Alfred Königsrainer

Does pancreas transplantation influence the course of diabetic retinopathy

SummaryBetween March 1983 and December 1989 a total of 57 pancreas transplants were performed in 54 patients, of whom 49 also received a kidney for end-stage diabetic nephropathy. Of the surviving 44 patients, 39 had regular pre-operative and post-operative ophthalmological examinations. Diabetic retinopathy was classified according to the original “Early treatment diabetic retinopathy study” (ETDRS) protocol. At the time of this analysis a total of 25 patients had a functioning pancreas transplant and 23 of them also a functioning renal allograft after a mean observation time of 43.2 months (Group 1). They were all free of exogenous insulin, HbA1c being 6.2% (5.1–6.9%;normal value 4.2–5.9%). Fourteen patients in Group 2 lost their pancreas transplant during the first four years. Six of them still have a functioning renal allograft, four patients regularly undergo hemodialysis. Mean HbA1c is 7.5% (5.7–9.2%). Before transplantation, grade of retinopathy according the ETDRS protocol was 6.7 (2–10) in group 1 patients and 7.9 (3–10) in group 2. In group 1 patients stabilisation of retinopathy was observed in 33 eyes (73.3%) and clear improvement achieved in 4 eyes (8.8%). Detonation occurred in 8 eyes (17.7%) only. In group 2, 14 eyes (54%) remained stable, whereas progression of the disease continued in 12 eyes (46%). From these results it is concluded that the course of diabetic retinopathy is positively influenced by successful pancreas transplantation.

Rotavirus infection as cause of tacrolimus elevation in solid‐organ‐transplanted children

Abstract: Rotavirus (RV) is the most common cause of diarrheal illness in children. We report three solid‐organ‐transplanted patients in whom RV infection caused increased trough levels of the immunosuppressive macrolide tacrolimus (TAC) by mechanisms that are still under investigation. The virus was detected for longer in the feces of these patients than in infants not receiving immunosuppressive therapy. In association with short‐term monitoring of blood trough levels of TAC, the dosage should be reduced early if symptoms of an acute gastroenteritis are present.

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.

Effects of pancreas transplantation on distribution and composition of plasma lipoproteins

In type I (insulin-dependent) diabetic patients, peripheral hyperinsulinemia due to subcutaneous insulin treatment is associated with increased high-density lipoprotein (HDL) cholesterol, and also with an altered surface composition of HDL. Pancreas grafts also release insulin into the systemic rather than into the portal venous system, giving rise to pronounced peripheral hyperinsulinemia. We hypothesized that if peripheral hyperinsulinemia is responsible for high HDL cholesterol and/or altered surface composition of HDL in diabetic subjects, similar changes in the lipid profile should be present in pancreas-kidney transplant recipients (PKT-R). Using zonal ultracentrifugation, we isolated HDL2, HDL3, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) from fasting plasma of 14 type I diabetic PKT-R, eight nondiabetic kidney transplant recipients (KT-R), and 14 healthy control subjects and determined the level and composition of the above lipoproteins. HDL2 cholesterol was increased in PKT-R as compared with KT-R and healthy controls (both P < .05), whereas HDL3 cholesterol was unchanged. However, an altered lipoprotein surface composition was evident in PKT-R: HDL2, HDL3, and LDL were enriched in unesterified cholesterol ([UC] PKT-R v KT-R, P=.13, P < .005, and P < .05, respectively; PKT-R v controls, all P < .005); HDL2 was enriched in phospholipids; and LDL was depleted of phospholipid. KT-R, in contrast, showed no changes in lipoprotein surface composition but a substantial triglyceride enrichment of HDL2 as compared with PKT-R and healthy controls (both P < .05). LDL size as determined by gradient gel electrophoresis was increased in PKT-R compared with controls (P < .005). The plasma concentration of cholesteryl ester (CE) transfer protein (CETP), involved also in phospholipid transfer, was increased in both transplant groups compared with healthy controls (both P < .05). Insulin concentrations in fasting plasma were directly related to CETP levels and to the weight-percentage of UC in HDL3, and inversely to the weight-percentage of phospholipids in LDL (all P < .05). We explain the increase in HDL2 cholesterol and LDL size in PKT-R by their high lipoprotein lipase (LPL) activity conferring an excellent capacity to clear chylomicron triglycerides. Effective handling of postprandial triglycerides, high HDL2 cholesterol, and predominance of LDL pattern A, respectively, are established indicators of a low risk of atherosclerosis. However, it is presently unclear what effects the compositional changes on the surface of HDL and LDL may have on cardiovascular risk in clinically stable PKT-R.

