Yuji Urabe

Background Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non‐drinker and non‐smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. Methods The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic …

BackgroundAccurate evaluation of tumor invasion depth is essential to determine the appropriate treatment strategy for patients with superficial esophageal cancer. The pretreatment tumor depth diagnosis currently relies on the magnifying endoscopic classification established by the Japan Esophageal Society (JES). However, the diagnostic accuracy of tumors involving the muscularis mucosa (MM) or those invading the upper third of the submucosal layer (SM1), which correspond to Type B2 vessels in the JES classification, remains insufficient. Previous retrospective studies have reported improved accuracy by considering additional findings, such as the size and macroscopic type of the Type B2 vessel area, in evaluating tumor invasion depth. Therefore, this study aimed to investigate whether incorporating the size and/or macroscopic type of the Type B2 vessel area improves the diagnostic accuracy of …

Background and Aims The therapeutic outcome of endoscopic submucosal dissection (ESD) for large protruding tumors has not yet been evaluated. We aimed to compare the outcomes of ESD in protruding tumors with those of laterally spreading tumors (LSTs). Methods Endoscopic submucosal dissection was attempted in 218 patients with 220 colorectal tumors ≥30 mm in diameter (67, protruding tumors; 153, LSTs) from July 2007 to June 2014. We retrospectively reviewed patient medical records, therapeutic outcomes, and procedure-related adverse events. This study defined lesions with a height of 10 mm or more as protruding tumors and those with a height under 10 mm as LSTs. Results The mean lesion diameter, height, and volume were 43.8, 9.5 mm, and 13.6 cm3, respectively. The mean procedure time was …

Objective Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. Methods A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. Results The median age of patients was 74 years, and the median prostate-specific antigen value …

BackgroundMethods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC.MethodsAmong 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage …

In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa …

BackgroundWhen total submucosal dissection is difficult to achieve during conventional colorectal endoscopic submucosal dissection (C-ESD), the lesion can be resected by final snaring through salvage hybrid ESD (SH-ESD). This study aimed to examine the outcomes of SH-ESD and identify its indications that could achieve en bloc resection.MethodsWe recruited 1039 consecutive patients with colorectal lesions that underwent ESD at Hiroshima University Hospital between January 2015 and December 2020. C-ESD was attempted thoroughly in 924 lesions (C-ESD group, including 9 lesions in which ESD was discontinued), and SH-ESD was performed owing to some difficulties in 115 lesions (SH-ESD group). Risk factors for incomplete resection by SH-ESD and ESD discontinuation were evaluated using multivariate analysis. The outcomes were compared between cases with remaining undissected …

Currently, no consensus exists regarding endoscopic resection methods for small-bowel tumors. Underwater endoscopic mucosal resection (UEMR) has been reported as an effective treatment option for superficial non-ampullary duodenal epithelial tumors (SNADETs). 1 Although the usefulness of UEMR for small-bowel tumors has also been reported, 2 it may not be equally effective in all cases because of the difficulty in filling the lumen of the small-bowel for visualization and access. VISCOCLEAR®(Otsuka Pharmaceuticals Factory, Tokushima, Japan), a gel used to enhance the visual field during endoscopy, is only available in Japan. This endoscopic gel tends to stay in the lumen due to its high viscosity. We report a case of an inflammatory fibroid polyp (IFP) of the ileum that was safely resected using gel immersion EMR (GIEMR) with doubleballoon endoscopy (DBE)(Video 1).A 78-year-old man was …

A 69-year-old woman presented to our department with the chief complaint of diarrhea. She had undergone left nephrectomy for renal cancer 14 years earlier. Three years earlier, metastasis was detected in the left retroperitoneal cavity, and pazopanib administration was initiated. In the 29th month after the start of chemotherapy, the patient developed diarrhea, and on the 31st month, computed tomography showed thickening of the intestinal wall. Colonoscopy revealed white villi, intramucosal hemorrhage in the terminal ileum, and rough inflammatory mucosa with inflammatory polyps extending from the transverse to the sigmoid colon. Suspecting pazopanib-induced enteritis, we discontinued the medication, and the diarrhea resolved within 3 days. On the 21st day after discontinuation, colonoscopy revealed that the inflammatory polyps had shrunk, and the inflammatory findings had improved. Biopsy of the white …

PurposeA vertical margin (VM) distance of< 500 µm is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRCMethodsWe enrolled 154 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients had lymph node metastasis (pStage I) and were followed up for> 5 years. A total of 154 patients were classified into patients with VM distance of< 500 µm including positive VM (n= 62, VM distance< 500 µm group) and patients with VM distance of≥ 500 µm (n= 92, VM distance≥ 500 µm group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM).ResultsTumor size and the rate of budding grade 2/3 in the VM distance< 500 µm group was significantly smaller and higher, respectively, than those in the VM distance≥ 500 µm group. Tumors recurred in six of the 154 patients with VM distance< 500 µm. The 5-year recurrence-free survival rate was significantly higher in the VM distance≥ 500 µm group than that in VM distance< 500 µm group after PSM (100% vs. 90%, p< 0.012).ConclusionsComplete en bloc resection of T1 CRC via ESD must include a sufficient amount of submucosa to reduce the risk of metastasis and recurrence after additional surgery.

