Everolimus Improves Microcirculatory Derangements in Experimental Postischemic Pancreatitis Modulating the Expression of Vascular Endothelial Growth Factor, Interleukin 6, and Toll-Like Receptor 4.

OBJECTIVES: Ischemia/reperfusion injury (IRI) of the pancreas is a serious complication following pancreatic transplantation and hemorrhagic shock. The present study was designed to investigate the influence of the potent mammalian target of rapamycin inhibitor everolimus interfering via microvascular permeability changing key proteins hypoxia-inducible factor (HIF) and vascular endothelial growth factor on pancreatic IRI-induced microvascular disturbances. METHODS: Anesthetized male Sprague-Dawley rats were assigned to 3 groups (n = 7/group): (1) sham, (2) 60-minute ischemia/reperfusion of the pancreas (I/R), and (3) I/R and everolimus (10 mg/kg BW orally). Quantification of the effective microvascular permeability (P), functional capillary density (FCD), and leukocyte-endothelial cell interaction (LEI) was performed using digital and analog intravital epifluorescence microscopy. Serum-amylase, lipase, interleukin 6, and vascular endothelial growth factor concentration were quantified using enzyme-linked immunosorbent assay. RESULTS: Sham compared with I/R (P: [×10 cm/s] 0.068 ± 0.079 vs 1.516 ± 0.314; FCD: [cm/cm] 357 ± 14 vs 258 ± 13; LEI: [cells/mm] 148 ± 25 vs 349 ± 75) demonstrates a significant increase in microcirculatory damage and all previously mentioned serum parameters. Except amylase, I/R + everolimus led to a statistically significant improvement of almost all increased parameters (P: 0.434 ± 0.296, FCD: 347 ± 16, LEI: 178 ± 30). CONCLUSIONS: Everolimus attenuated experimental microvascular and inflammatory IRI of the pancreas. Therefore, these results may warrant further investigation of everolimus as a therapeutic agent following clinical states with pancreatic ischemia/reperfusion.

Poor organ quality and donor-recipient age mismatch rather than poor donation rates account for the decrease in deceased kidney transplantation rates in a Germany Transplant Center.

Kidney transplantation is limited not by technical or immunological challenges but by lack of donor organs. Whereas the number of patients on waiting list increased, the transplantation rate decreased. We analyzed the development of decline rates and reasons as well as the fate of declined organs. In total, 1403 organs offered to 1950 patients between 2001 and 2010 were included. Of 440 organs offered between 2009 and 2011 that were declined, we investigated whether these organs were transplanted elsewhere and requested delayed graft function, creatinine, graft and patient survival. Data were compared to results of transplantations at the same time at our center. Decline rate increased from 47% to 87%. Main reasons were poor organ quality and donor-recipient age or size mismatch. Of the rejected organs, 55% were transplanted at other centers with function, graft and patient survival equivalent to patients transplanted at our center during that period. The number of decline has increased over time mainly due to a growing number of marginal donors accounting for poor organ quality or a mismatch of donor and recipient. If proper donor-recipient selection is performed, many organs that would otherwise be discarded can be transplanted successfully.

Hyperacute rejection of a living unrelated kidney graft.

We present a case report of a 59-year-old man, who received a blood group identical living unrelated kidney graft. This was his second kidney transplantation. Pretransplant T-cell crossmatch resulted negative. B-cell crossmatch, which is not considered a strict contraindication for transplantation, resulted positive. During surgery no abnormalities occurred. Four hours after the transplantation diuresis suddenly decreased. In an immediately performed relaparotomy the transplanted kidney showed signs of hyperacute rejection and had to be removed. Pathological examination was consistent with hyperacute rejection. Depositions of IgM or IgG antibodies were not present in pathologic evaluation of the rejected kidney, suggesting that no irregular endothelial specific antibodies had been involved in the rejection. We recommend examining more closely recipients of second allografts, considering not only a positive T-cell crossmatch but also a positive B-cell crossmatch as exclusion criteria for transplantation.

Impact of transplant nephrectomy on peak PRA levels and outcome after kidney re-transplantation.

