Efficacy and safety of tacrolimus compared with ciclosporin-A in renal transplantation: 7-year observational results.

The European Tacrolimus versus Ciclosporin-A Microemulsion (CsA-ME) Renal Transplantation Study demonstrated that tacrolimus decreased acute rejection rates at 6 months. Primary endpoints of this investigator-initiated, observational 7-year follow-up study were acute rejection rates, patient and graft survival rates, and a composite endpoint (BPAR, graft loss, and patient death). We analyzed data from the original intent-to-treat population (n = 557; 286 tacrolimus, 271 CsA-ME). A total of 237 tacrolimus and 208 CsA-ME patients provided data. At 7 years, Kaplan-Meier estimated rates of patients free from BPAR were 77.1% in the tacrolimus arm and 59.9% in the CsA-ME arm, graft survival rates amounted to 82.6% and 80.6%, and patient survival rates to 89.9% and 88.1%. Estimated combined endpoint-free survival rates were 60.2% in the tacrolimus arm and 47.0% in the CsA-ME arm (P = <0.0001). A higher number of patients from the CsA-ME arm crossed over to tacrolimus during 7 year follow-up: 19.7% vs. 7.9% (P = <0.002). More patients in the tacrolimus group stopped steroids and received immunosuppressive monotherapy. Significantly, more CsA-ME patients received lipid-lowering medication and experienced cosmetic and cardiovascular adverse events. Tacrolimus-treated renal transplant recipients had significantly higher combined endpoint-free survival rates mainly driven by lower acute rejection rates despite less immunosuppressive medication at 7 years.

Multicenter double-blinded randomized controlled trial of standard abdominal wound edge protection with surgical dressings versus coverage with a sterile circular polyethylene drape for prevention of surgical site infections: a CHIR-Net trial (BaFO; NCT01181206).

OBJECTIVE: To determine whether circular plastic wound edge protectors (CWEPs) significantly reduce the rate of surgical site infections (SSIs) in comparison to standard surgical towels in patients undergoing laparotomy. BACKGROUND: SSIs cause substantial morbidity, prolonged hospitalization, and costs and remain one of the most frequent surgical complications. CWEPs have been proposed as a measure to reduce the incidence of SSIs. METHODS: In this randomized controlled, multicenter, 2-arm, parallel-group design, patient- and observer-blinded trial patients undergoing open elective abdominal surgery were assigned to either intraoperative wound coverage with a CWEP or standard coverage with surgical towels. Primary endpoint was superiority of intervention over control in terms of the incidence of SSIs within a 30-day postoperative period. RESULTS: Between September 2010 and November 2012, 608 patients undergoing laparotomy were randomized at 16 centers across Germany. Three patients in the device group and 11 patients in the control group did not undergo laparotomy. Patients' and procedural characteristics were well balanced between the 2 groups. Forty-eight patients discontinued the study prematurely, mainly because of relaparotomy (control, n=9; intervention, n=9) and death (control, n=4; intervention, n=7). A total of 79 patients experienced SSIs within 30 days of surgery, 27 of 274 (9.9%) in the device group and 52 of 272 (19.1%) in the control group (odds ratio=0.462, 95% confidence interval: 0.281-0.762; P=0.002). Subgroup analyses indicate that the effect could be more pronounced in colorectal surgery, and in clean-contaminated/contaminated surgeries. CONCLUSIONS: Our trial shows that CWEPs are effective at reducing the incidence of SSIs in elective and clean or clean-contaminated open abdominal surgery.

Mesenteric histiocytosis or only an inflammatory infiltration of histiocytes? A case report from a surgical point of view.

The mesenteric sclerosing processes are very rare tumors. There are only a few cases of mesenteric fibromatosis described in literature. A case of mesenteric histiocytosis or a mesenteric infiltration by histocytes as a reactive inflammatory process is not described in the surgical literature. Because of its clinical and macroscopic similarity to a fibromatosis or a reactive inflammatory process and a lack of articles in the literature on mesenteric histiocytosis we concentrated our research in literature on the mesenteric fibromatosis and its differential diagnosis.

