Biocompatibility and buffers: effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function.

BACKGROUND: Conventional peritoneal dialysis fluids (PDF) have been shown to compromise the function of both leukocytes and human peritoneal mesothelial cells (HPMC). Various in vitro studies have identified the low initial pH in combination with high lactate content, as well as the hyperosmolality and high glucose concentration present in currently used solutions as the primary determinants of their bioincompatibility. Bicarbonate buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, lactate buffered PDF. However, little information is currently available regarding the potential impact of PDF on the function of human peritoneal fibroblasts (HPFB), the major cell population present in peritoneal interstitium. METHODS: The current study compares the effect of bicarbonate and lactate buffered PDF in a model system of resting peritoneal mesothelial cells and fibroblasts cultured from human omentum. Interleukin-1 beta-stimulated IL-6 release from HPMC and HPFB was used as the cell functional parameter. RESULTS: While short (30 min) pre-exposure to lactate buffered PDF significantly reduced the IL-1 beta-stimulated IL-6 release from HPMC during a subsequent recovery period (24 hr), a significant decrease in HPMC IL-6 secretion with bicarbonate buffered PDF was only observed after prolonged (> or = 60 min) exposure. In contrast, no significant IL-6 inhibition was detected with HPFB pre-exposed to PDF for up to 90 minutes. A significant suppression of HPFB IL-6 secretion was only observed in coincubation experiments (24 hr) with dilutions of both types of PDF. CONCLUSIONS: These results indicate that (i) bicarbonate buffered PDF are less inhibitory to peritoneal cell function as compared to conventional, lactate buffered PDF; and (ii) HPFB may be more resistant than HPMC to bioincompatible PDF.

[Partial hepatectomy after post-traumatic liver abscess]. / Leberteilresektion nach posttraumatischem Leberabscess.

Post-traumatic pyogenic liver abscess is a rare disease. We present the case of a 38-year-old man with multilocular liver abscess and pleural empyema following blunt abdominal trauma. The patient had a prodrome lasting 3 months before presenting in our department. The therapy included partial hepatectomy and pleural drainage. Clinical signs, diagnosis and possible therapy are discussed in this case report.

Effective therapy for hepatic M. Osler with systemic hypercirculation by ligation of the hepatic artery and subsequent liver transplantation.

Hereditary hemorrhagic teleangiectasia, or M. Osler (Osler-Weber-Rendu disease), is an autosomal dominant, systemic fibrovascular dysplasia. This may lead to increased liver blood flow from arteriovenous fistulas. A 45-year-old woman with a known M. Osler was admitted for liver transplantation. On admission, exertional dyspnea was the predominant symptom. Radiological investigations revealed multiple intrahepatic arteriovenous fistulas and consecutive high-output heart failure. Laboratory findings revealed remarkably elevated bilirubin and alkaline phosphatase. To alleviate the high-output cardiac failure, the hepatic artery was ligated. Fourteen months later, the patient presented again with increased levels of bilirubin and recurrent bleeding episodes from esophageal varices grade IV. The patient underwent liver transplantation and post-transplant recovery was excellent. A hyperdynamic circulatory state due to a hepatic M. Osler has been treated in several cases by ligation or embolization of the hepatic artery. This procedure, however, is recommended only for patients with normal liver function and carries a considerably risk of bile duct necrosis.

A randomized, placebo-controlled trial with anti-interleukin-2 receptor antibody for immunosuppressive induction therapy after liver transplantation.

The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor (IL-2R) antibody (BT563) has decreased the incidence of serious side effects, such as tachycardia, hypertension, rash, fever and nausea since it does not lyse its target cell. To investigate the immunosuppressive efficacy of BT563, a placebo-controlled trial was performed and BT563 was added to the standard triple induction after liver transplantation. Forty consecutive recipients of primary orthotopic liver transplants (OLT) (median age 47 yr [range 18-65]) were randomized. All patients received triple immunosuppression with cyclosporine A (CyA), prednisolone (PRED) and azathioprine (AZA). In addition, 19 patients received BT563 (Biotest, Dreieich, Germany) at a dose of 10 mg/d from day 0 until day 12. The remaining 21 patients received a placebo infusion at the same days after transplantation. Minimal follow-up for all patients was 3 yr. Patient survival at 3 yr was 74% in the BT563 group and 90% in placebo group. Similar results were observed for graft survival. Two acute rejection episodes were detected in the BT563 group and 9 acute rejections (5 steroid-resistant) were observed in the placebo group (p < 0.034). The incidences of sepsis, pneumonia, cholangitis, urinary tract infections as well as cytomegalo-virus (CMV) infections were similar in both groups. Side effects of the BT563 therapy and/or post-transplant lymphoproliferative disease (PTLD) were not detected. Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation, while infectious complications and/or PTLD is not increased. Therefore, the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT.

