Ventral incisional hernia (VIH) repair after liver transplantation (OLT) with a biological mesh: experience in 3 cases.

BACKGROUND: Hernias after orthotopic liver transplant (OLT) occur in about 30 % of cases. Predisposing factors in liver cirrhotic patients of cases are ascites, low abdominal muscle mass and cachexia before and immunosuppression after OLT. Standard operative transplant-technique even in small hernias is to implant a mesh. For patients after liver transplantation a porcine non-cross linked biological patch being less immunogenic than synthetic and cross-linked meshes is chosen for ventral incisional hernia repair. METHODS: 3 patients (1 female, 2 male), OLT indications Hepatitis C, exogenous- toxic cirrhosis, median-age 53 (51 - 56) and median time to hernia occurrence after OLT were 10 month (6 - 18 m) are documented. 2 patients suffered from diabetes, 2 from chronic-obstructive lung disease. Maintenance immunosuppressions were Everolimus in 1 patient, Everolimus + MMF in the second and Everolimus +Tacrolimus in the third patient. The biological was chosen for hernia repair due to the preexisting risk- factors. Meshes, 10 × 16 cm were placed, in IPOM (Intra-Peritonel-Onlay-Mesh) -position by relaparatomy. Insolvable, monofile, interrupted sutures were used. RESULTS: All patients recovered primarily, and were dismissed within 10 d post OP. No wound healing disorders or signs of postoperative infections occurred. All are free of hernia recurrence in a mean observation time of 22 month (10 - 36). CONCLUSION: The usage of porcine non-cross-linked biological patches seems feasible for incisional hernia repair after OLT. Wound infections in these patients have been observed with other meshes. Further investigation is needed to prove potential superiority of this biological to the other meshes.

Direct comparison of regulators of calcification between bone and vessels in humans.

Calcification is not only physiologically present in bone but is a main pathophysiological process in vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators during vascular calcification in bone and vasculature. Levels of gene expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue samples of transplant donors. Histological stages of atherosclerosis (AS) in vessels are defined as "no changes", "intima thickening", or "intima calcification". Patients' bone samples were subgrouped accordingly. We demonstrate that in vessels BSP and OPN expression significantly increased during intima thickening and decreased during intima calcification, whereas the expression of regulators of calcification did not significantly change in bone during intima thickening and intima calcification. At the stage of intima thickening, MGP, OPG, and SMAD6 expression and at stage of intima calcification only MGP expression was lower in bone than in vessel. The expression of BSP and RANKL was regulated in opposite ways in bone and vessels, whereas the expression of MGP, OC, RUNX2, and OPN was regulated in a tissue-specific manner. Our study is the first direct comparison of gene expression changes during AS progression in bone and vessels. Our results indicate that changes in the expression of regulators of calcification in the vessel wall as well as in bone occur early in the calcification process, even prior to deposition of calcium/phosphate precipitation.

Long-term quality of life of liver transplant recipients beyond 60 years of age.

Due to ameliorated surgery as well as better immunosuppression, the recipient age after liver transplantation has been extended over the past years. This study aimed to investigate the health related quality of life after liver transplantation in recipients beyond 60 years of age. The SF-36 was used to evaluate the recipients' health-related quality of life as standardized tool. It comprises 36 items that are attributed to 8 subscales attributed to 2 components: the physical component score and the mental component score. Differences in the health-related quality of life between the included aged recipients and age-matched general population as well as among female and male recipients. Aged recipients showed significantly lower scores in physical functioning (29 vs. 76, p = 0.001), role physical (42 vs. 73, p = 0.003), bodily pain (34 vs. 71, p = 0.003), general health (28 vs. 59, p = 0.001), vitality (25 vs. 61, p = 0.001), social functioning (36 vs. 87, p =0.001), role emotional (46 vs. 89, p = 0.001) as well as the physical component score (28 vs. 76, p = 0.001). Aged female recipients showed lower results as compared to males in social functioning, physical functioning, role physical, and social functioning (p = 0.03 respectively) but comparable results in the remaining. Quality of life seems to be an issue among aged recipients and should be assessed on a regular basis.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

BACKGROUND: The subjective global assessment (SGA) or the body mass index (BMI) is used to determine the nutritional state after LTX. Bioelectrical impedance analysis (BIA) is used as tool to determine body composition by nutritional care professionals. METHODS: BIA, SGA, BMI, and serum albumin (SA) levels were performed to assess malnutrition following liver transplantation. BIA measurement was used as reference standard to determine existing malnutrition. A phase angle (PA) <5 was used to define potentially existing chronic disease-related malnutrition as a standard. All other measured parameters were compared with respect to their prognostic accuracy regarding the prediction of malnutrition as compared to the mentioned standard. RESULTS: Seventy-one recipients (51 men, 20 women) were included. Median age was 58, weight 77 kg, BMI 26 kg/m(2) , PA 4.1°, and SA 4.3 g/dL. According to the Nutritional Risk Screening 2002, 9.4% (6/71), to BMI 15.4% (11/71), to SA 30.9% (22/71), and to BIA 36.5% (28/71) of the patients were malnourished. PA did not correlate with BMI or NA, there was a significant correlation with SA (p = 0.001). Univariate analysis revealed SA as independent predictor for malnutrition. ROC analysis for all parameters revealed a significantly (p < 0.05) better area under the receiver operating characteristic curve for SA (0.812) than for BMI (0.603) for the prediction of malnutrition. CONCLUSION: SGA or BMI calculation alone does not suffice to evaluate the nutritional status. SA seems to play a crucial role in the prediction of severe disease-related malnutrition in this special patient cohort.