Influence of heme oxygenase-1 on microcirculation after kidney transplantation.

BACKGROUND: Cytoprotective proteins, such as heme oxygenase-1 (HO-1), play a decisive role in ischemia-reperfusion injury during kidney transplantation. The aim of this study was to investigate the impact of heme oxygenase-1 on microcirculation and on ischemia-reperfusion injury in an isogenic kidney transplantation rat model. MATERIALS AND METHODS: Seventy male Lewis rats were distributed into three groups. In Group 1(control), the kidneys were only mobilized. In Groups 2 and 3, bilateral nephrectomy was performed, and a kidney from another Lewis rat was orthotopically transplanted on the left side. The donor animals in Group 3 received preconditioning with the HO-1 inductor hemin. 24 h after reperfusion graft function and morphology were examined. Microcirculation was investigated by in vivo microscopy of the renal surface 1 h after reperfusion. RESULTS: HO-1 preconditioning led to significantly lower serum creatinine and serum urea, as well as less histological damage and inducible nitric oxide synthase expression. Microcirculation was improved by a significant enlargement of the vascular diameter and an increase of the capillary flow. CONCLUSIONS: Treatment with hemin improves microcirculation by induction of HO-1 and reduces ischemia-reperfusion injury after kidney transplantation. HO-1 induction was shown to be a promising approach in the preconditioning of donor kidneys.

A new laparoscopic technique for weight reduction with implanted gastric banding basket.

BACKGROUND: Nowadays, obesity is frequently an indication for implantation of an adjustable stomach or gastric band. Among the side effects, in addition to band erosion and port chamber complications, pouch dilation in the sense of increasing enlargement of the forestomach and resulting insufficiency of initial surgical measures consistently occurs. Implantation of a soft basket band will prevent this. The objective of this study was to investigate the practical feasibility of the soft basket band. METHODS: Ten patients were investigated in an observation study over a period from November 2006 to June 2007. Seven patients were women and three patients were men, with an average age of 43.6 years (25-66 years). RESULTS: The average body mass index (BMI) at the time of the operation was 47.4 +/- 5.5 kg/m(2), with an average body weight of 134.5 +/- 24.6 kg. After a median follow-up period of 1 month, an average BMI of 44.9 +/- 5.8 kg/m(2) was achieved, and after 3 months, an average BMI of 41.4 +/- 4.8 kg/m(2). The excessive weight loss was 7.4 +/- 4.3 kg after 1 month and 17.9 +/- 6.4 kg after 3 months. A local wound infection occurred as a complication in one patient. CONCLUSION: Laparoscopy procedures enable mortality to be lowered compared to bypass operations with minimal complications and substantial reduction of weight.

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results.

BACKGROUND: The European tacrolimus versus ciclosporin A microemulsion (CsA-ME) renal transplantation study showed that tacrolimus was significantly more effective in preventing acute rejection and had a superior cardiovascular risk profile at 6 months. METHODS: The endpoints of this investigator-initiated, observational, 36-month follow-up were acute rejection incidence rates, rates of patient and graft survival and renal function. An additional analysis was performed using the combined endpoints BPAR, graft loss and patient death. Data available from the original ITT population (557 patients; 286 tacrolimus and 271 CsA-ME) were analysed. RESULTS: A total of 231 tacrolimus and 217 CsA-ME patients participated. At 36 months, Kaplan-Meier-estimated BPAR-free survival rates were 78.8% in the tacrolimus group and 60.6% in the CsA-ME group, graft survival rates were 88.0% and 86.9% and patient survival rates were 96.6% and 96.7%, respectively. The estimated combined endpoint-free survival rate was 71.4% with tacrolimus and 55.4% with CsA-ME (P 6 mmol/L (26.3% versus 12.6%, P

Nephron-sparing surgery of a low grade renal cell carcinoma in a renal allograft 12 years after transplantation.

