Ryu Ishihara

Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer : A prospective randomized controlled trial

OBJECTIVES:With conventional methods of endoscopic mucosal resection for early gastric cancer (EGC), proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) have a similar effect on preventing bleeding from artificial ulcers. An objective of this study is to investigate whether a stronger acid suppressant (i.e., PPI) more effectively prevents bleeding after the recent advanced technique of endoscopic submucosal dissection (ESD) for EGC.METHODS:This was a prospective randomized controlled trial performed in a referral cancer center. A total of 143 patients with EGC who underwent ESD were randomly assigned to the treatment groups. They received either rabeprazole 20 mg (PPI group) or cimetidine 800 mg (H2RA group) on the day before ESD and continued for 8 wk. The primary end point was the incidence of bleeding that was defined as hematemesis or melena that required endoscopic hemostasis and decreased the hemoglobin count by more than 2 g/dL.RESULTS:In baseline data, the endoscopists who performed the ESD were significantly different between the groups. Finally, 66 of 73 patients in the PPI group and 64 of 70 in the H2RA group were analyzed. Bleeding occurred in four patients in the PPI group and 11 in the H2RA group (P = 0.057). Multivariate analysis revealed that treatment with the PPI significantly reduced the risk of bleeding: adjusted hazard ratio 0.47, 95% confidence interval 0.22–0.92, P = 0.028. One delayed perforation was experienced in the H2RA group.CONCLUSIONS:PPI therapy more effectively prevented delayed bleeding from the ulcer created after ESD than did H2RA treatment.

Longterm outcomes after endoscopic mucosal resection for early gastric cancer

BackgroundDespite the widespread use of endoscopic mucosal resection (EMR) in patients with early gastric cancer (EGC), its longterm outcomes have not been fully evaluated. Our aim was to evaluate longterm survival after complete EMR for EGC.MethodsFrom patients who underwent EMR between 1978 and 1996 at our center, we enrolled 131 patients with differentiated mucosal EGCs less than 2 cm (without ulcerative change) that had been completely removed by EMR. The vital status of the patients at the end of December 1998 was confirmed by the hospital cancer registry, which is linked to the Osaka Cancer Registry.ResultsA total of 124 patients (95%) were completely followed-up. Two patients (1.5%) died of gastric cancer and 26 died of other causes during the mean observation period of 58 months. The overall 5- and 10-year survival rates were 84% and 64%, respectively. The disease-specific 5- and 10-year survival rates were 99% and 99%.ConclusionEn bloc EMR ensured an excellent prognosis, and should be the first choice of treatment in patients with small differentiated mucosal EGC. Careful histological examination and longterm endoscopic surveillance are important.

Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis

PurposeCharacteristics of hepatocellular carcinoma (HCC) complicating nonalcoholic steatohepatitis (NASH) are still controversial. Most NASH related HCCs are believed to develop from cirrhotic liver, but case reports about HCC arising from non-cirrhotic NASH have been accumulating recently. This study is designed to elucidate characteristics of NASH related HCC diagnosed with high accuracy by using surgically resected specimens that contain larger areas to validate than biopsy specimens.MethodsFor this study, 1168 patients who underwent hepatic resection at Osaka Medical Center for Cancer and Cardiovascular Diseases were enrolled. Patients who had clinically obvious causes of chronic liver dysfunction, such as viral and alcoholic hepatitis, were excluded. Histological diagnosis of NASH was confirmed according to Brunt’s criterion.ResultsEight (1%) patients were diagnosed with NASH. Six (75%) of them showed non-cirrhosis in non-cancerous areas. Stages of fibrosis in the non-cirrhotic patients were mild fibrosis (F2) in five and moderate fibrosis (F3) in one. All patients complicated with metabolic diseases. Although all these patients without cirrhosis were evaluated pathologically at tumor-node-metastasis stages I or II, three (50%) had multiple recurrences of tumor within a short time after surgery.ConclusionThis study indicates HCC might arise frequently from non-cirrhotic NASH. While further studies are needed to confirm this observation, both cirrhotic and non-cirrhotic NASH warrant regular screening for HCC.