Background and Aim Although small‐bowel capsule endoscopy (CE) is widely used for obscure gastrointestinal bleeding (OGIB), long‐term outcomes for OGIB patients after negative CE remain unclear. Herein, we defined negative CE as P0 (no bleeding potential) or P1 (less likely to bleed), based on the P classification using CE. We aimed to clarify long‐term outcomes of patients with OGIB after negative CE. Methods This single‐center observational study enrolled 461 consecutive patients with OGIB who underwent CE from March 2014 to October 2021 and were followed up for >1 year. We examined rebleeding rates and predictive factors. Results Two hundred and twenty‐four (49%) patients had P0, and 237 (51%) had P1 findings. Rebleeding occurred in 9% and 16% of patients in the P0 and P1 groups, respectively. Two patients in the P0 group and 15 in the P1 group showed rebleeding from the small …

BackgroundThe validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in elderly persons with comorbidities remains unclear. This study evaluated the safety and efficacy of ESD and additional treatment for ESCC in elderly patients.MethodsThis study retrospectively evaluated the clinicopathological characteristics and clinical outcomes of 398 consecutive elderly patients (age≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019. Additionally, the prognoses of 381 patients who were followed up for> 3 years were assessed.ResultsThe mean patient age was 73.1±5.8 years old. The mean procedure time was 77.1±43.5 min. The histological en bloc resection rate was 98%(496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%(mean follow-up time: 71.1±37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists Classification of Physical Status class≥ Ⅲ (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p= 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group compared to the low-risk follow-up and high-risk additional treatment groups (p< 0.01). However, no significant difference in disease-specific survival was observed between the three groups.ConclusionsESD is safe for …

Background/AimsChronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients.MethodsA retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC.ResultsA total of 114 patients …

BACKGROUNDX-ray gastric cancer (GC) screening has been shown to decrease mortality. Population-based X-ray GC screening has been performed in Hiroshima Prefecture, Japan, since 1983 but time trends and the efficacy of the method over 39 years have not been assessed.AIMTo evaluate time trends and efficacy of population-based X-ray GC screening and identify challenges and suggested solutions for the future.METHODSThis was a population-based retrospective study. The data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization, including the number and rate of participants and those requiring esophagogastroduodenoscopies (EGDs), the number and rate of participants diagnosed as having GC, and the positive predictive value of the abnormal findings detected by X-ray and confirmed by EGDs. The number and rate of esophageal cancers were …

Objectives Underwater endoscopic mucosal resection (UEMR) is a simpler procedure for superficial non‐ampullary duodenal epithelial tumors (SNADET) than conventional endoscopic mucosal resection (cEMR). This study aimed to evaluate whether cEMR can be substituted by UEMR for SNADET in terms of effectiveness, safety, and learning curve. Methods A total of 157 consecutive patients with 203 SNADETs ≤20 mm in diameter, including 107 lesions resected by cEMR and 96 lesions resected by UEMR, between January 2019 and May 2023, were retrospectively recruited. The treatment outcomes were compared between the cEMR and UEMR groups. The risk factors for incomplete resection by UEMR were analyzed using univariate and multivariate analyses. Lesions in the UEMR group were divided chronologically into five periods; thereafter, the en bloc resection rate and procedure time were …

Simple Summary In API2-MALT1-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy is known to be ineffective. Among API2-MALT1-negative cases, eradication therapy is effective for Helicobacter pylori (Hp)-positive cases and partially effective for Hp-negative cases. Herein, we explored predictive markers for eradication therapy efficacy in cases that were negative for both API2-MALT1 and Hp. Among 164 gastric MALT lymphoma patients, 36 were negative for both API2-MALT1 and Hp. We divided cases of MALT lymphoma negative for both API2-MALT1 and Hp into complete-response (CR) and no-change (NC) groups based on eradication therapy efficacy and conducted comprehensive gene expression analysis. Pathway analysis showed that cancer- and infection-related genes were highly expressed in the NC and CR groups, respectively. Sixteen candidate genes for predictive markers were extracted and validated with real-time PCR. Olfactomedin-4 and Nanog homeobox were positive and negative predictive factors, respectively, for eradication therapy efficacy against gastric MALT lymphoma; they were negative for both API2-MALT1 and Hp. Abstract Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp …

Objectives Recent innovations in prophylactic treatment with steroids have overcome the issue of esophageal stricture after endoscopic submucosal dissection (ESD), except in entire circumferential esophageal squamous cell carcinoma (EC‐ESCC). Current Japanese guidelines weakly recommend performing ESD for clinical epithelial/lamina propria EC‐ESCC with a longitudinal extension <50 mm upon implementing prophylactic treatment against stricture. However, the accurate indications for ESD in EC‐ESCC remain unknown, and strategies differ among institutions. The aim of this study was to understand the initial treatment strategy for EC‐ESCC and prophylactic treatment after ESD against esophageal stricture. Methods A questionnaire survey was conducted across 16 Japanese high‐volume centers on the initial treatment for EC‐ESCC according to the invasion depth and longitudinal extension, and …

We present a rare case that showed the coexistence of gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma in Helicobacter pylori-naive stomach. A 72-year-old man was followed up after surgery for epithelial carcinoma of the glottis at the Department of Otolaryngology. He underwent an upper gastrointestinal endoscopy for an abnormal PET-CT accumulation, which revealed gastric adenocarcinoma of fundic gland type in the gastric fundus and MALT lymphoma in the upper gastric body. Hence, we performed an endoscopic submucosal dissection for gastric cancer and diagnosed gastric adenocarcinoma of fundic gland type derived from a hamartomatous–inverted polyp. Subsequently, Gastric MALT lymphoma was treated with radiation therapy because the API2-MALT1 gene was positive and the Helicobacter pylori infection was negative. A complete response was observed. Even in Hp …

MethodsWe retrospectively collected data from patients with lung cancer who participated in CGM at Hiroshima University Hospital between October 2019 and July 2022.ResultsSeventy-four patients with lung cancer were eligible. There were 40 males and 34 females with a median age of 63.8. The type of CGP testing was mainly FoundationOne-CDx (54 patients). Adenocarcinoma was the most common histological type (49 patients). Of the 74 patients, 59 were recommended for clinical trials based on the genetic variants detected by CGP testing, but only two patients have been confirmed to have actually participated in a clinical trial. Approved drugs were recommended for seven patients (excluding 15 cases of EGFR-TKI), among whom three patients were confirmed to have been administered such drugs in practice.ConclusionsOnly a few patients were able to apply the results of CGP testing in practice …

