Dietlind Tittelbach-Helmrich

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.

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.

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.

[Insurance costs in pancreatic surgery : does the pecuniary aspect indicate formation of centers?].

BACKGROUND Pancreatic resections in specialized centers are associated with low mortality, however, still with high morbidity. The complication rate can be reduced by long-term experience in high volume centers. In this study the influence of complications on costs in the German DRG system were analyzed. PATIENTS AND METHODS Data regarding operation time, hospital stay, complications and costs of 36 patients undergoing pancreatic head resection in the years 2005 and 2006 were collected and analyzed retrospectively. Statistical analysis was performed using the Mann-Whitney U-test. A p-value of p<0.05 was considered statistically significant. RESULTS Postoperative complications caused an increase in the duration of hospital stay from a median of 16 (range 11-38) to 33 (10-69) days. Costs, especially for ICU treatment and radiographic diagnostics, rose significantly. The average overall costs were 10,015 EUR (range 8,099-14,785 EUR) in patients without complications (n = 21) and 15,340 EUR (9,368-31,418 EUR) in patients with complications (n = 15). In contrast, according to the German DRG system 13,835 EUR (10,441-15,062 EUR) and 15,062 EUR (10,441-33,217 EUR) were refunded on average, respectively. CONCLUSIONS This case-cost calculation proves that pancreatic surgery in the context of the German DRG system can only be performed economically neutral in centers with low complications rates. The concentration of pancreatic surgery to centers with low complications rates, namely high volume centers, must be recommended from an economic point of view.

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.

Kostenträgerrechnung in der Pankreaschirurgie

BACKGROUND Pancreatic resections in specialized centers are associated with low mortality, however, still with high morbidity. The complication rate can be reduced by long-term experience in high volume centers. In this study the influence of complications on costs in the German DRG system were analyzed. PATIENTS AND METHODS Data regarding operation time, hospital stay, complications and costs of 36 patients undergoing pancreatic head resection in the years 2005 and 2006 were collected and analyzed retrospectively. Statistical analysis was performed using the Mann-Whitney U-test. A p-value of p<0.05 was considered statistically significant. RESULTS Postoperative complications caused an increase in the duration of hospital stay from a median of 16 (range 11-38) to 33 (10-69) days. Costs, especially for ICU treatment and radiographic diagnostics, rose significantly. The average overall costs were 10,015 EUR (range 8,099-14,785 EUR) in patients without complications (n = 21) and 15,340 EUR (9,368-31,418 EUR) in patients with complications (n = 15). In contrast, according to the German DRG system 13,835 EUR (10,441-15,062 EUR) and 15,062 EUR (10,441-33,217 EUR) were refunded on average, respectively. CONCLUSIONS This case-cost calculation proves that pancreatic surgery in the context of the German DRG system can only be performed economically neutral in centers with low complications rates. The concentration of pancreatic surgery to centers with low complications rates, namely high volume centers, must be recommended from an economic point of view.

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.

Late-onset proteinuria after antithymocyte globulin induction and de novo sirolimus monotherapy in kidney transplant recipients.

