Rejection and survival after total orthotopic liver-small bowel allotransplantation in pigs immunosuppressed with FK 506.
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Publications and source records attributed to R Biffi.
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Alterations in the luminal microflora and increased intestinal translocation have been reported to occur following experimental and clinical small bowel transplantation (SBT). Selective intestinal decontamination (SID) has been used to prevent luminal overgrowth and bacterial translocation. Despite the wide use of SID in clinical SBT, there are no data supporting its usefulness in this situation. Thus, the aim of this investigation was to examine the effects of cyclosporine A (CsA) and SID upon bacterial overgrowth and translocation in a swine model of SBT. Nineteen Large White female pigs weighing 30 +/- 2 kg underwent a total orthotopic SBT and were randomly allocated to one of the following experimental groups as follows: Group 1 (No. 8) CSA 25 mg/kg body weight (b.w.)/day administered subcutaneously and Cefazolin 2 g/day im. Group 2 (No. 6) received the identical immunosuppression but the Cefazolin 2 g/day im was discontinued on the 5th Postoperative Day (pod) and switched to a SID regimen consisting of Vancomycin, 1 g, Nystatin, 500,000 IU, Colistin, 1,500,000 IU, and Tobramycin, 100 mg, given through a gastrostomy tube. Group 3 (No. 5) received no immunosuppression but antibiotic consisting of Cefazolin 2 g im/day. Group 4 (No. 7) underwent a small bowel autotransplantation. Group 4 received SID as in group 2 but no immunosuppression was given. Finally, 17 normal animals were sham-operated and were used as normal controls (N group). The animals in groups 1, 2, and 4 were sacrificed on the 29th pod. Those in group 3 were sacrificed on the 7th pod.(ABSTRACT TRUNCATED AT 250 WORDS)
A study of 57 patients admitted to the Department of Emergency Surgery at the Ospedale Maggiore in Milan between 1980 and 1992 following the recent ingestion of a caustic substance is presented herein. Through this study, an aggressive diagnostic and therapeutic approach has been employed, including early surgery which plays a fundamental role in the prevention of acute hemorrhagic or perforative complications as well as in the development of scar tissue and neoplastic strictures over time. The criteria for early emergency surgery were the presence of endoscopic grade 3 and 4 lesions as well as those on the borderline between grades 2 and 3 with clinical symptoms. In 11 patients with lesions of moderate severity, the treatment of choice was medical therapy, which required subsequent surgical intervention for strictures in 5 patients. In 13 patients with severe lesions, an early surgical approach was performed with a mortality rate of 23%.
OBJECTIVE: To examine the effects of two immunosuppressant regimens on composition of the bowel flora and rate of translocation after transplantation of the small bowel in pigs. DESIGN: Randomised controlled study. SETTING: University hospital, Italy. MATERIAL: 35 female Large White pigs. INTERVENTIONS: 9 Animals were not operated on (normal controls). 19 Animals underwent total orthotopic small bowel allotransplantation and were then randomised to receive: group A (n = 8) cyclosporin A 25 mg/kg subcutaneously and cephazolin 2 g intramuscularly daily; group B (n = 6) 15-deoxyspergualin (15-dos) 3 mg/kg for 7 days then 1.5 mg/kg, cephazolin 2 g intramuscularly daily for 4 days then selective intestinal decontamination with colistin 1.5 million U, tobramycin 100 mg, vancomycin 1 g, and nystatin 500,000 U daily; and group C (n = 5) cephazolin 2 g intramuscularly daily for 8 days. A further group (D, n = 7) underwent orthotopic autotransplantation and received the same antibiotic and selective decontamination regimens as group B. Animals in group C were killed on day 8, and the rest on day 29. MAIN OUTCOME MEASURES: Signs of rejection, graft versus host disease, luminal overgrowth, and evidence of translocation to mesenteric lymph nodes. RESULTS: All animals in group C, and 2 in group B, showed signs of acute rejection. There was a significant overgrowth of both aerobic and anaerobic bacteria in all 3 groups after allotransplantation compared with normal controls. Bacterial translocation was similar in autografted and allotransplanted animals. Mesenteric lymph nodes were colonised in 4/9 controls, 7/8 in group A, 4/4 in group B, 5/5 in group C, and 7/7 in group D. CONCLUSION: Neither cyclosporin A nor 15-dos prevented luminal overgrowth or bacterial translocation to mesenteric nodes up to one month after operation. The rate of translocation was similar in autotransplantation and allotransplantation, suggesting that non-immunological factors (for example, denervation and interruption of lymphatics) may have a role in these alterations.
