Naoki Tomizawa

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.

Results of duct-to-mucosa pancreaticojejunostomy for pancreaticoduodenectomy Billroth I type reconstruction in 100 consecutive patients.

BACKGROUND This study retrospectively analyzed 100 consecutive patients who underwent pancreaticoduodenectomy (PD) and pylorus-preserving PD (PPPD) with a Billroth I type reconstruction and pancreaticojejunostomy by duct-to-mucosal anastomosis using a continuous running suture. STUDY DESIGN Seventy patients underwent PD and 30 patients PPPD for pancreatic cancer in 33, bile duct cancer in 28, ampullary or duodenal tumor in 22, chronic pancreatitis in 8, and other gastrointestinal cancer in 9. Postoperative pancreatic anastomotic leakage was diagnosed from skin excoriation around the drain site, and was defined as a high concentration of amylase in drainage fluid or leakage demonstrated on x-ray. RESULTS The mortality rate was 2% overall (2.8% in PD, 0% in PPPD). The morbidity rate was 23% overall (12.8% in PD, 46.7% in PPPD). Pancreatic anastomotic leakage was 4.0% overall (2.8% in PD, 6.7% in PPPD).. The incidence in the ampullary or duodenal tumors was 9.1% overall (0% in PD, 14.3% in PPPD). Biliary leakage occurred in four patients, 4.0% overall (4.3% in PD, 3.3% in PPPD), intraabdominal hemorrhage in 2% (2.8% in PD, 0% in PPPD), and lethal anastomotic leakage in one patient, overall rate 1% (1.4% in PD, 0% in PPPD). Delayed gastric emptying had the highest morbidity and was seen exclusively in PPPD (39.3%). CONCLUSIONS A simple continuous running suture and parachuting for duct-to-mucosal pancreaticojejunostomy makes pancreaticoduodenectomy a safe procedure, even in a Billroth I type reconstruction.

Concomitant major hepatectomy and inferior vena cava reconstruction

The development of techniques for liver transplantation and preservation has led to several surgical innovations for the resection of hepatic malignancies that invade the inferior vena cava (IVC) and the hepatic venous confluence. The resection of hepatic malignancies invading the IVC has become technically feasible and relatively safe since the introduction of total hepatic vascular exclusion (HVE), with or without bypass. The more aggressive approach, involving concomitant hepatic and IVC resection and subsequent replacement of the IVC using autologous or synthetic materials, has also been adopted. If a subtotal hepatectomy could not be performed, total hepatectomy with liver transplantation was a valuable option. But there is no agreement on the management of these tumors in a cirrhotic liver, so the choice of operative procedures used for these patients remains debatable. We reviewed the records of eight hepatic malignancies, including histologically proven five hepatocellular carcinomas (HCC) in cirrhotic livers, and the records of patients with metastatic carcinoma in noncirrhotic livers who underwent concomitant hepatic resection and IVC reconstruction.

Left renal vein graft for vascular reconstruction in abdominal malignancy.

BackgroundAdvanced abdominal malignancies are occasionally invasive for the major blood vessels, such as the portal vein (PV), inferior vena cava (IVC), and major hepatic veins (HVs), and complete removal of the tumors is required for patients undergoing vascular resection and reconstruction. We used left renal vein (LRV) grafts for vascular reconstruction in patients with these malignancies and evaluated their clinical relevance.MethodsA total of 113 patients underwent vascular resection including the PV (42 patients), IVC (68 patients), and HV (3 patients) for hepatobiliary-pancreatic or abdominal tumor resection. Of these, 11 patients underwent vascular reconstruction with a LRV graft of the PV, superior mesenteric vein (SMV), and HVs in 3 patients each, and the IVC in 2 patients. The HVs were resected with segmentectomy involving Couinaud’s segments VII, VIII, and IV; VII, VIII, and II; or III, IV, VIII in each patient. The PV and SMV were resected in 5 patients undergoing pancreaticoduodenectomy for pancreatic carcinoma, and in 1 patient being treated with extended right hepatectomy and pancreaticoduodenectomy for hepatic hilar carcinoma. The IVC was partially resected in 1 patient with advanced colon cancer and 1 with malignant schwannoma.ResultsThe mean graft length of LRV obtained was 3.6 (3.5–4.0) cm. The graft was used as a tube in 9 patients, and as a patch in 2 patients. The mean duration of clamping time was 41.9 (35–60) min. Portal vein thrombosis was encountered in 2 patients, and anastomotic stenosis in 1 patient. Other morbidity was not related to vascular reconstruction. One patient who underwent extended right hepatectomy and pancreaticoduodenectomy died of liver failure in the hospital. The serum creatinine level after surgery did not deteriorate except in the one patient who died in the hospital. Graft patency was maintained during the follow-up period in all patients.ConclusionsA LRV graft may enhance the possibility of vascular reconstruction without deteriorating serum creatinine level, and it provides sound graft patency.

