Moon phases and moon signs do not influence morbidity, mortality and long-term survival, after living donor kidney transplantation.

BACKGROUND: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. METHODS: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. RESULTS: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. CONCLUSION: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases.

Donor-derived tuberculosis in an anesthetist after short-term exposure : An old demon transplanted from the past to the present.

We report a case of a 27-year-old anesthetist who acquired tuberculosis (TB) while performing general anesthesia in a renal transplant (RTX) patient who had donor-derived contagious TB. The anesthetist developed pleural TB 6 months after exposure. Contact investigations (CIs) did not include health care workers (HCWs) of the Department of Anesthesiology, thereby missing the opportunity for the early diagnosis and treatment of TB. Genomic fingerprinting revealed identical Mycobacterium tuberculosis (MT) isolates in the anesthetist and in the RTX patient. The recipient had acquired disseminated TB from the harvested renal graft. The donor (liver and kidneys), a 67-year-old immigrant, had died from brain death by cerebral herniation after a stroke. She had been treated for tuberculosis with a pneumectomy 40 years ago. Since that time, she had been suffering from latent tuberculous infection (TBI), but had been considered to have been cured.

Donor-derived tuberculosis after solid organ transplantation in two patients and a staff member.

Because of global mobility and migration resulting in a growing diversity of the donor pool, the risk for donor-derived tuberculosis in solid organ transplant recipients becomes more and more relevant, even in countries with a low overall tuberculosis incidence. Here, we describe a case series of donor-derived tuberculosis in 2 of 3 solid organ transplant recipients and one medical staff member in Germany resulting in the death of one recipient. This case series highlights the relevance of this topic to clinicians. It advocates for a better communication between organ procurement organizations and transplant centers regarding donor information and transplant recipient outcome. Furthermore, it underpins the necessity for a standardized critical incident reporting system in the german transplant system to improve short- and long-term recipient's safety, health and survival.

Automated low flow pump system for the treatment of refractory ascites: a single-center experience.

INTRODUCTION: Ascites is a common complication of liver cirrhosis and represents the main cause of hospitalization among patients with cirrhosis. First-line therapy for those patients is the use of diuretics and dietary sodium restriction. However, 10 % of patients per year become therapy refractory to diuretic treatment with the need of repeated high-volume paracentesis or transjugular intrahepatic portosystemic shunt (TIPS). For these patients, an automated pump system (Alfapump/Sequana Medical) was developed. Here, we describe our single-center experience of ten consecutively implanted pump systems. PATIENTS AND METHODS: Between 08/13 and 11/14, ten Alfapump systems were implanted in patients with refractory ascites all suffering from liver cirrhosis. Those patients were treated as a bridge to transplant (4/10) or as an end-stage therapy (6/10). Median follow-up was 165 days (23-379 days). RESULTS: Postimplant, the need of paracentesis could be markedly reduced to a mean of 0.45 (0-4/month) per month. In eight patients, paracentesis was not needed after implantation of the pump system. The median daily output volume was 1000 ml/day (450-2000 ml/day). Prerenal insufficiency was a recurrent complication in the postoperative period. DISCUSSION: The Alfapump system is a useful system in the treatment of patients suffering from therapy refractory ascites. However, due to the high level of comorbidities, careful patient selection and postoperative monitoring are required.

Near-infrared spectroscopy based neurofeedback training increases specific motor imagery related cortical activation compared to sham feedback.

In the present study we implemented a real-time feedback system based on multichannel near-infrared spectroscopy (NIRS). Prior studies indicated that NIRS-based neurofeedback can enhance motor imagery related cortical activation. To specify these prior results and to confirm the efficacy of NIRS-based neurofeedback, we examined changes in blood oxygenation level collected in eight training sessions. One group got real feedback about their own brain activity (N=9) and one group saw a playback of another person's feedback recording (N=8). All participants performed motor imagery of a right hand movement. Real neurofeedback induced specific and focused brain activation over left motor areas. This focal brain activation became even more specific over the eight training sessions. In contrast, sham feedback led to diffuse brain activation patterns over the whole cortex. These findings can be useful when training patients with focal brain lesions to increase activity of specific brain areas for rehabilitation purpose.