BackgroundThe presence of post-endoscopic submucosal dissection (ESD) scars renders complete metachronous superficial esophageal squamous cell carcinoma resection difficult. We aimed to identify the risk factors for incomplete resection of metachronous esophageal squamous cell carcinoma close to the post-ESD scar by ESD.MethodsWe enrolled patients who developed post-ESD superficial esophageal squamous cell carcinoma at Hiroshima University Hospital between January 2006 and March 2020. We analyzed the outcomes and risk factors of incomplete resection between patients whose lesions were close to (close-to group) and away from (away-from group) the post-ESD scar.ResultsWe included 111 patients with 212 lesions. The close-to group had a significantly lower complete resection rate (88.6% [62/70] vs. 98.6% [69/70], p = 0.033), longer procedure time (80.2 ± 47.2 min vs. 60.4 ± 29 …

Background and study aims Prevention of bleeding and perforation during gastric endoscopic submucosal dissection (ESD) is important. Scissor-type knives can accurately grasp and incise the targeted tissue using electrosurgical currents, thereby eliminating unexpected incisions. The SB Knife GX, a scissor-type knife specialized for gastric ESD, was released in June 2016 in Japan. The aim of the present study was to evaluate the efficacy and safety of gastric ESD using the SB Knife GX. Patients and methods A total of 716 patients who underwent gastric ESD at Hiroshima University Hospital between July 2016 and December 2020 were retrospectively reviewed. From these, 671 patients underwent ESD using the IT Knife 2 (IT-2 group), while 45 underwent ESD using an SB Knife GX (SB-GX group). After propensity score matching, the procedure time, specimen size, en bloc and complete resection rates, and …

BackgroundDefinitive chemoradiotherapy (DCRT) is a curative treatment option for cT1bN0M0 esophageal squamous cell carcinoma (ESCC); however, local residual disease and recurrence after complete remission may occur. We aimed to identify endoscopic findings associated with the risk of non-radical cure (local remnant or recurrence) after DCRT for cT1bN0M0 ESCC.MethodsWe retrospectively analyzed 40 consecutive patients with cT1bN0M0 ESCC who had undergone DCRT between January 2007 and December 2017. We examined the endoscopic findings in patients with residual or recurrent (RR) disease (RR group) and those without RR disease [non-RR (NRR) group] after DCRT. We also evaluated outcomes after DCRT for each endoscopic finding.ResultsThere were 10 patients in the RR group and 30 patients in the NRR group. The RR group had a significantly larger tumor size and a higher …

Simple Summary In advanced colorectal cancer (CRC), tumor-infiltrating T cells (TILs) are reportedly associated with lymph node (LN) metastasis and prognosis. However, there are no reports focusing on early-stage CRC or examining changes in TILs according to the degree of CRC invasion. Therefore, we investigated the relationship between LN metastasis and TILs in early-stage CRC using the triple immunofluorescence method for CD4, CD8, and Foxp3. We also examined changes in TILs during invasion from early-stage CRC to advanced CRC. We found that a higher number of Foxp3+ T cells and higher Foxp3/CD4 and Foxp3/CD8 ratios at the invasive front of the tumor were associated with LN metastasis. Furthermore, tumor invasion was positively correlated with the number of TILs in CRC. This study provides new predictors of LN metastasis in T1b CRC and provides insight into the tumor microenvironment in CRC invasion. Abstract The role of tumor-infiltrating T cells (TILs) in colorectal cancer (CRC) and their significance in early-stage CRC remain unknown. We investigated the role of TILs in early-stage CRC, particularly in deep submucosal invasive (T1b) CRC. Sixty patients with CRC (20 each with intramucosal [IM group], submucosal invasive [SM group], and advanced cancer [AD group]) were randomly selected. We examined changes in TILs with tumor invasion and the relationship between TILs and LN metastasis risk. Eighty-four patients with T1b CRC who underwent initial surgical resection with LN dissection or additional surgical resection with LN dissection after endoscopic resection were …

Objectives Capsule endoscopy (CE) has been shown to have poor diagnostic performance when the capsule passes quickly through the small bowel, especially the proximal jejunum. This study aimed to evaluate the diagnostic yield of proximal jejunal lesions with third‐generation CE technology. Methods We retrospectively examined 138 consecutive patients, 76 (55.0%) of whom were men. The patients’ median age was 70 years, and proximal jejunal lesions were detected by CE and/or double‐balloon endoscopy at Hiroshima University Hospital between January 2011 and June 2021. We analyzed the diagnostic accuracy of CE for proximal jejunal lesions and compared the characteristics of the discrepancy between the use of CE and double‐balloon endoscopy with Pillcam SB 2 (SB2) and Pillcam SB 3 (SB3). Results SB2 and SB3 were used in 48 (35%) and 90 (65%) patients, respectively. There was no …

ObjectiveFor low-grade intraepithelial neoplasia cases, pharyngolaryngeal lesions equal to or less than 5 mm in size do not generally progress to invasive carcinoma. However, micro-superficial lesions equal to or less than 5 mm that showed rapid growth have been recently encountered. This study aimed to identify the characteristics of preferential progression of lesions equal to or less than 5 mm in size.MethodGross findings, endoscopic findings and pathological results of 55 lesions measuring equal to or less than 5 mm in diameter were retrospectively reviewed to identify factors that distinguish squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions.ResultsThe overall sensitivity, specificity, accuracy, and positive and negative predictive value of background colouration and intrapapillary capillary loop pattern in differentiation of squamous …

PurposeDental floss clip (DFC) traction-assisted endoscopic submucosal dissection (ESD) is widely performed owing to its simplicity. This study aimed to clarify the appropriate indications for the DFC traction method in early gastric cancer when ESD is performed by less-experienced endoscopists.

