A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

BACKGROUND: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). METHODS: EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50 years) and intervals (2/5/10 years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. RESULTS: Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45 years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20 mm in size, and the deep submucosal invasion rate was less than 30%. CONCLUSIONS: A mathematical simulation model revealed that screening every 5 years starting at 45 years of age could efficiently assist in identifying HpNGNs at an early stage.

[Malignant lymphoma diagnosed by gallbladder wall thickness in an autoimmune hepatitis patient].

A 77-year-old female patient was undergoing steroid treatment for cirrhosis with autoimmune hepatitis. Periodic imaging acquisitions revealed both irregular gallbladder wall thickness and an isovascular tumor in segment one of the liver. After cholecystectomy and segmental hepatectomy, the pathological diagnosis was diffuse large B-cell lymphoma in both organs. Accordingly, she received chemotherapy but the disease rapidly spread;she died five months after surgery. Malignant lymphoma of the gallbladder is an uncommon disease;we consider that autoimmunity factors were associated with this pathogenesis.

Tip-in endoscopic mucosal resection for large colorectal sessile polyps.

BACKGROUND: Tip-in endoscopic mucosal resection (EMR) is a modified EMR technique using which en bloc resection of large colorectal sessile polyps can be performed; however, its usefulness for colorectal sessile polyps of > 20 mm has not been reported. This study examined treatment outcomes of tip-in and conventional EMR for large colorectal sessile polyps of ≥ 20 mm. METHODS: This was a retrospective case-control study conducted at a single tertiary center in Japan. Subjects included those with large colorectal sessile polyps of ≥ 20 mm, excluding pedunculated-type polyps, who underwent endoscopic resection between January 2010 and January 2019. The primary outcome was endoscopic treatment outcomes when using tip-in and conventional EMR, and the secondary outcome was the local recurrence rate after endoscopic treatment. RESULTS: Forty-three colorectal lesions were treated using tip-in EMR and 83 using conventional EMR. Tip-in EMR had a significantly higher en bloc resection rate (90.7% vs. 69.8.%), and significantly shorter treatment duration (6.64 ± 0.64 min vs. 10.47 ± 0.81 min) than conventional EMR. However, for lesions > 30 mm, en bloc resection rate was 50.0% and 52.6% for tip-in and conventional EMR, respectively, indicating no significant difference. Perforation rates with tip-in and conventional EMR were 4.6% and 3.6%, respectively, indicating no significant difference. Local recurrence was examined in 80 cases who were followed up for > 6 months after endoscopic resection; recurrence rate was 0% and 7.0% in tip-in and conventional EMR cases, respectively, without significance difference. CONCLUSIONS: Tip-in EMR showed high en-block resection rate, particularly in polyps of < 30 mm, and no residual tumor was found. This technique is a potential endoscopic treatment alternative for large colorectal sessile polyps of ≥ 20 mm.

Endoscopic small-capacity forceps increase the pathological diagnosis of gastric indefinite neoplasia.

BACKGROUND/AIMS: A definitive biopsy-based diagnosis of gastric cancer is sometimes difficult, and some cases are pathologically diagnosed as gastric indefinite neoplasia (GIN). The most appropriate forceps size for gastric biopsy has yet to be determined. In this study, we investigated the relation between the forceps size and the frequency of GIN diagnosis. MATERIALS AND METHODS: The records of patients from two historical groups were reviewed. The first group comprised patients evaluated during the period when standard biopsy forceps (StF) were used (April 2010-March 2011), and the second group comprised patients evaluated during the period when small biopsy forceps (SmF) were used (April 2011-March 2013). Patients in whom GIN lesions were diagnosed with biopsy were identified, and pertinent data were compared between the two groups of patients. RESULTS: Among the 8,420 patients who underwent esophagogastroduodenoscopy (EGD) during the first period, 2,584 (30.7%) underwent gastric biopsy with StF. Among the 15,968 patients who underwent EGD during the second period, 4,204 (26.3%) underwent gastric biopsy with SmF. GIN was diagnosed in a significantly greater number of patients in the SmF group than in the StF group (52 [1.25%] vs. 19 [0.73%]; p=0.048). The mean minor-axis lengths of the biopsy samples were 1.50±0.50 mm and 1.38±0.40 mm in the StF group and the SmF group, respectively, with the SmF group samples tending to be shorter (p=0.088). CONCLUSION: Because the SmF use may increase the rate of GIN diagnosis, the use of SmF with a standard-caliber endoscope should be avoided.

Successful endoscopic fragmentation of large hardened fecaloma using jumbo forceps.

We present a rare case of fecaloma, 7 cm in size, in the setting of systemic scleroderma. A colonoscopy revealed a giant brown fecaloma occupying the lumen of the colon and a colonic ulcer that was caused by the fecaloma. The surface of the fecaloma was hard, large and slippery, and fragmentation was not possible despite the use of various devices, including standard biopsy forceps, an injection needle, and a snare. However, jumbo forceps were able to shave the surface of the fecaloma and break it successfully by repeated biting for 6 h over 2 d. The ability of the jumbo forceps to collect large mucosal samples was also appropriate for achieving fragmentation of the giant fecaloma.