[Transplantation and hepatic, pancreatic, and biliary (HPB) surgery fellowship--a pilot project for a structured training in Germany]. / Fellowship für Transplantation und hepato-pankreatiko-biliäre (HPB) Chirurgie - Pilotprojekt für eine strukturierte Weiterbildung in Deutschland.

Currently, there is no structured training plan to become a transplant surgeon in Germany. Similar to the Anglo-Saxonian educational system we have implemented a 3-year fellowship in transplant and hepatic-, pancreatic-, biliary (HPB) surgery. The educational curriculum is based on the guidelines of the European Board of Surgery (EBS) for transplant and HPB surgery. Here, we describe the underlying thoughts, the selection process, structure and curriculum for this fellowship. Furthermore, we critically compare our programme to the established international training standards. So far, our programme has proven valuable. We believe a fellowship for transplant and HPB surgery is a reasonable approach to ensure a high quality training of the following generations of surgeons in this field.

Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation.

BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.

Extracellular factors and immunosuppressive drugs influencing insulin secretion of murine islets.

Approximately 60% of transplanted islets undergo apoptosis within the first week post-transplantation into the liver attributed to poor engraftment, immune rejection and toxicity of immunosuppressive drugs. Understanding how extracellular matrix (ECM) components, immunosuppressive drugs and proinflammatory cytokines affect insulin secretion will contribute to an improved clinical outcome of islet transplantations. In this study, functional activity of isolated murine islets was measured by glucose-stimulated insulin secretion (GSIS) and by electrophysiological measurements using patch-clamp. Cultivating islets with soluble fibronectin or laminin, as opposed to with coated laminin, markedly increased GSIS. Addition of cyclosporin A reduced GSIS and suppressed glucose-induced spike activity. Tacrolimus affected neither GSIS nor spike activity, indicating a different mechanism. To evaluate the influence of proinflammatory cytokines, islets were incubated with interleukin (IL)-1ß, tumour necrosis factor (TNF)-α or with supernatants from cultured Kupffer cells, the main mediators of inflammation in the hepatic sinusoids. IL-1ß exerted a bimodal effect on insulin secretion, stimulating below 2 ng/ml and suppressing above 10 ng/ml. Soluble laminin in combination with a stimulatory IL-1ß concentration further increased insulin secretion by 20% compared to IL-1ß alone, while with high IL-1ß concentrations soluble laminin slightly attenuated GSIS inhibition. TNF-α alone did not affect GSIS, but with stimulatory IL-1ß concentrations completely abolished it. Similarly, supernatants derived from Kupffer cells exerted a bimodal effect on GSIS. Our data suggest that improved insulin secretion of transplanted islets could be achieved by including soluble laminin and low IL-1ß concentrations in the islet cultivation medium, and by a simultaneous inhibition of cytokine secretion from Kupffer cells.

Effect of perioperative administration of a drug regimen on the primary function of human renal allografts.

Delayed graft function (DGF) has one of the greatest effects on short- and long-term outcomes of cadaveric renal allografts. Ischemia reperfusion injury in the context of cold ischemia time and acute calcineurin inhibitor (CNI) nephrotoxicity is a major factor predisposing to DGF. A drug regimen consisting of prostaglandin E(1) (PGE(1)) furosemide and dopamine has been used to reduce DGF after kidney transplantation. Prostaglandin E(1) has multiple anti-ischemic and tissue-protective abilities, furosemide improves diuresis, and dopamine augments renal blood flow and urinary volume. To evaluate a potential positive effect of this drug regimen on the primary function of cadaveric renal allografts, we performed a retrospective single-center study that compared 100 patients who received this regimen with a control group. The results showed no significant improvement in renal function. In contrast, plasma levels of creatinine and urea were increased in the drug regimen group. Thus, the effectiveness of PGE(1) in combination with high-dose furosemide and dopamine in diminishing DGF was not demonstrated in this trial.

