N.C Nüssler

Venous complications after orthotopic liver transplantation

Complications involving the portal vein or the vena cava, are rare after orthotopic liver transplantation. We report on the incidence and treatment of venous complications following 1000 orthotopic liver transplantations in 911 patients. Twenty‐six of the adult patients (2.7%) suffered from portal complications after transplantation, whereas complications of the vena cava were observed in only 17 patients (1.8%). Technical problems or recurrence of the underlying disease (e.g. Budd–Chiari syndrome) accounted for the majority of complications of the vena cava, whereas alteration of the vessel wall or splenectomy during transplantation could be identified as important risk factors for portal vein complications. In patients undergoing modification of the standard end‐to‐end veno‐venous anastomosis of the portal vein due to pathological changes of the vessel wall, complications occurred in 8.3%, whereas only 2.4% of patients who received a standard anastomosis of the portal vein experienced complications of the portal vein. Furthermore, splenectomy during transplantation was also associated with an increased incidence of portal vein complications (10.5 vs. 2.2% in patients without splenectomy). Treatment was dependent on the signs and symptoms of the patients, and varied considerably between patients with portal vein complications and patients suffering from complications of the vena cava. Complications of the vena cava led to retransplantation in about one‐third of the patients, whereas in patients with occlusion of the portal vein, retransplantation was necessary in only 15%, and more than half of the patients suffering from portal vein complications did not require any treatment at all. Usually, treatment of patients with portal vein complications only became necessary when additional complications such as arterial occlusion or bile duct injuries occurred.

Liver transplantation for alcoholic cirrhosis.

Abstract Because of the donor shortage, there are concerns for liver transplantation in patients with alcoholic cirrhosis. We therefore analyzed patients transplanted for alcoholic cirrhosis at our center with respect to patient and graft survival, recurrence of disease, and postoperative complications. Out of 1000 liver transplantations performed in 911 patients, 167 patients were transplanted for alcoholic cirrhosis; 91 patients received CsA‐ and 76 patients FK506‐based immunosuppression. Recurrence was diagnosed by patients or relatives declaration, blood alcohol determination, and delirium. Diagnosis and treatment of acute and chronic rejection was performed as previously described. One‐ (96.8 % versus 91.3 %) and 9‐year patient survival (83.3 % versus 80%) compared well with other indications. Five of 15 patients died due to disease recurrence. Recurrence of disease was significantly related to the duration of alcohol abstinence prior to transplantation. In patients who were abstinent for less than 6 months (17.1 %), recurrence rate was 65 %, including four of the five patients who died of recurrence. Recurrence rate decreased to 11.8%, when abstinence time was 6‐12 months and to 5.5%, when the abstinence times was > 2 years. Next to duration of abstinence, alcohol relapse was significantly related to sex, social environment, and psychological stability. The incidence of acute rejection compared well with other indications (38.1%); CsA: 40.1% versus 33.3% in FK506 patients. In all, 18.2% of CsA patients experienced steroid‐resistant rejection compared with 2.6 % of FK506 patients. Seven patients (7.6%) in the CsA group and one patient (1.3%) in the FK506 group developed chronic rejection. A total of 57.1% developed infections; 5.7% were life‐threatening. CMV infections were observed in 14.3% (versus 25% for other indications). New onset of insulin‐dependent diabetes was observed in 8.6% and hypertension in 32.4%. In conclusion, alcoholic cirrhosis is a good indication for liver transplantation with respect to graft and patient survival and development of postoperative complications. FK506 therapy was favourable to CsA treatment. Patient selection is a major issue and established criteria should be strictly adhered to. Patients with alcohol abstinence times shorter than 6 months should be excluded, since recurrence and death due to recurrence was markedly increased in this group of patients.

Changing impact of cytomegalovirus in liver transplantation -- a single centre experience of more than 1000 transplantations without ganciclovir prophylaxis.

