Toru Koyama

Low-Dose Erythromycin Reduces Delayed Gastric Emptying and Improves Gastric Motility After Billroth I Pylorus-Preserving Pancreaticoduodenectomy

ObjectiveTo test the hypothesis that early and low doses of erythromycin reduce the incidence of early delayed gastric emptying (DGE) and induce phase 3 of the migratory motor complex in the stomach after Billroth I pylorus-preserving pancreaticoduodenectomy (PPPD). Summary Background DataDelayed gastric emptying is a leading cause of complications after PPPD, occurring in up to 50% of patients. High doses of erythromycin (200 mg) accelerate gastric emptying after pancreaticoduodenectomy and reduce the incidence of DGE, although they induce strong contractions that do not migrate to the duodenum. MethodsThirty-one patients were randomly assigned to either the erythromycin or control groups. The patients received erythromycin lactobionate (1 mg/kg) every 8 hours, or H2-receptor antagonists and gastrokinetic drugs from days 1 to 14 after surgery. On postoperative day 30, gastroduodenal motility was recorded in 14 patients. ResultsPreoperative, intraoperative, and postoperative factors were comparable in the erythromycin and control groups. The erythromycin group had a shorter duration of nasogastric drainage, earlier resumption of eating, and a 75% reduction in the incidence of DGE. Erythromycin was an independent influence on nasogastric tube removal, and preservation of the right gastric vessels was a significant covariate. Low doses of erythromycin induced phase 3 of the migratory motor complex and phase 3-like activity, with the same characteristics as spontaneous phase 3, in 86% of patients: two had quiescent stomachs and the others had spontaneous phase 3 or phase 3-like activity. ConclusionsLow doses of erythromycin reduced the incidence of DGE by 75% and induced phase 3 of the migratory motor complex after Billroth I PPPD. Low doses of erythromycin are preferable to high doses in the unfed period after PPPD.

Effects of a dual inhibitor of tumor necrosis factor-α and interleukin-1 on lipopolysaccharide-induced lung injury in rats : Involvement of the p38 mitogen-activated protein kinase pathway

ObjectiveSepsis is a major cause of adult respiratory distress syndrome. In this study, we evaluated the effect of FR167653, which is a potent suppressant of tumor necrosis factor (TNF)-&agr; and interleukin (IL)-1 production, on lipopolysaccharide (LPS)-induced lung injury and lethality in rats, and we examined the involvement of p38 mitogen-activated protein (MAP) kinase in the action of FR167653. DesignProspective, randomized study. SettingAnimal research facility in a university. SubjectsMale Sprague-Dawley rats weighing 200–270 g. InterventionsAll the animals were assigned to one of the following four groups: control group, FR-only group, LPS-only group, and LPS/FR group. Animals in the LPS-only and LPS/FR groups received 6 mg/kg of LPS intravenously. The animals in the FR-only and LPS/FR groups also received an infusion of FR167653 at 0.2 mg·kg−1·hr−1, commencing 30 mins before the LPS (or vehicle) injection and continuing for 5.5 hrs. Measurements and Main Results LPS significantly induced the accumulation of pulmonary neutrophils and lung edema, both of which were significantly attenuated by treatment with FR167653. FR167653 also significantly decreased the LPS-induced lethality. Histologically, tissue damage was milder in the LPS/FR group than in the LPS-only group. Serum concentrations of TNF-&agr; and IL-1&bgr; and plasma concentrations of thromboxane B2 were all suppressed in the LPS/FR group compared with the LPS-only group. Western blot analysis revealed that FR167653 inhibited the phosphorylation of p38 MAP kinase in lung tissues. ConclusionsFR167653 administration decreased serum TNF-&agr; and IL-1&bgr; concentrations, which was associated with decreased lung injury and lethality. The mechanism responsible for the decreased TNF-&agr; and IL-1 may be related to the inhibitory effect of FR167653 on p38 MAP kinase activation.

Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to university of wisconsin solution on reperfusion injury in liver transplantation.