Current immunosuppressive regimens reduce rejection rates and improve graft survival after kidney transplantation. But calcineurin inhibitors (CNIs) and steroids have long-term side effects, increasing the risks of cardiovascular events and chronic allograft nephropathy. In addition, overimmunosuppression increases the risk of opportunistic infections (1) and malignant diseases (2). Therefore, steroidand CNI-free protocols (1, 3– 6) are being tested. Five nonsensitized recipients of human leukocyte antigen-nonidentical postmortal kidney grafts were enrolled in a prospective Institutional Review Board-approved trial to test de novo sirolimus monotherapy following antithymocyte globulin induction (Reference No: UKF 000105). Inclusion criteria were a first kidney transplantation, negative T/B crossmatch, panel reactive antibody level less than 10%, serum CD 30 negative ( 100 U/mL), IgG anti-human leukocyte antigen class I/II negative ( 300), and IgA anti-Fab more than 1000. Patients received 3 mg/kg of rabbit antithymocyte globulin (rATG) (Thymoglobulin, Genzyme, Cambridge, MA) on day 0 and 2 mg/kg on day 1. rATG doses on day 2 to 10 were adjusted to lymphocyte counts. Five hundred milligram of prednisolone was applied on day 0 and 250 mg on day 1 and 2. Sirolimus was started on day 4 or 5, if serum creatinine was less than 3 mg/dL. A fixed sirolimus dose of 1.0 mg/kg body weight was given for 3 days to reach a target level of 12 to 15 ng/mL by day 8. Concomitantly, patients received pravastatin, valganciclovir, fluconazole (for 90 days), and trimethoprim/sulfamethoxazole (for 180 days). Adverse events included serum sickness (two), mouth ulcer (one), postoperative (three) and recurrent urinary tract infection (one), and one graft loss on day 33, which lead our local Ethics Committee to abort the pilot study. The remaining grafts currently function. Serum creatinine was 70.8, 79.65, 106.2, and 177 mol/L. Glomerular filtration rates were 77, 67, 67, and 45 mL/min, respectively. No patient showed signs of clinical rejection during follow-up. Patient 1: A 49-year-old woman developed proteinuria with 1.31 g/24 hr 18 months after transplantation. Therefore tacrolimus was added to her regimen. Patient 2: A 64-year-old woman was restarted on 5 mg prednisolone 5 months after transplantation due to preexistent rheumatoid arthritis with persistent joint pain. Current graft function is stable with a proteinuria of 110 mg/24 hr. Patient 3: A 48-year-old man developed severe proteinuria of 3.5 g/24 hr 18 months after kidney transplantation. A graft biopsy showed no signs of immunologic damage. This patient’s regimen was converted to the standard triple therapy of tacrolimus, mycophenolate mofetil, and prednisolone. Under this regimen, proteinuria improved to 945 mg/24 hr in December 2008. Patient 4: A 48-year-old woman had postoperative bleeding and required surgical revision on day 1, resulting in two warm ischemic periods and delayed graft function. For this reason, sirolimus was discontinued, and the patient was transferred to the standard triple therapy with tacrolimus, mycophenolate mofetil, and prednisolone on day 20. Once the graft function stabilized, the patient was retransferred to sirolimus monotherapy after 6 months. The patient had severe recurrent urinary tract infections. Current serum creatinine is stable approximately 2.0 mg/dL with no signs of increased proteinuria (707 mg/24 hr). Patient 5: A 46-year-old man with nephrosclerosis lost his graft due to therapy-resistant thrombotic microangiopathy on postoperative day 33. The initial graft function was excellent up to day 14. Repeated graft biopsies revealed no signs of rejection. On postoperative day 24, fibrinogenic thrombi were detected in three of nine glomeruli. On day 33, diagnostic imaging revealed complete thrombosis of the graft, which was therefore removed. Later on, the patient developed Guillain-Barré-syndrome with severe paralysis. After recovery, the patient had a myocardial infarction. Coronary angiography revealed severe arteriosclerosis of the coronary arteries, thus excluding interventional treatment options. A coronary artery bypass operation was rejected by the patient. During rehabilitation, the patient had a second myocardial infarction and died. In the 1-year follow-up, four patients were maintained on a CNI-free immunosuppression protocol. Three patients received only sirolimus, and one patient received a combination therapy of sirolimus and prednisolone. This study confirms that de novo sirolimus monotherapy after rATG induction therapy in renal transplant recipients is feasible and probably not associated with an increased risk of rejection episodes in patients with a lowrisk immunologic profile. All patients tolerated this protocol well. Despite this study’s strong limitations due to the small patient population, the authors conclude, in accordance to Swanson et al. (3), Diekmann et al. (5), and Arellano et al. (7), that in well-selected immunologically low-risk patients sirolimus monotherapy is safe. However, because of severe, late-onset proteinuria, we cannot recommend de novo sirolimus monotherapy for renal transplantation.

Single Kidney Transplantation from Young Pediatric Donors in the United States

In a recent issue of the American Journal of Transplantation, Kayler et al. reported on kidney transplantations from very young donors (1). In general, the elaborated analysis confirms the excellent results after pediatric en bloc kidney transplantation published by our group and others (2–4). However, we disagree with the conclusion drawn from Kayler et al. (1) that the cut-off for split versus en bloc kidney transplantation from very young donors ought to be set at a donor weight of 10 kg.