Assessment of the Clinical Impact of a Liver-Specific, BCAA-Enriched Diet in Major Liver Surgery.

BACKGROUND: The relationship between nutrition and liver disease is relevant for the outcome after surgery. Patients with liver cirrhosis characteristically show protein-energy malnutrition with decreased levels of branched-chain amino acids (BCAA) and increased levels of aromatic amino acids. MATERIALS AND METHODS: We conducted a prospective controlled clinical trial including 57 patients after liver transplantation or major liver resection surgery in order to test the effect of early postoperative nutrition on the outcome and nutrition profile of these patients. The test group received a dietetic program composed of ingredients naturally rich in BCAA (BCAA group), and the control group received standard hospital meals. Patient survival, liver function tests, subjective well-being, and a nutritional status including amino acid profiles were analyzed immediately and 14 days after major liver surgery (secondary end points). General health and well-being were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (primary end point). RESULTS: In-depth analysis of amino acid profiles was performed for patients undergoing liver resection (n = 21) and liver transplantation (n = 36). Interestingly, amino acid profiles did not correlate with body mass index or the Model for End-Stage Liver Disease score. Patients scheduled for liver transplantation showed significantly lower levels of BCAA pretransplant compared to patients undergoing liver resection. Patients in the liver resection subgroup were more likely to benefit from the BCAA cuisine in terms of significantly higher food intake and subjective rating. The clinical liver function tests, however, did not show statistical difference between the BCAA group and the control group in the examination period of 14 days. CONCLUSION: Our specifically designed BCAA-enriched diet resulted in greater patient satisfaction and compliance with nutrition. A larger trial or longer-term follow-up may be required to identify an effect on survival, recovery, surgical complications, protein profiles, and amino acid profiles.

Outcomes of pancreas retransplantation in patients with pancreas graft failure.

BACKGROUND: Pancreas retransplantation is still a controversial option after loss of a pancreatic graft. This article describes the experience of pancreas retransplantation at a high-volume centre. METHODS: This was a retrospective observational study of all pancreas retransplantations performed in a single centre between 1997 and 2013. Pancreatic graft loss was defined by the return to insulin dependence. Risk factors for graft loss as well as patient and graft survival were analysed using logistic and time-to-event regression models. RESULTS: Of 409 pancreas transplantations undertaken, 52 (12·7 per cent) were identified as pancreas retransplantations. After a median follow-up of 65·0 (range 0·8-174·3) months, 1- and 5-year graft survival rates were 79 and 69 per cent respectively, and 1- and 5-year patient survival rates were 96 and 89 per cent. During the entire follow-up, 22 grafts (42 per cent) were lost. Patient survival was not associated with any of the donor- or recipient-related factors investigated. Five-year graft survival was better after simultaneous kidney-pancreas retransplantation than pancreas retransplantation alone: 80 per cent (16 of 20) versus 63 per cent (20 of 32) (P = 0·226). Acute rejection (odds ratio 4·49, 95 per cent c.i. 1·59 to 12·68; P = 0·005) and early surgical complications (OR 3·29, 1·09 to 9·99, P = 0·035) were identified as factors with an independent negative effect on graft survival. CONCLUSION: Pancreas retransplantation may be considered for patients whose previous graft has failed.

Pancreatic graft survival despite partial vascular graft thrombosis due to splenocephalic anastomoses.

Thrombotic complications following pancreas transplantation are still the most common cause of nonimmunologic graft loss. The aim of this study was to analyze pancreatic graft function after partial arterial graft thrombosis and the investigation of the pancreatic arterial anatomy with regard to intraparenchymal anastomoses. We retrospectively analyzed the data for 175 consecutive pancreas transplants performed between January 2002 and October 2007. Selective Y-graft angiography was performed in 10 and rubber-milk injection in 5 fresh pancreas specimens. Thrombosis of one leg of the Y-graft was diagnosed in 18 (10.3%) patients. Only one of these patients with thrombosis of the splenic artery required exogenous insulin. Sufficient graft perfusion was demonstrated in all of the remaining grafts. One graft was lost due to acute rejection. In all specimens angiography showed an excellent perfusion of the pancreaticoduodenal arcade, even after selective cannulation of the splenic artery. Arterial collaterals between the gastroduodenal, splenic artery and the superior mesenteric artery were demonstrated. Our results demonstrate that global perfusion of the pancreatic graft and sufficient graft function is sustained after the thrombotic occlusion of one branch of the Y-graft by a complex system of intraparenchymal anastomoses. These anatomical findings may have consequences for resection strategies in pancreas surgery.