As cytomegalovirus (CMV) disease was a leading cause of death following liver transplantation in earlier reports, general CMV prophylaxis is widely used. We re‐evaluated the impact of CMV in a recent time period under balanced immunosuppression and effective CMV diagnostics and therapy. A retrospective analysis of 1200 liver transplantations between 1988 and 2000 was performed comparing the incidence of CMV infection and disease and patient survival rates in two different time periods (before and after availability of the pp65‐antigenaemia assay). In addition, risk factors for CMV in the recent time period were analysed. No ganciclovir prophylaxis was administered during the whole study period. The incidence of CMV tissue invasive disease decreased from 9.4% in period I to 2.7% in period II, whereas the incidence of viral syndrome was about 6% in both periods. Especially CMV pneumonia and generalized disease were almost abandoned in period II. Patients with tissue invasive disease, but not with infection or viral syndrome had reduced survival rates in both periods. However, the disease‐specific mortality was 10% and 0% respectively. The overall rate of CMV infection in period II was low (25.9%). Risk factors for CMV infection in the univariate analysis were: Initial nonfunction, D+R− seroconstellation, acute liver failure, triple or quadruple immunosuppression, OKT3 or ATG treatment, transfusion of >10 packed red cells, steroid boluses, postoperative mechanical ventilation and retransplantation. In the multivariate analysis only quadruple or triple immunosuppression, OKT3‐treatment, transplantation for acute liver failure and initial nonfunction. The incidence of CMV tissue invasive disease as well as the disease‐specific mortality has markedly decreased during the last years. Using routine surveillance with the pp65‐antigenaemia assay, CMV infection and disease rates compare well to data with long‐term ganciclovir prophylaxis. As D+R− patients still more often develop symptomatic disease, pre‐emptive therapy could be useful in this patient group.

Prevalence of Thyroid Nodules and Carcinomas in Patients Operated on for Renal Hyperparathyroidism: Experience with 339 Consecutive Patients and Review of the Literature

The association between renal hyperparathyroidism (HPT) and differentiated thyroid carcinoma is discussed. To determine the prevalence and potential risk factors, we performed a retrospective analysis of our patients (1998–2004) and compared the data with the data from other surgical and autopsy studies. At our hospital, a total of 347 parathyroidectomies in 339 patients with renal HPT were performed. Most patients underwent preoperative ultrasound investigation of the thyroid gland and, if indicate, thyroid scintigraphy. Intraoperatively, both thyroid lobes were mobilized and palpated. Detected thyroid nodules were adequately resected and investigated histologically. A systematic analysis of the international literature was performed using the PubMed/MEDLINE system to identify publications on the prevalence of papillary thyroid carcinoma (PTC) in patients with renal HPT and in the overall population. Altogether, 133 patients (39.2%) underwent simultaneous thyroid surgery. The initial operation was hemithyroidectomy in 55 (16.2%), Dunhill operation in 36 (10.6%), unilateral subtotal resection in 17 (5.0%), bilateral subtotal resection in 5 (1.5%), and enucleation of a thyroid nodule in 18 (5.3%). A PTC was found in 8 of 339 patients (2.4%) and a follicular thyroid carcinoma in 1. Among 311 patients with primary cervical operation, 6 (1.9%) had a papillary thyroid carcinoma. All papillary tumors were classified as pT1 with a diameter of 1 to 12 mm; three were bifocal, and only one patient had positive lymph nodes. None of the analyzed factors showed a significant correlation with the occurrence of thyroid carcinoma. Depending on the screening method, the prevalence of occult PTC in European autopsy studies ranged from 5% to 9% and was markedly higher in almost all studies than in the present one. The prevalence of PTC in the present study makes an etiologic association between renal HPT and PTC unlikely. The clinical significance of these tumors remains unclear becauses all incidental tumors were small. However, if easily and safely feasible, relevant thyroid nodules should be removed during parathyroid surgery.

Enhanced cytolytic activity of intestinal intraepithelial lymphocytes in patients with Crohn's disease.

Abstract  Background and aims: Dysfunction of the immune system with inappropriate responses of lymphocytes to various antigens has been implicated in the development of Crohn’s disease. Therefore, the functional and phenotypic characteristics of intestinal intraepithelial lymphocytes (IEL) in comparison to peripheral blood lymphocytes (PBL) were analyzed in patients with and without Crohn’s disease. Patients and methods: Six patients with Crohn’s disease and six control patients were studied. Isolated IEL and PBL were tested for cytolytic activity against the human adenocarcinoma cells DLD-1 and the human leukemia cells K562 in a 51Cr-release assay. Two-color flow cytometry was performed for phenotype analysis of isolated lymphocytes. Results: IEL from patients with Crohn’s disease showed significantly increased cytolytic activity against epithelial-derived target cells when compared with IEL from control patients. In contrast, no functional changes were detectable among PBL from patients with Crohn’s disease. IEL from patients with Crohn’s disease contained a significantly higher percentage of CD8+ lymphocytes when compared with IEL from control patients, whereas no phenotypic changes were observed among PBL. Conclusions: In Crohn’s disease, the functional and phenotypic changes of T cells are limited to lymphocytes of the intestinal mucosa. Furthermore, it is conceivable that the increased cytolytic activity of IEL contributes to the tissue damage in this disease.