Renal cell carcinoma (RCC) occurring in renal allografts after cadaveric kidney transplantation has rarely been observed. RCC accounts for 2.3% of all malignancies in the general population, but up to 4.8% of malignancies in renal transplant recipients. Most have been reported in the patient's own diseased kidneys, whereas RCC in the renal allograft occur in only 10%. Here, we describe an organ-preserving surgical technique of a malignant renal tumor in a kidney allograft using a harmonic scalpel (Ultracision) for tumor enucleation. Furthermore we demonstrate by DNA microsatellite analysis the tumor's genetic origin as donor related. Collectively, we suggest that patients with a well defined low grade RCC in the kidney allograft and altogether low malignancy and good allograft function should only undergo an organ-preserving procedure and short-term postoperative screening.

Stress associated proteins metallothionein, HO-1 and HSP 70 in human zero-hour biopsies of transplanted kidneys.

Light microscopic alterations reflecting both previous and preservation-induced changes in the donor organ are usually not very distinctive. The ischemia/reperfusion-associated injury depends primarily on the conditions of donor organ preservation. The present study examined human kidney biopsies with special attention paid to the molecular mechanisms of preservation-induced injury preceding reperfusion. Stress-associated proteins hemeoxygenase-1 (HO-1), heat shock protein 70 (HSP 70), and metallothionein (MT) were studied in human zero-hour biopsies of transplanted kidneys prior to reperfusion in 29 patients. Protein expression was evaluated by semiquantitative immunohistochemistry and Western blotting for HO-1 and HSP 70. These findings were correlated with terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-digoxigenin nick end labeling (TUNEL) staining and follow up. Compared to controls, MT and HSP 70 expression was significantly higher at zero hour. In contrast, HO-1 and the number of TUNEL-positive cells were not elevated. MT and HO-1 immunoexpression were inversely associated with graft function, and hence, were of prognostic relevance. MT and HSP 70 were sensitive to the duration of cold ischemia. MT and HO-1 are suitable indicators for tissue injury during ischemia and may serve as new predictive markers that need to be validated in further independent studies.

Detrimental effect of sinusoidal overperfusion after liver resection and partial liver transplantation.

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.

Long-term follow-up of double kidney transplantation using a score for evaluation of marginal donors*.

To face the problem of organ shortage, marginal grafts from 36 donors which had been refused for single transplantation were used for double-kidney transplantation (D-KTX). The residual kidney function was evaluated by the Muenster double kidney score. In a 5-year period kidneys from 57 marginal donors were transferred to our center. According to the Muenster double kidney score, the kidneys were distributed to single, double or refusal of transplantation. Sixteen male and 20 female donors were used for D-KTX (70+/-9.3 years, range 53-86). Thirty-six recipients (23 male, 13 female; 60.5+/-6.9 years) were double-grafted within a mean cold ischemic time of 19.3+/-3.4 h. Immunosuppression varied according to human leukocyte antigen (HLA)-mismatch. Graft and patient survival was observed up to 5 years. Initial graft function rate was 69%. Two recipients had a primary nonfunction (5.5%) and nine recipients suffered from delayed graft function (DGF; 25%). One-, 2-, 3-year creatinine values were 1.6 +/- 0.5, 1.9 +/- 0.6 and 2.2 +/- 0.7 mg/dl, respectively. One-, 2-, 3-, 4- and 5-year function rate was 93.7%, 93.5%, 81.8%, 76.4% and 55%, respectively (n = 32, 31, 22, 17 and 9). Acute rejection rate was 19%. 4 grafts were lost to chronic rejection (months 22, 25, 28, 48). Six (16%) died in long-term follow-up because of pneumonia (n = 2), carcinoma of the lung (n = 1), cardial complications (n = 2) and multiorgan failure (n = 1). D-KTX is a safe way to face the problem of organ shortage. However, a score for preoperative evaluation of marginal kidneys for single, dual or refusal of transplantation is essential.

Strategies for compensating for the declining numbers of cadaver donor kidney transplants.