Non-invasive monitoring of kidney allograft rejection through IDO metabolism evaluation.

The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma (IFN-gamma) and via tryptophan depletion, suppresses adaptive T cell-mediated immunity in inflammation, host immune defense, and maternal tolerance. Its role in solid organ transplantation is still unclear. Therefore, we investigated the usefulness of IDO-mediated tryptophan catabolism in the evaluation of kidney allograft rejection. Blood, urine, and tissue samples were collected from 34 renal transplant patients without rejection and from nine patients with biopsy-confirmed episodes of acute rejection (n=12). Concentrations of kynurenine and tryptophan in serum and urine were analyzed by high-pressure liquid chromatography. Kynurenine to tryptophan ratio (kyn/trp) was calculated to estimate IDO activity. Immunostaining for IDO was performed on renal biopsies. Neopterin was assessed using radioimmunoassay. Kyn/trp and neopterin were detectable at low levels in serum of healthy volunteers and were increased in non-rejecting allograft recipients. Serum levels of kyn/trp were higher in recipients with rejection compared to non-rejectors as early as by day 1 post-surgery. Rejection episodes occurring within 13+/-5.9 days after transplantation were accompanied by elevated kyn/trp in serum (114+/-44.5 micromol/mmol, P=0.001) and urine (126+/-65.9 micromol/mmol, P=0.02) compared to levels during stable graft function. Kyn/trp correlated significantly with neopterin suggesting an IFN-gamma-induced increase in IDO activity. Immunostaining showed upregulation of IDO in rejection biopsies, localized in tubular-epithelial cells. Non-rejected grafts displayed no IDO expression. Acute rejection is associated with simultaneously increased serum and urinary kyn/trp in patients after kidney transplantation. Thus, IDO activity might offer a novel non-invasive means of immunomonitoring of renal allografts.

Excellent results with calcineurin inhibitor-free initial immunosuppression in old recipients of old kidneys.

The ever increasing demand for donor organs has forced transplant surgeons to liberalize selection criteria. To avoid initial nephrotoxicity to kidneys from donors over 65 years of age, immunosuppression was begun with an IL-2 receptor antibody, mycophenolate mofetil, and steroids in a total of 38 recipients over 65 years. Calcineurin inhibitors (CI) were added after sufficient graft function was reached. After a mean cold ischemia time of 14:01 hours and a delayed function rate of 31%, patient survival, graft survival, and serum creatinine were 97.4%, 94.7%, and 1.5 mg/dL at 1 and 92.1%, 92.1%, and 1.7 mg/dL at 2 years, respectively. Thus, excellent results can be achieved in old recipients of old donor kidneys with CI-free initial immunosuppression.

Increased tacrolimus levels during diarrhea.

While it is well known that diarrhea results in decreased trough levels of cyclosporin A, experience with levels of tacrolimus (FK506) and diarrhea is limited. We have therefore measured the tacrolimus trough levels of four male and two female recipients of solid organs before, during, and after gastroenteritis. The average age of these six patients was 31 (1-60) years. Four patients had received a kidney transplant, one patient had undergone simultaneous kidney-pancreas transplantation, and another patient had received a liver transplant. Rotavirus was identified in the feces specimen of a 1-year-old child that had undergone liver transplantation. All patients showed an elevated tacrolimus trough level (peak 20-60 ng/ml) after onset of gastroenteritis. Under symptomatic therapy and adequate adjustment of tacrolimus dose, the gastroenteritis stopped and tacrolimus levels returned to the therapeutic range. We recommend that FK506 levels be carefully monitored during diarrhea in order to prevent intoxication.

Renal allograft rupture is associated with rejection or acute tubular necrosis, but not with renal vein thrombosis.

BACKGROUND: Whereas rejection was reported to be the most common cause of renal allograft rupture (RAR) in the pre-cyclosporin era, renal vein thrombosis (RVT) is purported to be the main cause of RAR in patients taking cyclosporin. The extremely low incidence of RVT in our series (0.11%) prompted us to analyse our collective with regard to RAR. METHOD: Between 1974 and 1999, 1811 renal transplants were performed. Patients with RAR, defined as a tear of the renal capsule and parenchyma, were identified and possible underlying factors studied. RESULTS: RAR was diagnosed in nine male and five female recipients (0.8%) with a median age of 36 years. Immunosuppression consisted of azathioprine and prednisolone in seven patients and of cyclosporin-based therapy in the seven others. At exploration five grafts were removed immediately: three because of irreversible rejection, one because of deep wound infection, and one with a twisted renal vein. Six of the nine salvaged kidneys have been functioning after a mean observation time of 45 months. In the pre-cyclosporin era RAR was associated with acute rejection in five out of seven cases as compared with only three of the seven on cyclosporin treatment. Core biopsies might have been the cause in three cases. CONCLUSION: RAR is a rare complication after renal transplantation. Acute rejection still represents the most frequent cause of RAR in the cyclosporin era.

