Wolfgang Steurer

Infectious complications following 72 consecutive enteric‐drained pancreas transplants

New immunosuppressive protocols and advanced surgical technique resulted in an improved outcome of pancreatic transplantation (PTx) with infection remaining the most common complication. Seventy‐two enteric‐drained whole PTxs performed at the Innsbruck University Hospital between September 2002 and October 2004 were retrospectively analyzed. Prophylactic immunosuppression consisted of either the standard protocol consisting of single bolus antithymocyteglobuline (ATG) (Thymoglobulin, Sangstat or ATG Fresenius) induction (9u2003mg/kg), tacrolimus (TAC), mycophenylate mofetil (MMF) and steroids (38u2003patients) or a 4‐day course of ATG (4u2003mg/kg) tacrolimus and steroids with MMF (nu2003=u200319), or Sirolimus (nu2003=u200315). Perioperative antimicrobial prophylaxis consisted of Piperacillin/Tazobactam (4.5u2003g q 8u2003h) in combination with ciprofloxacin (200u2003mg q 12u2003h) and fluconazole (400u2003mg daily). Ganciclovir was used for cytomegalovirus (CMV) prophylaxis if donor was positive and recipient‐negative. Patient, pancreas, and kidney graft survival at 1u2003year were 97.2%, 88.8%, and 93%, respectively, with no difference between the groups. All retransplants (nu2003=u20038) and single transplants (nu2003=u20038) as well as all type II diabetics and nine of 11 patients older 55u2003years received standard immunosuppression (IS). The rejection rate was 14% and infection rate 46% with no difference in terms of incidence or type according to the three groups. Severe infectious complications included intra‐abdominal infection (nu2003=u200312), wound infection (nu2003=u20037), sepsis (nu2003=u200313), respiratory tract infection (nu2003=u20034), urinary tract infection (nu2003=u200312), herpes simplex/human herpes virus 6 infection (nu2003=u20035), CMV infection/disease (nu2003=u20037), post‐transplant lymphoproliferative disorder (PTLD, nu2003=u20033), invasive filamentous fungal infection (nu2003=u20034), Clostridial/Rotavirus colitis (nu2003=u20031), and endocarditis (nu2003=u20031). All four patients in this series died of infectious complications (invasive aspergillosis nu2003=u20032) (one with Candida glabrata superinfection), invasive zygomycosis (nu2003=u20031), PTLD (nu2003=u20031). Five grafts were lost (vascular thrombosis nu2003=u20033, pancreatitis nu2003=u20031, noncompliance nu2003=u20031). Infection represented the most frequent complication in this series and all four deaths were of infectious origin. Better prophylaxis and management of infections now should be the primary target to be addressed in the field of pancreas transplantation.

A prospective randomized multicenter trial comparing histidine-tryptophane-ketoglutarate versus University of Wisconsin perfusion solution in clinical pancreas transplantation

We aimed to evaluate early pancreas transplant graft function after histidine–tryptophan–ketoglutarate (HTK) versus University of Wisconsin (UW) perfusion. Prospective randomized multicenter study including 68 pancreas transplantations stratified according to preservation fluid used (27 HTK vs. 41 UW). Primary endpoint was pancreas graft survival at 6u2003months. Serum α‐amylase, lipase, C‐peptide, HbA1C and exogenous insulin requirement were compared at several time points. Mean pancreas cold ischemia time was 10.8u2003±u20033.7 (HTK) vs. 11.8u2003±u20033.4u2003h (UW) (Pu2003=u20030.247). Simultaneous pancreas–kidney transplantation was performed in 95.6% of the patients, pancreas transplantation alone in 2.9%, and pancreas after kidney transplantation in 1.5%. Six months graft survival was 85.2% (HTK) vs. 90.2% (UW) (Pu2003=u20030.703). Serum amylase and lipase values did not differ between both the groups during the observation period. C‐peptide levels were elevated in both the groups without significant differences at each time point. Higher exogenous insulin requirement early after transplantation in the UW group had resolved at 3u2003months. Six month patient survival was 96.3% (HTK) vs. 100% (UW) (Pu2003=u20030.397). With a mean cold ischemia time of 10u2003h in this study, HTK and UW solutions appear to be equally suitable for perfusion and organ preservation in clinical pancreas transplantation.

