Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

Outcome of hepaticojejunostomy for biliary tract obstruction following liver transplantation.

BACKGROUND: Strictures and concrements are the most common biliary complications following liver transplantation. Endoscopic treatment might not lead to a definitive cure in all patients, especially in strictures involving the biliary bifurcation. The aim of this study was to determine the efficacy and the long-term outcome of hepaticojejunostomy (HJS) for post-transplant biliary tract obstruction. MATERIAL AND METHODS: Thirty-seven patients were retrospectively studied for resolving of cholestasis and the incidence of recurring biliary obstruction. RESULTS: Surgery was performed because of anastomotic strictures in 11, ischemic strictures at the donor common bile duct in seven, strictures involving the bile duct bifurcation in 10, hepatolithiasis without strictures in one and biliary cast formation diagnosed by endoscopic retrograde cholangiography or T-tube cholangiography in eight patients. Cholestasis instantly improved in 82% of the patients. After a long-term follow-up of median 33 months (range 3-149), 28 of the patients (76%) required no further intervention for recurring biliary obstruction following HJS. Anastomotic strictures were observed in six (16%), recurring biliary concrements in two patients (5%). CONCLUSION: HJS did prevent recurrent biliary obstruction in the majority of the patients. We therefore recommend early HJS for complicated post-transplant biliary tract obstruction not treatable by a limited number of endoscopic interventions.

Post-transplant acute myeloid leukemia (PT-AML).

Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, <1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.

Tacrolimus, Mycophenolate Mofetil, and Low-Dose Steroids With or Without Interleukin-2 Receptor Antibody Induction Therapy: A Retrospective Cohort Analysis.

BACKGROUND: Selective interleukin-2 receptor (IL2R) blockade is one option to decrease acute rejection rates in kidney transplant recipients. However, there are little data on the impact of basiliximab in a triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and low-dose steroids). Thus, this analysis aims at investigating the impact of basiliximab induction on rejection rates and immediate graft function following kidney transplantation. METHODS: Basiliximab was introduced in our center according to our center's policy in the beginning of 2011. Patients who received basiliximab (n = 83) were compared with patients without induction therapy (n = 65) transplanted before the introduction of IL2R antibody induction. RESULTS: The use of basiliximab as induction therapy decreased the incidence of biopsy-proven acute rejection (BPAR) within the 1st year after transplantation (21.5% vs 14.5%; P = .283). Overall rejection episodes (including BPAR and borderline rejection) were significantly reduced in patients with basiliximab compared with patients without (41.5% vs 24.1%; P = .033). However, graft function (incidence of delayed graft function, primary nonfunction, slow graft function, and serum creatinine decline) and overall outcome (patient and graft survivals) were similar in both groups. CONCLUSIONS: We found a favorable impact of basiliximab induction therapy on early acute rejection rate. The impact on long-term outcome must be addressed in further randomized controlled trials.

Efficacy of liver transplantation for alcoholic cirrhosis with respect to recidivism and compliance.

Many transplant centers are reluctant to accept alcoholic patients for OLT because of their supposed potential for alcoholic recidivism and poor compliance with the required immunosuppressive regimen, both of which result in graft failure. Only inconclusive data related to these arguments are available. From May 1982 to January 1993, 58 patients received OLT at our institution for end-stage cirrhosis, where alcohol was the only toxic component. The indication for OLT in these patients was considered with particular attention to recidivism and compliance. Overall survival in this group was 71% and 63% at 1 and 5 years, respectively, with an average survival time of 78 months. Actuarial survival of patients transplanted since January 1989 (n = 37) was 86% and 83% at 1 and 2 years (average survival 42 months). Nonfatal clinical endpoints were analyzed in those patients surviving at least 3 months (n = 44). Return to alcohol abuse has been documented in 14 persons at routine short-term outpatient checkups. The estimated risk for alcoholic recidivism amounts to 31%, with a median follow-up of 33 months. Compliance with immunosuppressive regimen was expressed as a dependent value of acute rejection episodes (0.3 per patient, median follow-up 33 months), chronic rejection (occurred in none of the patients), and measurements of CsA HPLC blood trough level (92.2% within the target range). The preversus postoperative improvement of employment, marital, and social status after OLT showed a statistically significant difference. Unwillingness to offer OLT to individuals with alcoholic liver disease because of failure to demonstrate 100% long-term abstinence appears difficult to defend in the face of good results in survival, compliance, and social rehabilitation.

