Dietmar Jacob

Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients

Abstract: 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, 1553 liver transplantations were performed in 1415 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 Corticosteroids were withdrawn three to six months after OLT.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 recipients 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 patients survival.

MMF and Calcineurin Taper in Recurrent Hepatitis C After Liver Transplantation: Impact on Histological Course

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal. The optimal immunosuppression for these patients is still under discussion. We designed a retrospective case‐control study to evaluate the effect of mycophenolate mofetil (MMF) treatment in patients with recurrent hepatitis C.

Prospective Randomized Comparison between a New Mattress Technique and Cattell (duct-to-mucosa) Pancreaticojejunostomy for Pancreatic Resection

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.

Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells

Background and Aim:  Poly (ADP‐ribose) polymerase (PARP) inhibitors such as 3‐aminobenzamide (3‐ABA) enhance the in vitro cytotoxicity of DNA mono‐functional alkylating agents such as radiation or chemotherapeutic agents. The aim of this study was to test an approach combining the PARP inhibitor 3‐ABA with standard gemcitabine therapy in human pancreatic cancer cells.

Carcinoma of the distal and middle bile duct: surgical results, prognostic factors, and long-term follow-up

BACKGROUND/PURPOSE Carcinoma of the distal bile duct is associated with poor prognosis. Surgical resection remains the only potentially curative treatment. We conducted a retrospective study to identify prognostic factors determining longterm survival. METHODS From 1990 to 2006, 95 patients with distal and/or middle bile duct carcinoma had resections. Fifty-four patients underwent pylorus-preserving pancreaticoduodenectomy (57%) and 41 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (43%). Nine patients underwent pancreaticoduodenectomy including portal vein resection (9%). RESULTS Overall 1-, 3-, and 5-year survival rates were 60%, 36%, and 29%, respectively. Five-year survival after R0 resection was 34%, and after R1 resection it was 0%. Four patients died during their hospital stay (4%). Multivariate analysis showed negative resection margins (P = 0.040), lymphatic vessel invasion (P = 0.036), and portal vein infiltration (P = 0.027) as strong predictors for survival, whereas the location of the tumor (distal bile duct vs middle bile duct) and lymph node status were not identified as independent prognostic factors. CONCLUSIONS Five-year survival depends strongly on negative resection margins, independent of nodal status. Portal vein resections in patients with portal vein involvement fail to ameliorate long-term survival. Primary tumor site--middle bile duct or distal bile duct--did not determine prognosis.

Outcome after liver re-transplantation in patients with recurrent chronic hepatitis C

Long‐term outcome after liver retransplantation for recurrent hepatitis C has been reported to be inferior to other indications. The identification of factors associated which improved long‐term results may help identify hepatitis C positive patients who benefit from liver retransplantation. Outcome after liver retransplantation for recurrent hepatitis C was analyzed in 18 patients (group 1) and compared with hepatitis C positive patients undergoing liver retransplantation for initial nonfunction (group 2, n = 11) and patients with liver retransplantation for other indications (group 3, n = 169). Five‐year patient survival following retransplantation for groups 1, 2 and 3 was 59% 84% and 60%. Increased alanine aminotransferase (ALT) and serum bilirubin, as well as white cell count and MELD score at day of retransplantation were associated with impaired patient outcome. Five‐year survival after retransplantation in patients with recurrent hepatitis C is similar to that in patients undergoing liver retransplantation for other indications. Our analysis showed MELD score, bilirubin, ALT levels and white cell counts preorthotopic liver transplantation are important predictive factors for outcome. This observational study may help select patients and identify the optimal time‐point of liver retransplantation in ‘‘Hepatitis C’’ virus positive patients in the future.

Prospektiv-randomisierter Vergleich von Anastomosentechniken der Pankreatojejunostomie nach partieller Duodenopankreatektomie

Die pankreatojejunale Anastomose bei der partiellen Duodenopankreatektomie gilt wegen ihrer Dehiszensgefahrdung gerade bei gesundem Restpankreas als „Schwachpunkt“ der Operation. Ein Grosteil der letalen Komplikationen resultiert aus Nahtinsuffizienzen mit konsekutiver Peritonitis. In vielen Kliniken gilt neben der Einzelknopfnaht die Gang-zu-Mukosa Anastomosentechnik nach Warren-Cattell als Standardtechnik fur die Pankreatojejunostomie. Um die bei diesen Techniken beim Knoten auftretenden Scherkrafte zu vermeiden, entwickelten wir eine neue Matratzentechnik fur die Pankreatojejunostomie. Bei dieser Technik fuhrt der Stichkanal gerade von dorsal nach ventral durch den Pankreasrest und die Knoten werden nach Einstulpen des Pankreasrestes in den Darm auf der Darmserosa angezogen. So werden die Scherkrafte vermieden. Diese neue Technik wurde prospektivrandomisiert mit der Standardtechnik nach Warren-Cattell verglichen. Methodik:Von Juli 1999 bis Dezember 2000 wurden 162 Pankreasresektionen durchgefuhrt. Nach Ausschlus von Duodenum-erhaltenen Resektionen (10), Links- und Segmentresektionen (21), erweiterten Resektionen (8), Einzelknopftechnik fur die Anastomose (6) und fehlender Einwilligung (4), wurden 113 Patienten nach Pankreaskopfresektion randomisiert (56 fur Warren-Cattell und 57 fur Matratzennahttechnik). Das mittlere Alter der Patienten betrug in der Cattell-Gruppe 61 Jahre und in der Matratzennaht-Gruppe 59 Jahre. Das Pankreaskarzinom war die haufigste Indikation (Cattell-Gruppe: 24 [42,9%]; Matratzennaht-Gruppe 28 [49,2%]). Periampullare Karzinome fuhrten in 9 Fallen (16,1%) in der Cattell-Gruppe und in 15 Fallen (26,3%) in der Matratzennaht-Gruppe zur Operation. Als benigne Indikationen zur Resektion beobachteten wir in 17 (30,3%)(Cattell-Gruppe) und 10 Fallen (17,5%)(Matratzennaht-Gruppe) eine chronische Pankreatitis und in einem (1,8%) (Cattell-Gruppe) und in 4 Fallen (7,0%)(Matratzennaht-Gruppe) ein Adenom der Papilla Vateri. Funf Patienten (8,9%) mit verschiedenen weiteren malignen Lasionen des Pankreas erhielten ein Cattell Anastomose. Das Sekret des Pankreasrestes wurde fur 10 - 12 Tage drainiert. Ergebnisse:Die Anastomosenkomplikationen in Abhangigkeit von der verwendeten Technik sind in Tabelle 1 aufgefuhrt. Der Vergleich der mittleren Werte fur Amylase, Lipase und Menge des Easyflow-Sekretes ergab keine signifikanten Unterschiede. Diskussion:Unsere Ergebnisse zeigen, das beide Anastomosentechniken sicher sind und mit geringer Inzidenz von Insuffizienzen, Fistelbildung und konsekutiven Reoperationen einhergehen. Neben der einfachen Technik und somit der zeitsparenden Anlage scheint die Matratzentechnik nach unserer Erfahrung insbesondere fur „weiche“ Restpankreata zu eignen, da sie durch die veranderte Stichtechnik beim Knoten die tangentialen Scherkrafte vermeidet.