Hideaki Ritsuno

Process of wound healing of large mucosal defect areas that were sutured by using a loop clip–assisted closure technique after endoscopic submucosal dissection of a colorectal tumor

3. van Boeckel PG, Dua KS, Weusten BL, et al. Fully covered self-expandable metal stents (SEMS), partially covered SEMS and self-expandable plastic stents for the treatment of benign esophageal ruptures and anastomotic leaks. BMC Gastroenterol 2012;12:19. 4. van Boeckel PG, Sijbring A, Vleggaar FP, et al. Systematic review: temporary stent placement for benign rupture or anastomotic leak of the oesophagus. Aliment Pharmacol Therap 2011;33:1292-301. 5. van Heel NC, Haringsma J, Spaander MC, et al. Short-term esophageal stenting in the management of benign perforations. Am J Gastroenterol 2010;105:1515-20. 6. Dan DT, Gannavarapu B, Lee JG, et al. Removable esophageal stents have poor efficacy for the treatment of refractory benign esophageal strictures (RBES). Dis Esophagus. Epub 2012 Nov 2.

Asymptomatic anisakiasis of the colon incidentally found by colonoscopy

Asymptomatic anisakiasis of the colon is a rare condition that is difficult to diagnose. A 42-year-old man with no symptoms was referred to our department because of elevated serum carcinoembryonic antigen (CEA) levels detected previously at another hospital. A colonoscopy was performed to find the reason for these elevated CEA levels, and Anisakis larvae were identified by chance in the ascending colon wall. This is only the fourth case of asymptomatic anisakiasis of the colon to be reported worldwide.

The 'Loop Clip' is useful for closing large mucosal defects after colorectal endoscopic submucosal dissection: a preliminary clinical study.

Endoscopic submucosal dissection (ESD) is applied for the treatment of large early-stage superficial colorectal cancers. Bleeding and perforation are common complications of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Metallic clips have been used for endoscopic closure of mucosal defects to reduce the risk of these complications, but they can only be used for small defects even though the presence of large mucosal defects increases the risk of complications. Some cases of delayed perforations after ESD require surgical treatment. To overcome such complications, we developed a simple technique using a new closure device named the ‘Loop Clip’ that can close large mucosal defects following ESD (Fig. 1). However, the number of cases in that report was small. We report a greater number of cases and provide in-depth data. After we obtained assent and written informed consent from the patients who were thought to be high risk, such as patients who required continual anticoagulant therapy, 28 patients (19 men, nine women; median age 70.3 years) with 28 flat-type colorectal tumors (right colon 20, left colon two, rectum six) larger than 20 mm in diameter with using loop clip-assisted method after ESD were studied. The exclusion criteria were tumors suspicious of submucosal massive invasive cancers. Using the loop clip was approved by Juntendo University Institutional Review Board. Mean tumor size in these patients was 30.6 8.0 mm. Mean procedure time was 13.1 7.2 min. Closure was achieved in all cases at any location (Fig. 2). Complete closure without residual ulcer was achieved in 83.3% (20/24), which were smaller than 40 mm in tumor size. These preliminary results suggest that the loop clip-assisted method is useful for closure of large mucosal defects at any location. Only one delayed bleeding (3.6%) occurred in the patient who received anticoagulant therapy during this procedure

Continuation of antithrombotic therapy may be associated with a high incidence of colonic post-polypectomy bleeding

Post‐polypectomy bleeding (PPB) is the most common complication of endoscopic procedures. To reduce the risk of thromboembolic incidents, Japanese guidelines for gastroenterological endoscopy were revised to indicate that antithrombotic agents were not to be discontinued for endoscopic treatment. However, carrying out endoscopic procedures under antithrombotic medication potentially increases the incidence of hemorrhagic complications. The present study investigated the impact of the revised guidelines on the frequency of complications after colonoscopic procedures.

Histological Distinction between the Granular and Nongranular Types of Laterally Spreading Tumors of the Colorectum.

Colorectal laterally spreading tumors (LSTs), which are classified into granular (LST-G) and nongranular (LST-NG) types, are a good indication for endoscopic treatment. In practice, the nongranular type is more difficult to remove endoscopically than the granular type. It might be assumed that some histological differences exist between these subtypes. The objective of this study was to analyze histological features of laterally spreading tumors and compare between the granular and the nongranular types. A total of 32 cases of LSTs resected endoscopically being intramucosal tumors with no previous treatment were analyzed. The disposition of the muscularis mucosae, the vascular density, and the degree of fibrosis of the submucosal layer were determined. The outline of the muscularis mucosae in LST-NG was almost flat, but that of LST-G was wavy. The submucosal vascular density was significantly greater in the LST-NGs (61.4 ± 24.3/mm2) than in the LST-Gs (43 ± 22.4/mm2; P = 0.033). There was no clear difference in the degree of submucosal fibrosis between the subtypes. A flat disposition of the muscularis mucosae and a more densely vascularized submucosal layer were characteristics of LST-NGs compared to the LST-Gs. These findings may play a role when performing the endoscopic resection of LSTs.