AIM: To determine the impact of transplant nephrectomy on peak panel reactive antibody (PRA) levels, patient and graft survival in kidney re-transplants. METHODS: From 1969 to 2006, a total of 609 kidney re-transplantations were performed at the University of Freiburg and the Campus Benjamin Franklin of the University of Berlin. Patients with PRA levels above (5%) before first kidney transplantation were excluded from further analysis (n = 304). Patients with graft nephrectomy (n = 245, NE+) were retrospectively compared to 60 kidney re-transplants without prior graft nephrectomy (NE-). RESULTS: Peak PRA levels between the first and the second transplantation were higher in patients undergoing graft nephrectomy (P = 0.098), whereas the last PRA levels before the second kidney transplantation did not differ between the groups. Age adjusted survival for the second kidney graft, censored for death with functioning graft, were comparable in both groups. Waiting time between first and second transplantation did not influence the graft survival significantly in the group that underwent nephrectomy. In contrast, patients without nephrectomy experienced better graft survival rates when re-transplantation was performed within one year after graft loss (P = 0.033). Age adjusted patient survival rates at 1 and 5 years were 94.1% and 86.3% vs 83.1% and 75.4% group NE+ and NE-, respectively (P < 0.01). CONCLUSION: Transplant nephrectomy leads to a temporary increase in PRA levels that normalize before kidney re-transplantation. In patients without nephrectomy of a non-viable kidney graft timing of re-transplantation significantly influences graft survival after a second transplantation. Most importantly, transplant nephrectomy is associated with a significantly longer patient survival.

Early mortality and long-term survival after abdominal surgery in patients with liver cirrhosis.

BACKGROUND: Patients with liver cirrhosis have an increased risk of postoperative mortality. In addition, cirrhotic patients per se have a reduced life expectancy. Little is known about the combined effect of these factors on long-term outcomes after surgery. We thus evaluated early -and long-term survival in patients with cirrhosis who underwent abdominal surgery. METHODS: We evaluated 30- and 90-day mortality as well as long-term survival after 212 general surgical procedures performed in 194 patients with liver cirrhosis. Risk factors for early and late mortality were assessed by uni- and multivariate methods. To avoid multicollinearity of data, different models (Child Turcotte Pugh [CTP], model for end-stage liver disease [MELD], or American Society of Anesthesiologists [ASA] score) were used in multivariate analysis. RESULTS: The 30- and 90-day mortality rates were 20% and 30%, respectively. CTP, MELD, and ASA were all independently associated with 30- and 90-day mortality. Although emergency operations and intraoperative transfusions independently influenced 30-day mortality, 90-day mortality also was influenced by the extent of the procedure and thrombocytopenia. Survival after surgery (n = 180) was 54% after one and 25% after 5 years (median survival 1.24 years). Long-term survival was independently influenced by CTP, MELD, ASA, hyponatremia, emergency operations, thrombocytopenia, and underlying malignancies. Survival in patients discharged after surgery (n = 140) was 69% after 1 and 33% after 5 years (median survival 2.8 years). Survival after discharge was independently influenced by MELD, CTP, hyponatremia, underlying malignant disease, and (partially) by serum creatinine. The inclusion of serum sodium into MELD scores did not further facilitate prediction of early and late mortality. CONCLUSION: A high postoperative mortality as well as a strongly reduced survival even after hospital discharge contribute to the very poor life expectancy in patients with liver cirrhosis requiring general surgery. Postoperative outcome is influenced by liver function, comorbidity and "surgical" factors such as the need for blood transfusion and emergent or major operations. However, after hospital discharge, "surgical" factors did not influence survival.

One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease.