BACKGROUND: The living-donor and dual kidney transplantation programmes were initiated in the transplantation centre of Münster (TCM) as two approaches to compensate for the declining numbers of cadaver donor kidney transplants after the implementation of the new Eurotransplant Kidney Allocation System (ETKAS). We analysed the outcome of cadaver, living-donor and dual kidney transplantation and their effects on the waiting list in the TCM. METHODS: Between January 1990 and December 2000, 1184 kidney transplants were performed in the TCM. They were subdivided into cadaver, living-donor and dual kidney transplants and retrospectively analysed in terms of the number of kidney transplants performed, waiting time and waiting coefficient. In addition four representative groups were formed to reflect donor origin (I: cadaver kidney transplants allocated by the old ETKAS, n = 180; II: cadaver kidney transplants allocated by the new ETKAS, n = 139; III: living-donor kidney transplantation, n = 59; IV: dual kidney transplantation, n = 31) and compared according to graft function (initial diuresis, creatinine, 3-year graft function), patient survival and median waiting time. RESULTS: After the implementation of the new ETKAS, the number of cadaver donor kidney transplants at the TCM almost halved, but the proportion of living-donor kidney transplantations increased significantly by 12.8% and of dual kidney transplantations by 8.5%. Patients who had received kidneys from cadaver donors allocated by the new ETKAS (group II) had a better survival rate, short- and long-term function but a longer waiting time than in group I (old ETKAS). Patients with dual kidney transplants (group IV) showed the lowest survival and short-term function rate, but had long-term function equivalent to that of cadaver kidney transplants (groups I and II). Patients who had received kidneys from living donors (group III) had the best survival, and short- and long-term function rate as well as the shortest mean waiting time. CONCLUSIONS: Living-donor and dual kidney transplantation proved to be functionally equivalent alternatives and successful strategies for compensating the declining numbers of cadaver donor kidney transplants.

Trypsinogen activation peptide (TAP) expression in gallbladder bile identifies bilio-pancreatic carcinoma.

BACKGROUND: The prognosis of bilio-pancreatic cancer (pancreas, bile duct and gallbladder) is poor due to the fact of late diagnosis. The only curative treatment for such tumors is surgery. The 5-year survival rate is still below 5% and less than one-third of patients suffering from such carcinomas are resectable at the time of diagnosis. Although specific tumor markers do exist, to date there is no screening marker for these diseases. MATERIALS AND METHODS: Gallbladder bile of 44 consecutive cholecystectomized patients were prospectively analyzed for TAP concentrations. Group one (n = 14) consisted of the patients suffering from malignancies of the bilio-pancreatic system, group 2 (n = 22) comprised patients suffering from benign biliar or pancreatic diseases and group 3 (n = 6) included patients suffering from gastrointestinal carcinoma outside the bilio-pancreatic system with no affection of the bilio-pancreatic system. RESULTS: The median TAP gallbladder bile concentration in malignant disease of the bilio-pancreatic system was 1328.00 nmol/l (range: 83.69-5133.00). Benign bilio-pancreatic disease revealed a median TAP bile concentration of 2.02 nmol/l equaling the concentration of patients suffering from other gastrointestinal carcinomas with a median of 2.00 nmol/l. In the control groups (2 + 3) there was a significant difference for TAP bile concentrations with an increase in the case of acute inflammation. CONCLUSION: Gallbladder bile TAP concentration discriminates between benign and malignant lesions of the bilio-pancreatic system. In the case of benign disease there is a significantly higher TAP concentration in the case of acute inflammation.

Sympathetic nerve activity in end-stage renal disease.