BACKGROUND Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the development of ischemia/reperfusion injury in nonhepatic organs, such as the heart. However, the role of p38 MAPK activation in the liver is unclear. We examined the effects of FR167653, a novel p38 MAPK inhibitor, as an additive to University of Wisconsin (UW) solution in rat liver transplantation. METHODS Rat orthotopic liver transplantation was performed after 30 hr of cold storage using UW solution with or without FR167653. Ten-day survival rates, serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels, liver tissue blood flow, histological findings, and activities of p38 MAPK and p46/p54 c-Jun N-terminal kinase (JNK) in liver grafts were evaluated. RESULTS The addition of FR167653 significantly increased animal survival rates. FR167653 significantly suppressed serum ALT and LDH levels and improved liver tissue blood flow after transplantation. FR167653 also ameliorated histological damage to the liver graft. Neither p38 MAPK nor p46/p54 JNKs was activated during cold storage, whereas both were markedly activated within 30 min of reperfusion and remained activated until 60 min after reperfusion. FR167653 inhibited the activation of p38 MAPK both 30 and 60 min after reperfusion, but it did not affect the activation of p46/p54 JNKs. CONCLUSIONS The addition of FR167653 to UW solution improved liver graft viability and animal survival rates associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting the activation of p38 MAPK may attenuate ischemia/reperfusion injury in liver transplantation.

Effect of FR167653 on Small Bowel Ischemia-Reperfusion Injury in Dogs

IL-1 and TNF-α are known to be pleiotropiccytokines associated with various inflammatoryconditions such as small intestinal injury afterischemia-reperfusion. FR167653 has been characterized asa potent suppressant of IL-1 and TNF-αproduction. The effect of FR167653 on intestinalreperfusion injury was investigated in a warm ischemiamodel of the canine gut. Sixteen mongrel dogs weredivided into two groups: a control group and a FR groupto which FR167653 was administered. Both the superiormesenteric artery and vein were clamped for 2 hr.Arterial pH, hepatic venous hemoglobin oxygensaturation, intramucosal pH, and the survival rate werewell maintained in the FR group in comparison with thecontrol group after reperfusion. FR167653 inhibited theexpression of IL-1β mRNA. Histologically,ischemia-reperfusion injury was more severe in the control groupthan the FR group. This study suggests that FR167653inhibits proinflammatory cytokines and amelioratesischemia-reperfusion injury of the smallintestine.

A Hemophagocytic Syndrome-Like Condition After Emergency Colectomy for Perforated Colon Cancer: Report of a Case

Abstract Hemophagocytic syndrome is a rare but often fatal condition, and little is known about why this disorder can occur following surgery. We report herein the case of a patient successfully treated for a hemophagocytic syndrome-like condition that developed after emergency right hemicolectomy for a retroperitoneal abscess secondary to perforated colon cancer. The 62-year-old man initially presented after the sudden development of severe right back pain, and computerized tomography scans revealed a retroperitoneal abscess continuous with a tumor in the ascending colon. An emergency right hemicolectomy was subsequently performed. On postoperative day (POD) 2, his blood platelet count suddenly dropped to 1 × 104/μl and histological examination of a bone marrow specimen taken on POD 5 showed abnormal histiocytes that had phagocytosed not only megakaryocytes, but also erythrocytes and leukocytes, and a normocellular marrow with a normal number of megakaryocytes. Hemophagocytic syndrome was suspected, and predonine was administered. The patients condition improved remarkably and he was discharged on POD 51.

Endoscopic balloon dilation for benign esophageal anastomotic stricture

BACKGROUND/AIMS The aim of this study was to identify factors that might affect the results of treating benign anastomotic stricture of the esophagus with balloon dilation. METHODOLOGY Balloon dilation was performed on 35 patients with benign esophageal anastomotic stricture of the upper (esophageal cancer: 18) or lower (gastric cancer: 15, esophageal varices: 2) esophagus. The procedure was considered effective when patients were able to maintain a solid diet more than 12 months after the last dilation. The follow-up period ranged from 15-130 months (mean: 51 months). RESULTS A total of 245 dilations were performed, with an average of 6.6 dilations per patient. Treatment was effective in 29 patients (83%). Balloon dilation was successful when treating strictures shorter than 12 mm in length. The strictures were significantly shorter in patients treated effectively (5.6 vs. 30.8 mm). The diameter of the stricture did not affect the results. All the strictures in the lower esophagus and all those resulting from stapled anastomoses were treated successfully, while the effectiveness of treating strictures in the upper esophagus or those resulting from hand-sewn anastomoses was 67% and 57%, respectively. Strictures without prior leakage were treated effectively 92% of the time, while the success rate fell to 56% if there was a preceding leak. An average of 4.4 dilations were performed in effective cases, while the average was 17.5 dilations in ineffective cases. The number of repeat dilations was correlated with the length of the stricture. CONCLUSIONS Balloon dilation can successfully treat strictures shorter than 12 mm long. The correlation equation may be used to predict the number of repeat dilations and treatment results, and is useful for deciding when to use an alternative method to balloon dilation.