The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated …

BackgroundThe ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate “patients without gastritis” (defined as true A patients) from those “with gastritis.” A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis.MethodsPatients who underwent endoscopy and blood tests at Hiroshima University …

Introduction The virtual scale endoscope (VSE) is a newly introduced endoscope that helps endoscopists in measuring colorectal polyp size (CPS) during colonoscopy by displaying a virtual scale. This study aimed to determine the usefulness of the VSE for CPS measurement and the educational benefit of using VSE images to improve CPS estimation accuracy. Methods This study included 42 colorectal polyps in 26 patients treated at Hiroshima University Hospital. In study 1, CPS measured using a VSE before endoscopic mucosal resection was compared with CPS measured on resected specimens, and the agreement between the two measurement methods was evaluated via Bland-Altman analysis. In study 2, 14 endoscopists (5 beginners, 5 intermediates, and 4 experts) took a pre-test to determine the size of 42 polyps. After the pre-test, a lecture on CPS measurement using VSE images was given. One month …

Simple Summary The large neutral amino acid transporter family (LAT1-4) plays an important role in the intracellular uptake of essential amino acids. Among them, LAT1 is specifically expressed in cancer cells. A novel LAT1-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, the anti-tumor mechanism for colorectal cancer (CRC) remains unclear. In this study, we clarified the significance of LAT1 expression in cancer progression in database analysis and clinical specimens and demonstrated the utility of JPH203, in vitro and in vivo, using a unique stroma-abundant allogeneic immunoreactive mouse colorectal tumor created by the orthotopic transplantation of a mouse-derived CRC cell line and mesenchymal stem cells into mouse cecum. Comprehensive analysis with RNA sequences showed the efficacy of JPH203 not only in cancer proliferation, but also in tumor stromal activation. These findings will be useful when considering its application in other stroma-abundant carcinomas and its use in combination with other drugs. Abstract A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell …

EP60 CLINICOPATHOLOGICAL FEATURES AND GENOMIC CHARACTERIZATION OF SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN NON DRINKER, NON SMOKER FEMALES Motomitsu Fukuhara, Yuji Urabe, Shiro Oka, Hikaru Nakahara, Kazuki Ishibashi, Hirona Konishi, Junichi Mizuno, Yuichi Hiyama, Akira Ishikawa, CN Hayes, Naohide Oue, Shinji Tanaka Background and aim: This study aimed to examine the clinicopathological and genomic characterizations of esophageal squamous cell carcinomas (ESCCs) in females without a history of drinking of smoking. Methods: Out of 1198 ESCCs in 884 cases who underwent endoscopic submucosal dissection in our department between January 2008 and December X: 30083$ CH1D 04-23-23 05: 03: 43 Page 1203 PDFd: 30083B: o S-1203 AGA Abstracts 2019, 95 cases and 118 lesions that occurred in women were included. The cases …

Objectives To examine the clinical usefulness of transoral ultrasonography (US) in determining the invasion depth of superficial pharyngeal carcinoma (SPC). Determining the invasion depth of SPC is crucial for transoral surgery including determining treatment strategy. This study aimed to examine the usefulness of transoral US in determining the invasion depth of SPC. Methods Forty‐six patients with 51 lesions who underwent both magnifying endoscopy with narrow‐band imaging (ME‐NBI) and transoral US were included. The primary outcomes were the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of ME‐NBI and transoral US findings for pathological tumor depth in SPCs. Results The accuracy (82.4%), sensitivity (85.2%), PPV (82.1%), and NPV (82.6%) rates of US for subepithelial propria (SEP) were higher than those of ME‐NBI and macroscopic classification, indicating that …

BackgroundNon-Helicobacter pylori Helicobacter (NHPH) has recently been linked to various gastric diseases. However, the relationship between NHPH infection and gastric cancer remains controversial. This study aimed to identify the effect of NHPH infection on gastritis and gastric cancer development.Materials and methodsFormalin-fixed paraffin-embedded tissues were obtained from 73 patients with gastric cancer, of whom 21 cases were Helicobacter pylori (Hp) current infection, 37 cases were Hp previous infection, and 15 cases were Hp naïve infection, and were screened for NPHPs using polymerase chain reaction. The results were compared with NHPH infection rates in the patients with gastritis-related diseases reported in the previous study. We evaluated the association of NHPH infection with gastritis and clinicopathological features of gastric cancer.ResultsNHPH infection rates were 4/21 (19%) in …

Transoral surgery (TOS) has been widely used to treat laryngopharyngeal cancers. Although TOS is a minimally invasive procedure, postoperative complications, such as postoperative dysphagia, may occur, which can lead to a poor quality of life for patients undergoing TOS. This study aimed to investigate factors that may affect swallowing function in patients who underwent TOS for laryngopharyngeal cancers. Swallowing function of 84 patients who underwent endoscopic resection for oropharyngeal, hypopharyngeal, and supraglottic lesions was evaluated by the Functional Outcome Swallowing Scale, and predictors for postoperative dysphagia were identified. Multivariate analysis identified the following factors as independent predictors for postoperative dysphagia: Eastern Cooperative Oncology Group Performance Status (ECOG PS, p = 0.008), prior neck radiation therapy (p = 0.008), and operative time (p = 0.021). This study suggests that patients with poor ECOG PS or those who received prior neck radiation therapy should be fully assessed for preoperative swallowing function. In the future, we would like to clarify the criteria for preoperative swallowing evaluation to create a system that can identify patients suitable for TOS.

