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Background: Previous morphological studies indicated that the eradication of Helicobacter pylori (H. pylori) made gastric neoplasms endoscopically indistinct through the flattening and covering of tumors with a non-neoplastic epithelium (NE)., Aim: To validate these alterations., Methods: We reviewed and compared the endoscopic and histological findings of early gastric carcinomas and high-grade dysplasias resected endoscopically from H. pylori-infected and H. pylori-eradicated patients. The extent of NE covering a tumor was expressed as the histological length ratio of NE to the tumor. Tumor morphology was compared before and after therapies in patients who received H. pylori eradication treatments during the period from tumor discovery to endoscopic resection., Results: NE-covered ratios were higher in the 59 tumors detected after the eradication of H. pylori than in the 152 tumors detected during the infection (median 8 vs. 0 %, respectively), whereas the frequency at which an elevated morphology and whitish discoloration of a tumor were observed was less (14 vs. 56 %, and 14 vs. 43 %, respectively). These were also independent characteristics for tumors detected after the eradication of H. pylori. Two elevated tumors showing whitish discoloration out of 16 tumors became endoscopically indistinct following H. pylori eradication treatments through the flattening of tumors and muting of the discoloration., Conclusion: The eradication of H. pylori promoted covering with NE, the flattening of tumors, and muting of the whitish discoloration, which may make a subset of tumors, potentially including whitish elevated neoplasms, indistinct.

It remains unclear why Barrett esophagus (BE)-associated adenocarcinoma (EAC) frequently occurs in the 0 to 3 o'clock area of the BE. The aims of this study were to clarify the localization of specialized intestinal metaplasia (SIM) as a precancerous lesion and of molecular alterations among different locations using 4-quadrant biopsies based on the "Seattle" protocol. We prospectively evaluated microsatellite instability; methylation status at the APC, CDKN2A, hMLH1, RUNX3, and MGMT genes; the immunoreactivity of the monoclonal antibody Das-1 for the colonic phenotype; and Ki-67 staining in 10 early EACs and 128 biopsy samples from 32 BE patients. Among the molecular changes, only APC gene hypermethylation was an independent predictive marker of EAC (odds ratio, 24.4; P = .01). SIM was more frequently identified in the 0 to 3 o'clock quadrant than in the 6 to 9 o'clock quadrant (P = .08). The Ki-67 index was higher in SIM than in the columnar-lined epithelium (CLE) without goblet cells (P < .0001) and in both SIM and CLE with Das-1 reactivity than in those without (P = .04 and P = .06, respectively). Furthermore, the index was relatively higher in the 0 to 3 o'clock quadrant than in the 6 to 9 o'clock quadrant in cases with Das-1 reactivity. RUNX3 methylation was more frequently found in SIM than in CLE (P = .04), whereas the incidence of the other biomarkers did not show a significant difference between the 0 to 3 o'clock and 6 to 9 o'clock areas, nor between SIM and CLE. SIM with Das-1 reactivity, but not molecular alterations, in the 0 to 3 o'clock quadrant may have higher proliferative activity compared to the other areas of the BE., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To examine the efficacy of non-magnifying narrow-band imaging (NM-NBI) imaging for small signet ring cell carcinoma (SRC)., Methods: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection (ESD) and 14 randomly selected whitish gastric ulcer scars (control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging (WLI) were assessed with Image J (NIH, Bethesda)., Results: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index (P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle (C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs (P = 0.001). According to the receiver-operating characteristic analysis, the resulting cut-off value of the circularity index (C-index) for SRC was 0.60 (85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar (OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009)., Conclusion: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.

Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of β-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA.

Background: The number of cases of metastatic colorectal cancer treated by chemotherapy without primary tumor resection has recently increased. However, evaluation of primary tumor response by computed tomography is difficult in such cases. In this study, the usefulness of evaluation of primary tumor response to chemotherapy by endoscopy was investigated., Methods: This retrospective analysis was performed at the Shizuoka Cancer Center and included 31 patients (88 evaluations) with metastatic colorectal cancer. Computed tomography and endoscopy were performed concomitantly between September 2002 and June 2006. Patients were treated by systemic chemotherapy without prophylactic primary tumor resection. Definitions of primary tumor response were as follows: (1) complete response, confirmed by colorectal biopsy; (2) progressive disease, enlargement of at least one of five tumor parameters; and (3) neither (1) nor (2). Computed tomography was performed to evaluate primary tumor response according to the Response Evaluation Criteria in Solid Tumors and to identify colorectal stenosis secondary to primary tumors., Results: The rate of concordance between endoscopy and computed tomography for evaluation of primary tumor response was 75%. Colorectal stenosis was detected 14 times by endoscopy (9 cases) and 3 times by computed tomography (3 cases). Of the 7 patients in whom surgery was required, 6 exhibited stenotic symptoms before endoscopic detection., Conclusions: With regard to primary tumor response evaluation, a high concordance rate was observed between endoscopy and computed tomography, although endoscopic evaluation appeared more sensitive in detecting colorectal stenosis requiring surgical treatment.

