Porcine endogenous retrovirus released by a bioartificial liver infects primary human cells.

BACKGROUND: Porcine endogenous retrovirus (PERV) remains a safety risk in pig-to-human xenotransplantation. There is no evidence of in vivo productive infection in humans because PERV is inactivated by human serum. However, PERV can infect human cell lines and human primary cells in vitro and inhibit human immune functions. AIMS: We investigated the potential of primary porcine liver cells to transmit PERV to primary human cells in a bioreactor-based bioartificial liver (BAL). METHODS: Primary human hepatocytes, endothelial cells and the human cell line HEK 293 were exposed to supernatants from BAL or from the porcine cell line PK-15. PERV polymerase-specific reverse-transcriptase polymerase chain reaction (RT-PCR) and PCR were used to investigate PERV transmission to human cells. An assay of RT activity was used to detect the presence of retrovirus in the supernatants of BAL, primary human hepatocytes and endothelial cells. RESULTS: Primary human hepatocytes (hHep), endothelial cells and HEK 293 cells were reproducibly infected by PERV, originating from primary porcine liver cells within the BAL and from PK-15 cells. Infected cells were positive for PERV-specific DNA and RNA after 8-10 days on an average, and RT activity was detectable in the supernatants of infected hHep and HEK 293 cells. CONCLUSION: A risk of PERV infection in human cells is documented in this study, indicating that short-term contact of primary porcine liver cell supernatants with primary human cells could result in PERV transmission.

Impact of intraoperative radiotherapy (IORT) on survival of patients with unresectable hilar cholangiocarcinoma.

BACKGROUND/AIMS: The cure or long-term survival of hilar cholangiocarcinoma patients can only be achieved after complete tumor resection. Many patients though suffer from unresectable hilar cholangiocarcinoma, and palliative treatment is therefore the only therapeutic option. In cases of unresectable bile duct cancer, intraoperative radiotherapy (IORT) is an additional option during surgery. The aim of this study was to compare the efficacy of IORT to surgery alone in patients with unresectable hilar cholangiocarcinoma. METHODOLOGY: Palliative IORT (group 1) was performed on 9 patients (4 female/5 male); surgery alone (group 2) was performed in a case-matched group of 9 patients (4 female, 5 male) with unresectable hilar cholangiocarcinoma. The mean ages were 52.9 years (group 1) and 57.2 years (group 2). The two groups had comparable local tumor extension and stages of tumor disease according to UICC 6th edition. Group 1 was also compared to all 36 patients (n=36) suffering from unresectable cholangiocarcinoma treated without IORT (Group 3). RESULTS: The survival of patients after IORT was significantly improved compared to surgery alone in this study. The median survival time was 23.3 months (group 1) versus 9.4 months (group 2) and 5.7 month (group 3). The one year and two year actuarial survival rates are: 56% and 42% (group 1), 33% and 0% (group 2), 25% and 8% (group 3). CONCLUSIONS: Palliative surgery including IORT is safe for patients with unresectable hilar cholangiocarcinoma. The benefit shown by this investigation is a significant improvement of survival time after application of IORT in the palliative situation. A prospective study with randomization is needed to confirm these first results in a larger cohort.

Major bile duct injuries after laparoscopic cholecystectomy: a tertiary center experience.

Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 1.4% incidence of bile duct injuries during laparoscopic cholecystectomy. The aim of this study was to report on an institutional experience with the management of complex bile duct injuries and outcome after surgical repair. Data were collected prospectively from 40 patients with bile duct injuries referred for surgical treatment to our center between April 1998 and December 2003. Prior to referral, 35 patients (87.5%) underwent attempts at surgical reconstruction at the primary hospital. In 77.5% of the patients, complex type E1 or type E2 BDI was found. Concomitant with bile duct injury, seven patients had vascular injuries. Roux-en-Y hepaticojejunostomy was carried out in 33 patients. In two patients, Roux-en-Y hepaticojejunostomy and vascular reconstruction were necessary. Five patients, one with primary nondiagnosed Klatskin tumor, required right hepatectomy. Two patients, both with bile duct injuries and vascular damage, died postoperatively. Because of progressive liver insufficiency, one of them was listed for high-urgency liver transplantation but died prior to intervention. At the median follow-up of 589 days, 82.5% of the patients are in excellent general condition. Seven patients have signs of chronic cholangitis. Major bile duct injuries remain a significant cause of morbidity and even death after laparoscopic cholecystectomy. Because they present a considerable surgical challenge, early referral to an experienced hepatobiliary center is recommended.