Increasing Use of Colonoscopy Over a Decade has Detected an IncreasedPrevalence of Colorectal Tumors on the Elderly

Objective: The advancement of endoscopic technology has brought an increase in colonoscopic examinations. We analyzed the change in the prevalence of colorectal tumors in elderly patients (80 years or older) over a decade. Method: A total of 10,516 patients who were admitted to our hospital for colonoscopic examinations from 2009 to 2011 (recent period) were analyzed and compared with 8,767 historical cases from 1999 to 2001 (prior period). The proportion of patients who were elderly, reason for colonoscopy, completion rate and detection of tumors were analyzed in each period. Results: The rate of elderly patients significantly increased from 2.86% in the prior period to 5.40% in the recent period (p<0.001). As to the reasons for colonoscopy, a double-contrast barium enema X-ray study suggestive of colorectal carcinoma significantly decreased from 6.4% to 1.1% (p<0.001) and screening studies in the elderly significantly increased from 12.7% to 25.2% (p<0.001). The completion rate in the elderly improved (prior period 87.2%, recent period 93.59%, p=0.005). The detection of colorectal tumors was significantly higher in elderly (47.5%) than in non-elderly patients (37.3%, p<0.001) and the proportion of elderly with colorectal adenoma significantly increased from 2.95% in the prior period to 6.54% in the recent period (p<0.001). However, the detection rate of tumors in the elderly significantly decreased over a decade (prior period 54.2%, recent period 47.5%, p<0.001). Conclusions: The proportion of the elderly population is increasing with increasing frequency of colonoscopic examinations performed. Extra care might be required when performing endoscopic examination in the elderly

Sa1986 Clinicopathologic Characteristics and Molecular Associations of Wnt/β-Catenin Signal in the Serrated Neoplasia Pathway of the Colorectum

Background: Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the serrated neoplasia pathway leading to colorectal cancer with high levels of microsatellite instability. Recent studies have shown associations of SSA/P with predominance of proximal colon, MLH1 methylation, a CpG island methylator phenotype, and BRAF mutations. However, clinicopathlogical features of SSA/P with dysplasia or carcinoma remain unclear, and potential roles ofWNT/β-catenin signaling in serrated lesions are still controversial.Materials and methods: The materials for our study were 144 colorectal lesions, including 29 SSA/ Ps, 22 SSA/Ps with high-grade dysplasia and 13 SSA/Ps with submucosal carcinoma, as well as 29 conventional adenomas, 26 adenomas with high-grade dysplasia and 25 adenomas with submucosal carcinoma.We studied clinicopathological features of each group, including patient age, sex, location, macroscopic type, and tumor size, and performed β-catenin immunostaining, methylation specific PCR for MLH1 and WNT signaling associated genes such as AXIN2, APC,MCC and secreted frizzled-related proteins (SFRPs), and direct sequencing of BRAF/KRAS in all cases. Results: There was no difference in the age and sex distribution across each group of patients. SSA/P series were significantly located in the proximal colon compared with adenoma series (P < 0.001). SSA/P with high-garde dysplasia and submucosal carcinoma were significantly smaller in size than the corresponding adenoma counterparts. Immunohistochemically, nuclear β-catenin labelings were significantly lower in the serrated series than in their adenoma counterparts, and a significant increment in those labelings was found from SSA/P to SSA/P with high-grade dysplasia or submucosal carcinoma. In addition, their labelings were most prominent in the lower crypt zone in all SSA/P categories. The frequency of MLH1 methylation was significantly higher in SSA/P series, as compared to corresponding adenoma series. Similar trends were found in the frequency of SFRP4 methylation. AXIN2 and MCC were more frequently methylated in SSA/P with high-grade dysplasia and SSA/P with submucosal carcinoma than in adenoma counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/P through SSA/P with high-grade dysplasia to SSA/P with submucosal carcinoma. Interestingly, a significant correlation was seen between nuclear β-catenin expression and methylation of AXIN2 or MCC in the SSA/P series (P < 0.001, respectively). BRAF mutation was more frequent, while KRAS mutation was less frequent in the SSA/P series as compared to the adenoma series. Conclusions: The serrated neoplasia pathway showed distinct clinicopathologic features, a high frequency of MLH1 methylation, and different WNT/β-catenin signal activation patterns, compared to conventional adenoma-carcinoma sequence.

Advanced colorectal cancer with double-hump camel-like appearance.

Recently, various shapes of colorectal epithelial tumors have been found, although submucosal tumor (SMT)-like epithelial tumors are extremely rare. We report here a case of SMT-like colonic cancer with a ‘double-hump camel’-like appearance. A 58-year-old man underwent colonoscopy because of a positive fecal occult blood test. Endoscopic examination revealed a tumor with a ‘double-hump camel’like appearance, in which each of the ‘humps’ was approximately 10 mm in diameter. The ‘hump’ on the oral side was reddish in color and well circumscribed. The connecting ‘hump’ on the anal side was a smooth-surfaced protrusive lesion, indicating that the lesion was covered by normal mucosa like an SMT (Fig. 1). Laparoscopy-assisted colectomy was carried out with curative intent because endoscopic ultrasonography diagnosed this tumor as a deeply invasive cancer. Macroscopically, the tumor had a broad-based appearance measuring 22 ¥ 12 mm in size. Histological findings revealed that a well-differentiated tubular adenocarcinoma had invaded into the muscularis propria on the oral side, and that the SMT-like lesion on the anal side represented cystic dilatation of a tumor gland with a mucinous carcinoma component invading into the subserosa (Fig. 2). Advanced colorectal carcinoma resembling SMT is very rare. Nakajima et al. described the characteristics of this lesion from an analysis of 24 cases of SMT-like carcinoma. They stated that a central depression of the tumor was found endoscopically in 22 out of 24 cases. However, no central depression was observed in the present case. In line with our case, 15 of the 24 tumors had invaded into the muscularis propria or deeper and one case had a mucinous carcinoma component in the submucosa. Of note is the fact that 31% of mucinous carcinomas are associated with villous adenomas, implying a histogenetic relationship. This fact supports that in our case a well-differentiated tubular adenocarcinoma had transformed into a mucinous-type carcinoma in the submucosa. Invasive mucinous carcinoma component had grown expansively towards the anal side, resulting in the ‘double-hump camel’-like SMT.