Liver transplantation in the rat: single-center experience with technique, long-term survival, and functional and histologic findings.

OBJECTIVE: Orthotopic liver transplantation (OLT) in rats is frequently used as an experimental model. Numerous surgical techniques have been developed that enable the investigator to conduct clinically relevant studies. The objective of this study was to develop a rat model of acute and chronic rejection, to explicitly study technical modifications of vascular anastomoses with precision, and to examine histopathologic and functional changes in the graft. MATERIALS AND METHODS: With DA-(RT1av1) rats as donors and Lewis-(RT1) rats as recipients, arterialized OLT was performed using a combined suture, cuff, and splint method. Recipients were divided into 5 groups: syngeneic control rats (group 1), allogeneic control rats (group 2), allogeneic OLT rats with low-dose tacrolimus (FK506) immunosuppression (group 3), allogeneic OLT rats with high-dose tacrolimus immunosuppression (group 4), and allogeneic OLT rats with high-dose tacrolimus immunosuppression and retrograde reperfusion via the infrahepatic caval vein (group 5). After OLT, serum parameters were determined and hepatic biopsy specimens were sampled. We examined the effects of acute rejection with or without immunosuppression therapy at histopathologic evaluation. RESULTS: Liver grafts in syngeneic and allogeneic rats (groups 1, 2, 4, and 5) demonstrated normal serum parameters and histopathologic findings at 10 days after OLT, and 93% survival at 3 months. The simplified technique using 1 suture and 2 cuff anastomoses provided the best short- and long-term survival after OLT in all groups. Retrograde perfusion via the infrahepatic caval vein resulted in lower postoperative liver enzyme values. CONCLUSION: The present model is feasible, enabling comprehensive preclinical experimental research on liver transplantation. Furthermore, we provide helpful instructions for learning this surgical technique.

Microsurgical technique of simultaneous pancreas/kidney transplantation in the rat: clinical experience and review of the literature.

BACKGROUND: For experimental basic research, standardized transplantation models reflecting technical and immunologic aspects are necessary. This article describes an experimental model of combined pancreas/kidney transplantation (PKTx) in detail. MATERIALS AND METHODS: Donor rats underwent en bloc pancreatectomy and nephrectomy. Revascularization was performed using the aorta with the superior mesenteric artery and the inferior vena cava with the portal vein. Exocrine drainage of the pancreas took place over a segment of the duodenum which was transplanted side-to-side to the jejunum. The kidney vessels were transplanted end-to-side. The ureter was anastomosed by patch technique. Postoperatively, serum parameters were monitored daily. Biopsies for histopathology were taken on days 5, 8 and 12. RESULTS: All 12 recipients survived the combined PKTx without serious surgical complications. One thrombosis of the portal vein led to organ failure. Blood glucose levels were normal by the 3rd postoperative day. The transplanted duodenal segment showed slight villous atrophy, and the kidneys were well perfused without vascular complications. The anastomosis between ureter and bladder was leakproof. CONCLUSIONS: Excellent graft function and survival rates can be achieved due to simplified operation technique and short operation time. It may thus have high clinical relevance to immunologic issues within the scope of basic research.

Liver transplantation for hilar cholangiocarcinoma: a German survey.

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

Noninvasive therapy of incidental de novo renal cell carcinoma in a kidney allograft 12 years after transplantation: report of a case and review of literature.