Sensitive serum parameters for hepatocellular carcinoma recurrence monitoring after liver transplantation: a case report.

Liver cell malignancy can be seen as one of the most common indications for hepatic transplantation, but the recurrence potential of the disease significantly limits its beneficial effects. Hepatic factors influencing the recurrence rate, such as nodule size and criteria wherein transplantations are expedited, are still investigated. Pretransplant intraarterial or percutaneous treatment seem to be predictive for recurrence-free patient survival. Early detection of malignancies via serum parameters as a prognostic factor seems promising. This article reports a special case, where despite an elevated, sensitive, serum marker profile, no HCC recurrence was detected over a 2-year follow-up.

Lessons learned with noninvasive cardiac monitoring for acute rejection.

INTRODUCTION: Computerized Heart Allograft Rejection Monitoring (CHARM), used for noninvasive rejection monitoring in heart transplant recipients, is based on the analysis of ventricular evoked response (VER) signals. This study evaluated the prognostic validity of the TslewC, a parameter extrapolated from the VER. METHODS: During orthotopic heart transplantation (OHT) 2 unipolar, fractally coated, screw-in leads implanted epimyocardially were connected to a telemetric pacemaker. Recordings of IEGMs were performed routinely at hospital and at outpatient visits. Data processing yielded trend curves. TslewC was calculated from the tangent of VER. One hundred five patients divided into survivors and nonsurvivors, were compared using a two-tailed Student's t test. RESULTS: In the final follow-up a significant lower TslewC was observed among patients in the nonsurvivor compared with the other group (P<.001). Tests to find an optimal prognostic threshold of the TslewC yielded the value of 26 mV. CONCLUSION: TslewC functioned as a prognostic factor after OHT. Further studies must provide a prognostic threshold to avoid patient visits all 4 weeks. Patients would only have to be admitted to the hospital if the TslewC was under this prognostic threshold.

Nonnephrotoxic immunosuppression in patients after liver transplantation.

INTRODUCTION: Calcineurin inhibitor (CI)-associated renal impairment and renal failure after liver transplantation has been recognized since the early days of its use. Various strategies have been used to prevent or slow down the progression of renal dysfunction in liver transplant recipients, but did not succeed. In this report, we describe the course of renal function of 58 stable liver transplant recipients and compared 2 groups with different immunosuppressive protocols. METHODS: In the study group, 22 patients at various intervals from liver transplantation were included. The immunosuppressive therapy consisted of Sirolimus (SRL). Additional all patients except 2 received Mycophenolate Mofetil (MMF) and 14 of them also received Tacrolimus. Patients of the control group (36 patients) had an immunosuppressive therapy with calcineurin inhibitors. Patients were monitored for creatinine monthly and creatinine clearance (CCr) every sixth month. Risk factors for renal dysfunction were evaluated. RESULTS: After introduction of SRL in patients with renal impairment and after a mean follow-up time of 12 (2-26) months, there was a decrease of 28.3% in mean creatinine and of 41.8% in mean urea. We observed an improvement of renal function in all patients initially after introduction of SRL. In the control group, in comparison to preoperative levels, there was an increase of 27.5% in mean creatinine and of 13.3% in mean urea after a mean follow-up time of 3.6 years with CI therapy. CONCLUSION: The results of our retrospective study showed that with SRL renal impairment could be stopped and renal function could be improved. We suggest administering immunosuppressive therapy with SRL in combination with low dose Tacrolimus and/or MMF for patients with renal impairment.

Center experience in liver transplantation (LTX): management of dermal side effects caused by sirolimus.

INTRODUCTION: Sirolimus improves post transplant maintenance therapy in LTX. Dermal side effects causing pain and discomfort can limit patients' compliance. The package insert mentions such skin disorders as acne and rash. One case of sirolimus-induced leucocytoclastic vasculitis is reported in the literature. METHODS: From July 1998 to October 2003, Sirolimus was implemented in the immunosuppressive protocol in 23 out of 60 liver recipients. Sirolimus target levels are between 3 and <10 ng/dl. Combination with a calcineurinblocker and/or MMF (mycophenolate mofetil) depending on liver function and creatinine is standard. Weekly patient monitoring in the first month after discharge included physical examination, blood samples and immunosuppresant trough levels. Biopsies were taken from untypical efflorescences. RESULTS: Three patients with non-specific effloresces were reported: one with leucocytoclastic vasculitis and one with exfoliate forearm dermatitis required change of medication while one perivascular lymphocytic eosinophilic dermatitis subsided after dose reduction. In three cases of mouth ulcer, trough levels exceeded 10 ng/dl and in six patients acne diminished after dose reduction. Eighteen out of 23 patients are still receiving sirolimus. Reasons for removal from the study were incompliance and incompatibility. Two patients died. DISCUSSION: Immunosuppressants inevitably produce side effects in TX recipients. The positive management of troublesome side effects contributes importantly to compliance and patient survival.

