Controversial data exists concerning the impact of immunosuppressive therapy on the development of post-transplantation diabetes mellitus (PTDM). Therefore, we investigated glucose metabolism in healthy donors and in recipients of living-donor liver transplants (LD-LTX, nϭ18) without pre-existing diabetes mellitus before, on day 10, month 6, and month 12 after intervention. The computer-assisted analysis of glucose, insulin, and C-peptide profiles obtained from frequently sampled intravenous glucose tolerance tests allows to achieve an integrated view of factors controlling glucose tolerance, i.e., insulin sensitivity (SI), first and second phase insulin secretion (⌽ 1 and ⌽ 2 ). SI of donors declined by day 10 after operation (SI 2.65 Ϯ 0.41 vs. 4.90 Ϯ 0.50 10 Ϫ4 minute Ϫ1 U ml Ϫ1 , P Ͻ 0.01) but returned to values as before after 6 months. ⌽ 1 did not change. ⌽ 2 , however, significantly increased by day 10 (8.57 Ϯ 0.82 10 9 minute Ϫ1 to 13.77 Ϯ 1.53 10 9 minute Ϫ1 , P Ͻ 0.01) but was in the same range as before after 6 months. In parallel to donors SI of recipients progressively increased after LD-LTX. ⌽ 1 did not alter in recipients. ⌽ 2 continuously decreased and was not different from donors by month 12. The extent of liver injury assessed by liver enzyme concentrations and liver function represented by cholinesterase activity, albumin, and INR were closely related with changes of SI in donors and recipients during the first year after intervention. In conclusion, the extent of liver damage plays a predominant role in regulating glucose tolerance. No impact of immunosuppressive therapy on SI, ⌽ 1 and ⌽ 2 was detected. Liver Transpl 12: 535-543, 2006. © 2006 AASLD. Received April 15, 2005 accepted October 20, 2005. Since survival after liver transplantation increased significantly in past decades clinical effects of long-term complications are of increasing importance. Post-transplant diabetes mellitus (PTDM) is a common complication following orthotopic liver transplantation (OLT) and contributes to micro-and macro-vascular alterations finally leading to increased morbidity and mortality.1 The pathogenesis is rarely understood, which is caused by the heterogeneous study groups and the different methods used to clarify the steps towards PTDM. The state of liver disease, chronic infection with hepatitis C (HCV), and diabetes mellitus prior to organ transplantation may promote the development of PTDM. 2-6 HCV infection, especially, early impairs glucose tolerance and this effect is closely related with liver damage. 7,8 In contrast to these findings liver transplan-

BackgroundThe treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease.Methods20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy.ResultsResponse of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed.ConclusionThis study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC.

Background: Adiponectin and proinsulin are commonly used biomarkers in patients with metabolic syndrome. In individuals without cirrhosis adiponectin serum levels correlate inversely with insulin resistance and mortality. Proinsulin is a surrogate parameter of β-cell function, its level increases due to β-cell insufficiency while insulin resistance occurs. Metabolic syndrome is often associated with steatohepatitis, and thus liver cirrhosis. An increasing interest in adiponectin and proinsulin as a marker for metabolic syndrome associated morbidity and mortality might be observed in the literature. Still, a diagnostic value of both markers in cirrhotic state is not fully understood. Methods: Eighteen recipients and donors undergoing living donor liver transplantation were included. Routine parameters, insulin resistance, adiponectin, and proinsulin serum levels were measured at evaluation, 10 th , 180 th , and 365 th postoperative day (POD). Results: Adiponectin levels before operation were lower in the donor than in the recipient group. Adiponectin levels in donors increased at the 10 th and did not change until the 365 th POD. In the recipient group levels improved already at 10 th and increased slightly till 365 th POD. Proinsulin levels in the recipient group were higher before transplantation and improved already at the 10 th POD. It decreased continuously till 180 th and rose slightly till 365 th POD. Proinsulin levels in the donors remained constant regardless of the postoperative acute insulin resistance. Conclusions: The grade of liver cirrhosis is positively correlated with the adiponectin serum level. In patients with liver cirrhosis, in contrast to liver healthy population, insulin resistance does not cause an adiponectin serum level down regulation. Therefore, the use of adiponectin as a marker of cardiovascular risk associated mortality in patients with cirrhosis is limited. Contrariwise, proinsulin might be used as a marker for hepatic insulin resistance in patients with liver cirrhosis. β-cell insufficiency seems not to play a major role in case of postoperative insulin resistance.

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