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Abstract Trousseau syndrome is a paraneoplastic syndrome associated with a risk of poor prognosis. We reviewed the survival time and prognosis of patients with Trousseau syndrome. We identified 40 cases from 28 reports of Trousseau syndrome due to pancreatic cancer. We analyzed 20 cases based on reports providing sufficient information on the stage/location of pancreatic cancer and survival time after Trousseau syndrome. The median survival time was 2.0 months. There was no statistical difference between performance status (PS) 0–1 and PS 4, stages I–III and IV, and pancreatic head and body/tail. However, statistically significant differences were noted between the median survival time of patients who continued treatment for pancreatic cancer even after Trousseau syndrome and those who discontinued treatment (P = 0.005). Although only a small number of cases were analyzed in this study, the results indicated that patients with pancreatic cancer who developed Trousseau syndrome had a poor prognosis, and chemotherapy should be continued, if possible.

Abstract Following the increase in colorectal neuroendocrine tumors (NETs), there is a consequent increase in the importance of their appropriate treatment and post‐treatment management. It is widely accepted that colorectal NETs sized ≥20 mm and those with muscularis propria invasion are indicated for radical surgery, and those sized

Abstract Background 10‐mm self‐expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent‐related adverse events (AEs). Methods We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent‐related non‐event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent‐related AEs). Secondary outcomes included stent‐related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined. Results A total of 76 patients were included (6‐mm group: 23; 10‐mm group: 53). Stent‐related NER (57% vs. 64%, p = 0.610), stent‐related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95–5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk‐reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration. Conclusions Stent‐related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6‐mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.

Abstract Objectives This study aimed to extract endoscopic findings for diagnosing colorectal neoplasia associated with sessile serrated lesions (SSLs), which are of significant interest. Methods To compare the magnifying narrow‐band imaging (NBI) findings with microscopic morphology, we classified SSLs into two groups: Group A SSLs included the majority of uniform SSLs and any dysplasia other than that classified as group B SSLs. Group B SSLs included SSLs with intramucosal and invasive carcinoma. We also quantitatively assessed visible vessels using ImageJ software. Results This study included 47 patients with 50 group B SSLs who underwent endoscopic resection between 2012 and 2020. The results were retrospectively compared with those of 237 patients with 311 group A SSLs that underwent endoscopic resection. Using conventional white‐light endoscopy, significantly more group B SSLs had uneven shapes and some reddening compared to group A SSLs. The diagnostic odds ratios for group B SSLs were as follows: lesions with a diameter ≥10 mm, 9.76; uneven shape, 3.79; reddening, 15.46; and visible vessels with NBI, 11.32. Regarding visible vessels with NBI, the specificity and diagnostic accuracy for group B SSLs were 94.9% and 93.1%, respectively. The percentage of the vascular tonal area of NBI images was significantly larger for group B SSLs than for group A SSLs (3.97% vs. 0.29%; p < 0.01). Conclusions SSLs with reddening and/or a diameter ≥10 mm are suspected to contain cancerous components. Moreover, visible vessels observed using magnifying NBI can serve as objective indicators for diagnosing SSLs with cancerous components with a high degree of accuracy.

Background/Aims: Many Japanese institutions use electromagnetic extracorporeal shock wave lithotripsy (ESWL) systems for treating pancreatic duct stones. However, there are no reports on direct comparisons between recent electromagnetic lithotripters. This study aimed to verify whether the new electromagnetic lithotripter can improve the efficiency of pancreatic stone fragmentation, and to clarify the role of combined endoscopic treatment on the clearance of pancreatic duct stones. Methods: We retrospectively identified 208 patients with pancreatolithiasis who underwent endoscopic adjunctive treatment after pancreatic ESWL at a single Japanese center over a 17-year period. We evaluated the outcome data of this procedure performed with SLX-F2 (last 2 years; group A) and Lithostar/Lithoskop (first 15 years; group B), as well as additional endoscopic treatments for pancreatolithiasis. We also performed logistic regression analysis to detect various factors associated with the procedure. Results: For pancreatic head stones, ESWL disintegration was achieved in 93.7% of group A patients and 69.0% of group B patients (p=0.004), and adjunctive endoscopic treatment removed stones in 96.8% of group A patients and 73.0% of group B patients (p=0.003). Multivariate analysis revealed that lithotripter type (odds ratio, 6.99; 95% confidence interval, 1.56 to 31.33; p