Mesenterialarterienverschluss als seltene Komplikation bei Thrombangiitis obliterans

ZusammenfassungMesenterialarterienverschlüsse sind eine seltene Komplikation der Thrombangiitis obliterans. Wir berichten über einen 30-jährigen Patienten mit einer Thrombangiitis obliterans und einem Mesenterialarterienverschluss als Komplikation dieser Erkrankung. Bei unklaren abdominellen Schmerzen wurden im Rahmen einer Laparoskopie ein Dünndarminfarkt und eine Minderperfusion der Leber bei dem Patienten diagnostiziert, sodass zunächst eine Dünndarmteilresektion durchgeführt werden musste. Bei weiterhin bestehender Dünndarmischämie erfolgte dann eine Angiographie, die einen zentralen Verschluss des Truncus coeliacus und der A. mesenterica superior zeigte. Daraufhin wurde der Pat. relaparotomiert, die A. mesenterica superior embolektomiert, ein Venenbypass von der A. mesenterica superior zu beiden Leberarterien gelegt und eine erneute Dünndarmteilresektion durchgeführt. Nach initial unauffälligem Verlauf und Entlassung wurde der Patient bei erneuter abdomineller Symptomatik 3 Wochen später wieder stationär aufgenommen und aufgrund eines akuten Verschlusses der A. colica dextra eine Hemikolektomie rechts durchgeführt. Seit einem Jahr ist bei dem Patienten keine abdominelle Symptomatik im Rahmen seiner Erkrankung mehr aufgetreten.AbstractMesenteric artery occlusions are rare complications of Thrombangiitis obliterans (Buergers disease). We report on a 30-year old male with Thrombangiitis obliterans and mesenteric occlusion as a complication of this disease. Because of unclear abdominal pain, laparoscopy was performed which showed small bowel infarction and reduced liver perfusion. After small bowel resection and a second examination, ischemia of the intestinum continued. Angiography was performed, which showed central occlusion of the celiac trunk and the superior mesenteric artery. Relaparotomy with the embolectomy of the superior mesenteric artery, venous bypass from the sup.mes.art. to the hepatic arteries and repeated small bowel resection was performed. The patient recovered completely and was discharged from hospital after 3 weeks. After a further admission to the hospital 3 weeks later with abdominal pain caused by acute occlusion of the right colonic artery and severe ischemia of the right hemicolon, a right hemicolectomy was performed.Now, one year after the last hospital admission, the patient shows no sign of having any abdominal problems.

Hepatic Artery Resistance as a Marker for Preservation/Reperfusion Injury

EPATIC artery resistance (HAR), a potential markerfor graft function after liver transplantation, is be-lieved to be influenced by (1) microcirculatory disturbances,probably due to disruption of sinusoidal lining cells thathappens when a liver graft is reperfused with warm andoxygenized blood, (2) adhesion of immunocompetent cellsand subsequent activation of procoagulative factors, and (3)preservation/reperfusion injury. The aim of this study wasto reveal dependency of HAR on preservation/reperfusioninjury. To exclude immunologic mechanisms, isolated per-fused pig livers were perfused with different preservationsolutions and reperfused with autologous whole blood.

Immunologisches und pharmakodynamisches Monitoring zur Abstossungsprävention und -behandlung nach Dünndarmtransplantation