Initially unresectable hilar cholangiocarcinoma: hepatic regeneration after transarterial embolization.

PURPOSE: To assess with volumetric computed tomography (CT) the pattern and extent of hepatic regeneration induced with transarterial embolization of initially unresectable hilar cholangiocarcinoma (Klatskin tumor). MATERIALS AND METHODS: In this prospective study, 13 patients (four men, nine women) with hilar cholangiocarcinoma, aged 43-74 years (mean +/- 1 standard deviation, 59.9 years +/- 9.6), underwent preoperative embolization of the right hepatic lobe. Embolization was performed transarterially by using four to 15 embolization coils. Volumetric measurements of the entire liver, left hepatic lobe, and spleen were performed with contrast material-enhanced and unenhanced helical CT before and after embolization in all patients. RESULTS: After right lobe embolization, volumetric helical CT measurements revealed a 2%-33% decrease (mean, 10%) in the volume of the affected right hepatic lobe, an 11%-68% increase (mean, 37%) in the volume of left hepatic lobe parenchyma, and variations in splenic volume of -5% to +28% (mean, +11%). Nine patients underwent extended hepatectomy 27-75 days (mean, 44 days) after embolization. No patient had severe complications due to embolization. CONCLUSION: In patients with an initially unresectable bilateral Klatskin tumor, right lobar arterial coil embolization results in enlargement of the left hepatic lobe (as verified with volumetric helical CT), thus allowing right hemihepatectomy.

Orthotopic liver transplantation after extended bile duct resection as treatment of hilar cholangiocarcinoma. First long-terms results.

Although the surgical treatment of hilar cholangiocarcinoma represents the only potentially curative option, survival figures remain low over the long term. After hilar and partial hepatic resections for hilar cholangiocarcinoma, loco-regional tumor recurrence appears as the primary site of failure. From April 1992 to April 1996, 14 patients underwent extended bile duct resections. Extended bile duct resections combine total hepatectomy, partial pancreatoduodenectomy, and liver transplantation in an attempt to eradicate the entire biliary tract without dissecting the hepatoduodenal ligament. The postoperative 60-day mortality rate was 14% (n = 2). The rate of curative resections was 93% (13 of 14 extended bile duct resections). One- and 4-year survival rates after curative resections were 56% and 30%, respectively. The rate of curative resections increased by combining total hepatectomy, partial pancreatoduodenectomy, and liver transplantation, i.e., extended bile duct resection. However, survival figures have not improved accordingly. Therefore, this extended surgical procedure has to be implemented with caution and possibly not without modifications (e.g., multimodal treatment).

Changes at the extracellular matrix during acute and chronic rejection in human liver transplantation.