Carbohydrate deficient transferrin for detection of alcohol relapse after orthotopic liver transplantation for alcoholic cirrhosis.

Early diagnosis and monitoring of an alcohol relapse in patients after orthotopic liver transplantation for alcoholic cirrhosis is of importance for the long-term outcome. A prospective study of 97 patients who underwent orthotopic liver transplant for alcoholic cirrhosis has been performed. All of the recipients considered for analysis survived for at least 3 months and were under the care of one specialist psychologist. Mean follow-up amounted to 48.5+/-1.4 months. The rates of alcohol relapse at 1 and 3 years after orthotopic liver transplant were 6 and 9%, respectively. Carbohydrate-deficient transferrin is a biological marker for alcohol abuse independently of liver disease and has been used for the first time ever in liver graft recipients. A total of 830 values were included prospectively in the study population. Detection of alcohol relapse had a sensitivity of 92% and a specificity of 98%. Changes in carbohydrate-deficient transferrin levels indicated clandestine and sporadic drinking after transplantation. Furthermore, clinical events were not found to influence carbohydrate-deficient transferrin, either in patients with or without alcoholic relapse. In our opinion, carbohydrate-deficient transferrin is a useful screening marker for alcohol relapse in patients after orthotopic liver transplant for alcoholic cirrhosis, to select those patients who need special attention from the psychologist.

Parenchymal liver injury in orthotopic liver transplantation.

BACKGROUND: A 35-year period of clinical development resulted in orthotopic liver transplantation (OLT) becoming a standardized surgical procedure. Despite this progress, the rate of technical complications is still high. Although the main problem in most analyses is vascular or bile duct failure, we observed a remarkable number of parenchymal liver injuries that led to intraoperative problems. Our aim, therefore, is to present an overall report on the incidence, treatment, and clinical course of parenchymal liver injuries in OLT. METHODS: Five hundred seventy-two consecutive OLT procedures performed between 1988 and 1998 were analyzed in a retrospective study. Parenchymal liver injury was diagnosed by means of examination of the surgical reports. Donor- and recipient-related data followed the medical report. The lesions were classified according to the Organ Injury Scale. RESULTS: Parenchymal liver injury was diagnosed in 23 patients (4%). The lesions were classified as grade Ia (13.1%), grade Ib (13.1%), grade IIb (52.1%), grade IIIa (17.1%), and grade IIIb (4.3%). In 19 patients (82.6%), the lesion was detected during OLT, and in four patients (17.4%), during relaparotomy. The latter group showed significantly higher-grade injuries. Treatment was suture or fibringlue alone, 17.4%; fibringlue and hemostyptics, 26.1%, mesh wrapping 30.4%, and mesh packing 26.1%. Seven patients (30.4%) underwent relaparotomy. Further active bleeding was not found in any of them. Statistical analysis found a correlation between injury grade and relaparotomy rate. No patients died as a result of parenchymal liver injury. CONCLUSIONS: Parenchymal liver injuries can be treated well, with no adverse effect on patient or graft survival. An early decision concerning the surgical procedure for controlling hemorrhage is required. A basically aggressive therapeutic approach might avoid further complications relating to reperfusion edema.

Simultaneous heart and kidney transplantation as treatment for end-stage heart and kidney failure.

BACKGROUND: The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations (pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing. METHODS: Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period. RESULTS: Survival for HNTX is 100% with a mean follow-up of 32.7+/-21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5+/-1.0 hr vs. 22.1+/-6.8 hr, P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients. CONCLUSIONS: Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

The importance of the effect of underlying disease on rejection outcomes following orthotopic liver transplantation.

Despite major advances in immunopharmacology, virtually all patients receive the same center-specific immunosuppressive regimen following orthotopic liver transplantation (OLT). The present analysis was performed on the hypothesis that the original disease representing the indication for OLT leads to a different initial immunological situation of the patient. The type of original disease might therefore be a predisposing factor for acute rejection episodes and influence graft and patient survival. From January 1988 to July 1994, 34 patients received OLT at our institution for end-stage primary biliary cirrhosis (group 1) and 66 patients for end-stage alcoholic cirrhosis (group 2). Overall survivals at 1 and 5 years in group 1 versus group 2 were 67% versus 80% and 50% versus 68%, respectively (P<0.04). Retransplantation was performed in 21% of patients from group 1 and in 6% from group 2. The estimated risk for freedom from acute rejection amounts to 38% in group 1 compared with 59% in group 2 (P<0.02). Multivariate regression analysis of potential risk factors identified only the underlying disease as independent predictor. Analysis of cumulative rates of clinically relevant rejection episodes stratified by group revealed 0.29 and 0.05 episodes per patient at one month and 0.80 and 0.06 at six months (P<0.009) respectively. In our clinical experience it was possible to confirm the hypothesis that the underlying disease is the reason for a significantly different incidence of acute rejection episodes and that it subsequently influences graft and patient survival. This approach to an individually adapted immunosuppressive therapy should be taken into consideration and other appropriate parameters investigated.