The effects of a neutrophil elastase inhibitor (ONO-5046.Na) and neutrophil depletion using a granulotrap (G-1) column on lung reperfusion injury in dogs

BACKGROUND Activated neutrophils are reported to be closely involved in ischemia-reperfusion injury after lung transplantation. We investigated the beneficial effects of a new recombinant specific neutrophil elastase inhibitor, ONO-5046.Na, and an extracorporeal-type granulotrap (G-1) column on ischemia-reperfusion lung injury, by using an in situ warm lung ischemia model in dogs. METHODS Warm ischemia was induced for 3 hours by clamping the pulmonary arteries and veins. The left main bronchus was bisected and reanastomosed prior to reperfusion. The left lung was collapsed for 3 hours. A total of 27 adult mongrel dogs were divided into three groups: the control group (n = 9) treated with a saline vehicle; the ONO group (n = 9), in which ONO-5046.Na was continuously administrated from before induced ischemia and to ending 2 hours after reperfusion; and the G-1 group (n = 9), in which a G-1 column was applied for 90 minutes starting 30 minutes before reperfusion under passive bypass support. RESULTS Circulating neutrophils in the G-1 group decreased significantly (p<.05) compared to preischemia, and significantly decreased compared with the other groups after reperfusion. Oxygenation was improved actually and pulmonary vascular resistance was kept lower level after the administration of ONO-5046.Na. The increase of lung weight was significantly ameliorated in both the G-1 and ONO groups. In the histopathological study, lungs from the control group demonstrated diffuse alveolar edema, neutrophil infiltration, massive alveolar exudate and hemorrhage, and thickening of the interstitium. Lungs from the G-1 group showed mild swelling of the alveolar wall and neutrophil infiltration. Lungs from the ONO group showed virtually no abnormalities. CONCLUSION This study demonstrated that a neutrophil elastase inhibitor and neutrophil depletion prevented lung reperfusion injury. These treatments may prevent ischemia and reperfusion injury in lung transplantation.

The effect of cyclooxygenase-2 inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model

BACKGROUND Liver grafts from non-heart-beating donors inevitably suffer from warm ischemic injury. In these grafts, large quantities of inflammatory cytokines and arachidonic acid metabolites are induced, further aggravating injury. Cyclooxygenase (COX) is an intracellular enzyme that converts arachidonic acid into prostaglandin (PG)G2 and PGH2. COX has two isoforms: constitutive COX-1 and inducible COX-2. The aim of this study was to evaluate the effects of COX-2 inhibition by FK3311 (FK) on warm ischemic injury in a canine total hepatic vascular exclusion (THVE) model. STUDY DESIGN Sixteen mongrel adult dogs were studied. The portal triad of the hilum and the inferior vena cava above and below the liver was clamped for 1 hour. Splanchnic decompression was achieved by active splenofemorojugular bypass. The animals were divided into two groups. FK (1 mg/kg) was administered in the FK group (n = 8), and saline was administered in the control group (n = 8). Hepatic venous blood was collected to measure serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and hyaluronic acid levels. Serum thromboxane (Tx)B2 and 6-keto-PGF1alpha levels were also measured. Hepatic tissue blood flow was estimated simultaneously. Liver specimens were harvested for histologic study and polymorphonuclear neutrophils were counted. RESULTS Alanine aminotransferase, aspartate aminotransferase, and hyaluronic acid 2 and 6 hours after reperfusion and LDH 30 minutes and 2 and 6 hours after reperfusion were significantly (p < 0.05) lower in the FK group than in the control group. Hepatic tissue blood flow remained significantly (p < 0.05) higher in the FK group than in the control group 1, 2, and 6 hours after reperfusion. Histologic tissue damage was mild and polymorphonuclear neutrophil infiltration was significantly lower (p < 0.05) in the FK group than in the control group 1 and 6 hours after reperfusion. Thirty minutes after reperfusion, TxB2 was significantly reduced (p < 0.05) in the FK group, and 6-keto-PGF1alpha was not significantly lower. CONCLUSIONS FK protected against hepatic warm ischemia-reperfusion injury by marked inhibition of TxA2.

Ileal Perforation Caused by Cytomegalovirus Infection in a Patient with Recurrent Gastric Cancer: Report of a Case

Abstract.We report a case of ileal perforation caused by cytomegalovirus (CMV) infection in a patient with peritoneal recurrence of gastric cancer. Emergency laparotomy revealed a pinhole-sized perforation in a reddish segment of the small bowel, 100 cm proximal to the terminal ileum, and peritoneal carcinosis of recurrent gastric cancer invading the transverse colon and the gastrojejunal anastomosis of a Billroth-II procedure. The affected ileum was resected, a primary anastomosis was performed, and a colostomy was made in the ascending colon. The histology of the ileum revealed acute inflammation with vasculitis and CMV inclusions in the macrophages and endothelial cells and evidence of CMV on immunostaining. There was no evidence of cancer cell invasion or any other pathogens. Although the prognosis associated with bowel perforation due to CMV infection is poor, emergency surgery saved our patients life.