BACKGROUND: Immunosuppressive therapy increases the incidence of posttransplantation cancer. Primary renal cell carcinoma (RCC) represents 4.6% of all cancers in transplant recipients. The treatment options for RCC in a renal allograft include radical nephrectomy or nephron-sparing surgery. We report the case of a patient who underwent percutaneous radiofrequency ablation (RFA) of a RCC in the grafted kidney. PATIENT AND METHODS: Twelve years after undergoing heterotopic, allogenic kidney transplantation, a de novo lesion was diagnosed in the upper pole of the kidney graft in a 77-year-old patient during routine duplex ultrasonography. The magnetic resonance image showed a spherical lesion of 17 mm in diameter, which undoubtedly showed radiological signs of a RCC. After adequately informing the patient about alternative treatment strategies and the associated risks, we made an interdisciplinary decision for a percutaneous RFA of the lesion. RESULTS: After the intervention, graft function remained unchanged and is still good at 6 months with no signs of local recurrence on follow-up MRI. A small coagulation defect at the site of the former lesion was the only morphological change. There was also no evidence of distant tumor spread. CONCLUSION: Percutaneous RFA seems an acceptable, allograft-preserving treatment option associated with low morbidity and mortality for RCC in a renal allograft considering the significant risks associated with open partial nephrectomy in a kidney graft.

Outcome of living donor renal transplantation in obese recipients.

The increasing prevalence of obesity among patients with end-stage renal disease accompanies more common renal transplantation from living donors. Since several studies have shown a negative impact of recipient obesity on renal transplantation outcomes, we investigated the influence of recipient-weight and donor-recipient-weight ratio on the outcome of living related renal transplantations. From October 2000 until December 2004, we performed 81 living donor renal transplantation with 30.8% (n = 25) of recipients with a body mass index >25 donor. In this group 6 patients lost their grafts (1-year survival rate, =76%). Among 56 recipients of normal body weight only 3 patients lost their graft (1-year graft survival rate, 94.6%; P < .001). Upon multivariate analysis body mass index was an independent risk factor for graft loss within the first year. When the body weights of the donor and recipient were analyzed in detail the quotient (body weight recipient(2)/ body weight donor) was also an independent risk factor. This study confirmed the results of larger analyses suggesting that body weight matching could significantly improve the outcomes in living donor renal transplantation. As a result of this study, in our institutional policy has changed; recipients of living donor grafts are only accepted when their body mass index is <25.

Nitric oxide inhibition and consecutive Aspisol application show a prolonged survival of orthotopic transplanted livers in a rat model.

BACKGROUND: It is generally accepted that nitric oxide (NO) plays a crucial role in acute rejection caused by inflammatory responses. Therefore, the purpose of this study was to investigate the effect on survival following arterialized orthotopic rat liver transplantations (o-RLTx) of NO inhibition and consequent blockade of platelet aggregation by application of Aspisol. MATERIALS AND METHODS: Inbred LEWIS-(RT(1)) rats underwent arterialized o-RLTx under ether anesthesia with DA-(RT1av1) rats as organ donors. After liver transplantation, serum parameters were determined and hepatic biopsy specimens were sampled on postoperative days 5, 8, 10, 30, and 90. Sixty-one rats were divided into 5 groups: syngenic controls (group I, n = 12); allogenic controls (group II, n = 11); allogenic with FK506 immunosuppression (group III, n = 12); allogenic with AGH-treatment (group IV, n = 13); and allogenic with AGH/low- dose Aspisol treatment for 5 days after liver transplantation (group V, n = 13) (Bayer, Leverkusen, Germany). RESULTS: Rats of group V with AGH/low-dose Aspisol treatment showed significantly longer graft survival (18.2 days +/- 1.8 days) compared with group II rats with untreated grafts (11.3 days +/- 1.7 days) the allogenic group IV with AGH treatment (11.2 days +/- 1.8 days; P < .05). Histological examination revealed moderate graft rejection among the AGH-treated group IV; however, marked platelet aggregation in sinusoids was present, which was not observed in the AGH/low-dose Aspisol-treated animals (group V). CONCLUSION: Our data suggested that simultaneous treatment with AGH/low-dose Aspisol leads to a significant increase in survival and inhibition of platelet aggregation in the graft after orthotopic liver transplantation.