PURPOSE: Surgical management of autosomal dominant polycystic kidney disease (ADPKD) in patients awaiting renal transplantation is a challenging task. METHODS: From 1998 to 2009, a total of 100 consecutive renal transplantations with simultaneous unilateral nephrectomy were performed in 59 men and 41 women with ADPKD and end-stage renal failure. About 38% received kidney allografts from living donors. The ipsilateral polycystic kidney was removed at the time of renal transplantation. Immunosuppressive therapy was not modified. Cold ischaemia time was 155 (38-204 min) versus 910 min (95-2760 min) for living versus deceased donor transplantation. Mean weight of removed kidneys was 2002 g (414-8850 g). Mean follow-up was 3.0 years (0.8-10.0 years). RESULTS: Overall patient and graft survival were 97 and 96% at 1 year and 93 and 80% at 5 years, respectively. Serum creatinine at current follow-up was 1.49 (0.8-2.8) mg/dL. Surgical complications, which might be associated with simultaneous nephrectomy requiring re-operation, occurred in 12% (lymphocele 4%, hernia 4%, post-operative haematoma or bleeding 4%). None of the patients died peri-operatively. CONCLUSION: Renal transplantation with simultaneous unilateral nephrectomy in ADPKD is a reasonable procedure for patients suffering from massively enlarged native kidneys.

Short- and long-term results of duodenum preservation versus resection for the management of chronic pancreatitis: a prospective, randomized study.

BACKGROUND: Individualization of operations for chronic pancreatitis (CP) offers tailored operative approaches for the management of complications of CP. For the management of the inflammatory head mass and its complications, duodenum-preserving procedures (Frey and Beger operations) compete in efficacy and quality of life with pancreatoduodenectomy procedures (PPPD and Whipple operations). Our aim was to compare the short- and long-term results of duodenum-preserving and duodenum-resecting techniques in a prospective, randomized trial. METHODS: Eighty-five patients with CP were randomized to undergo either pylorus-preserving (PPPD) or duodenum-preserving pancreatic head resection (DPPHR). Perioperative and long term results were evaluated. RESULTS: Although the duodenum-preserving operations had a lesser median operating time (360 vs 435 minutes; P = .002), there were no differences in the need for intraoperative blood transfusion (76% vs 79%) or the duration of hospital stay (13 vs 14 days). Postoperative complications in general (33% vs 30%), surgical complications (21% vs 23%), and severe complications such as pancreatic leakage (10% vs 5%) or the need for reoperation (2% vs 2%) did not differ between the DPPHR and the PPPD groups, and there was no mortality (0%). The long-term outcome after a median of >5 years showed no differences between the DPPHR and PPPD regarding quality of life, pain control (67% vs 67%), endocrine status (45% vs 44%), and exocrine insufficiency (76% vs 61%). CONCLUSION: Both types of pancreatic head resections are equally effective in pain relief and eventual quality of life after long-term follow-up (>5 years) without differences in endocrine or exocrine function.

Twenty-year graft survival and graft function analysis by a matched pair study between pediatric en bloc kidney and deceased adult donors grafts.

BACKGROUND: Pediatric en bloc kidney grafts, especially those from donors aged younger than 12 months, are still regarded controversially with respect to long-term graft survival and function as well as the postoperative development of serious hypertension and proteinuria. PATIENTS AND METHODS: This retrospective single-center study analyzed 78 pediatric en bloc kidney grafts transplanted between October 1989 and December 2008. Mean donor age was 15 months in the pediatric en bloc kidney donor group and 37.8 years in the matched pair group. The mean follow-up period was 9.3 years (range, 1-19 years). Statistical analysis was performed using the Kaplan-Meier test for patient and graft survival. Continuous variables were compared using independent sample t test. RESULTS: Graft survival for the pediatric donors after 1, 5, and 10 years were 83.1%, 76.0%, 73.9% and for the matched pair control group 89.6%, 78.7%, and 57.8%, respectively. Serum creatinine levels after 1, 5, and 10 years were 1.0, 0.8, 1.1 mg/dL and for the matched pair control group 1.5, 1.7, and 1.6 mg/dL, respectively. No significant long-term differences were detected between the study cohort groups with respect to the postoperative development of hypertension and proteinuria. CONCLUSION: Overall, pediatric en bloc kidney grafts are well suited to extend the scarce kidney donor pool in experienced centers because of a superior long-term outcome for graft survival and function in comparison with deceased adult kidney grafts. Special attention has to be paid to the substantial higher initial graft loss rate during the first postoperative year.