Aim: To evaluate clinical outcomes and risk factors for endoscopic perforation during endoscopic submucosal dissection (ESD) in a prospective study., Methods: We investigated the clinical outcomes and risk factors for the development of perforation in 98 consecutive gastric neoplasms undergoing ESD regarding. Demographic and clinical parameters including patient-, tumor-, and treatment-related factors, clinical parameters, and duration of hospital stay were analyzed for risk factors for perforation. In subgroup analysis, we also compared the clinical outcomes between perforation and "silent" free air without endoscopically visible perforation detected only by computed tomography., Results: Perforation was identified in 8.2% of patients. All patients were managed conservatively by the administration of antibiotics. The mean procedure time was significantly longer in patients with endoscopic perforation than in those without. According to the receiver-operating characteristic analysis, the resulting cutoff value of the procedure time for perforation was 115 min (87.5% sensitivity, 56.7% specificity). Prolonged procedure time (≥ 115 min) was associated with an increased risk of perforation (odds ratio 9.15; 95%CI: 1.08-77.54; P = 0.04). Following ESD, body temperature and C-reactive protein level were significantly higher in patients with perforation than in those without (P = 0.02), whereas there was no difference between these patient groups on the starting day of oral intake or of hospitalization. In subgroup analysis, the post-ESD clinical course was not different between endoscopic perforation and silent free air., Conclusion: Only prolonged procedure time (≥ 115 min) was significantly associated with perforation. The clinical outcomes of perforation are favorable and are comparable to those of patients with or without silent free air.

We report a case of multiple flat adenomas and cancer of the rectum that occurred 15 years after pelvic irradiation following surgery for uterine cancer. Adenoma borders were diagnosed accurately by magnifying chromoendoscopy, leading to their adequate excision using endoscopic submucosal dissection. This enabled minimal dissection of the irradiated pelvis that would have otherwise been difficult. Furthermore, our approach probably helped minimize loss of bowel function, thereby preserving the patient's quality of life as much as possible. Pathology of the resected specimens revealed thickened walls of the submucosal layer vessels, indicating chronic radiation proctitis. Pelvic irradiation of the bowel carries a high risk of causing flat adenomas and cancer. Close and long-term surveillance may be useful in such cases, using not only conventional colonoscopy but also chromoendoscopy with indigo carmine dye spray and magnifying endoscopy.