The choice of material for above-knee femoropopliteal bypass. A 20-year experience.

OBJECTIVE: The choice of material for above-knee femoropopliteal bypass grafting is a matter of continuing controversy for various reasons. The most important argument in favor of alloplastic grafts is to preserve the autologous saphenous vein for a below-knee bypass, which might become indicated at a later date. DESIGN: A consecutive series of above-knee reconstructions were analyzed with regard to long-term behavior. Early graft occlusions were not included, and the median follow-up was 83 months. SETTING: A university hospital with a particular interest in vascular surgery. PATIENTS AND METHODS: Four hundred forty-two patients received either autologous saphenous vein (n = 310) or alloplastic graft (n = 132) material, and were analyzed in a univariate (Kaplan-Meier) and multivariate (Cox) manner. MAIN OUTCOME MEASURES: Analysis as to whether alloplastic graft material provides equal or less favorable results as compared with autologous saphenous vein material, in terms of primary and secondary patency, secondary below-knee bypass grafting, limb salvage, and survival. RESULTS: Although univariate analysis demonstrated a significantly better primary patency rate for autologous saphenous vein material, multivariate analysis did not show any effect of the material in terms of patency, limb salvage, and survival. The frequency of secondary below-knee repair was 7% (31 patients); 56% were performed in the first 2 years postoperatively. This amounted to an estimated probability of 4.4% and 12.3% at 18 years, respectively. CONCLUSION: The small probability of secondary below-knee repair in our series does not support the policy to use alloplastic grafts routinely for a primary above-knee bypass, to spare the saphenous vein. Therefore, patients should be offered the best material for the first operation even at the above-knee level.

Underlying disease as a predictor for rejection after liver transplantation.

BACKGROUND: As significantly more patients die of infection than of rejection after liver transplantation, we have to conclude that overimmunosuppression is common. Our analysis was performed to investigate underlying disease as an appropriate parameter for individually reduced immunosuppression. DESIGN: A consecutive series of patients receiving primary liver transplantation was analyzed with regard to acute rejection. SETTING: Department of transplantation surgery in a university hospital. PATIENTS AND METHODS: From 1988 to 1995, 252 patients received liver transplantation for posthepatitic cirrhosis, alcoholic cirrhosis, cholestatic disease, or hepatoma and were analyzed in a univariate and multivariate manner. MAIN OUTCOME MEASURE: The influence of various underlying diseases on the incidence of acute rejection. RESULTS: The estimated risk for freedom from acute rejection and analysis of cumulative rates of acute rejection stratified by group showed significant differences between the groups, except for alcoholic and posthepatitic cirrhosis. Severity of acute rejection episodes, as assessed by the need for rescue therapy, was similar in both univariate analysis and cumulative rates for alcoholic and posthepatitic cirrhosis. As expected, patients with cholestatic disease exhibited a significantly increased requirement for rescue therapy. For patients with hepatoma, a low incidence of initial and a high rate of repeated rescue therapy were observed. The varying immunological behavior within this group may have influenced both expansion of the tumor and severity of acute rejection. Multivariate analysis of potential risk factors identified underlying disease as a variable of independent prognostic significance for acute rejection and the need to receive rescue therapy. CONCLUSION: These results indicate the importance of taking the original disease into consideration where immunosuppressive therapy is concerned.

A decade of oral anticoagulant treatment to maintain autologous vein grafts for femoropopliteal atherosclerosis.

To determine whether long-term oral anticoagulant treatment was effective in improving graft performance and preventing major amputation following vein bypass surgery for femoropopliteal atherosclerosis, a clinical trial was conducted in one single center and continued during 10 years. After 130 patients had electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group (treatment with phenprocoumon [n = 66]) or to a control group (n = 64) that remained without any anticoagulant treatment. Primary end points of the study were graft reocclusion and limb loss. The median durations of primary patency and limb salvage were significantly longer for treated patients than that for controls. In addition, survival in the therapy group was longer. Following autologous vein bypass surgery in the treated group, the results were superior in terms of graft patency, limb salvage, and survival.

