Analysis of anti-tumor effect and mechanism of GLS1 inhibitor CB-839 in colorectal cancer using a stroma-abundant tumor model.

BACKGROUND: Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC). METHODS: Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed. RESULTS: Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through in vitro and in vivo experiments and clinical specimen analysis. CONCLUSIONS: GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.

Long-term prognosis after endoscopic submucosal dissection for esophageal cancer in older adult patients.

BACKGROUND: The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. METHODS: The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. RESULTS: The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. 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%, respectively (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 than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups. CONCLUSIONS: ESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient's general condition.

Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females.

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 alterations were validated using immunohistochemistry. RESULTS: Multiple logistic regression revealed that older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. CONCLUSION: Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0-IIa ESCC with keratinization of the posterior wall of the mid-thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

Verrucous gastritis-like lesion in intramucosal Helicobacter pylori-uninfected signet ring cell carcinoma with poorly differentiated adenocarcinoma.

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 into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.

Gel immersion EMR of small-bowel inflammatory fibroid polyp using double-balloon endoscopy.

Video 1A case of an inflammatory fibroid polyp of the ileum that was safely resected using gel immersion EMR with double-balloon endoscopy.

Predictive factors for esophageal stenosis in patients receiving prophylactic steroid therapy after endoscopic submucosal dissection for esophageal squamous cell carcinoma.

BACKGROUND: Methods 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. METHODS: Among 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, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups. RESULTS: Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively. CONCLUSIONS: Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.

Long-term outcomes of patients with obscure gastrointestinal bleeding after negative capsule endoscopy.

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 bowel. The rate of small-bowel rebleeding was significantly lower in the P0 group than that in the P1 group (1% vs 6%, P = 0.002), as was the cumulative rebleeding rate (P = 0.004). In the multivariate analysis, history of endoscopic hemostasis (hazard ratio [HR] = 15.958, 95% confidence interval [CI]:4.950-51.447, P < 0.001) and P1 CE findings (HR = 9.989, 95% CI: 2.077-48.030, P = 0.004) were independently predicted small-bowel rebleeding. CONCLUSIONS: OGIB with P0 CE findings rarely showed rebleeding from the small bowel. Rebleeding may occur in patients with OGIB. Patients with history of endoscopic hemostasis for small-bowel lesions or P1 CE findings should be followed up intensively.

Comparison of clinical utility of deep learning-based systems for small-bowel capsule endoscopy reading.

BACKGROUND AND AIM: Convolutional neural network (CNN) systems that automatically detect abnormalities from small-bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real-world SBCE setting. METHODS: Thirty-six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening. RESULTS: The mean number of small-bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1-5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2). CONCLUSIONS: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed.

Indications for Dental Floss Clip Traction During Gastric Endoscopic Submucosal Dissection by Less-Experienced Endoscopists.

PURPOSE: Dental 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. METHODS AND METHODS: We retrospectively analyzed 1,014 consecutive patients who had undergone gastric ESD performed by less-experienced endoscopists between January 2015 and December 2020. Gastric ESD was performed without DFC in all cases before December 2017 [DFC (-) group, 376 cases], and ESD was performed with DFC in all cases after January 2018 [DFC (+) group, 436 cases]. The procedure time and rates of en bloc resection, complete resection, and adverse events of the groups were compared. RESULTS: The procedure time did not differ significantly between the 2 groups. However, when comparing lesions >20 mm, the procedure time in the DFC (+) group was significantly shorter than that in the DFC (-) group (95±46 vs. 75±31, P<0.01). The procedure time for lesions located in the greater curvature of the upper or middle stomach and lesions >20 mm located in the lesser curvature side of the stomach in the DFC (+) group was significantly shorter than that in the DFC (-) group. CONCLUSIONS: The indications for DFC during gastric ESD by less-experienced endoscopists include lesions located in the greater curvature of the upper or middle stomach, and lesions >20 mm located in the lesser curvature of the stomach.

Disease surveillance evaluation of primary small-bowel follicular lymphoma using capsule endoscopy images based on a deep convolutional neural network (with video).