We have previously observed changes at the extracellular matrix (ECM) which significantly correlated with the extent of preservation and reperfusion injury. In the present study, we attempted to investigate whether the ECM may be also involved in the pathophysiological sequelae of acute and chronic rejection. Of 81 patients monitored for the ECM parameters laminin, hyaluronic acid, fibronectin receptor, and transforming growth factor (TGF)-beta, 28 patients developed acute rejection (< 1 month), in 14 patients (17.4%) acute rejection was steroid resistant, 4 patients (4.5%) developed early chronic rejection following acute steroid-resistant rejection. Acute and chronic rejection were confirmed by established clinical and histological criteria. Laminin levels were significantly increased in patients experiencing acute steroid-resistant rejection (4204 +/- 133 ng/ml; P < or = 0.01) compared with patients with steroid-sensitive rejection (1059 +/- 27.3 ng/ ml) and with an uneventful postoperative course (1214 +/- 17.4 ng/ml). No increase in laminin was observed in those four patients who developed early chronic rejection (1099 +/- 58.7 ng/ml). Hyaluronic acid, fibronectin receptor, and TGF-beta levels also increased in patients with acute steroid-resistant rejection; hyaluronic acid: 290 +/- 10.8 micrograms/l vs 154 +/- 13.6 micrograms/l and 131 +/- 11.7 micrograms/l in patients with steroid-sensitive and no rejection, respectively; fibronectin receptor: 1003 +/- 23.5 ng/ml vs 573 +/- 24.8 ng/ml and 428 +/- 13.6 ng/ ml in patients with steroid-sensitive and no rejection, respectively; and TGF-beta: 393 +/- 14.9 pg/ml versus 315 +/- 10.7 pg/ml and 233 +/- 8.9 pg/ml in patients with steroid-sensitive and no rejection, respectively. A further increase in hyaluronic acid levels was observed in patients who developed early chronic rejection, while fibronectin receptor and TGF-beta levels remained low, similarly to laminin levels. The increase in laminin, hyaluronic acid, fibronectin receptor, and TGF-beta during acute steroid-resistant rejection may be stimulated by the rejection-related release of cytokines and adhesion molecules which paralleled the increase in ECM parameters. The lack of increase in laminin and fibronectin receptor levels in those patients who developed early chronic rejection may reflect an inability to recover from acute rejection.

[Extended partial Kausch-Whipple duodenopancreatectomy by resection of tumor infiltrated vascular segments]. / Erweiterte partielle Duodenopankreatektomie nach Kausch-Whipple durch Resektion tumorinfiltrierter Gefässabschnitte.

The experience with standard Kausch-Whipple procedure is reviewed and compared with partial duodenopancreatectomies extended by partial resection of the portal vein. Perioperative morbidity has decreased to below 5% and survival rates with and without vessel resection are not significantly different. Therefore, infiltration of mesentericoportal vessels is not a contraindication for Kausch-Whipple procedure.

[Results of laparoscopic fundoplication for treatment of gastroesophageal reflux]. / Ergebnisse nach laparoskopischer Fundoplikatio zur Behandlung der gastroösophagealen Refluxkrankheit.

We report on 48 patients, treated by laparoscopic fundoplication for pronounced gastroesophageal reflux disease. The results show that laparoscopic fundoplication is a very safe, gentle, and successful procedure for the therapy of gastroesophageal reflux disease. We regard laparoscopic fundoplication as a good alternative to long term medical therapy if a careful diagnosis and indication is provided.

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.

Mycophenolate mofetil added to immunosuppression after liver transplantation--first results.

Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive agent after kidney and heart transplantation, but experience with MMF after liver transplantation is still limited. Between August 1995 and January 1996, we treated 20 patients with MMF after orthotopic liver transplantation in an open, prospective study. Five out of eight patients with acute rejection and one patient with early chronic rejection showed a complete response after MMF was added to the immunosuppression. Three patients with chronic rejection did not improve, one died, and two have stable graft function at present. In eight patients who suffered from toxicity, a reduction in the dosage of tacrolimus was attempted with simultaneous MMF therapy. One patient died due to multiple organ failure. Liver function improved completely in one other patient, and partially in three patients after adding MMF. In the remaining three patients, a reduced dosage of tacrolimus or cyclosporin, together with MMF, reduced toxicity, not significantly. In conclusion, MMF appears to be a safe and potentially useful adjuvant immunosuppressive agent for rescue and maintenance therapy.

[Outcome of primary surgical management of liver trauma]. / Ergebnisse der primär-operativen Versorgung von Lebertraumata.

We evaluated retrospectively 43 patients with liver trauma undergoing laparotomy between 1/89 and 12/95. Blunt trauma (27 patients) and penetrating trauma (16 patients) to the liver had a mortality of 37% and 0%, respectively. The overall mortality was 23.3% and was significantly related to concomitant injuries (p = 0.002), whereas age, severity of the liver trauma as well as the surgical treatment had no significant influence on the outcome.