Dyslipidemia during sirolimus therapy in patients after liver transplantation.

INTRODUCTION: Sirolimus (SRL) is an immunosuppressive agent of potential benefit in clinical liver transplantation (LTX). One of the major side effects of SRL is hyperlipidemia, which is reported in up to 44% of patients. In this report, we describe the lipid profiles of 20 stable liver transplant recipients who received SRL for immunosuppression. METHODS: The study group received SRL in combination with tacrolimus and/or mycophenolate mofetil (MMF). The control group was administered calcineurin inhibitor (CI) and MMF. Fasting serum cholesterol level, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) were measured regularly. Furthermore, the total cholesterol/HDL ratio and the LDL/HDL ratio were evaluated. Diabetes and hypertension were monitored as well. RESULTS: In the SRL group, hypercholesterolemia was found in three patients (15%) and hypertriglyceridemia in two patients (10%). There was no marked difference from the control group, although a higher association of SRL with hyperlipidemia was described in the literature. Furthermore, HDL and LDL levels were similar in both groups, as well as total cholesterol/HDL ratio and LDL/HDL ratio. Diabetes and hypertension had a similar incidence in both the groups. Thus, there was no difference concerning the cardiovascular atherosclerosis risk between the immunosuppressive protocol with SRL or with CI. DISCUSSION: The results of our retrospective study demonstrated that the immunosuppressive regimen can potentially influence the incidence of hyperlipidemia in patients after LTX. SRL in combination with tacrolimus and/or MMF had no higher incidence of hyperlipidemia than CI and MMF. The combination of immunosuppressive therapy with low dose and low levels of each immunosuppressive agent could decrease the risk of atherosclerosis and its complications in long-term survivors after LTX.

Experiences in liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Beside surgical resection, orthotopic liver transplantation (OLT) is not only effective but also the only potentially curable treatment in selected cases of small tumors. We report our experience in 11 male patients transplanted for HCC from August 1998 to July 2002. Selection criteria for OLT were unresectability of the hepatic tumor and severity of the underlying liver disease. The tumor diagnosis was confirmed by histology, imaging techniques, and tumor markers. All patients received an orthotopic liver allograft using a modified piggyback technique. Six of the 11 patients are alive; one died due to acute rejection and four died from recurrent disease. In all four patients with recurrent disease, vascular invasion was shown histologically, whereas only one patient without evidence of recurrence showed vascular invasion. To prevent recurrence after OLT the immunosuppressive regime was adjusted to the underlying disease by early cessation of prednisolone and reduction in the long-term exposure to immunosuppressive drugs. Patients were screened for recurrence by ultrasound and computed tomography. Recurrent HCC were treated symptomatically. OLT is an effective treatment for subgroups of patients with HCC. It might be possible to downstage the liver tumor by chemoembolization and/or radiofrequency ablation and allow the patients to wait for a suitable donor. After OLT the early withdrawal of prednisolone and the reduction of other immunosuppression is feasible. In conclusion, OLT can be a potentially curative therapy for HCC.

Occurance of apoptosis during ischemia in porcine pancreas islet cells.

PURPOSE: Pancreas islet transplantation is a potential treatment of diabetes mellitus and porcine organs provide an easily available source of cells. Unfortunately quality and quantity of isolated islets are still not satisfactory. Apoptosis occurs in freshly isolated islets and plays a significant role in early graft loss. We evaluated the influence of four storage solutions on porcine pancreas islets. METHOD: After warm ischemia of 15-20 minutes 12 organs were stored in 4 cold preservation solutions: Histidine-Tryptophan-Ketoglutarate solution (HTK), Hank's buffered saline solution (HBSS), University of Wisconsin (UW) solution and Ringer-Lactate (R). After cold ischemia for 100 minutes, organs were fixed in 3% formalin. Apoptotic cells were counted on hematocylin-eosin stainings. RESULTS: Most apoptotic cells were found in organs stored in R. Low numbers were found in the other groups. The difference between organs stored in R and organs stored in UW, HTK, or HBSS was highly significant. No significant difference could be found between UW, HTK and HBSS. CONCLUSION: Cold and warm ischemia of the pancreas seems to induce apoptosis in islet cells. Preservation solutions cause less apoptosis than electrolyte solution. No significant differences could be found among the preservation solutions.

Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients.

BACKGROUND: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10-14 g/dL in men and 10-12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients. METHODS: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non-anemic patients. RESULTS: Forty-three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non-anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non-anemic patients (p<0.02). CONCLUSIONS: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.