Orthotopic liver transplantation (OLT) is the only effective curative therapy for end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent, although recent data have shown a recurrence rate of PBC of up to 32% after transplantation. The aim of this study is to investigate the course after disease recurrence, particularly with regard to liver function and survival in a long-term follow-up. Between April 1989 and April 2003, 1,553 liver transplantations were performed in 1,415 patients at the Charité, Virchow Clinic. Protocol liver biopsies were taken after one, three, five, seven, 10 and 13 yr. One hundred (7%) patients suffered from histologically proven PBC. Primary immunosuppression consisted of cyclosporine (n = 54) or tacrolimus (Tac) (n = 46). Immediately after OLT, all patients received ursodeoxycholic acid. Corticosteroids were withdrawn three to six months after OLT. The median age of the 85 women and 15 men was 55 yr (range 25-66 yr). The median follow-up after liver transplantation was 118 months (range 16-187 months) and after recurrence 30 months (range 4-79 months). Actuarial patient survival after five, 10 and 15 yr was 87, 84 and 82% respectively. Ten patients (10%) died after a median survival time of 32 months. Two of these patients developed organ dysfunction owing to recurrence of PBC. Histological recurrence was found in 14 patients (14%) after a median time of 61 months (range 36-122 months). Patients with Tac immunosuppression developed PBC recurrence more often (p < 0.05) and also earlier (p < 0.05). Fifty-seven patients developed an acute rejection and two patients a chronic rejection episode. Liver function did not alter within the first five yr after histologically proven PBC recurrence. Multivariate analysis of the investigated patients showed that the recipient's age and Tac immunosuppression were significant risk factors for PBC recurrence. Long-term follow-up of up to 15 yr after liver transplantation, owing to PBC, in addition to maintenance of liver function, shows excellent organ and patient survival rates. Although protocol liver biopsies revealed histological recurrence in 14 (14%) patients, only two patients developed graft dysfunction. Tac-treated patients showed more frequently and also earlier histologically proven PBC recurrence; however, in our population we could not observe an impact on graft dysfunction and patient's survival.

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.

With the Internet-based English- and German-language hernia register, a new instrument is now available for outcome research in hernia surgery.

IntroductionMore than 20 years since the introduction of TAPP and TEP into clinical routine, there is a lack of clarity due to conflicting comparative data. Therefore, more results from registries are needed.Patients and methodsA total of 17,587 patients were enrolled prospectively between September 1, 2009, and April 15, 2013, in the Herniamed registry. Of these patients, 10,887 (61.9 %) had a TAPP and 6700 (38.1 %) a TEP repair. The dependent variables were intra- and postoperative complication rates, number of reoperations as well as absolute and relative frequencies. The results of unadjusted analyses were verified via multivariable analyses.ResultsMultivariable analysis verified the results of unadjusted analysis, indicating that the surgical technique did not have any significant impact, also while taking account of other factors, on occurrence of intraoperative [p = 0.1648; OR = 1.214 (0.923; 1.596)] and general postoperative complications [p = 0.0738; OR = 1.315 (0.974; 1.775)]. Postoperative surgical complications [OR = 2.323 (1.882; 2.866); p < 0.0001] were noted more often after TAPP. Furthermore, the hernia defect size [p < 0.0001; I vs III: OR = 0.439 (0.313; 0.615), II vs III: OR = 0.712 (0.582; 0.872)] or scrotal [p < 0.0001; OR = 2.170 (1.501; 3.137)] hernia and age [p = 0.0002; 10-year OR = 1.135 (1.062; 1.213)] had a significant impact on the occurrence of postoperative complications. Complications were observed more commonly for larger hernia defects and a scrotal hernia. However, the difference in the postoperative complication rate between TEP and TAPP did not result in any difference in the reoperation rate (TEP 0.82 % vs TAPP 0.90 %; p = 0.6165).ConclusionThe intraoperative and general postoperative complication rates as well as the reoperation rate for complications show no significant difference between TEP and TAPP. The higher postoperative complication rate for TAPP, which could be managed conservatively, is partly explained by larger defect sizes, more scrotal hernias and older age.