The effect of FK409—a nitric oxide donor—on canine lung transplantation

BACKGROUND Nitric oxide (NO) is known to have beneficial effects in ischemia-reperfusion (I/R) injury through maintaining endothelial integrity, inhibiting leukocyte adhesion and platelet aggregation, and inducing vasodilation. The effect of FK409 (FK), a spontaneous NO donor, was investigated in a canine lung transplantation model. METHODS Ten pairs of weight-matched dogs were used. Five pairs were assigned to the FK group, to which FK (5 microg/kg/min) was administered intravenously from 30 minutes prior to ischemia until the induction of ischemia in the donor, and from 15 minutes prior to reperfusion until 45 minutes after reperfusion in the recipient. The others were assigned to the control group. After 8-hour preservation in 4 degrees C Euro-Collins solution, orthotopic single-lung transplantation was performed. During a 5-minute clamping test of the right pulmonary artery, left pulmonary arterial pressure (L-PAP), left pulmonary vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar-arterial oxygen pressure difference (A-aDO(2)) were measured. The lung specimens were harvested for histologic study, and polymorphonuclear neutrophils (PMNs) were counted. Pulmonary perfusion and ventilation scintigraphy (Tc-99m-MAA and Xe-133) were performed. RESULTS PAP, L-PVR, PaO(2), and A-aDO(2) revealed significantly (p < 0.05) better function in the FK group than in the control group. Histologically, edema was more mild, and PMN infiltration was significantly (p < 0.05) lower in the FK group than in the control group. Xe-133 and Tc-99m-MAA were widely distributed throughout the graft lung in the FK group. The 2-day survival rate was 100% in the FK group, which was significantly (p < 0.05) better than the rate (40%) in the control group. CONCLUSIONS FK appears to generate a protective effect on I/R injury in lung transplantation.

FR167653 ameliorates pulmonary damage in ischemia-reperfusion injury in a canine lung transplantation model

BACKGROUND Interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) are recognized as important factors in ischemia-reperfusion (I/R) injury. FR167653 has been characterized as a potent suppressant of IL-1 and TNF-alpha production. We previously reported that FR167653 suppressed the expression of IL-1 beta mRNA after reperfusion and ameliorated pulmonary I/R injury following 3-hour left lung warm ischemia in dogs. The aim of this study was to investigate the effects of FR167653 on I/R injury in a canine left, single, lung transplantation model. METHODS We used 10 pairs of weight-matched dogs. We assigned 5 pairs to the FR group, in which each animal received FR167653 (1 mg/kg/hr) IV from 30 minutes before ischemia until 2 hours after reperfusion; we treated the transplanted lungs with FR167653 after the onset of reperfusion. The others were assigned to the control group. After 8-hour preservation with 4 degrees C Euro-Collins solution, orthotopic left, single, lung transplantation was performed. During a 5-minute clamping test at the right pulmonary artery of each recipient, the left (transplanted) pulmonary arterial pressure (L-PAP), left (transplanted) pulmonary vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar-arterial oxygen pressure difference (A-aDO(2)) were measured. We harvested transplanted lung specimens for histologic study, and we counted polymorphonuclear neutrophils (PMNs), which were identified by staining with naphthol AS-D cholroacetate esterase. Pulmonary perfusion and ventilation scintigraphy (Tc-99m-MAA and Xe-133) were performed. We observed the animals for 3 days after transplantation. RESULTS The PAP, L-PVR, PaO(2), and A-aDO(2) revealed significantly (p < 0.05) better function in the FR group than in the control group. Histologically, lung edema was milder, and PMN infiltration was significantly (p < 0.05) lower in the FR group than in the control group. Xe-133 and Tc-99m-MAA were widely distributed throughout the graft lung in the FR group. Three-day survival rates in FR and control groups were 60% and 20%, respectively. CONCLUSIONS FR167653 appears to generate a protective effect on I/R injury in lung transplantation in dogs.

Effect of Lazaroid U-74389G on Pulmonary Ischemia - Reperfusion Injury in Dogs

Lipid peroxidation induced by oxygen free radicals is a contributing factor in ischemia-reperfusion injury. Lazaroid U-74389G (LAZ-G) is a group of new synthetic 21-aminosteroids and inhibits irondependent lipid peroxidation. We investigated the effects of LAZ-G on pulmonary ischemia-reperfusion injury in dogs. Twenty dogs were divided into three groups. In the LAZ-G group (