The effect of selective inhibition of inducible nitric oxide synthase on cytochrome P450 after liver transplantation in a rat model.

BACKGROUND: Activity levels of cytochrome P450 (CYP) provide markers for liver function and graft rejection episodes after orthotopic liver transplantation (OLT). Some in vitro studies have shown decreased CYP activation of inducible nitric oxide synthase (iNOS) in rejecting liver grafts. The aim of this study was to evaluate CYP isoenzyme activity changes in vivo and to examine histopathologic aspects during inhibition of iNOS after treatment with aminoguanidine (AG) using OLT in the rat. MATERIALS AND METHODS: Thirty DA-(RT1av1) rats that served as donors and LEWIS-(RT(1)) rats as recipients were divided into three groups: group I (controls, syngeneic rats; n = 6), group II (allogeneic rats without immunosupression; n = 11), and group III (allogeneic rats with AG treatment; n = 13). On postoperative days 5, 8, and 10 we performed laboratory investigations and liver biopsies for histopathologic investigations. RESULTS: On postoperative day 5, activities of CYP-1A1 and -3A4 were significantly lower (P = .022) in group III and the activity of CYP-1A2 higher (P < .05) compared with group II. At postoperative days 8 and 10, the activities of all CYP isoenzymes were significant higher in AG-treated rats (group III) in contrast with group II after allogeneic OLT without immunosuppression. Histopathologic findings revealed less distinct rejection signs in group III specimens after AG treatment compared with group II. CONCLUSION: Summarizing our results, we concluded that AG treatment led to increased CYP activity and less distinction of graft rejection after OLT in rats.

High-risk constellation in living renal transplantation.

There is only limited information about recipient risk factors for graft survival in living- donor kidney transplantation. This study aimed to investigate prognostic factors and their impact on living-related and unrelated renal transplant recipients. From October 2000 until October 2004, 81 adult living-related renal transplantations were performed at our institution. Using multivariate analysis, the association of the following variables with kidney graft outcome was studied: ages of donors and recipients, gender and body mass index, cold and warm ischemia, HLA mismatches, identity and compatibility of blood group, duration of dialysis, cytomegalovirus (CMV) status, recipient original disease, surgical and general complications, and status of retransplantation. Multivariate analysis revealed significant reduction of graft function and graft survival in recipients with retransplantation, more than 4 mismatches, and a high body mass index. Thus, living-donor kidney transplantation can be regarded as a safe and standardized operation relating to surgical technique, but further consideration of the recipient body mass index and the number of mismatches are recommended during the preparation for transplantation.

Efficacy of conventional immunosuppressive therapy in related and unrelated living renal transplantation.

BACKGROUND: The application of antibody induction therapy in adult living-related kidney transplantation remains under discussion. The purpose of this study was to compare the outcome of living-related (LRT) and unrelated renal transplant recipients (LURT) using standardized immunosuppressive protocols. From October 2000 to October 2004, 72 adult LRT (TX) were performed at our institution. Thirty-nine LRT (group A) and 33 LURT (group B) recipients received a standardized immunosuppressive therapy consisting of tacrolimus (Tac), steroids and mycophenolate mofetil (MMF) without antibody induction therapy. This prolective analysis included immediate graft function, rejection rate and loss of the transplanted organ. The incidence of post-operative good graft function (>90%) was similar for both groups, as well as the rejection rate showed 57.8% for patients of group A and 58.8% for patients of group B (p < 0.5). However, the number of rejections (>1 rejection) was significantly higher in group B (11.8%) compared to patients in group A (4.4%). No difference concerning loss of transplanted kidney was observed for both groups. Conventional Tac, MMF and steroid-based immunosuppression therapy is equivalent in efficacy of therapy in living-related and unrelated renal transplants. In our opinion, induction therapy in patients without immunologic risk factors has no favourable effect.