A cluster of rotavirus enteritis in adult transplant recipients

Diarrhea following solid organ transplantation is a common side effect of some immunosuppressive agents but can also be caused by many pathogens. An outbreak of rotavirus (RV) enteritis presenting with severe diarrhea in four solid organ recipients was analyzed. The first case was diagnosed in a 6‐month‐old liver recipient who was prehospitalized on a pediatric ward. Within 1u2003month, three adult patients (two liver, one renal recipient) presented with enteritis. During diarrhea a significant rise in tacrolimus levels was observed. One patient developed toxic megacolon with ulcerative colitis. Infections were self‐limiting but led to secondary infectious complications and prolonged hospitalization. This is the first reported outbreak of RV enteritis in a multiorgan transplant unit involving adult patients. Although no fingerprinting or subtyping of the virus was performed we assume the child was the primary source. In transplant recipients presenting with diarrhea RV infection should be considered.

Incidence of intraabdominal infection in a consecutive series of 40 enteric-drained pancreas transplants with FK506 and MMF immunosuppression

Abstract Although the introduction of FK506 and MMF has markedly improved patient and graft outcome after pancreas transplantation, this procedure is still associated with a high surgical complication rate. The aim of the following study was to retrospectively analyze a series of 40 consecutive pancreas transplants with enteric drainage with regard to intraabdominal infection (IAI). Between March 1997 and December 1998 a total of 40 whole pancreas transplants were performed. Prophylactic immunosuppression consisted of an intraoperative single shot ATG (Thymoglobulin), FK506, MMF, and prednisone. The mean observation period was 14.6 (5‐26) months. Overall incidence of IAI was 27.5 % (n = 11) leading to pancreatectomy in 5 patients (12.5 %). In the remaining 6 patients the graft could be rescued by necrosectomy and radical drainage of the abscess (5 patients) or percutaneous drainage (1 patient). Pancreatectomy or local infection did not alter kidney graft function in the 11 patients with simultaneous pancreas kidney transplantation. In 10 patients no evidence for leakage at the site of enteric anastomosis was present, one duodenal leak occurred due to ischemia. IAI in the early postoperative period was the predominat risk factor for graft loss. An early and invasive diagnostic approach is recommended to maximize the chance of graft rescue.

Preoperative evaluation of potential living related kidney donors with high-spatial-resolution magnetic resonance (MR) angiography at 3 tesla comparison with intraoperative findings

Purpose:The purpose of this prospective study was to determine the feasibility and accuracy of high-spatial-resolution MR imaging at 3 Tesla (T) in the preoperative evaluation of potential living related kidney donors. Materials and Methods:Eighteen potential donors (8 men, 10 women; mean age, 50.1 ± 14.2 years) for renal transplantation were evaluated with 3 T MR imaging. A high-spatial-resolution 3-dimensional (3D) gradient-echo MR angiography (repetition time/echo time, 3.0/1.14 ms; flip, 19–23°; matrix, 512; slice thickness, 1.0 mm) using parallel acquisition technique (GRAPPA) with an acceleration factor of 3 was performed on a whole body scanner. Images were evaluated in a prospective and blinded fashion by 2 MR radiologists. The number of renal arteries, presence of early branches (defined as a branch arising within 2 cm of the main renal ostium), and renal artery stenosis were analyzed. The renal parenchyma, collecting system and ureters, were evaluated on the MR urograms. Interpretation of MR images were compared with surgical findings. Results:Based on MR angiography data sets, a total of 36 main and 9 accessory renal arteries was found. There were 5 renal arteries presenting an early branching (≤2 cm). The correct venous anatomy was identified in 13 of 14 patients (93%), including a single left renal vein anterior to the aorta (n = 3), retroaortic left renal vein (n = 2), and single right renal vein (n = 9). A single collecting system in all harvested kidneys was identified correctly with MR imaging. Overall, the sensitivity and positive predictive value of MRI in correctly determining the vascular and parenchymal anatomy in the harvested kidney was 85% and 93%, respectively. Conclusions:High-spatial-resolution contrast-enhanced MR angiography at 3 T can predict successful donor nephrectomy in potential living related kidney donors.

The 4-amino analogue of tetrahydrobiopterin efficiently prolongs murine cardiac-allograft survival

We tested the 4-amino analogue of tetrahydrobiopterin (H(4)aminobiopterin), a novel pterin-based inhibitor of nitric oxide synthases, for its efficacy in a murine cardiac-transplant model employing an improved cuff technique. We treated groups of 5 animals each for the first 7 post-operative days with various doses of H(4)aminobiopterin, with Cyclosporin A (15 mg/kg/day), or no treatment. H(4)aminobiopterin (3 times 50 mg/kg/day) proved to be as efficient as high-dose Cyclosporin A (15 mg/kg/day) in prolonging allograft survival and in suppressing histologic changes caused by the immunoreaction. Surprisingly, the doses of H(4)aminobiopterin effective in prolonging allograft survival did not change the plasma nitrite plus nitrate, or the expression of inducible nitric oxide synthase, interferon-gamma, tumor necrosis factor-alpha, and B7-1 (CD80), indicating that H(4)aminobiopterin may act through a novel, yet undiscovered mechanism.