Comparison of progression of macrovascular diseases after kidney or pancreas and kidney transplantation in diabetic patients with end-stage renal disease.

AIMS/HYPOTHESIS: The aim of the study was to examine the effect of pancreas-kidney transplantation on the progression of macrovascular diseases in Type I diabetic patients with end-stage renal disease. METHODS: The progression of cerebrovascular disease, coronary heart disease and peripheral vascular disease in uraemic patients with Type I (insulin-dependent) diabetes mellitus and who had had simultaneous pancreas-kidney transplantation was compared with that of recipients of a kidney transplant alone. Between 1986 and 1998 a total of 11 uraemic diabetic patients received a simultaneous pancreas-kidney transplantation and 10 diabetic patients a kidney transplant alone. All transplants functioned for at least 24 months, the mean observation period was 69 +/- 37 compared with 70 +/- 33 months in both patient groups. Macroangiopathic diseases were classified in four stages as described earlier. RESULTS: In the group with simultaneous pancreas-kidney transplantation progression of cerebrovascular and coronary heart disease was observed in four patients (36%) and progression of peripheral vascular disease in five subjects (45%). In the cohort with kidney transplant alone four patients (40%) showed progression of cerebrovascular and coronary heart disease and five progression of peripheral vascular disease (50%); the difference is not significant. Mean values of HbA1c (5.8 +/- 0.2 vs 7.5 +/- 0.6%, p < 0.001) and serum triglycerides (1.2 +/- 0.4 vs 2.0 +/- 1.0 mmol/l, p < 0.05) were significantly lower in the patients with pancreas-kidney transplantation than in the patient group with kidney transplant alone. Serum cholesterol concentrations and blood pressures were similar in both cohorts. CONCLUSION/INTERPRETATION: From our results we concluded that pancreas-kidney transplantation reduces risk factors for the development of macroangiopathy but fails to halt progression of macrovascular diseases similar to Type I diabetic patients with kidney transplant alone.

Lipoprotein(a) plasma concentrations after renal transplantation: a prospective evaluation after 4 years of follow-up.

The highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.

[Extensive plasma exchange in treatment of acute vascular graft rejection of the kidney and pancreas]. / Extensiver Plasma-Austausch zur Behandlung der akuten vaskulären Abstossungsreaktion der Niere und des Pankreas.

Twenty-eight histologically proven severe acute vascular rejection episodes in renal grafts were reversed in 22/28 (78%) cases by extensive plasma exchange, which was well-tolerated by all but one patient. CMV infection was the most frequent complication. As 1-year survival of 93% (patient) and 71% (graft) is considered a good result in this severe immunological complication, the extensive plasma exchange can be recommended for the treatment of acute vascular rejection.

[Personal experience with prevention and therapy of infection after 53 liver transplantations]. / Unsere Erfahrungen mit der Infektionsprophylaxe und -therapie nach 53 Lebertransplantationen.

An attempt was made to reduce the risk of infection following liver transplantation by means of selective bowel decontamination with tobramycin, polymyxin E and amphotericin B, as well as short-term systemic antibiotics with cephotaxim and tobramycin. After 53 consecutive orthotopic hepatic transplants performed in 51 patients between 1985 and 1987, a total of eight pneumonias occurred as the clinically most significant infection. Two pneumonias were caused by cytomegalovirus, one by Pneumocystis carinii, one by Candida and the remaining four by various bacteria. In 6 patients, bacteria were cultured from the blood, but only in one case was an indwelling catheter identified as the source of the septicemia. Taking all samples together, Streptococcus faecalis was the bacterium most frequently cultured, which was not covered by the prophylactic antimicrobial regime applied. Pseudomonas, however, and gram-negative bacteria were demonstrated much less frequently. Vaginal and oral Candida infections, as well as oral and genital herpes simplex infections, responded well to topical therapy with fungicide and aciclovir, respectively. Three patients developed cytomegalovirus (CMV) hepatitis. All five CMV infections were successfully treated with ganciclovir and hyperimmunoglobulin, as well as reduction of prophylactic immunosuppression. Out of 15 patients transplanted for posthepatitic cirrhosis, 7 developed a recurrence of the infection (5 hepatitis B virus) 2 hepatitis C virus) in the graft. Two died of the cirrhosis, three are still alive with cirrhosis but sufficient graft function, and one patient is suffering from chronic active hepatitis. One patient grafted for acute hepatic failure was able to clear the delta virus within 1 year post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical experiences with 50 pancreas transplantations]. / Klinische Erfahrungen mit 50 Pankreastransplantationen.