Background and Aims: The change of therapeutic strategy for large colorectal tumors after the introduction of endoscopic submucosal dissection (ESD) has not yet been clarified. The aim of this study was to estimate the impact of ESD as an initial treatment strategy., Methods: A questionnaire was administered to nine expert panelists in colorectal ESD. The questionnaire used retrospective data from consecutive case series. Forty-seven cases of early colorectal tumors (≥ 20 mm) were included. Endoscopic growth types were 25 laterally-spreading tumors (LST) of granular type (G), 15 LST of non-granular types (NG), and seven protruded types. Pathological diagnoses included 15 adenomas (Ad), 18 intramucosal cancers (M), three submucosally-shallow invasive cancers (< 1000 µm) (SMs), and 11 submucosally-deep invasive cancers (≥ 1000 µm) (SMd). The expert panelists completed questionnaires about recommended initial treatment under suppositions of before and after the introduction of ESD. Over-surgery was defined as surgery for Ad, M, and SMs. Non-curative endoscopic resection (ER) was defined as ER for SMd., Results: After the introduction of ESD, the reduction in the over-surgery rate was estimated at 10.8% for Ad, M, and SMs, and the increase in the non-curative ER rate was estimated at 27.2% for SMd. By endoscopic growth type, the reduction of over-surgery rates for LST-NG, LST-G, and protruded type was 15.5%, 10.5%, and 2.2%, respectively., Conclusions: The endoscopists changed their therapeutic strategy for large colorectal tumors to reduce over-surgery, especially in LST-NG, demonstrating the impact of ESD., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aims: Early colorectal cancer (CRC) with submucosal deep (s.m.-d.) invasion should not be treated with endoscopic mucosal resection due to the higher incidence of lymph-node metastasis. It is, therefore, clinically important to accurately diagnose s.m.-d. lesions before treatment., Methods: We analyzed the endoscopic features, including pit patterns, of early CRC with s.m.-d. invasion observed using magnifying colonoscopy. We retrospectively investigated 379 cases of early CRC. Lesions were divided into three macroscopic subtypes (pedunculated type, sessile type and superficial type) based on endoscopic findings. Eight endoscopic factors were evaluated retrospectively for association with s.m. invasion and then compared to histopathological findings., Results: The superficial type had a significantly higher frequency of s.m.-d. invasion (52.4% [77/147] vs 24.6% [14/57] and 39.4% [69/175], P-value < 0.05, respectively, for pedunculated and sessile types). Based on multivariate analysis, an independent risk factor for s.m.-d. invasion was the existence of an invasive pit pattern in sessile and superficial types (odds ratios of 52.74 and 209.67, respectively). Fullness was also an independent risk factor for s.m.-d. invasion in the superficial type (odds ratio = 9.25). There were no independent risk factors for s.m.-d. invasion in the pedunculated type., Conclusion: High magnification pit pattern diagnosis proved to be useful for predicting s.m.-d. invasion in sessile and superficial types although it was not as helpful with the pedunculated type.

A 73-year-old woman was referred to our hospital complainting of swelling of both eyelids and submandibular glands, nausea, and weight loss. She was given a diagnosis of autoimmune pancreatitis because of a marked elevation of serum IgG and IgG4 levels and diffuse swelling of the pancreas with stenosis of the main pancreatic duct. Biopsy obtained from the lachrymal gland revealed aggregated IgG4-positive plasma cells, leading to the diagnosis of Mikulicz's disease. PET-CT revealed an accumulation of FDG in the pancreas, lachrymal glands and submandibular glands, and lymph nodes in the mediastinum, hepatic hilium, bile duct and retroperitoneum. Three months after the initiation of steroid therapy, the serum levels of IgG and IgG4 decreased and FDG accumulations of the systemic lesions were no longer visible on PET.

Background and Aims: Endoscopic submucosal dissection (ESD) has recently been applied to the treatment of superficial colorectal cancer. Clinical outcomes compared with conventional endoscopic mucosal resection (EMR) have not been determined so our aim was to compare the effectiveness of ESD with conventional EMR for colorectal tumors >or=20 mm., Methods: This was a retrospective case-controlled study performed at the National Cancer Center Hospital in Tokyo, Japan involving 373 colorectal tumors >or=20 mm determined histologically to be curative resections. Data acquisition was from a prospectively completed database. We evaluated histology, tumor size, procedure time, en bloc resection rate, recurrence rate, and associated complications for both the ESD and EMR groups., Results: A total of 145 colorectal tumors were treated by ESD and another 228 were treated by EMR. ESD was associated with a longer procedure time (108 +/- 71 min/29 +/- 25 min; p < 0.0001), higher en bloc resection rate (84%/33%; p < 0.0001) and larger resected specimens (37 +/- 14 mm/28 +/- 8 mm; p = 0.0006), but involved a similar percentage of cancers (69%/66%; p = NS). There were three (2%) recurrences in the ESD group and 33 (14%) in the EMR group requiring additional EMR (p < 0.0001). The perforation rate was 6.2% (9) in the ESD group and 1.3% (3) in the EMR group (p = NS) with delayed bleeding occurring in 1.4% (2) and 3.1% (7) of the procedures (p = NS), respectively, as all complications were effectively treated endoscopically., Conclusions: Despite its longer procedure time and higher perforation rate, ESD resulted in higher en bloc resection and curative rates compared with EMR and all ESD perforations were successfully managed by conservative endoscopic treatment.

