Patients' clinical courses during pregnancy and labor along with gestational period and birth weight were catalogued. Changes in liver function, renal function, and immunosuppression also were recorded. The birth weight percentile was calculated on the basis of the gestational period using a standard chart. RESULTS: Thirty-seven mothers delivered 49 babies. Three mothers delivered three times, and six mothers delivered two times. Thirty-six mothers (97%) survived the pregnancy, and 36 allografts (97%) survived. The one death and graft loss was in a patient who demonstrated infra-aortic arterial graft, which clotted by the gravid uterus during labor. The patient developed a gangrenous liver and died before she could undergo retransplantation. The mean gestational period was 36.4+/-3.2 weeks, excluding two premature deliveries at 23 and 24 weeks gestation. Twenty-two babies (46.9%) were delivered by cesarean section, and the other babies were delivered vaginally. In addition to the two premature babies, one baby, who was born to a mother with Alagille syndrome, died from congenital birth defects. The rest of the newborns survived. The mean birth weight was 2,797+/-775 g, with 38 babies (78%) weighing more than 2,000 g. The mean birth weight percentile to gestational period was 54+/-23. Four babies (8.5%) had a birth weight percentile of less than 25, and 28 babies (59.6%) had a birth weight percentile greater than 50. Twelve patients demonstrated an increase in hepatic enzymes without jaundice during the pregnancy. All of them responded to augmentation of immunosuppression. CONCLUSION: The present report reconfirms the safety of tacrolimus during pregnancy after LTx. Preterm delivery and low birth weight seem to be a persistent problem in all solid-organ transplantation under any form of immunosuppression. However, toxemia of pregnancy and new onset of hypertension seem to be have a low occurrence with the use of tacrolimus.

Ribavirin dose modification based on renal function is necessary to reduce hemolysis in liver transplant patients with hepatitis C virus infection.

Hepatitis C virus (HCV) is currently the most common etiology for liver transplantation (LTx) in the United States. A significant number of patients develop recurrent HCV after LTx. Although there is no completely satisfactory treatment for recurrent HCV, a combination of interferon-alpha (INF) and ribavirin remains the most widely used. Ribavirin is eliminated through the kidneys and tends to accumulate in the presence of renal dysfunction. The primary side effect of ribavirin is hemolysis. The goal of the present study was to correlate the incidence of hemolysis with renal function in LTx patients with recurrent HCV who were being treated with ribavirin. The incidence of hemolysis and the renal function were examined in 72 liver transplant patients (58 male and 14 female patients) with recurrent HCV receiving INF (3 million units, three times per week) and ribavirin (initial dose of 400 mg twice daily). Patients were grouped according to the decrease in the percentage of hematocrit after the introduction of ribavirin, with their baseline serum creatinine and creatinine clearance calculated using the Cockcroft-Gault formula. The decrease in the percentage of hematocrit after ribavirin treatment was also examined with respect to creatinine clearance as a continuous variable. In addition, for purposes of presentation, patients were analyzed in three groups: creatinine clearance of >/= 70 mL/min (group A), creatinine clearance < 70 mL/min and >/= 40 mL/min (group B), and creatinine clearance < 40 mL/min (group C). Forty-five (62.5%) patients experienced a decrease in hematocrit (Hct) >/=15% after starting INF and ribavirin. The mean serum creatinine was 1.3 +/- 0.5 mg/dL (median, 1.3) in this group, and the mean calculated creatinine clearance was 71 +/- 29 mL/min (median, 66.47). In the 27 patients who did not show a significant decrease (< 15%) in hematocrit, the mean serum creatinine was 1.1 +/- 0.3 mg/dL (median, 1.0) and the mean creatinine clearance was 95 +/- 39 (median, 96) mL/min (P =.018). On continuous variable of calculated creatinine clearance, there was a trend in the decrease in hematocrit after ribavirin treatment compared with pretreatment (P =.09). However, the rate of hemolysis was significantly different in group A (53.7%), group B (70.8%), and group C (100%) (P =.042). Patients on INF and ribavirin therapy who experienced hemolysis had significantly higher serum creatinine levels and lower creatinine clearances compared with those who did not have hemolysis. The incidence of hemolysis was significantly associated with higher serum creatinine and decreased creatinine clearance. Because ribavirin is eliminated by the kidneys, this observation points to the need for adjustments in the dose of this agent in LTx patients, who tend to have some degree of renal dysfunction, to reduce the incidence of hemolysis. Further pharmacokinetic studies of ribavirin in LTx patients with varying degrees of renal function may allow the development of an algorithm for the safer use of ribavirin in HCV-positive LTx patients.