Percutaneous portal vein embolisation in preparation for extended hepatic resection of primary nonresectable liver tumours

BACKGROUNDnIn patients with malignant primary and secondary liver tumours or proximal bile duct carcinoma radical surgery is superior to all other therapeutic modalities in terms of survival and quality of life. Radical resection, however, often requires the removal of a large amount of liver parenchyma, resulting in a marked reduction of functional liver tissue with the risk of liver failure.nnnAIMnPreoperative partial portal vein embolisation induces hypertrophy of the controlateral liver and thereby increases the safety of extended liver resections.nnnPATIENTS AND METHODSnBetween January 1997 and February 2001 we applied this strategy in 19 patients with primary and secondary nonresectable hepatobiliary malignancies, in whom the estimated amount of the remnant liver was < or =25% of the liver volume.nnnRESULTSnThe increase in volume ranged between 7 and 245%. Radical extended liver resection was performed in 13 patients (68%) without mortality. After a mean observation time of 22 months patient survival was 19 months with six tumour-related deaths during the second year after surgery. The remaining seven patients are alive and well with tumour recurrence in one.nnnCONCLUSIONnPreoperative partial portal vein embolisation allows more patients with previously unresectable liver tumours to benefit from a potentially curative resection.

Influence of hyperinsulinemia on lipoproteins after pancreas transplantation with systemic insulin drainage.

Successful pancreas transplantation with systemic drainage is followed by a normalization of carbohydrate and lipid metabolism with low levels of plasma cholesterol and triglycerides. HDL cholesterol concentration and CETP plasma levels were found to be increased and the composition of lipoproteins altered in that LDL and HDL2/HDL3 were enriched in UC, HDL2 enriched in PL, and LDL depleted in PL. The mechanisms by which hyperinsulinemia may cause the observed changes in surface composition of plasma lipoproteins are unknown, as is their clinical relevance. It remains to be seen whether these changes counterbalance the favorable effects of an increased triglyceride clearance capacity on the cardiovascular risk of diabetic patients.

Optimization of phagocyte chemiluminescence measurements using microplates and vials

In order to cope with large amounts of samples for chemiluminescence (CL), vials were replaced with microplates. Although various types of plates have been commercially available for quite some time and the free-plate mode is advocated by the producer of the counter, little is known about their impact on the outcome of CL measurements. We tested two different 24-well microplates and six different 96-well microplates in two different luminometers, and results were compared with those achieved with vials. Before these comparative tests, we attempted to optimize measurement conditions. CL sensitivity was highest with luminol concentrations of 0.8-3.3 micromol/L, PMA concentrations of 0.06-80 micromol/L, a pH value of 10 and a temperature of 20 degrees C. An indirect correlation was found between fluid volume and yield in counts: the lower the volume, the higher the counts. With regard to sensitivity and cross-talk, the 96-well Isoplatetrade mark was superior to all other plates tested. While all white plates tested gave acceptable results, usage of the black 96-well plates resulted in an extremely low sensitivity. Plates designed for cell culturing gave even lower counts and a cross-talk of up to 31%. All attempts to reduce cross-talk and improve sensitivity, such as aluminium foil or grids, irrespective of the position of the photomultiplier, did not give results comparable to the original 96-well isoplate. Our results suggest that, with the exception of black 96-well microplates and cell culture plates, all other plates tested have a sufficient sensitivity when compared to vials and acceptable cross-talk, the 96-well Isoplatetrade mark being the best. Both types of luminometers used gave reproducible results, Wallac having a somewhat higher sensitivity, Canberra Packard somewhat less cross-talk.

Is the traditional open donor nephrectomy in living donor renal transplantation still up to date