BACKGROUND: Uremia is proposed to increase sympathetic nerve activity (SNA) in hemodialysis patients. The aims of the present study were to determine whether reversal of uremia by successful kidney transplantation (RTX) eliminates the increased SNA and whether signals arising in the diseased kidneys contribute to the increased SNA in renal failure. METHODS AND RESULTS: We compared muscle sympathetic nerve activity (MSNA) in 13 hemodialysis patients wait-listed for RTX and in renal transplantation patients with excellent graft function treated with cyclosporine (RTX-CSA, n=13), tacrolimus (RTX-FK, n=13), or without calcineurin inhibitors (RTX-Phi, n=6), as well as in healthy volunteers (CON, n=15). In addition to the above patients with present diseased native kidneys, we studied 16 RTX patients who had undergone bilateral nephrectomy (RTX-NE). Data are mean+/-SEM. MSNA was significantly elevated in hemodialysis patients (43+/-4 bursts/min), RTX-CSA (44+/-5 bursts/min), RTX-FK (34+/-3 bursts/min), and RTX-Phi (44+/-5 bursts/min) as compared with CON (21+/-3 bursts/min), despite excellent graft function after RTX. RTX-NE had significantly reduced MSNA (20+/-3 bursts/min) when compared with RTX patients. MSNA did not change significantly with RTX in 4 hemodialysis patients studied before and after RTX (44+/-6 versus 43+/-5 bursts/min, P=NS). In contrast, nephrectomy resulted in reduced MSNA in all 6 RTX patients studied before and after removal of the second native kidney. CONCLUSIONS: Despite correction of uremia, increased SNA is observed in renal transplant recipients with diseased native kidneys at a level not significantly different from chronic hemodialysis patients. The increased SNA seems to be mediated by signals arising in the native kidneys that are independent of circulating uremia related toxins.

sTNF-RII: is it useful for the early diagnosis of rejection and for prognosis after renal transplantation?

Changes in soluble tumour necrosis factor receptor II (sTNF-RII) correlate with transplant rejection, and it increases in the course of sepsis. These changes might help to identify rejection early, and thus lead to more effective treatment. Serum and urine sTNF-RII levels were measured in 70 patients during the first 3 weeks after kidney transplantation and correlated with clinical and laboratory findings. Retrospectively, three groups were identified: I. stable transplant function ( n=23), II. at least one rejection episode ( n=38) and III. other complications (infection or reperfusion injury) ( n=9). The pre-operative maximum for serum sTNF-RII was 22.4 +/- 10.7 ng/ml. In group I it decreased to 9.5 +/- 6.7 ng/ml on day 6 after transplantation ( P<0.01), while in group II sTNF-RII serum levels were significantly higher on day 6 (24.9 +/- 15.0 ng/ml, P<0.01). High levels of sTNF-RII in serum (>40 ng/ml for at least 2 days) predicted a higher risk of an unfavourable outcome. High serum levels of sTNF-RII are not specific but seem to be a prognostic indicator of a complicated course; sTNF-RII in urine has no diagnostic value.

Stent graft of abdominal aortic aneurysm after renal transplantation.

The necessity of operative treatment of abdominal aortic aneurysm (AAA) is reported in an increasing number of patients after renal transplantation as a result of improved renal graft long-term survival. In these patients, aortic surgery however, places the allograft at risk for ischemic damage. We present a first case of AAA stenting in a kidney-grafted patient. This procedure helped us avoid ischemia of the graft, which showed excellent function pre- and postoperatively. The patient had an uneventful recovery with no evidence of renal dysfunction and was discharged in good condition 7 days after stenting. This case demonstrates a useful alternative for the repair of AAA in kidney-grafted patients.

The Analysis of Bacterial Results in the Kidney Perfusion Fluid and Bone Allografts in Human Multiorgan Donors.

In 19 young human multiorgan donors, we simultaneously analyzed the bacterial contamination of the kidney perfusion fluid and all retrieved bone allografts. Donor exclusion criteria were done according to the American and European Association of Tissue Banks excluding all patients with perforating wounds. The kidney perfusate revealed a contamination in 17 of 19 (89.5%) donors. Allograft testing demonstrated positive bacterial growth in 34 of 76 allografts (44.7%). Microorganisms originated from the normal skin flora and could be related to contamination during the harvesting procedure. In 5 cases we cultured identical bacterial subspecies in both cultures as a possible sign for systemic bacterial spreading during the multiorgan harvesting procedure.