BACKGROUND AND AIMS: Capsule endoscopy (CE) is useful in evaluating disease surveillance for primary small-bowel follicular lymphoma (FL), but some cases are difficult to evaluate objectively. This study evaluated the usefulness of a deep convolutional neural network (CNN) system using CE images for disease surveillance of primary small-bowel FL. METHODS: We enrolled 26 consecutive patients with primary small-bowel FL diagnosed between January 2011 and January 2021 who underwent CE before and after a watch-and-wait strategy or chemotherapy. Disease surveillance by the CNN system was evaluated by the percentage of FL-detected images among all CE images of the small-bowel mucosa. RESULTS: Eighteen cases (69%) were managed with a watch-and-wait approach, and 8 cases (31%) were treated with chemotherapy. Among the 18 cases managed with the watch-and-wait approach, the outcome of lesion evaluation by the CNN system was almost the same in 13 cases (72%), aggravation in 4 (22%), and improvement in 1 (6%). Among the 8 cases treated with chemotherapy, the outcome of lesion evaluation by the CNN system was improvement in 5 cases (63%), almost the same in 2 (25%), and aggravation in 1 (12%). The physician and CNN system reported similar results regarding disease surveillance evaluation in 23 of 26 cases (88%), whereas a discrepancy between the 2 was found in the remaining 3 cases (12%), attributed to poor small-bowel cleansing level. CONCLUSIONS: Disease surveillance evaluation of primary small-bowel FL using CE images by the developed CNN system was useful under the condition of excellent small-bowel cleansing level.

Endoscopic findings suggestive of a high risk of non-radical cure after definitive chemoradiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: Definitive 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. METHODS: We 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. RESULTS: There 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 proportion of lesions with type 0-I. The 5-year relapse-free survival rate was significantly lower in type 0-I and in the presence of B3 vessels. Endoscopic findings in 15 patients with cT1bN0M0 ESCC, type 0-I, who underwent DCRT revealed significantly more reddish lesions in the RR group compared to the NRR group. CONCLUSIONS: cT1bN0M0 ESCC large size, with B3 vessels, and type 0-I has a high risk of non-radical cure after DCRT, especially the reddish type 0-I, which may need to be considered for treatment similar to advanced cancer, including surgery with preoperative DCRT.

Efficacy of the specialized scissor-type knife for gastric endoscopic submucosal dissection: a propensity score matched retrospective study.

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 intraoperative bleeding, delayed bleeding, and perforation rates were evaluated. Results No significant differences were observed in mean procedure time (SB-GX group: 115 ±â€Š165 min; IT-2 group: 95 ±â€Š61 min; P  = 0.82) and en bloc and complete resection rates between the two groups. Intraoperative bleeding rates were significantly lower in the SB-GX group than in the IT-2 group (18 % vs. 40 %; P  = 0.01), and there were no differences in delayed bleeding (4 % vs. 4 %) or perforation (0 % vs. 4 %) between the two groups. Conclusions The SB Knife GX was proven to be useful for control of intraoperative bleeding during gastric ESD, although the procedure time tended to be longer.

Diagnostic yield of proximal jejunal lesions with third-generation capsule endoscopy.

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 difference in baseline characteristics between these groups. Small-bowel lesions in the proximal jejunum comprised 75 tumors (54%), 50 vascular lesions (36%), and 13 inflammatory lesions (9%). The diagnostic rate was significantly higher in the SB3 group than in the SB2 group for tumors (91% vs. 72%, p < 0.05) and vascular lesions (97% vs. 69%, p < 0.01). For vascular lesions, in particular, the diagnostic rate of angioectasia improved in the SB3 group (100%) compared with that in the SB2 group (69%). Conclusions: SB3 use improved the detection of proximal jejunal tumors and vascular lesions compared with SB2 use.

Predictive factors for the progression of primary localized stage small-bowel follicular lymphoma.