Background We have previously reported that eradication therapy was more effective against Helicobacter pylori (Hp)‐negative gastric mucosa‐associated lymphoid tissue (MALT) lymphoma in non‐Helicobacter pylori Helicobacter (NHPH)‐positive cases than in NHPH‐negative cases and that the infection status of NHPH could be a predictive marker for the efficacy of eradication therapy for H. pylori negative gastric MALT lymphoma. However, a diagnostic test for NHPH infection has not yet been clinically established. In this study, we investigated the endoscopic findings in cases of H. suis‐infected gastritis associated with gastric MALT lymphoma reported at our institution. Materials and Methods Participants were selected from cases of gastric MALT lymphoma who underwent esophagogastroduodenoscopy at Hiroshima University Hospital, who were negative for the API2‐MALT1 gene, and who received …

Background and purposeRadiotherapy (RT) has recently received increasing attention as an additional treatment for organ preservation after non-curative endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer. Esophageal stenosis is an adverse event related to RT after ESD that is not widely studied. The aim of this study was to investigate esophageal stenosis related to salvage RT in superficial esophageal cancer after non-curative ESD.Materials and methodsFifty patients who received salvage RT after non-curative ESD at a single institution between 2011 and 2018 were included in this study. The Common Terminology Criteria for Adverse Events, version 5.0, was used to assess esophageal stenosis. Data were compared using Fisher’s exact test. Statistical significance was set at P < 0.05.ResultsMedian follow-up time was 48 months (range, 12–95 months). Grade 2 and 3 …

Early recurrence detection of head and neck squamous cell carcinoma (HNSCC) is important for improving prognosis. Recently, circulating tumor DNA (ctDNA) has been reported to be useful in early detection or treatment response determination in various carcinomas. This study aimed to identify the utility of ctDNA for predicting recurrent metastasis in patients with HNSCC. We collected pre-treatment tissues (malignant and normal tissues) and multiple plasma samples before and after treatment for 20 cases of HNSCC treated with radical therapy. ctDNA was detected in pre-treatment plasma in 10 cases; however, there were no significant associations with tumor recurrence and staging. During follow-up, ctDNA was detected in 5 of the 7 plasma samples of recurrent cases but not in the 13 recurrence-free cases. Moreover, there was a significant difference in post-treatment relapse-free survival time between the …

METHODS:We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER.RESULTS:A total of 992 patients with pMM-ESCC (n= 749) and pSM1-ESCC (n= 243) were registered. According to the multivariate Cox proportional-hazards analysis, pSM1-ESCC (hazard ratio (HR)= 1.88, 95% confidence interval (CI) 1.15–3.07, P= 0.012) and LVI (HR= 6.92, 95% CI 4.09–11.7, P< 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1–233), among the patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients …

Since colorectal metastases from primary lung cancer are rare, the location of metastatic lesion and prognostic factors have not been well evaluated. Therefore, we carried out a systematic review and meta-analysis to assess the clinicopathological characteristics and prognostic factors of Japanese patients with colorectal metastasis from lung cancer. We searched the Ichushi-Web database from January 1964 to December 2020. We found 59 colorectal metastases in 52 cases for this meta-analysis. Small cell carcinoma was shown to have significantly more metastases to the appendix than non-small cell carcinoma. However, there was no significant correlation between location and histology when classified into right and left colons (P = 0.247). The median overall survival after diagnosis was 6 months. Univariate analysis showed that adenocarcinoma (Hazard Ratio (HR) 0.383, P = 0.024 …

Results(1) Of all cases, 68.7%(230 lesions from 199 patients) classified into Group A and 31.3%(108 lesions from 83 patients) into Group B. Univariate analysis showed a significant difference in mean age (69.5 vs. 72.4 years, p= 0.047), smoking history (with/without: 111/88 vs. 57/26, p= 0.044), and mean tumor diameter (17.4 mm vs. 14.1 mm, p= 0.048) between Group A and Group B. In multivariate analysis, only smoking showed a significant difference in Group B (odds ratio [OR] 1.89; 95% confidence interval [CI], 1.00–3.55; p= 0.045);(2) 89.9%(304 lesions from 253 patients) were differentiated-type carcinomas, whereas 10.1%(34 lesions from 32 patients) were undifferentiated-type carcinomas. Univariate analysis showed a significant difference in sex ratio (male/female: 185/65 vs. 18/14, p= 0.010), mean age (71.2 vs. 66.4 years, p= 0.007), mean tumor diameter (15.4 mm vs. 21.5 mm, p= 0.023), gastric mucosal …

Simple Summary Cancer-associated fibroblasts (CAFs) are abundant in colorectal cancer (CRC) tissues and are essential for tumor growth. Histological analysis of CRC clinical specimens showed that the number of CAFs in liver metastases correlated with the number of CAFs in primary tumors. We hypothesized that the presence of CAFs in metastatic CRC contributes to immune evasion, and thus evaluated the efficacy of dasatinib in targeting CAFs in combination with immunotherapy in a mouse model of liver metastasis. Immunotherapy in combination with dasatinib was shown to reduce stromal components and subsequent immune cell infiltration and promote the activation of tumor immunity and tumor regression in liver metastatic tumors with abundant CAF components. These results suggest that CAFs play an important role in the immune evasion of CRC and that dasatinib is a promising combination agent for increasing immunotherapy sensitivity in metastatic CRC. Abstract In this study, we investigated the in vivo metastasis suppression effects of the platelet-derived growth factor receptor inhibitor dasatinib, which targets cancer-associated fibroblasts (CAFs), in combination with an anti-programmed cell death-1 (PD-1) antibody. We classified clinical CRC cases as inflamed, excluded, or desert using immunohistochemical analysis and evaluated the tumor stroma. The excluded type was the most common, and cases with high-volume stroma in the primary lesions also had a high stromal volume in the liver metastatic lesions. Liver-metastasis mouse models with different stromal volumes were established and …