Twelve-year natural history of a gastric adenocarcinoma of fundic gland type.

A 77-year-old woman underwent an upper gastrointestinal (UGI) endoscopy screening examination, and a 10-mm reddish, submucosal tumor-like lesion was found on the posterior wall of the fornix. Biopsy was performed, but there was no evidence of malignancy, so annual follow-up by UGI endoscopy was decided upon. After 12 years, examination of another biopsy specimen revealed an adenocarcinoma of the fundic gland type. There had been no significant change in the size or shape of the lesion over the long follow-up period. Endoscopic submucosal dissection (ESD) was performed, and en bloc resection was achieved. Histopathologically, the tumor appeared as a flat elevated lesion measuring 11 × 10 mm. It was composed of irregularly shaped glands and invaded the submucosa up to 300 µm. Immunohistochemical examination involving specific antibodies to pepsinogen I, MIST-1, MUC6, and H+/K+-ATPase confirmed the fundic gland differentiation of the irregularly shaped glands together with a very low Ki-67 labeling index. Thus, gastric adenocarcinoma of the fundic gland type (GAFG) was diagnosed. Four years have passed since the ESD, and there has been no recurrence. To the best of our knowledge, this is the first report of the long-term natural history of GAFG. Over the 12 years, no morphologic changes were observed; the tumor remained within the submucosal layer. Our observations in this case strengthen the notion that GAFG is a specific type of gastric adenocarcinoma of low-grade malignancy.

[Detection of early gastric cancer facilitated by surveillance for a pyogenic liver abscess caused by Streptococcus intermedius].

We report a case of early gastric cancer that was detected during surveillance of a pyogenic liver abscess caused by Streptococcus intermedius, an oral microbiota. Treatment with proton pump inhibitors can result in the alteration of gastric bacterial flora by altering intragastric acidity. This can place immunocompromised patients, such as those with diabetes mellitus and the elderly, at an increased risk for disease of the upper gastrointestinal tract to be a route of bacterial transmission. In this case, the patient developed a pyogenic liver abscess.

Hemostasis Achieved Endoscopically for Diverticular Bleeding from the Horizontal Portion of the Duodenum.

Diverticulum of the horizontal portion of the duodenum is a rare cause of upper gastrointestinal (GI) bleeding. Since it is difficult to access the horizontal portion of the duodenum by standard upper GI endoscopy, only a very few cases of endoscopic hemostasis have been reported. Herein, we report a case of diverticular bleeding from the horizontal portion of the duodenum for which hemostasis was achieved using a small-caliber colonoscope, which has an insertion part designed with a passive-bending function/high-force transmission and a transparent tip hood.

Enteral metallic stenting by balloon enteroscopy for obstruction of surgically reconstructed intestine.

We present three cases of self-expandable metallic stent (SEMS) placement using a balloon enteroscope (BE) and its overtube (OT) for malignant obstruction of surgically reconstructed intestine. A BE is effective for the insertion of an endoscope into the deep bowel. However, SEMS placement is impossible through the working channel, because the working channel of BE is too small and too long for the stent device. Therefore, we used a technique in which the BE is inserted as far as the stenotic area; thereafter, the BE is removed, leaving only the OT, and then the stent is placed by inserting the stent device through the OT. In the present three cases, a modification of this technique resulted in the successful placement of the SEMS for obstruction of surgically reconstructed intestine, and the procedures were performed without serious complications. We consider that the present procedure is extremely effective as a palliative treatment for distal bowel stenosis, such as in the surgically reconstructed intestine.

Urgent computed tomography for determining the optimal timing of colonoscopy in patients with acute lower gastrointestinal bleeding.

OBJECTIVE: We evaluated the diagnostic performance of computed tomography (CT) as an initial radiologic test for assessing the optimal timing of colonoscopy in patients with acute lower gastrointestinal bleeding (LGIB) and investigated the effectiveness of contrast-enhanced (CE) CT for detecting colonic diverticular bleeding. METHODS: This was a retrospective study of 1,604 consecutive patients who visited or were referred to St. Marianna University Hospital due to acute LGIB and underwent colonoscopy within three months after presentation between September 2004 and December 2012. The clinicopathological data of the subjects were obtained from their medical records. RESULTS: Among the 1,604 patients presenting with LGIB, 879 (55%) underwent a CT scan. Elective colonoscopy was considered in cases in which typical colonic wall thickening was observed on CT, suggesting colonic inflammation or malignancy (239 patients; 27%). The diagnoses in the elective cases included ischemic colitis (38%), infectious colitis (8%), inflammatory bowel disease (8%) and malignancy (5%). Urgent colonoscopy was performed after the CT examination in 640 cases (73%). The most common presumptive CT diagnosis was diverticulum (402/640; 63%). Of the 638 patients who underwent CE-CT, diverticula were observed in 346 cases, including 104 cases of extravasation indicating ongoing diverticular bleeding. Among these 104 patients, the site of bleeding was identified in 71 subjects (68%) during colonoscopy. The rate of detection of the bleeding source on colonoscopy was significantly higher in the patients with extravasation on CE-CT than in those without extravasation on CE-CT (68% vs. 20%, respectively; p<0.001). CONCLUSION: Urgent CT is useful for determining the optimal timing of colonoscopy in cases of acute LGIB. CE-CT may be used to depict the presence and location of active hemorrhage and provides useful information for subsequent colonoscopy, especially in patients with diverticular bleeding.