BACKGROUND: Primary 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. METHODS: We 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 according to the clinicopathological and endoscopic findings. Endoscopic findings were focused on the color tone, circumferential location of follicular lesions (circumference ≥ 1/2 or < 1/2), fusion of follicular lesions (fusion [ +] or [ -]), and protruded lesions (≥ 6 mm or < 6 mm). RESULTS: Progressive disease was observed in 12 (20%) patients (mean observation period, 76.4 ± 55.4 months). In the multivariate analysis, "circumference ≥ 1/2" and "fusion (+)" were significant predictive factors for progression. According to the Kaplan-Meier analysis, progression-free survival was significantly shorter in the "circumference ≥ 1/2" and/or "fusion (+)" group than in the "circumference < 1/2" and "fusion ( -)" group. CONCLUSIONS: Endoscopic findings of "circumference ≥ 1/2" and "fusion (+)" were significant predictive factors for the progression of primary localized stage small-bowel FL.

Efficacy of single-balloon overtube for endoscopic submucosal dissection in the proximal colon: A propensity score-matched analysis.

Objectives: A single-balloon overtube (SBO) can improve poor scope operability during colonic endoscopic submucosal dissection (ESD). We aimed to evaluate the clinical usefulness of SBO for ESD in the proximal colon and the predictive factors for cases in which SBO is useful. Methods: A total of 88 tumors located in the proximal colon resected by balloon-assisted ESD (BA-ESD) using SBO and 461 tumors resected by conventional ESD (C-ESD) between June 2015 and November 2020 were considered. Seventy-eight tumors each in the BA-ESD and C-ESD groups were matched by propensity score matching. ESD outcomes were compared between the groups, and a decision tree analysis was performed to explore the predictive factors for cases in which SBO is useful. Results: There were no significant differences between the groups in the major outcomes such as en bloc resection rate (95% vs. 99%, p = 0.17), R0 resection rate (92% vs. 96%, p = 0.30), mean dissection speed (16 mm2/min vs. 16 mm2/min, p = 0.53), and intraoperative perforation rate (5% vs. 6%, p = 0.73). Even when considering cases with poor preoperative scope operability, there were no significant differences between the groups. Comparison of tumors ≥40 mm in diameter between the groups confirmed that the intraoperative perforation rate was significantly lower in the BA-ESD group than in the C-ESD group (0% vs. 24%, p = 0.0188). Conclusion: SBO is useful for ESD of tumors ≥40 mm in diameter in the proximal colon to prevent intraoperative perforation, which usually has a long procedure time.

Characteristics and Treatment Outcomes of Small-bowel Angioectasia in Systemic Sclerosis Patients: A Retrospective Observational Study.

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. Patients Patients were stratified according to the presence of small-bowel angioectasia. Among patients who underwent CE during the same period, those with small-bowel angioectasia without concomitant diseases were compared with SSc patients with small-bowel angioectasia. Clinical and endoscopic characteristics, treatment outcomes, and the incidence of metachronous small-bowel angioectasia after PDI were evaluated. Results SSc patients with small-bowel angioectasia exhibited significantly lower hemoglobin levels and a significantly higher incidence of skin telangiectasia than those without small-bowel angioectasia. On a multivariate analysis of the presence of small-bowel angioectasia, anemia and skin telangiectasia were significant independent factors. SSc patients with small-bowel angioectasia included a higher proportion of women and exhibited a significantly higher incidence of metachronous small-bowel angioectasia than X. The characteristics of small-bowel angioectasia and outcomes of PDI were not significantly different between the two groups. No post-treatment rebleeding cases or adverse events were noted. Conclusion CE should be performed for SSc patients with anemia and/or skin telangiectasia. PDI is effective for SSc patients with small-bowel angioectasia.

Endoscopic Delivery Method Using a Retrieval Net for Patients with Small-Bowel Capsule Endoscopy Stagnation in the Stomach.

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 69.2 ± 13.2 years. 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.

Capsule endoscopy findings reflect the gastrointestinal conditions of patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.

Genomic analysis for the prediction of prognosis in small-bowel cancer.

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 prediction in small-bowel cancers.

Exacerbation of Portal Hypertensive Enteropathy after Endoscopic Injection Sclerotherapy for Esophageal Varices.

INTRODUCTION: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. METHODS: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. RESULTS: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. CONCLUSIONS: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.