Background and Aim: An autofluorescence imaging (AFI) videoendoscope system produces pseudo-color images combining autofluorescence and green reflectance, with the utility of this system previously confirmed for the diagnosis of bronchial squamous cell carcinoma (SCC). Our aim was to evaluate visualization of esophageal and pharyngeal SCC comparing AFI with white light endoscopy (WLE)., Methods: Thirty-two patients with superficial esophageal SCC and 11 patients with superficial pharyngeal SCC diagnosed in other hospitals were enrolled in this prospective study. We observed the esophagus and pharynx with WLE followed by AFI and took both WLE and AFI images of the esophageal and pharyngeal SCC. Three experienced endoscopists subsequently evaluated the visualization quality of images from both systems on a three-tier scale: visible, illegible and invisible., Results: A total of 39 superficial esophageal SCC were diagnosed with 20, 11 and eight lesions classified as visible, illegible and invisible, respectively, by WLE compared to 31, three and five lesions, respectively, using AFI. Using AFI, 79% of superficial esophageal SCC lesions were visible, compared to only 51% with WLE (P < 0.05). In addition, 12 superficial pharyngeal SCC were diagnosed with four, five and three lesions considered as visible, illegible and invisible, respectively, using WLE in contrast to nine, three and 0 lesions, respectively, by AFI. Thus, using AFI, 75% of superficial pharyngeal SCC lesions were visible compared with only 33% with WLE (P = 0.13)., Conclusion: The AFI system appears to be more useful than WLE for early diagnosis of SCC of the esophagus and pharynx.

Background: Pancreatitis is the most common and serious complication to occur after endoscopic retrograde cholangiopancreatography (ERCP). It is often associated with additional diagnostic modalities and/or treatment of obstructive jaundice. The aim of this study was to determine the risk of post-ERCP pancreatitis associated with pancreaticobiliary examination and endoscopic biliary drainage (EBD)., Methods: A total of 740 consecutive ERCP procedures performed in 477 patients were analysed for the occurrence of pancreatitis. These included 470 EBD procedures and 167 procedures to further evaluate the pancreaticobiliary tract using brush cytology and/or biopsy, intraductal ultrasound and/or peroral cholangioscopy or peroral pancreatoscopy. The occurrence of post-ERCP pancreatitis was analysed retrospectively., Results: The overall incidence of post-ERCP pancreatitis was 3.9% (29 of 740 procedures). The risk factors for post-ERCP pancreatitis were: being female (6.5%; odds ratio [OR] 2.5, P= 0.02); first EBD procedure without endoscopic sphincterotomy (ES) (6.9%; OR 3.0, P= 0.003), and performing additional diagnostic procedures on the pancreatobiliary duct (9.6%; OR 4.6, P < 0.0001). Pancreatitis after subsequent draining procedures was rare (0.4%; OR for first-time drainage 16.6, P= 0.0003). Furthermore, pancreatitis was not recognized in 59 patients who underwent ES. Seven patients with post-EBD pancreatitis were treated with additional ES., Conclusions: Invasive diagnostic examinations of the pancreaticobiliary duct and first-time perampullary biliary drainage without ES were high-risk factors for post-ERCP pancreatitis. Endoscopic sphincterotomy may be of use to prevent post-EBD pancreatitis.

Background: In Japan, endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed by endoscopists on patients under sedation. There is an increased risk of anesthesia-related complications due to the higher sedative doses required during lengthier ESDs, so we sought to determine whether a local pain control method could safely reduce such doses., Methods: Twenty EGC patients enrolled in this study received local lidocaine injections during ESDs at our hospital (lidocaine group; LG). Electrocardiography, heart rate, oxygen saturation, and blood pressure were monitored during and after the ESDs, along with the doses of midazolam and pentazocine. Pain assessments were recorded for LG patients on the day of their ESDs and the following day., Results: The mean volume of lidocaine injection solution was 55.4 ml and the mean dose of lidocaine was 236 mg (range, 100-300 mg). The mean size of the resected specimens was 39.3 mm and mean procedure time was 66.0 min. There were no lidocaine-related complications, and electrocardiography, heart rate, oxygen saturation and blood pressure measurements were normal. In comparison to 157 consecutive patients (control group; CG), who had similar characteristics and had undergone ESDs previously with submucosal injections of conventional normal saline solution, the mean +/- SD pentazocine dose of 15.8 +/- 10.3 mg in the LG was significantly lower (P < 0.01) than the dose of 23.1 +/- 9.5 mg in the CG, and none of the LG patients complained of abdominal pain on the day of their ESDs, whereas such pain was reported by 17% (27/157) of the CG., Conclusion: Local lidocaine injections into the submucosal layer were safe when administered during ESDs performed on EGC patients under sedation.