Endoscopic retrograde cholangiography using an anterior oblique-viewing endoscope in patients with altered gastrointestinal anatomy.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is technically more challenging in patients who have undergone gastrointestinal (GI) reconstruction. AIMS: The aim of this study was to evaluate the utility of the anterior oblique-viewing endoscope (AOE) for ERCP in patients with a retained major duodenal papilla after GI reconstruction. METHODS: This was a retrospective study involving 40 patients (50 procedures) with a retained papilla after GI reconstruction who underwent ERCP using AOE. Reconstruction consisted of Billroth II gastrectomy (BII) in 25 patients (30 procedures) and Roux-en-Y anastomosis (RY) in 15 patients (20 procedures). In RY cases, the long single-balloon enteroscope (LSBE) was exchanged with AOE after reaching the papilla. RESULTS: The overall rate of reaching the papilla using AOE was 90.0 % (45/50) [BII; 86.7 % (26/30), RY; 95.0 % (19/20)]. The overall rate of biliary cannulation was 97.8 % (44/45) [BII; 100 % (26/26), RY; 94.7 % (18/19)], and the rate of biliary cannulation for intact papilla was 96.6 % (28/29) [BII; 100 % (14/14), RY; 93.3 % (14/15)]. Treatment success rate in cases of successful biliary cannulation was 97.7 % (43/44) [BII; 100 % (26/26), RY; 94.4 % (17/18)]. The rate of adverse events was 6.0 % (3/50) [BII; 3.3 % (1/30), RY; 10.0 % (2/20)], with mild pancreatitis occurring in 3 cases. CONCLUSIONS: High biliary cannulation and treatment rates can be achieved during ERCP using AOE in altered GI anatomy cases with a retained papilla, as long as the papilla can be reached. In RY cases, exchanging AOE with LSBE is useful after reaching the papilla.

An updated review of gastric cancer in the next-generation sequencing era: insights from bench to bedside and vice versa.

Gastric cancer (GC) is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs. Recent studies using next-generation sequencing (NGS) have revealed a number of potential cancer-driving genes in GC. Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4, a member of the cadherin gene family. Mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) have been found in 47% of GCs. Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC. Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery, such as DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs and microRNAs. Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings. The anti-human epidermal growth receptor 2 (HER2) antibody trastuzumab has led to an era of personalized therapy in GC. In addition, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR)-2, is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after first-line chemotherapy. Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets, as well as useful biomarkers. In this review, we will summarize the recent advances in the understanding of the molecular pathogenesis of GC, focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.

Risk factors for vertical incomplete resection in endoscopic submucosal dissection as total excisional biopsy for submucosal invasive colorectal carcinoma.

PURPOSE: Endoscopic submucosal dissection (ESD) for colorectal tumor is a minimally invasive treatment. Histologic information obtained from the entire ESD specimen is important for therapy selection in submucosal invasive colorectal carcinoma (SMca). This study aimed to identify risk factors for vertical incomplete resection (vertical margin-positive [VM+]) when ESD was performed as total excisional biopsy for SMca. METHODS: From June 2003 through December 2011, 78 SMca cases were resected by ESD at Hiroshima University Hospital. Patient and tumor characteristics, intraoperative variables, and histopathology were compared between the VM+ group and the vertical complete resection (vertical margin-negative) group. The ability of magnifying endoscopy (ME) and endoscopic ultrasonography (EUS) to predict VM+ was assessed. RESULTS: ESD resulted in VM+ in eight cases (10.3 %), with a greater percentage invading to a depth of ≥2,000 vs. <2,000 µm (P = 0.047). Severe submucosal fibrosis was found in five of the eight cases (62.5 %, P = 0.017). Poor differentiation was seen at the deepest invasive portion in six cases (75.0 %), and two of six cases had an invasion depth <2,000 µm. Of 39 EUS cases, 36 not showing deep invasion close to the muscularis propria were completely resected by ESD. CONCLUSIONS: Submucosal fibrosis and poor differentiation at the deepest invasive portion may be risk factors for VM+ in colorectal ESD for tumors with submucosal deep invasion. ME plus EUS is more likely to help determine whether ESD is indicated as complete total excisional biopsy for SMca.