Graft-versus-host disease (GVHD) and graft rejection are major problems following intestinal transplantation (IT). Natural killer (NK) cells may be important effector cells in both conditions. In this study, Sprague-Dawley (SD) or SD-Brown Norway (BN) F1 rat intestine was transplanted into BN recipients with and without associated graft mesenteric lymphadenectomy (GML). Cyclosporine (15 mg/kg day) was administered to all animals. Pieces of the intestinal graft were examined 4 days posttransplant and again at death. NK activity calculated using intestinal intraepithelial lymphocytes (IL) was determined utilizing an 18-hr cytotoxic assay assessing 51Cr release and the results are reported as lytic units. YAC-1 cells were used as the target. NK activity was reduced 4 days after IT both in native (8.02 +/- 0.64) and in grafted bowel (3.14 +/- 1.51), with histological evidence of rejection as compared with that of control bowel in ungrafted rats (21.1 +/- 2.14). Survival was increased, on mean, a total of 6 days with the addition of GML in both semiallogenic and allogenic transplanted rats. At the time of death, the NK activity in the native bowel had increased (17.1 +/- 3.02) and histologic evidence of GVHD was present. These data suggest that: (1) NK cells are important in GVHD and (2) both semiallogenic and allogenic transplants survive longer if they are combined with GML (P < or = 0.05 and P < or = 0.01, respectively).
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Ingestion of a large amount of corrosive agent results in a life-threatening condition which requires a much more aggressive diagnostic and therapeutic approach than was formerly recommended. Based on experience with a wide spectrum of upper g-i injuries in 56 patients treated through a 5-year-period, the Authors suggest an early staging of the lesions by immediate endoscopy, followed by adequate resective surgery for high-degree esophago-gastric lesions. Indications, techniques of artificial nutrition and the nutritional requirements of this condition are presented and fully discussed. The prompt institution of total parenteral nutrition is an essential part of the emergency management of these lesions. Fourteen patients underwent surgical treatment for the lesions; in all cases a Witzel's feeding jejunostomy was performed and postoperative enteral nutrition was started. Eight patients underwent a reconstructive operation of colon interposition and received home-based total enteral nutrition for a period of 8-25 weeks. No major complications relate to nutritional support occurred and nutritional indexes were normal at the end of the treatment.
Hepatic metastases from genito-urinary tract neoplasms are infrequently eligible for surgical treatment. Nevertheless, some patients affected by primary renal adenocarcinoma or by Wilms' tumor, with single or lobe-confined hepatic metastasis, can be enrolled for a surgical excision of the hepatic lesion. Selection criteria of the patients are fully discussed; surgical treatment by anatomical resections (segmentectomy or hepatectomy) with primary parenchymal dissection are preferred.
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In the period from 1976 to 1986, we performed 329 hepatic needle biopsies using a posterior extraperitoneal approach in patients with bleeding esophageal varices. The histologic findings subdivided according to a four-stage classification were correlated significantly with immediate survival. Specifically, 21 of 23 stage IV patients with severe degenerative and necrotic parenchymal lesions died after immediate emergency surgery, whereas 26 of 48 stage IV patients who did not undergo emergency surgery survived. Stage IV patients appeared unable to withstand major surgery. According to our data, histologic stage and Child's class are independent parameters, especially in emergency situations, since they quantify different aspects of functional liver failure. Therapeutic implications are presented based on cumulative analysis of histologic stages and Child's classes.
Percutaneous ultrasonic lithotripsy in association with endoscopic control and balloon catheter dilatation of stenosed cholangiojejunostomy was successfully used in the treatment of a 53-year-old man with intrahepatic gallstones and severe cholestasis. Previously, he had undergone several biliary surgery operations, but all interventions were complicated by stenosis. The good results obtained in this case lead us to consider percutaneous ultrasonic lithotripsy a possible alternative to surgical treatment of complicated gallstones.
The effect of somatostatin on the course and severity of experimental pancreatitis was tested. Acute pancreatitis was induced in 210 Sprague-Dawley rats by injecting a 4.3% sodium taurocholate solution, saturated with trypsin, into a temporarily closed duodenal loop. Immediately after the end of the surgical procedure somatostatin or, alternatively, normal saline were administered as a bolus followed by continuous subcutaneous infusion for 9 h. Ninety rats (30 untreated, 30 saline-treated and 30 somatostatin-treated) were sacrificed 10 h after the induction of pancreatitis to assess the histologic severity of pancreatic lesions, the amount of peritoneal exudate and the circulating levels of amylase. In another 120 rats (40 untreated, 40 saline-treated and 40 drug-treated) the mortality rate was evaluated so that the histologic examination of the pancreas followed spontaneous death. In sacrificed animals somatostatin treatment lowered serum amylase levels and definitely improved pancreatic histopathology (edema, leucocyte infiltration and necrosis). The drug prevented the occurrence of severe necrosis in all treated animals. Somatostatin did not affect the mortality rate of pancreatitic rats (70%) although post-mortem histologic examination revealed significantly less pancreatic histopathology in drug-treated rats than in their controls.