Severe steroid-unresponsive ulcerative colitis: outcomes of restorative proctocolectomy in patients undergoing cyclosporin treatment.

PURPOSE: The recent introduction of the immune suppressor cyclosporin for treatment of steroid-refractory ulcerative colitis has required surgeons to perform a colectomy in those patients who eventually fail this rescue treatment, thus raising questions as to the safety of surgery as performed in patients with a heavily manipulated immune system. To assess the rates of mortality and morbidity in this setting, we studied a cohort of consecutive patients who had surgery after failing cyclosporin for refractory ulcerative colitis at our center. METHODS: Between January 1991 and December 1996, 25 patients with ulcerative colitis underwent restorative proctocolectomy performed in three steps (21 patients) and in two steps (4 patients). Seventeen of the 25 patients (68 percent) were initial nonresponders to a dose of 2 mg/kg/day of intravenous cyclosporin and underwent surgery immediately, the remaining 8 (32 percent) relapsed as outpatients on oral cyclosporin and were readmitted for surgery. RESULTS: There was no operative mortality. Nine patients of the 25 developed postoperative (early) complications (36 percent). The three-step operation subset had a 28 percent complication rate, the two-step 75 percent. Three patients needed reoperation. A total of 11 patients (44 percent) reported with late complications: two patients required surgical treatment, one for obstruction and one for pouch-perianal fistula. Three cases of pouchitis were recorded. No patient required pouch removal. CONCLUSION: Given the absence of postoperative mortality and a low overall complication rate, restorative proctocolectomy can safely be performed in patients who fail rescue treatment with a dose of 2 mg/kg of cyclosporin for steroid-refractory ulcerative colitis. Corollary evidence in this article hints but does not prove that the three-step procedure is safer than the two-step operation.

Recurrence of hepatitis B in liver transplants treated with antiviral therapy.

BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver diseases, liver transplantation carries a consistent risk of Hepatitis B Virus recrudescence in the graft. In the attempt to reduce the reinfection rate with antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days) before transplantation and prolonged for 10 days after transplantation; four patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours before surgery and prolonged for 28 days after surgery. All received hepatitis B immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about 10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the 12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors, only the patient who maintained a titre of 10(6) virus/ml at the time of transplantation developed viral recurrence 4 months after surgery. Before transplantation, 2 of the patients treated with Lactosaminated Arabinoside-Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases, viraemia became undetectable at the end of therapy. None died and Hepatitis B Virus recurred 2 months after transplantation in one. The overall rate of Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in patients in whom the viraemic load decreased to around 10(4) virus/ml following treatment, compared to an overall recurrence rate of 50% in our historical series of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION: Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus reinfection of the liver graft by decreasing the viral load before surgery.

[Cyclosporin for steroid refractory ulcerative colitis. Results of a study conducted at Turin General Hospital between 1990 and 1997]. / La ciclosporina nel trattamento della rettocolite ulcerosa refrattaria al cortisone. Risultati dello studio condotto dal 1990 al 1997 all'Ospedale San Giovanni Battista di Torino.

BACKGROUND: Four every ten patients receiving high-dose parenteral steroids for severe ulcerative colitis fail and may have their colon removed. Intravenous followed by oral cyclosporin has been shown to initially rescue approx. 70% of these non-responder patients, but dosages and long term-efficacy are still debated. We reviewed the clinical outcomes of patients treated with cyclosporin for refractory ulcerative colitis at our Center in the last 7 years. METHODS: Fifty-four patients destined to colectomy because of refractory ulcerative colitis (previous failure to respond to 7 days of 1 mg/kg/day steroids) were enrolled to initially receive a two-week continuous infusion of 2 mg/kg/day cyclosporin. Responders (showing at least a 50% reduction of activity) were meant to be treated with oral drug at 6-8 mg/kg/day for 6 months with the maintenance of remission and the spare of steroids being the end-points. RESULTS: Data are available for 47 patients followed-up for a minimum of 6 months up to 6 years. Of these 47, 14 did not respond to the intravenous drug and were submitted to surgery; of the remaining 33 responders (70%) entering the oral 6-month phase, 17 relapsed before end or on leaving the drug and were considered as failures. The remaining 16 (34% of the 47) left cyclosporin in remission and in need of less than 20 mg steroids daily. Of them, 12 avoided colectomy in a follow-up of 6 months-6 years. CONCLUSIONS: Intravenous cyclosporin may be rapidly effective in 7 every 10 patients whose acute ulcerative colitis fails a full-dose steroid course. However, only 3 of the initial 10 may maintain remission over a 6-month oral course. Further efforts should concentrate on improving the long term efficacy of cyclosporin.

A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis.

Eighty patients with chronic non-A, non-B hepatitis completed a randomized controlled trial of the therapeutic efficacy of recombinant interferon alfa-2b. Twenty-nine received 1 million units and 26 received 3 million units of interferon subcutaneously thrice weekly for 6 months, and 25 were controls. Normalization or a significant decrease of alanine aminotransferase values was obtained in 19/29 (66%) patients treated with 1 million units, in 18/26 (69%) patients treated with 3 million units and in one control patient (4%, p less than 0.05). However, when control patients were randomized after the initial 24 weeks to receive 1 or 3 million units of interferon for 48 weeks, 12/14 (86%) patients receiving 3 million units responded to therapy versus 3/11 patients receiving 1 million units (27%, p less than 0.05). After a 1 to 6 months follow-up period post treatment, an alanine aminotransferase relapse was observed in 18/30 (60%) responders to 3 million units and in 17/22 (77%) responders to 1 million units. Cirrhotic patients responded less than patients with non-cirrhotic disease (47 vs. 78%, p less than 0.05). Only responders treated with 3 million units significantly ameliorated their histologic picture (pre-therapy Knodell's index = 8.9, post-therapy = 6.0, p less than 0.05). The data confirm that treatment with interferon is of benefit in patients with chronic non-A, non-B hepatitis.