Tomoki Michida

A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video)

BACKGROUND Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, although it is not widely used in the colorectum because of technical difficulty. OBJECTIVE To examine the current status of colorectal ESDs at specialized endoscopic treatment centers. DESIGN AND SETTING Multicenter cohort study using a prospectively completed database at 10 specialized institutions. PATIENTS AND INTERVENTIONS From June 1998 to February 2008, 1111 colorectal tumors in 1090 patients were treated by ESD. MAIN OUTCOME MEASUREMENTS Tumor size, macroscopic type, histology, procedure time, en bloc and curative resection rates and complications. RESULTS Included in the 1111 tumors were 356 tubular adenomas, 519 intramucosal cancers, 112 superficial submucosal (SM) cancers, 101 SM deep cancers, 18 carcinoid tumors, 1 mucosa-associated lymphoid tissue lymphoma, and 4 serrated lesions. Macroscopic types included 956 laterally spreading tumors, 30 depressed, 62 protruded, 44 recurrent, and 19 SM tumors. The en bloc and curative resection rates were 88% and 89%, respectively. The mean procedure time ± standard deviation was 116 ± 88 minutes with a mean tumor size of 35 ± 18 mm. Perforations occurred in 54 cases (4.9%) with 4 cases of delayed perforation (0.4%) and 17 cases of postoperative bleeding (1.5%). Two immediate perforations with ineffective endoscopic clipping and 3 delayed perforations required emergency surgery. Tumor size of 50 mm or larger was an independent risk factor for complications, whereas a large number of ESDs performed at an institution decreased the risk of complications. LIMITATIONS No long-term outcome data. CONCLUSIONS ESD performed by experienced endoscopists is an effective alternative treatment to surgery, providing high en bloc and curative resection rates for large superficial colorectal tumors.

Endogenous Nitric Oxide Modulates Ethanol-Induced Gastric Mucosal Injury in Rats

BACKGROUND/AIMS Endothelium-derived relaxing factor regulates vascular tone via vasodilation. The relative contribution of endogenous nitric oxide to the pathophysiology of ethanol-induced gastric mucosal microcirculatory disturbances was investigated in anesthetized rats. METHODS Macroscopic and microscopic gastric mucosal damage and gastric mucosal hemodynamics including blood flow and hemoglobin oxygen saturation (ISO2) were assessed by pretreatment with a specific NO synthase inhibitor, N omega-nitro-L-arginine (L-NNA), before and after intragastric administration of ethanol. RESULTS Pretreatment with L-NNA significantly increased macroscopic (7.7-fold) and microscopic damage caused by 30% ethanol. Concurrent administration of L-arginine, but not D-arginine, significantly reduced the increase in mucosal damage. Similar results were obtained with 60% ethanol. Pretreatment with L-NNA decreased both mucosal blood flow and ISO2 in the basal period and enhanced decreases in both mucosal blood flow (2.7-fold) and ISO2 (4.3-fold) induced by 30% ethanol compared with controls. Concurrent administration of L-arginine, but not D-arginine, significantly inhibited the effect of L-NNA on blood flow and ISO2 in the basal period as well as after intragastric administration of 30% ethanol. CONCLUSIONS Endogenous NO modulates ethanol-induced gastric mucosal injury through the regulation of gastric mucosal microcirculation.

SHORT-TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR EARLY GASTRIC NEOPLASM: MULTICENTER SURVEY BY OSAKA UNIVERSITY ESD STUDY GROUP

Background:  Endoscopic submucosal dissection (ESD) was developed for en bloc removal of large and flat gastrointestinal tract neoplasms. In Japan, ESD is performed under conscious sedation. The risks for sedation‐related complications of ESD, such as postoperative pneumonia, have not been evaluated. The aim of this study was to evaluate the incidence of postoperative pneumonia after ESD in a multicenter survey.

Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats

BACKGROUND/AIMS Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators regulating this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1) in hemorrhagic shock-induced gastric mucosal damage in rats. METHODS ET-1 contents in plasma and gastric mucosa were measured and gastric mucosal damage was evaluated during a control period, 60 minutes of ischemia, 15 minutes of reperfusion, and 30 minutes of postreperfusion. Next, effects of BQ-123, an endothelinA receptor antagonist, on the gastric mucosal damage and hemodynamics were studied. RESULTS Both plasma and mucosal ET-1 significantly increased after ischemia and reperfusion compared with the control values, but only mucosal ET-1 continued to increase after reperfusion, leading to the development of gastric mucosal damage. BQ-123, administered just before reperfusion, reduced mucosal damage in the postreperfusion period dose-dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin oxygen saturation during the 30-minute postreperfusion period. CONCLUSIONS These results suggest that endogenous ET-1 plays an important role in the pathogenesis of hemorrhage shock-induced gastric mucosal damage through impairment of mucosal microcirculation. Further, endothelinA antagonists may have therapeutic benefits for shock-induced gastric mucosal damage.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms: a multicenter retrospective cohort study