Objectives There are some endoscopic resection (ER) methods for neuroendocrine tumors (NETs), however, which method is most useful remains unclear. This study aimed to compare the outcomes of different ER techniques, such as conventional endoscopic mucosal resection (cEMR), endoscopic submucosal dissection (ESD), and endoscopic submucosal resection with a ligation device (ESMR‐L) for rectal NETs. Methods We retrospectively analyzed 96 consecutive patients with 102 rectal NETs of less than 10 mm in diameter who underwent ER between January 2001 and December 2019 at Hiroshima University Hospital. We compared the clinical outcomes of each ER method (cEMR 60 lesions, ESD 21 lesions, and ESMR‐L 21 lesions), divided according to the treatment periods, and evaluated the risk factors for vertical margin (VM) positivity in relation to clinicopathological and endoscopic characteristics …

BackgroundPrimary small-bowel follicular lymphoma (FL) is mainly diagnosed as a duodenal lesion during esophagogastroduodenoscopy. Recently, with the widespread use of small-bowel endoscopy, FL in the jejunum and ileum has been detected. Most patients with small-bowel FL are diagnosed at the localized stage, and a watch-and-wait policy is used. However, the predictive factors for the progression of small-bowel FL have not been clarified. This study retrospectively examined the predictive factors for the progression of primary localized stage small-bowel FL based on clinicopathological and endoscopic findings.MethodsWe enrolled 60 consecutive patients with primary small-bowel FL diagnosed at two tertiary hospitals between January 2005 and December 2020, with localized stage, low grade, and low tumor burden with the watch-and-wait policy. We examined the predictive factors for progression …

ResultsIn the DFC (+) and DFC (−) groups, the mean procedure time was 61±29 vs. 66±38 min, en bloc resection rate was 99% vs. 99%, complete resection rate was 99% vs. 99%, mean specimen size was 37.4±12.6 vs 36.7±11.6 mm, delayed bleeding rate was 4% vs. 3%, and perforation rate was 1% vs. 1%, respectively, with no significant differences between the 2 groups. When comparing lesions (> 20 mm), the procedure time was significantly shorter in the DFC (+) group (95±46 vs. 75±31, P= 0.0004). Furthermore, when they were examined in detail by location, the procedure time was significantly shorter in the DFC (+) group for lesions in the lesser curvature of the upper or middle stomach (110±43 vs. 84±43, P= 0.02), lesions in the greater curvature of the upper or middle stomach (145±81 vs.

Serum amyloid A (SAA) is an acute phase inflammatory protein that we previously described as a robust biomarker of colorectal inflammation in patients with ulcerative colitis (UC) in clinical remission. However, what induces SAA expression in UC remains unclear. This study demonstrates that SAA is significantly expressed in the intestinal tract of UC mouse models when compared with C-reactive protein, another inflammatory biomarker. Moreover, interleukin-6 and tumor necrosis factor-α were found to promote SAA1 expression, as were Toll-like receptor ligands flagellin and lipopolysaccharide. Furthermore, results suggested that the nuclear factor-kappa B (NF-κB) pathway may be involved in the promotion of SAA1 expression by flagellin, which was inhibited by treatment with 5-aminosalicylic acid (5-ASA). Therefore, the flagellin/NF-κB/SAA1 axis may represent one of the mechanisms by which 5-ASA suppresses intestinal inflammation.

BackgroundVertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000 μm) CRC on the prognosis of patients undergoing additional surgery after ER.MethodsIn total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of …

MethodsTwenty-one lesions of colorectal LST-G, nodular mixed subtype with diameter> 20 mm treated in Hiroshima University Hospital from August 2019 to November 2020 were enrolled [9 males (43%), 7 rectal lesions (33%), mean tumor diameter 37±11 mm, 20 endoscopic submucosal dissections and 1 surgery]. We obtained 3–4 tissues from nodules and/or flat granular areas in each lesion and extracted DNA from 96 tissues. Whole-exome sequencing was performed using the SureSelect Human All Exon V8 (Agilent Technologies, Santa Clara, CA, US) and NovaSeq 6000 (Illumina, San Diego, CA US) systems. Somatic mutations of tumor tissues were detected by comparing sequence data from leucocytes. Pathological variations were judged based on public databases such as COSMIC, CancerVar, ClinVar, and OncoKB. The clonal evolution of each case was examined by contrasting genomic variations in …

Objective Systemic sclerosis (SSc) is defined as an autoimmune disease presenting with fibrosis of various organs and vascular endothelial damage. Vascular lesions, including small-bowel angioectasias, are also frequently detected in SSc patients. Polidocanol injection (PDI) is a safe and effective hemostatic treatment for gastrointestinal bleeding. We evaluated the outcomes of PDI for small-bowel angioectasia in SSc patients.Methods We retrospectively evaluated 65 consecutive SSc patients (61 women; mean age, 64.3 years old) who underwent capsule endoscopy (CE) and/or double-balloon endoscopy at Hiroshima University Hospital between April 2012 and December 2019.

