Cytokine pattern during rejection and infection after liver transplantation--improvements in postoperative monitoring?

Despite improvements in immunosuppression, rejection occurs in 50% of liver transplant patients and may cause significant morbidity. The most frequent cause of death after liver transplantation is severe infection. Determination of the cytokine network may lead to earlier detection of patients at risk for severe rejection and infection. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines and neopterin on a daily basis. During the first postoperative month, 28 patients (34.6%) developed acute rejection; 14 patients were successfully treated with methylprednisolone (steroid-sensitive rejection), while 14 patients required additional treatment with FK506 and OKT3 (steroid-resistant rejection). Ten patients developed severe infections, and 11 patients experienced asymptomatic cholangitis. Patients with an uneventful postoperative course (n=37) were the control group. One-year patient survival was 88.9%: 1 patient died because of chronic rejection and Pseudomonas urosepsis; a further 4 patients died of aspergillus pneumonia and bacterial sepsis. Soluble TNF-RII, sIL-2R-, and IL-10 levels were significantly elevated 3 days prior to or at the onset of acute steroid-resistant rejection (P < or = 0.01 versus steroid-sensitive rejection and on uneventful postoperative course). An increase in IL-8, neopterin, and sTNF-RII was indicative of severe infection 3 days prior to onset of infection. In this group of patients, a simultaneous increase in IL-10 indicated a lethal outcome of severe infection. During the second week of acute steroid-resistant rejection and lethal infection, a significant rise in IL-1beta, IFN-gamma, and IL-6 was observed (P < or = 0.01 versus control groups). The different patterns in neopterin- and cytokine-increase could differentiate between severe rejection and severe infection. Furthermore, the increase in these parameters indicated severe rejection--i.e., steroid resistance at the onset of acute rejection--which could prompt us to initiate rescue therapy immediately. The ability to detect patients at risk for severe or lethal infection may result in intensified infectious screening and more aggressive antiinfectious treatment. Therefore, routine monitoring of these parameters may lead to changes in therapeutic management of severe acute rejection and infection after liver transplantation.

A prospective randomized trial comparing interleukin-2 receptor antibody versus antithymocyte globulin as part of a quadruple immunosuppressive induction therapy following orthotopic liver transplantation.

BACKGROUND: Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted. METHODS: Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine. RESULTS: Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups. CONCLUSIONS: Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.

[Resection with primary anastomosis in complicated diverticulitis. Risk analysis]. / Die Resektion mit primärer Anastomose bei der komplizierten Diverticulitis. Eine Risikoanalyse.

107 patients operated for complicated diverticulitis 1988 until 1993 were analysed retrospectively regarding perioperative risk of resection with primary anastomosis (n = 94). 53 of them had peridiverticulitis with stenosis (mortality 0), 41 had emergency operations (mortality 14.6%). Hartmann procedure (n = 13, mortality 7.6%) has been accepted only for the following situations: 1. ileus with secondary damage of the bowel, 2. extended diffuse peritonitis with secondary organ failure, 3. poor blood supply of the bowel, 4. the patient under immunosuppression after transplantation. Regarding these recommendations mortality rate in emergency operations (12.9%) has been lower as compared to 15 to 20% in literature. So regarding the recommendations named above resection with primary anastomosis seems to be a safe procedure in complicated diverticulitis.

[Ulcer disease. The role of the surgeon]. / Ulkuskrankheit. Die Rolle des Chirurgen.

Today the therapeutical approach towards the 'ulcer disease' consists mostly of medical treatment. Surgical intervention has decreased and is commonly used only for the treatment of emergencies, complications and in cases not responding to medical therapy. If surgical intervention is necessary because of recurring disease despite a complete conservative treatment, resection should be preferred for sufficient therapy of the 'ulcer disease'. Many acutely bleeding ulcers can be controlled by endoscopic methods, however, bleeding ulcers with a high rate of recurrence (Forrest Ia and IIa at the dorsal duodenum and at the small curvature of the stomach) should be treated by resection. Especially elderly, multimorbid patients in this situation should be considered for an early elective surgical procedure. Perforating ulcera duodeni can be treated sufficiently by excision and oversewing in most cases, whereas perforated ulcera ventriculi should always be resected because of possible malignant transformation.