Endoscopic submucosal dissection for early gastric cancer performed by supervised residents: assessment of feasibility and learning curve *

BACKGROUND AND AIM Endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer (EGC) when it is performed by an experienced endoscopist. We investigated whether it was feasible for novice endoscopists to perform ESD for EGC, and how difficult it was to learn the procedure. METHODS This case series study was performed in a cancer referral center. Three resident endoscopists, who had already learned basic procedures, performed ESD under supervision for 30 consecutive lesions, and their procedures were analyzed. The procedure was divided for assessment into (i) mucosal incision and (ii) submucosal dissection by completion of the circumferential mucosal cut. An insulated-tip knife was used for mucosal incision and submucosal dissection. A total of 90 mucosal EGCs (< or = 2 cm) without ulcers or scars in 87 patients were included. Outcomes were: rates of complete resection, complications, and self-completion; operation time; learning curve; and reasons for change of supervisor as an indicator of difficulty. RESULTS Among the 90 procedures, there was a good overall complete resection rate of 93 %, with an acceptable complication rate of 4.4 %; the complications were delayed hemorrhage in two patients, and perforations in another two patients that were repaired successfully by endoscopic clipping. The self-completion rate and operation time were significantly worse for submucosal dissection than for mucosal incision. Two of the three operators showed a flat learning curve for submucosal dissection. Difficulty with the procedure was related mainly to uncontrollable hemorrhage. CONCLUSIONS With appropriate supervision, gastric ESD by residents is feasible, with equivalent complete resection rates and acceptable complication rates compared with those of experienced endoscopists, although there was difficulty in achieving sufficient self-completion rates in submucosal dissection. Better control of bleeding during submucosal dissection may be a key to improving the procedure.

Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: a controlled prospective study

BACKGROUND AND STUDY AIMS The frequency of stricture after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma with a mucosal defect involving more than three-quarters of the circumference is 70% - 90%. Stricture decreases quality of life and requires multiple endoscopic balloon dilation (EBD) sessions. We investigated the efficacy and safety of a single session of intralesional steroid injections to prevent post-ESD stricture. PATIENTS AND METHODS We conducted a prospective study on 30 patients with esophageal squamous cell carcinoma treated by ESD, who had a more than three-quarter but less than whole circumferential defect. A single session of intralesional steroid injections was undertaken immediately after ESD. Esophagogastroduodenoscopy was performed whenever patients reported dysphagia and 2 months after ESD in patients without dysphagia. Results were compared with a historical control group of 29 patients who underwent ESD without intralesional steroid injection. The primary endpoint was the post-ESD stricture rate. Secondary endpoints were the number of EBD sessions and the complication rate. RESULTS Compared with the historical control group, the study group had a significantly lower stricture rate (10%, 3/30 patients vs. 66%, 19/29 patients; P < 0.0001) and a lower number of EBD sessions (median 0, range 0 - 2 vs. median 2, range 0 - 15; P < 0.0001). The study group had a complication rate of 7 % (2 /30 patients), comprising a submucosal tear in one patient and bleeding in another, which were not a direct result of EBD. CONCLUSIONS A single session of intralesional steroid injections showed promising results for the prevention of stricture after ESD for esophageal cancer.

Efficacy of an Endo-Knife With a Water-Jet Function (Flushknife) for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms

OBJECTIVES:Endoscopic submucosal dissection (ESD) is currently not a common treatment for colorectal neoplasms because it is time consuming and technically difficult. Flushknife—an electrosurgical endo-knife with a water-jet function—is expected to reduce the difficulty of colorectal ESD. The objective of this study was to investigate the efficacy of a water-jet function for colorectal ESD.METHODS:This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. A total of 49 patients, with a total of 51 superficial colorectal neoplasms (median tumor size of 30 mm), were enrolled and randomly assigned to undergo ESD using either the Flexknife (electrosurgical endo-knife without a water-jet function) or the Flushknife. Tumors were resected by ESD using each endo-knife. The procedures were conducted by two endoscopists. Operation time was defined as the main outcome measure.RESULTS:En bloc resection was achieved in 23 out of 26 (88%) lesions in the Flexknife group and in 24 out of 24 (100%) lesions in the Flushknife group. The mean operation time (95% confidence interval) was 87.3 (71.3–103.4) min in the Flexknife group and 61.0 (49.3–72.7) min in the Flushknife group (P=0.02). The Flushknife reduced the number of endoscopic device changes (P=0.001), the number of submucosal injections (P=0.001), and the mean amount of injected hyaluronate sodium (P=0.001) compared with the Flexknife. No severe adverse events were observed in either group.CONCLUSIONS:Without increasing adverse events, the endo-knife with a water-jet function efficiently reduced the operation time of colorectal ESD in patients with large superficial colorectal neoplasms. (University hospital Medical Information Network Clinical Trials Registry number UMIN000001302)

Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

PURPOSE To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. METHODS AND MATERIALS Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. RESULTS Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. CONCLUSION Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

Clinical features and outcomes of delayed perforation after endoscopic submucosal dissection for early gastric cancer

Perforation is a major complication of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). However, there have been no reports on delayed perforation after ESD for EGC. We aimed to elucidate the incidence and outcomes of delayed perforation after ESD. Clinical courses in 1159 consecutive patients with 1329 EGCs who underwent ESD were investigated. Delayed perforation occurred in six patients (0.45 %). All these patients had complete en bloc resection without intraoperative perforation during ESD. Five of six perforations were located in the upper third of the stomach, while one lesion was found in the middle third. Symptoms of peritoneal irritation with rebound tenderness presented within 24 h after ESD in all cases. One patient did not require surgery because the symptoms were localized, and recovered with conservative antibiotic therapy by nasogastric tube placement. The remaining five patients required emergency surgery. There was no mortality in this case series.

Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial

BACKGROUND Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions. OBJECTIVE To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms. DESIGN A 2 × 2 factorial designed, prospective, randomized, controlled trial. SETTING This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center. PATIENTS A total of 561 patients. INTERVENTIONS Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH--colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method. MAIN OUTCOME MEASUREMENT The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups. RESULTS Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93-1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002). LIMITATIONS Open trial performed in single cancer referral center. CONCLUSION AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH.

Long-Term Outcome and Metastatic Risk After Endoscopic Resection of Superficial Esophageal Squamous Cell Carcinoma

OBJECTIVES:Long-term outcomes after endoscopic resection (ER) provide important information for the treatment of esophageal carcinoma. This study aimed to investigate the rates of survival and metastasis after ER of esophageal carcinoma.METHODS:From 1995 to 2010, 570 patients with esophageal carcinoma were treated by ER. Of these, the 402 patients with squamous cell carcinoma (280 epithelial (EP) or lamina propria (LPM) cancer, 70 muscularis mucosa (MM) cancer, and 52 submucosal (SM) cancer) were included in our analysis. Seventeen patients had cancer invading into the submucosa up to 0.2 mm (SM1) and 35 patients had cancer invading into the submucosa more than 0.2 mm (SM2).RESULTS:The mean (range) follow-up time was 50 (4–187) months. The 5-year overall survival rates of patients with EP/LPM, MM, and SM cancer were 90.5, 71.1, and 70.8%, respectively (P=0.007). Multivariate analysis identified depth of invasion and age as independent predictors of survival, with hazard ratios of 3.6 for MM cancer and 3.2 for SM cancer compared with EP/LPM cancer, and 1.07 per year of age. The cumulative 5-year metastasis rates in patients with EP/LPM, MM, SM1, and SM2 cancer were 0.4, 8.7, 7.7, and 36.2%, respectively (P<0.001). Multivariate analysis identified depth of invasion as an independent risk factor for metastasis, with hazard ratios of 13.1 for MM, 40.2 for SM1, and 196.3 for SM2 cancer compared with EP/LPM cancer. The cumulative 5-year metastasis rates in patients with mucosal cancer with and without lymphovascular involvement were 46.7 and 0.7%, respectively (P<0.0001).CONCLUSIONS:The long-term risk of metastasis after ER was mainly associated with the depth of invasion. This risk should be taken into account when considering the indications for ER.