Background and aims Linked color imaging (LCI) improved the visibility of gastric cancer and colorectal flat lesions. This study aimed to investigate the usefulness of LCI in detecting superficial esophageal squamous cell carcinomas (SESCC). Methods We enrolled 37 consecutive SESCC patients (46 SESCCs) diagnosed using LCI and blue laser imaging bright mode (BLI-BRT) and treated in Hiroshima University Hospital between April 2018 and November 2018. Eight professional endoscopists compared images obtained on non-magnifying BLI-BRT and LCI versus conventional white light imaging (WLI). Identification and boundary diagnosis of SESCC with LCI and BLI-BRT were compared with WLI. Changes in lesion visibility were clarified. Interobserver agreement was assessed. Clinicopathological features of lesion that influence visibility with LCI …

Materials and methodsWe investigated the clinicopathological characteristics in patients with SPS accumulated through the" Multicenter Study on clinicopathological characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group, which was donated by the Japanese Society of Gastroenterology (JSGE). In this study, we diagnosed patients with SPS according to 2019 World Health Organization (WHO) SPS diagnostic criteria as follows; I)≥ 5 serrated lesions/polyps proximal to the rectum, all being≥ 5mm in size, with at least 2 being≥ 10mm in size; and II)> 20 serrated lesions/polyps of any size distributed throughout the large bowel, with≥ 5 being proximal to the rectum.ResultsA total of 94 patients were diagnosed with SPS at 9 institutes during a period from January 2001 until December 2017. The median (range) number of resected lesions per apatient was 6 (0− 85 …

The current understanding of clinicopathological features and genomic variants of small-bowel cancer is limited, in part due to the rarity of the disease. However, understanding of these factors is necessary for the development of novel therapeutic agents for small-bowel cancer. Thus, we aimed to identify the clinicopathological features and genomic variants associated with its prognosis and recurrence. We retrospectively examined 24 consecutive patients with primary small-bowel cancer surgically treated between May 2005 and August 2018 and collected 29 tumor specimens. The 29 lesions were subjected to mismatch repair status evaluation, using immunohistochemistry (IHC), and targeted genomic sequencing, after which they were analyzed using a panel of 90 cancer-related genes. IHC revealed that 45% (13/29) of the lesions exhibited deficient mismatch repair. The most common genomic variants in small-bowel cancers were in TP53 (48%, 13/27), followed by KRAS (44%, 12/27), ARID1A (33%, 9/27), PIK3CA (26%, 7/27), APC (26%, 7/27), and SMAD4, NOTCH3, CREBBP, PTCH1, and EP300 (22%, 6/27 each). Overall survival and disease-specific survival of patients with tumor mutational burden (TMB) ≥10 mutations/Mb (n = 17) were significantly better than those of patients with TMB <10 mutations/Mb (n = 6). Additionally, patients with a mutant SMAD4 had poorer recurrence-free survival than those with wild-type SMAD4. Our results suggested that TMB and SMAD4 mutations were associated with the prognosis of small-bowel cancer patients. Thus, cancer genomic analysis could be useful in the search for biomarkers of prognosis …

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; ) and after (11.9% vs. 0%, respectively; ) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients …

With the increasing use of capsule endoscopy (CE), screening tests for the small bowel can be performed with minimal invasiveness. However, occasionally, the entire small bowel cannot be observed because of decreased peristalsis of the stomach. For such cases, we perform delivery of CE by an endoscope. We retrospectively examined the usefulness of the endoscopic delivery method using a retrieval net for patients with CE stagnation in the stomach. From 2,270 patients who underwent small-bowel CE at Hiroshima University Hospital from January 2013 to January 2020, 29 consecutive patients (1.3% of the total number) in whom the small bowel could not be observed due to CE stagnation in the stomach at the time of the initial CE underwent the endoscopic delivery method using a retrieval net for secondary small-bowel CE. This study included 16 male (55%) and 13 female (45%) patients with a mean age of . 11 patients (38%) had a history of gastrointestinal surgical resection. The entire small bowel could be observed in 19 patients (66%), and CE reached the terminal ileum in the remaining patients. A history of gastrointestinal surgical resection was significantly more frequent in the group where the entire small bowel could not be observed. The rate of small-bowel lesion detection was 55% (16/29). There were no adverse events associated with our endoscopic delivery method. Thus, the endoscopic delivery method using a retrieval net for patients with initial CE stagnation in the stomach may be safe and useful for the detection of small-bowel lesions.

Backgrounds Colorectal neoplasias (CRN)s developing from the ulcerative colitis (UC) mucosa include both colitic and sporadic neoplasias. Although several genomic analyses of advanced colitis-associated cancer are available, such studies do not distinguish between colitic and sporadic cases, and the early-stage genomic alterations involved in the onset of colitic cancer remain unclear. To address this, we performed a genomic analysis of early-stage CRN developing from the UC mucosa (CRNUC). Methods We extracted DNA from 36 early-stage CRNUCs (T1 cancer, 10; dysplasia, 26) from 32 UC patients and performed targeted sequencing of 43 genes commonly associated with colitis-associated cancer and compared the results with sequencing data from the Japanese invasive colitis-associated cancer. Results The most frequently mutated gene in …

✓ There is an international consensus that rectal NETs less than 10mm in diameter are eligible for endoscopic resection (ER) because of their low lymph node metastasis, distant metastasis, and good 5-year survival rate. 1-4

Background and Aim Gastric antral vascular ectasia (GAVE) causes gastrointestinal bleeding. The initial treatment for GAVE bleeding is endoscopic hemostasis, and currently, the most performed technique to achieve hemostasis is argon plasma coagulation (APC). However, APC is associated with a high recurrence rate. To overcome this limitation, we examined the outcomes of the combination therapy of APC and polidocanol injection (PDI) for treating GAVE. Methods We retrospectively analyzed the outcomes of 15 consecutive GAVE patients treated with PDI + APC at Hiroshima University Hospital between November 2011 and September 2019 with respect to clinical characteristics, hemostatic efficacy, complications related to treatment, and recurrence rate. Results The mean age of patients (4 men and 11 women) was 74 ± 8.4 years. Patients had comorbidities of liver cirrhosis (seven patients, 47 …