The majority of lethal complications after pancreatic head resection are due to septic complications after leakage from the pancreatojejunostomy. Especially the smooth pancreatic remnant is prone to develop parenchymal leaks from shear forces applied during tying of the sutures. We developed a new mattress technique that avoids such shear forces, and we compared this method to the standard Cattell (duct-to-mucosa) technique. A total of 113 patients undergoing standard pancreatic head resection were prospectively randomized to receive either the standard Cattell anastomosis (n = 56) or the new mattress technique (n = 57). All patients were evaluated for surgical and medical complications until discharge. Primary diagnosis and further demographic data compared well between the groups. The time to perform the mattress anastomosis was significantly shorter (15 vs. 22 minutes; p < 0.0001). The incidence of complications at the pancreatojejunostomy, and the length of hospital stay and survival were not significantly different between the two groups; however, a trend toward more reoperations was noted in the Cattell group (10 vs. 5; p < 0.097). The new mattress technique is simple, and our data show that the two techniques yield similar incidences of complications. Therefore the mattress technique for pancreatojejunostomy seems to be safe and is, in our opinion, well suitable for training schedules in pancreatic surgery.

Introduction. Although ampullary carcinoma has the best prognosis among all periampullary carcinomas, its long-term survival remains low. Prognostic factors are only available for a period of 10 years after pancreaticoduodenectomy. The aim of this retrospective study was to identify factors that influence the long-term patient survival over a 15-year observation period. Methods. From 1992 to 2007, 143 patients with ampullary carcinoma underwent pancreatic resection. 86 patients underwent pylorus-preserving pancreaticoduodenectomy (60%) and 57 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (40%). Results. The overall 1-, 5-, 10-, and 15-year survival rates were 79%, 40%, 24%, and 10%, respectively. Within a mean observation period of 30 (0–205) months, 100 (69%) patients died. Survival analysis showed that positive lymph node involvement (P = 0.001), lymphatic vessel invasion (P = 0.0001), intraoperative administration of packed red blood cells (P = 0.03), an elevated CA 19-9 (P = 0.03), jaundice (P = 0.04), and an impaired patient condition (P = 0.01) are strong negative predictors for a reduced patient survival. Conclusions. Patients with ampullary carcinoma have distinctly better long-term survival than patients with pancreatic adenocarcinoma. Long-term survival depends strongly on lymphatic nodal and vessel involvement. Moreover, a preoperative elevated CA 19-9 proved to be a significant prognostic factor. Adjuvant therapy may be essential in patients with this risk constellation.

We recently found that repeated application of adenovectors expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or recombinant TRAIL proteins to TRAIL-susceptible cancer cells resulted in selection and expansion of TRAIL-resistant cells. Overcoming this acquired resistance to TRAIL is desirable for TRAIL-mediated cancer therapy. Here we demonstrate that several chemotherapeutic agents, including 5-fluorouracil (5-FU) and mitomycin, and calpain inhibitor I, an NFkappaB inhibitor, can overcome acquired resistance to TRAIL in DLD1 colon cancer cells. The combination of TRAIL (approved gene symbol TNFSF10) gene therapy and 5-FU enhanced tumor suppression in vivo in nude mice bearing subcutaneous tumors established from TRAIL-resistant colon cancer cells. Whereas treatment with the combination of TRAIL and 5-FU or mitomycin led to enhanced activation of caspase-3, the combination of TRAIL and calpain inhibitor I resulted in enhanced activation of both caspase-8 and caspase-3. Moreover, mitomycin, but not 5-FU or calpain inhibitor I, induced overexpression of the BAX gene, which was correlated with enhanced TRAIL-induced cell killing in TRAIL-resistant DLD1 cells. Together, these results suggest that acquired resistance to TRAIL can be overcome by different mechanisms and that combinations of TRAIL gene therapy and chemotherapy may be a useful approach for cancer treatment.

Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.