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.

A technique of pancreas transplantation in the rat securing pancreatic juice for monitoring

Abstract. In order to study exocrine pancreas graft function and cytological findings, a technique of vascularized pancreas transplantation with special reference to a pancreatic juice collecting system has been developed in the rat model. For this purpose, a catheter is introduced into the common bile duct, which is ligated close to the duodenum, thus covering all pancreatic ducts. This catheter is connected to a reservoir implanted subcutaneously, from which pancreatic juice can easily be aspirated. The amount of 0. 7–1. 2 cc of juice produced over a 24‐h period has proven to be sufficient for various analyses and cytological examination.

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.

Histological features of acute pancreatic allograft rejection after pancreaticoduodenal transplantation in the rat

Abstract. For characterization of histopathological changes during pancreas graft rejection, pancreaticoduodenal transplants were performed in three groups: (1) Brown Norway into diabetic Lewis rats without immunosuppression, (2) Brown Norway into diabetic Lewis rats with cyclosporin A, and (3) Lewis into Lewis rats. Diffuse inflammatory infiltration of the acini by mononuclear cells indicated the onset of rejection (stage I). Shortly after acinar infiltration, damage to small and large interlobular excretion ducts occurred. This took the form of florid circumferential inflammation and vacuolar degeneration of epithelium similar to the bile duct damage seen in primary biliary cirrhosis, graft‐versus‐host disease, and liver allograft rejection (stage II). Thereafter, endothelialitis and destruction of islets were evident, consistent with a more advanced and irreversible stage of rejection (stage III). Acinar inflammation and moderate duct lesions were not prevented by immunosuppression but were delayed. Nonetheless, severe vascular changes and loss of islets were avoided. We conclude that duct lesions are a reliable criterion for pancreas allograft rejection. They are more sensitive than vascular changes and more specific than cellular infiltration of acinar tissue, which may also occur in infection.

Functional vascular anatomy of the peritoneum in health and disease

Abstract The peritoneum consists of a layer of mesothelial cells on a connective tissue base which is perfused with circulatory and lymphatic vessels. Total effective blood flow to the human peritoneum is estimated between 60 and 100 mL/min, representing 1–2u2006% of the cardiac outflow. The parietal peritoneum accounts for about 30u2006% of the peritoneal surface (anterior abdominal wall 4u2006%) and is vascularized from the circumflex, iliac, lumbar, intercostal, and epigastric arteries, giving rise to a quadrangular network of large, parallel blood vessels and their perpendicular offshoots. Parietal vessels drain into the inferior vena cava. The visceral peritoneum accounts for 70u2006% of the peritoneal surface and derives its blood supply from the three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric. These vessels give rise to smaller arteries that anastomose extensively. The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to first-pass hepatic metabolism. Peritoneal inflammation and cancer invasion induce neoangiogenesis, leading to the development of an important microvascular network. Anatomy of neovessels is abnormal and characterized by large size, varying diameter, convolution and blood extravasation. Neovessels have a defective ultrastructure: formation of large “mother vessels” requires degradation of venular and capillary basement membranes. Mother vessels give birth to numerous “daughter vessels”. Diffuse neoangiogenesis can be observed before appearance of macroscopic peritoneal metastasis. Multiplication of the peritoneal capillary surface by neoangiogenesis surface increases the part of cardiac outflow directed to the peritoneum.

Pancreatic transplantation with delayed duct occlusion versus bladder drainage: long-term results

SummaryBetween April 1985 and August 1990 a total of 51 combined pancreas kidney transplants and 6 single pancreas transplants were performed in 51 Type 1 (insulin — dependent) diabetic patients suffering from end-stage diabetic nephropathy and three patients with proliferative retinopathy. In 17 transplants the pancreatic duct was occluded with a mean delay of 53 days (Group 1). Because of a high incidence of local complications associated with a prolonged hospitalization this technique was abandoned despite favourable results: The actual survival rates for patients, pancreas and renal allografts at 1 year are 94%, 72% and 93%, respectively. From 1987 a total of 39 consecutive segmental pancreas grafts were anastomosed with the urinary bladder (Group 2). Pancreatic secretions were temporarily drained to the exterior in all patients via a duct catheter. Monitoring of the exocrine function including pancreatic secretion cytology and pancreatic secretion neopterin excretion proved to be reliable rejection markers. Survival rates at 1 year were calculated to be 90%, 74% and 89% for all patients, pancreas grafts and renal grafts. Apart from local complications in group I which did not cause any graft loss, the surgical complication rate was comparably low in both groups.