Takayuki Miyauchi

Perioperative immune responses in cancer patients undergoing digestive surgeries

BackgroundTh1/Th2 cell balance is thought to be shifted toward a Th2-type immune response not only by malignancy but also by surgical stress. The aim of this study was to estimate perioperative immune responses with respect to the Th1/Th2 balance in patients with gastrointestinal cancer.MethodsNinety-four patients who underwent abdominal surgeries were divided into three groups: gastric resection (n = 40), colorectal resection (n = 34) and hepatic resection (n = 20). Twelve patients undergoing laparoscopic cholecystectomy and 20 healthy subjects were served as control groups. Intracellular cytokine staining in CD4+ T lymphocytes was identified to characterize Th1/Th2 balance. Th1/Th2 balance was evaluated before operation and until postoperative days (POD) 14.ResultsThe preoperative Th1/Th2 ratio was significantly lower in patients with malignancy compared with control. The Th1/Th2 ratio of patients in all groups decreased significantly postoperatively. Th1/Th2 balance on POD 2 in patients with malignancy was significantly decreased compared to patients with laparoscopic cholecystectomy, but there were no significant differences among the four groups on POD 14.ConclusionPatients with malignancy showed an abnormal perioperative Th1/Th2 balance suggesting predominance of a type-2 immune response. Major abdominal surgeries induce a marked shift in Th1/Th2 balance toward Th2 in the early postoperative stage.

Effect of donor-specific splenocytes via portal vein and FK506 in rat small bowel transplantation.

BACKGROUND To investigate the role of the liver in immune responses after small bowel transplantation, donor-specific splenocytes were infused perioperatively, via the portal vein, in a rat heterotopic small bowel transplant model. METHODS Heterotopic small bowel transplantation between the fully allogenic Brown Norway (BN) (RT1n) and Lewis (RT1[1]) strain rats were performed. We prepared donor splenocytes from BN or third-party WKA (RT1k) rat spleens for Lewis hosts and injected the splenocytes perioperatively via the host portal vein or the systemic vein. The hosts were treated with a short course of the immunosuppressive agent, FK506 (0.5 mg/kg, 0-3 days postoperatively), following the experimental protocols. RESULTS Untreated Lewis hosts rejected BN small bowel grafts at 5.4+/-0.9 days (n=8). BN splenocytes given alone caused fatal graft-versus-host disease in six of eight animals, and two others died from graft rejection. FK506 alone did not significantly prolong graft survival (6.3+/-1.0 days, n=10). However, BN splenocytes injected via the portal vein, combined with FK506, prolonged graft survival to 12.7+/-2.1 days (n=12, P < 0.01) and 10 of 12 rats survived more than 70 days. This was donor antigen specific. BN splenocytes administered systemically caused fatal graft-versus-host disease in all recipients, and FK506 did not ameliorate this. Histologic findings of graft rejection were remarkably mild in the recipients of the combined therapy, compared with the recipients that were given FK506 alone. Down-regulation of one-way mixed lymphocyte reaction to BN splenocytes was observed in the splenocytes of the tolerant hosts. CONCLUSIONS Combined administration of donor splenocytes and FK506 reduced allograft rejection and prolonged survival in this rat model of small bowel transplantation.

Limitations of endoscopic haemostasis by ethanol injection and surgical management for bleeding peptic ulcer.

Abstract Two hundred and fifty‐three patients with bleeding peptic ulcer underwent therapeutic endoscopy using local ethanol injection and were evaluated to determine the need for surgery and outcome. Permanent endoscopic haemostasis was achieved in 178 (70.4%) cases. Pulsatile arterial bleeding in ulcers and shock on admission (respectively, P < 0.01, P < 0.05) were significantly more frequent in patients with unsuccessful endoscopic treatment. Postoperative stay was significantly longer (P < 0.05) for patients with bleeding peptic ulcer than for patients requiring surgery for intractable ulcer without bleeding. Surgery was recommended if three attempts at endoscopic treatment did not achieve permanent haemostasis. The need for more than three such treatment sessions and the presence of a large excavated ulcer with an exposed vessel in an elderly patient were considered to indicate the necessity for surgery. Surgical procedures to which the operator is accustomed and intensive management were recommended for emergency cases to optimize the likelihood of survival.

ACETAMINOPHEN ABSORPTION TEST AS A MARKER OF SMALL BOWEL TRANSPLANT REJECTION

We recently evaluated the acetaminophen absorption test as a marker of graft rejection for small bowel transplantation(SBTX). Randomly bred male Wistar rats were used as recipients and donors. Rats (n=45) received heterotopic small intestinal transplants and were divided into three groups (n=15 for each group). In group A, a 10-cm segment of jejunum of was exteriorized as a Thiry-Vella loop. In group B, immunosuppression was not given after SBTX. In group C, rats were treated with FK506 after SBTX (0.3 mg/kg body weight, 0-6 postoperative days). Serum acetaminophen concentrations were measured 15 min after instillation of 0.15 g/kg acetaminophen into the intestinal loop on postoperative days 1, 3, and 7 (n=5 for each group). Blood flow and histology of the graft were also evaluated. In the SBTX group only, the grafts showed the histological change after acute rejection. On day 3, plasma acetaminophen concentrations in this group showed a significant decrease, which correlated with the mild histological changes of graft rejection. Graft blood flow of the SBTX group decreased significantly on day 7, following the severe graft destruction of advanced rejection. No remarkable changes were observed in the other two groups. The acetaminophen absorption test appears to be useful for the early detection of SBTX graft rejection.