Background Eradication therapy is known to be effective against Helicobacter pylori-positive gastric MALT lymphoma but predicting the efficacy of eradication therapy against Helicobacter pylori-negative gastric MALT lymphoma is difficult. Recent reports have shown that non-Helicobacter pylori helicobacter infections induce gastric MALT lymphoma, and we aimed to clarify whether non-Helicobacter pylori helicobacter infections are associated with the efficacy of eradication therapy. Methods We analyzed eradication therapy as a first-line treatment for 182 cases of gastric MALT lymphoma, classified according to Helicobacter pylori infection and API2-MALT1 mutation status. We also evaluated the non-Helicobacter pylori helicobacter infection status in 29 Helicobacter pylori-negative cases via PCR with DNA extracted from paraffin-embedded biopsy …

消化管悪性リンパ腫のすべて [各論 頻度の高い消化管原発悪性リンパ腫 消化管原発濾胞性リンパ腫] 消化管濾胞性リンパ腫の治療方針と長期経過

Background: Gastric cancer develops even in Helicobacter pylori-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in Helicobacter pylori-uninfected patients.Methods: Seventeen Helicobacter pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of Helicobacter pylori-infected patients with mucosal SRCCs. Seven SRCCs without Helicobacter pylori infection, including two invasive SRCCs, and seven Helicobacter pylori-positive SRCCs were subjected to a genetic analysis using next-generation sequencing.Results: Helicobacter pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the Helicobacter pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one Helicobacter pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without Helicobacter pylori infection. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples.Conclusions: Some SRCCs in Helicobacter pylori-uninfected patients may have a malignant potential similar to that of SRCCs in Helicobacter pylori-infected patients. Smoking is not a main carcinogenic factor for …

role of IKKb/NFkB signaling in the esophagus remains poorly understood. Recently, we have shown that expression of an active form of IKKb in murine esophageal epithelial cells was sufficient to cause esophagitis, with a phenotype of increased proliferation, angiogenesis, and immune cell infiltration. Objective: To determine the molecular roles and functional interplay of epithelial IKKb and STAT3 signaling pathways during esophageal inflammation. Methods: Mice with esophageal epithelial-specific constitutive activation of IKKb (IKKbcaEEKI) and/or knockout of STAT3 (STAT3EE-KO or IKKbcaEE-KI+ STAT3EE-KO) were generated using the ED-L2 promoter to drive Cre expression in a tissue dependent manner. Esophagi were harvested at 6 weeks of age for histological, protein, RNA, and flow cytometry analyses. Esophageal organoids were generated from IKKbcaEE-KI and littermate matched mice at 6 weeks …

Background Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients. Methods Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing. Results H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H …

Background and aims Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. Methods and results We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. Conclusion These data suggest that LRP1 mutation is an important change promoting the …

Background Endoscopic resection is widely used as an effective treatment for superficial esophageal cancer. However, the risk of lymph node metastasis increases in cases of muscularis mucosae or deeper invasion, for which additional treatment such as radiotherapy or surgery is required. Accordingly, the current study investigated the efficacy and toxicity of salvage radiotherapy after non-curative endoscopic resection as an organ preservation strategy. Methods We retrospectively reviewed 37 esophageal cancer patients who received salvage radiotherapy after non-curative endoscopic resection. The pathological invasion depths were the muscularis mucosae, submucosal layer, and muscularis propria in 14, 22, and one patient, respectively. All patients received external beam radiotherapy. Among them, eight received intraluminal brachytherapy following external beam radiotherapy. Elective nodal irradiation …

Correction to: Genomic landscape of epithelium with low-grade atypia on gastric cancer after Helicobacter pylori eradication therapy - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Springer Open Choice PMC7645463 Other Formats PDF (154K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Springer Open Choice PMC7645463 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Logo of springeropen Journal of Gastroenterology J Gastroenterol. 2020; 55…

METHODS:Of the 1,619 consecutive patients with 1,765 CRCs detected between 2008 and 2016, 63 patients with 67 PCCRCs, when colonoscopies were performed 6–60 months before diagnosis, were recruited. After excluding patients with inflammatory bowel disease, familial polyposis syndrome, CRCs that developed from diminutive adenomatous polyps, and recurrent CRCs after endoscopic resection, 32 patients with 34 PCCRCs were enrolled. The lesions' clinicopathological features, mismatch repair proteins (MMRs), and genomic alterations were investigated.RESULTS:The overall PCCRC-5y rate, rate of intramucosal (Tis) lesions, and rate of T1 or more deeply invasive cancers were 3.7%(66/1,764), 3.9%(32/820), and 3.6%(34/944), respectively. Thirty-three patients' MMRs were investigated; 7 (21%) exhibited deficient MMRs (dMMRs), comprising 4 with T2 or more deeply invasive cancers and 5 whose …

MethodsWe extracted DNA from 36 early-stage colorectal tumor tissues (T1 cancer 9, Dysplasia 27) from 32 UC patients using microdissection and performed targeted sequencing of 43 genes that were reported to be strongly associated with Japanese UCACs in a previous report. Mutations from each cancer tissue were compared with counterpart dysplasia tissue and normal colitic mucosa tissue.ResultsWe found 16 genes that were mutated in more than 3 patients and had a mutation rate of more than 10 mutations/Mb. The most frequently mutated gene in cancers of UC patients was APC (mutated in 47.2% of our cohort), followed by TP53 (44.4%), KRAS (27.8%), PRKDC (27.8%), CSMD3 (22.2%), LTBP4 (13.9%), KIF26B (13.9%), CREBBP (13.9%), TCF7L2 (11.1%), EP300 (11.1%), and ATM (11.1%). Next, we divided 36 early-stage colorectal tumors into 23 UC-associated colorectal neoplasms (UCANs) and 13 …