BACKGROUNDnLiving donor kidney transplantation is a well-established method to reduce time on the waiting list. Although the laparoscopic donor nephrectomy has already been established worldwide, more than 80% of the living donor nephrectomies are performed as a traditional open donor nephrectomy in Germany. The aim of our study was to analyze perioperative data and long-term outcome of donors and recipients following open donor nephrectomy.nnnMETHODSnFrom February 2004 to July 2008, a total of 51 open donor nephrectomies were performed in Tuebingen University Hospital. Forty-five data of corresponding transplant donors and recipients were analyzed. The Kocak classification which provides a format to compare postoperative complications after living donor nephrectomy was used.nnnRESULTSnFive-year graft survival was 100%. No intraoperative complications occurred. Postoperatively Grad I complications were observed in 10 donors (22.2%). In the long term no major complications occurred. Two donors (4.4%) had newly diagnosed hypertension and required antihypertensive medication. None of the donors developed proteinuria. Right-sided transabdominal donor nephrectomy was associated with a shorter mean hospital stay compared to left-sided lumbar nephrectomy. (7.8 ± 2.4 vs. 9.2 ± 1.8 days, p < 0.05).nnnCONCLUSIONnOpen donor nephrectomy is a safe procedure with an excellent graft survival. Complication rates in our center are comparable to recent results in laparoscopic living donor nephrectomy. Therefore, the open donor nephrectomy remains important.SummaryBACKGROUND: Living donor kidney transplantation is a well-established method to reduce time on the waiting list. Although the laparoscopic donor nephrectomy has already been established worldwide, more than 80% of the living donor nephrectomies are performed as a traditional open donor nephrectomy in Germany. The aim of our study was to analyze perioperative data and long-term outcome of donors and recipients following open donor nephrectomy. METHODS: From February 2004 to July 2008, a total of 51 open donor nephrectomies were performed in Tuebingen University Hospital. Forty-five data of corresponding transplant donors and recipients were analyzed. The Kocak classification which provides a format to compare postoperative complications after living donor nephrectomy was used. RESULTS: Five-year graft survival was 100%. No intraoperative complications occurred. Postoperatively Grad I complications were observed in 10 donors (22.2%). In the long term no major complications occurred. Two donors (4.4%) had newly diagnosed hypertension and required antihypertensive medication. None of the donors developed proteinuria. Right-sided transabdominal donor nephrectomy was associated with a shorter mean hospital stay compared to left-sided lumbar nephrectomy. (7.8 ± 2.4 vs. 9.2 ± 1.8 days, p < 0.05). CONCLUSION: Open donor nephrectomy is a safe procedure with an excellent graft survival. Complication rates in our center are comparable to recent results in laparoscopic living donor nephrectomy. Therefore, the open donor nephrectomy remains important.ZusammenfassungEINLEITUNG: Die Nierenlebendspende stellt ein etabliertes Verfahren dar, um die Zeit auf der Warteliste zur Nierentransplantation bei anhaltendem Organmangel zu verkürzen. Trotz weltweiter Etablierung laparoskopischer Verfahren zur Spendernephrektomie, werden in Deutschland mehr als 80 % der Nephrektomien im Rahmen der Lebendspende auf konventionelle Art durchgeführt. Ziel dieser Analyse war die retrospektive Auswertung der perioperativen Daten und die Neuerhebung von Langzeitnachsorge-Daten der Spender und Empfänger nach konventioneller Spendernephrektomie. METHODIK: Von Februar 2004 bis Juli 2008 wurden an der Abteilung für Transplantationschirurgie der Universität Tübingen insgesamt 51 konventionelle Nierenlebendspenden bei Erwachsenen durchgeführt. Ausgewertet wurden 45 Spenden. Postoperative Komplikationen wurden zur besseren Vergleichbarkeit nach der Kocak-Klassifikation eingeteilt. ERGEBNISSE: Das 5-Jahres-Transplantatüberleben betrug 100 %. Intraoperativ traten keine Komplikationen auf. Postoperativ fanden sich bei 10 Spendern (22,2 %) Komplikationen ersten Grades nach der Kocak-Klassifikation. In der Langzeitnachsorge traten bei keinem Spender schwerwiegenden Komplikationen auf. Zwei Spender (4,4 %) entwickelten eine behandlungsbedürftige arterielle Hypertonie. Eine Proteinurie trat bei keinem der Spender auf. Vergleicht man den stationären Aufenthalt unter Einbezug der Operationstechnik (transabdominell rechts vs. lumbal linksseitig), zeigt sich, dass die transabdominelle Entnahme in einer signifikant früheren Entlassung resultierte, als die linksseitige lumbale Nephroureterektomie (7,8 ± 2,4 vs. 9,2 ± 1,8 Tage, p < 0,05). SCHLUSSFOLGERUNG: Die konventionelle Spendernephrektomie stellt ein sicheres Verfahren bei der Nierenlebendspende mit exzellentem Transplantatüberleben dar. Die Komplikationsraten bei der konventionellen Spendernephrektomie in unserem Zentrum sind mit den aktuellen Ergebnissen zur laparoskopischen Spendernephrektomie vergleichbar. Daher hat die konventionelle Entnahmetechnik nach wie vor einen hohen Stellenwert.