Perioperative cytokines during orthotopic liver transplantation without venovenous bypass.

UNLABELLED: Since most of studies investigating cytokine levels during human orthotopic liver transplantation used venovenous bypass (VVB), it may be difficult to distinguish between the increase in proinflammatory mediators induced by VVB, by ischemia-reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The goal of this investigation was to assess the levels of interleukin-6 (IL-6) and soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble IL-2r concentrations were measured by means of luminescence enzyme immunometric assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of sampling were before induction of anesthesia (TP1), after cross-clamping of the inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24 hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6 increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the relative changes (DeltaTP %) in perioperative levels of cytokines compared with those previously published in studies using VVB. We observed higher values of DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data on sIL-2r were similar, suggesting no major effects of the operative technique on sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative trends. Our data suggest that cross clamping contributes more to cell activation, namely, increased release of IL-6 in the anhepatic phase than the use of VVB. However, no major differences were observed during the reperfusion period. The extent of clinical effect on graft function of higher IL-6 levels in the anhepatic period among recipients not supported with VVB remains to be clarified.

Clinical outcome of orthotopic liver transplantation.

Orthotopic liver transplantation (OLT) has become a standard procedure for end-stage cirrhosis. The purpose of this anlysis is to give a brief overview on the clinical outcome of OLT. According to a current survey of primary indications for liver transplantation in Europe, virus-induced cirrhosis represents the largest proportion with 25%. The next frequent indication is alcoholic cirrhosis with 19%. Cholestatic diseases amount to 13%, malignancy in cirrhosis 10%, and acute hepatic failure 10%. The outcome of these main indications will be discussed and critical considerations pointed out. Patient survival rates demonstrate for cirrhosis at 1-and 5-year about 80% and 70%, respectively. In acute hepatic failure, more patients are lost in the perioperative period. Not surprisingly, patients transplanted for malignancy show decreased long-term survival. Considering an average of 5-year survival in patients with end-stage liver disease of 20% or less, excellent patient survival can be achieved by liver transplantation.

Implication for bone marrow derived stem cells in hepatocyte regeneration after orthotopic liver transplantation.

The liver has the outstanding ability to regenerate itself and restore parenchymal tissue after injury. The most common cell source in liver growth/regeneration is replication of preexisting hepatocytes although liver progenitor cells have been postulated to participate in liver regeneration in cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC) have the formal capacity to act as a source for hepatic regeneration under special circumstances; however, the impact of this process in liver tissue maintenance and regeneration remains controversial. Whether BM-HSC are involved in liver regeneration or not would be of particular interest as the cells have been suggested to be an alternative donor source for the treatment of liver failure. Data from murine models of liver disease show that BM-HSC can repopulate liver tissue and restore liver function; however, data obtained from human liver transplantation show only little evidence for liver regeneration by this mechanism. The cell source for liver regeneration seems to depend on the nature of regeneration process and the extent of injury; however, the precise mechanisms still need to be resolved. Current data suggest, that in human orthotopic liver transplantation, liver regeneration by BM-HSC is a rather rare event and therefore not of clinical relevance.

Simultaneous pancreas-kidney transplantation nine years after liver transplantation--a case report.

In this case report we have described a patient suffering from sclerosing cholangitis, diabetes mellitus type I, and consequent end-stage renal disease who was successfully treated with simultaneous pancreas and kidney transplantation 9 years after orthotopic liver transplantation.

[2 cases of life threatening gastrointestinal hemorrhage from Meckel's diverticulum]. / Zwei Fälle von lebensbedrohlicher gastrointestinaler Blutung aus einem Meckel-Divertikel.

Meckel's diverticulum is one of the commonest congenital anomalies of the gastrointestinal tract. Two cases requiring emergency laparotomy due to massive gastrointestinal bleeding are presented. Only at laparotomy the correct diagnosis was established. In the first case a segment of small bowel was resected and diverticulectomy was performed in the second case. Both patients are free of complaints now at 2 and 3 years of follow-up respectively. The genesis of diverticular bleeding, the difficulties of the preoperative diagnosis of the complicated diverticulum and the uncertain indication for operation in cases of uncomplicated diverticulum are discussed and the literature is reviewed.