Between 1979 and December 1987 a total of 50 pancreas transplants were performed, 41 of them together with a kidney from the same donor. End-stage diabetic nephropathy was the indication for the combined procedure, and progressive pre-proliferative retinopathy for a single pancreas transplant. A segment consisting of body, tail but also major parts of the head of the gland was used. Technique-related complications or prolonged hospitalization prompted three changes in surgical technique. In the first five patients the pancreatic duct was occluded at the time of transplantation and in the subsequent eleven cases the graft was anastomosed to a Roux-Y-loop of jejunum. In a series of 17 patients thereafter the pancreatic duct was occluded after stabilization of graft function, and in the most recent 17 patients the pancreatic juice was drained into the urinary bladder. Prophylactic immunosuppression consisted of steroids and azathioprine for the first two patients. From 1981 to 1986 cyclosporin and prednisolone were given and from then on azathioprine was added as a third drug. Patient survival at one year was 25% in the first group, 80% in group II, 97% in group III and 88% in group IV. Cardiovascular and septic complications were the main causes of death. None of the group I transplants functioned at one year. Graft survival rates at one year for the pancreas and the kidney in groups II, III and IV were calculated at 30%, 70%, 58.8% and 77%, 86%, 72% respectively. In 16% of the long-term survivors significant amelioration and in another 50% stabilization of diabetic retinopathy occurred.

[The effect of donor conditioning and perioperative management of recipients on the initial and late function of kidney transplants]. / Einfluss von Spenderkonditionierung und perioperativem Management des Empfängers auf die Initial- und Spätfunktion nach Nierentransplantation.

On the basis of 88 consecutive cadaveric renal transplants, multiple variables concerning donor conditioning and perioperative recipient management which may have an influence on the occurrence of acute tubular necrosis (ATN), were analysed and their impact on long-term results assessed. Cold ischaemia time turned out to be the greatest risk factor and was seven hours shorter in patients with good initial function when compared with patients with ATN. Although actual one-year graft survival was similar in both groups, the postoperative course was more complicated in the ATN group and management more onerous. Furthermore, two patients of the initial non-function group died of complications directly related to renal replacement therapy. Seventeen hours cold ischaemia time was associated with more than 80% initial function. This time is sufficient to allow careful tissue typing and organ transportation.

[Infectious complications in the early phase following kidney transplantation]. / Infektiöse Komplikationen in der Frühphase nach Nierentransplantation.

A retrospective analysis of 533 patients receiving kidney transplantation was performed to study the incidence of infection in the early postoperative period. Mostly localized in the lungs and renal system, bacterial complications arose in 133 patients. As compared with the unproblematic management of the urinary tract infections, 45 pulmonary infections were characterized by difficulties in diagnosis and treatment. Poor graft function was closely related to pulmonary infections: mean creatinine was 2.4 mg% (in patients without pneumonia - 1.5 mg%). Out of 45 patients with pneumonia, the graft failed in 16 patients. 6 patients died as a result of pneumonia. Rapid detection of the pathogenic organism is required, if necessary by invasive diagnosis. The administration of erythromycin before identification of the responsible pathogen may be indicated, in view of the fatal outcome in several patients subsequently diagnosed as having Legionella infection.

Rejection of kidney and pancreas after pancreas-kidney transplantation.

On the basis of 26 combined pancreas-kidney transplants we questioned whether both organs undergo rejection simultaneously. Reliable diagnosis of pancreas-graft rejection was made possible by monitoring exocrine graft function, including quantitative measurements of pancreatic juice, its amylase content, and pancreatic juice cytology. In addition, diagnosis of pancreas rejection was based on regular flow studies, daily urinary neopterin excretion, and a retrospective analysis of the clinical course. Clinical symptoms, blood chemistry, and, primarily, histology were used to assess rejection of the kidney allograft. In 18 cases the kidney and pancreas were rejected together; in 8 cases the kidney or the pancreas was rejected. Although both organs were rejected at the same time in most cases, either organ can be rejected alone. Thus, the kidney cannot be used to monitor the pancreas allograft in every case.