Background: Severe acute rejections (AR) after intestinal transplantation (ITx) are associated with a mortality as high as 50 - 80%. Thus, various efforts were made to establish reliable and sensitive, noninvasive markers for acute rejection. Methods: 11 ITx were performed for irreversible short bowel syndrome. Pharmacodynamic and immunological monitoring comprised CD4 + CD25 + -T-cells, serum-IL2R, serum-TNFalpha, CD8 + HLA-DR-T-cells, LPS- binding protein (LBP), IL-6, IL8, and CRP. Results: 1-year-patient- and graft survival were 73% (9/11). The incidence of AR was 9% (1/11) within the first 6 month and 18% (2/11) within the first year. LBP was the only sensitive marker for protocol biopsy proven, otherwise not detectable indeterminate rejections (5/5; 100%). ARs were accompanied by a distinct rise of serum LBP and CRP (3/3), steroid-resistent AR by a significant increase of serum- TNF alpha (3/3). Pharmacodynamic monitoring of CD4 + CD25+ T-cells and serum IL2R allowed for individualized and reduced administration of daclizumab. Two patients experiencing OKT3-resistant AR received rescue treatment with infliximab (chimeric anti-TNF alpha mo Ab). According to pharmacodynamic monitoring of LBP and TNFa, four infusions (3 mg/kg KG body weight) were applied in each patient until complete recovery. Summary: LBP as marker for bacterial translocation revealed to be highly sensitive for indeterminate as well as acute rejections after ITx. Serum TNF alpha increase correlated with the onset of steroid- and OKT3-resistant AR. Pharmacodynamic monitoring allowed for individualized treatment regimens regarding daclizumab and infliximab. Infliximab turned out to be highly effective for the treatment of steroid- and OKT3-resistant rejections.

NF-kappa B vermittelte NOS-2 Expression wirkt protektiv bei isolierter Dünndarmischämie

Ischamie/Reperfusion (IR) des Darmes schadigt nicht nur die betroffenen Darmabschnitte, sondern kann auch in anderen, primar nicht ischamischen Organen wie z. B. der Leber zu schweren Veranderungen fuhren. Dieser IR-Schaden kann durch Stimulation der inflammatorischen Antwort mittels IL-2 vermindert werden. In dieser Studie wurde untersucht, ob der positive Effekt der IL-2 Gabe nach intestinaler Ischamie auf einer Aktivierung des nuklearen Faktor kappa B (NFkappaB) und einer nachfolgenden vermehrten Expression von NOS-2 beruht.

Interleukin-2 vermindert die hepatische Schädigung nach isolierter Ischämie des Darmes

Introduction: Intestinal ischemia/reperfusion (IR) results in tissue destruction in the gut, but may also induce oxidative stress and cellular damage in distant organs, such as the liver. It remains unclear whether inhibition or stimulation of the inflammatory response may help to reduce tissue destruction after IR. Therefore, the effects of pro- and anti-inflammatory cytokines on oxidative stress and tissue destruction in the intestine and liver after intestinal IR were analyzed. Methods: Male Lewis rats underwent 60 min of intestinal ischemia by clamping of the superior mesenteric artery or were sham operated. Animals received an IV bolus of 40 µg/kg IL-2, IL-10 or vehicle before reperfusion. At 20 min 1 h, 4 h, and 24 h after reperfusion animals were sacrificed and blood and tissue samples were obtained for analysis of serum levels of NO- 2/NO- 3, hyaluronic acid (HA), transaminases (AST), and tissue GSH levels, as well as for RT-PCR of the inducible nitric oxide synthase (NOS-2) and hemeoxygenase-1 (HO-1) mRNA. Results: IR resulted in tissue destruction and oxidative stress in both organs indicated by elevated HA and AST serum levels and significantly reduced GSH tissue levels. Concomitantly increased expression of NOS- 2 and HO-1 mRNA was detectable in liver and intestine after IR. IL-2 administration resulted in diminished hepatic tissue destruction despite sustained reduction of GSH. IL-2 further increased NOS-2 and HO-1 mRNA expression in both organs after IR. In contrast, IL-10 resulted in increased tissue damage, but failed to increase NOS-2 or HO-1 mRNA expression in the small intestine or liver after IR. Discussion: Intestinal IR does not only result in oxidative stress in the intestine but elicits also oxidative stress in the liver. The beneficial effect of IL-2 was not due to reduction of oxidative stress, but rather due to increased expression of NOS-2 and HO-1 mRNA. In contrast, IL-10 which failed to increase NOS-2 and HO-1 mRNA expression in both organs led to increased tissue destruction after IR. Conclusions: Tissue destruction and oxidative stress in intestinal IR are not limited to the intestine. The beneficial effect of IL-2 on IR may be due to decreased neutrophil infiltration and enhanced neutralization of oxygen intermediates by nitric oxide in the intestine and liver.