BACKGROUND AND STUDY AIMS The safety and efficacy of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms (SENs) have not been evaluated in a multicenter survey. The aim of this study was to investigate the clinical outcomes in a multicenter study that included municipal hospitals. PATIENTS AND METHODS Of 312 consecutive patients with 373 esophageal lesions treated by ESD at 11 hospitals from May 2005 to December 2012, a total of 368 SENs in 307 patients were retrospectively analyzed. RESULTS The median tumor size was 18 mm (range 2 - 85 mm). The median procedure time was 90 minutes (range 12 - 450 minutes). The en bloc resection and complete resection rates were 96.7 % (95 % confidence interval [CI] 94.4 % - 98.1 %) and 84.5 % (95 %CI 80.5 % - 87.8 %), respectively. Perforation (including mediastinal emphysema), postoperative pneumonia, bleeding, and esophageal stricture, occurred in 5.2 % (95 %CI 3.3 % - 7.9 %), 1.6 % (95 %CI 0.7 % - 3.5 %), 0 %, and 7.1 % (95 %CI 4.9 % - 10.2 %) of patients, respectively. All of these complications were cured conservatively. No procedure-related mortality occurred. Early treatment periods (odds ratio [OR] = 4.04; P < 0.01) and low volume institutions (OR = 3.03; P  = 0.045) were significantly independent risk factors for perforation. The circumference of the lesion was significantly associated with postoperative stricture (OR = 32.3; P < 0.01). The procedure times significantly decreased in the later period of the study (P < 0.01). Follow-up data (median 35 months; range 4 - 98 months) showed significant differences in overall survival (P = 0.03) and recurrence-free survival (P < 0.01) rates between patients with curative and noncurative resections. CONCLUSIONS Esophageal ESD has become feasible with acceptable complication risks and favorable long term outcomes.

Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C

Abstract: A 57-year-old man had abnormal hepatic function identified in April 1994. In October 1994, chronic hepatitis C was diagnosed. Based on the findings of a liver biopsy, administration of recombinant interferon (rIFN)-α2b was begun. In the 16th week of treatment, the patient experienced headache and fever and developed a markedly decreased, platelet count and hemolytic anemia. He was admitted on May 19, 1995 and thrombotic thrombocytopenic purpura (TTP) was diagnosed. He died on the 3rd hospital day. The causes of TTP have yet to be elucidated, but in this patient the occurrence of TTP appeared to be related to the IFN treatment for chronic hepatitis C.

Gastric ESD under Heparin Replacement at High-Risk Patients of Thromboembolism Is Technically Feasible but Has a High Risk of Delayed Bleeding: Osaka University ESD Study Group

Objectives. Heparin replacement (HR) is often performed in patients with a high risk of thrombosis undergoing endoscopic procedures. However, information about the influence of HR is scarce. The aim of this study is to assess the clinical impact of HR for gastric endoscopic submucosal dissection (ESD). Methods. This is a retrospective study comprising approximately 1310 consecutive gastric neoplasms in 1250 patients, who underwent ESD in 5 institutes. We assessed the clinical findings and outcomes of ESD under HR, compared to ESD without HR as control. Results. A total of 24 EGC lesions in 24 patients were treated by ESD under HR. In the HR group, the complete en-bloc resection rate was 100%. The delayed bleeding rate was, however, higher in the HR group than in the controls (38% versus 4.6%). The timing of bleeding in the HR group was significantly later than in controls. In the control group, 209 patients discontinued antithrombotic therapy during perioperative period, and their delayed bleeding rate was not different from those without antithrombotic therapy (5.7% versus. 4.4%). A thromboembolic event was encountered in 1 patient under HR after delayed bleeding. Conclusion. ESD under HR is technically feasible but has a high risk of delayed bleeding.

Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis

Aim:  Disorders of protein metabolism in liver cirrhosis can affect prognosis or cause complications. Treatment with branched‐chain amino acid (BCAA) and zinc supplements has been shown to be effective against abnormal nitrogen metabolism in liver cirrhosis. There are, however, few studies on the effects of combining these supplements. In this study, the effect of combining BCAA and zinc treatment in cirrhosis was investigated.

Plasma and Gastric Mucosal Endothelin-1 Concentrations in Patients with Peptic Ulcer

Peptic ulcer in the human stomach causeslocalized destruction of the gastric wall, which may beassociated with focal vascular insufficiency.Endothelin-1, an extremely potent vasoconstrictorpeptide, modulates regional blood flow in thevasculature of stomach, suggesting a role forendothelin-1 in peptic ulcer. We examined therelationship among endogenous plasma and mucosalendothelin-1 concentrations and the severity and area of ulcer in 19patients with gastric ulcers and eight healthy adults.Endothelin-1 concentrations were measured by enzymeimmunoassay in plasma and gastric mucosal specimens from ulcer margins, corpus, and antrum. The severityand area of ulcer were assessed endoscopically. Plasmaendothelin-1 concentrations in active (P < 0.01compared with normal) and healing (P < 0.05) stagesof ulcer were significantly greater than those innormal subjects. Plasma endothelin-1 concentrations, butnot mucosal endothelin-1 concentrations in the ulcermargin, were significantly associated with the severity of the ulcer. There was a significantpositive correlation between plasma endothelin-1concentration and area of ulcer (r = 0.70, P < 0.01).In conclusion, locally increased endothelin-1 may be an important mediator contributing to thepathogenesis of peptic ulcer.

ENDOSCOPIC FOLLOW-UP STUDY OF DEVELOPMENT OF GASTRIC ANTRAL VASCULAR ECTASIA ASSOCIATED WITH LIVER CIRRHOSIS

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1–2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickned and extended throughout the antrum, with the complete picture shown in 1.5–5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.