Abstract Background and Aim Percutaneous endoscopic gastrostomy (PEG) is often associated with early mortality. We therefore investigated factors associated with early death after PEG. Methods The present study comprised patients who had undergone PEG between April 2014 and March 2020. Patients were divided into two groups: an early mortality group who died within 1 month of PEG, and a non‐mortality group whose clinical course could be followed for more than 1 month after the procedure. Patient background, hematological data, and procedural duration were compared between groups. Results Univariate analysis identified older age, high blood urea nitrogen (BUN), low prognostic nutritional index (PNI), and high controlling nutritional status (CONUT) score as factors associated with early death after PEG. In multivariate analysis, high CONUT score remained an independent prognostic factor (P = 0.0035). Conclusion A high CONUT score may be a prognostic factor for early mortality after PEG.

Background/Aims: Endoscopic submucosal dissection (ESD) has been proposed for removal of gastrointestinal subepithelial tumors (GI-SETs), but data are still scanty. This study aimed to report a case series from a western country. Patients and Methods: Data of patients with upper GI-SETs suitable for ESD removal observed in 4 centers were retrospectively reviewed. Before endoscopic procedure, the lesion was characterized by endosonographic evaluation, histology, and CT scan. The en bloc resection and the R0 resection rates were calculated, as well as incidence of complications, and the 1-year follow-up was reported. Results: Data of 84 patients with esophageal (N = 13), gastric (N = 61), and duodenal (N = 10) GI-SETs were collected. The mean diameter of lesions was 26 mm (range: 12–110 mm). There were 17 gastrointestinal stromal tumors, 12 neuroendocrine tumors, 35 leiomyomas, 18 lipomas, and 2 hamartomas. En bloc and R0 resection were achieved in 83 (98.8%) and in 80 (95.2%) patients, respectively. Overall, a complication occurred in 11 (13.1%) patients, including bleeding (N = 7) and perforation (N = 4). Endoscopic approach was successful in all bleedings, but 1 patient who required radiological embolization, and in 2 perforations, while surgery was performed in the other patients. Overall, a surgical approach was eventually needed in 5 (5.9%), including 3 in whom R0 resection failed and 2 with perforation. Conclusions: Our study found that ESD may be an effective and safe alternative to surgical intervention for both benign and localized malignant GI-SETs.

Abstract Background and Aim Crohn's disease (CD) often causes intractable diarrhea after intestinal resection. Anion exchange resins have been reported to be effective in patients with bile acid diarrhea after distal ileectomy; furthermore, bile acid metabolism has been implicated in the pathogenesis of CD. Therefore, we aimed to examine the effectiveness of colestimide in the management of postoperative CD, and to compare its impact between patients with and those without ileocecal resection. Methods Postoperative CD patients prescribed colestimide for diarrhea between April 2017 and December 2020 were retrospectively evaluated for changes in the total Crohn's disease activity index (CDAI), each CDAI component including diarrhea frequency/week, albumin, and C‐reactive protein (CRP) was evaluated before and after the administration of colestimide. Furthermore, comprehensive patient and physician assessments were reviewed from medical records during the first outpatient visit as a global clinical judgment after the initiation of colestimide therapy. Results A total of 24 patients were included, of whom 17 had a previous history of ileocecal resection. Significant improvement was noted in CDAI and diarrhea frequency only in the ileocecal resection group (CDAI: 114.5 ± 52.7 and 95.4 ± 34.8, P

An appropriate post-polypectomy surveillance program requires the effectiveness of reducing colorectal cancer and safety. In addition, the post-polypectomy surveillance program should consider the burden of limited medical resource capacity, cost-effectiveness, and patient adherence. In this sense, a risk-stratified surveillance program based on baseline colonoscopy results is ideal. Major international guidelines for post-polypectomy surveillance, such as those from the European Union and the United States, have recommended risk-stratified surveillance programs. Both guidelines have recently been updated to better differentiate between high- and low-risk individuals. In both updated guidelines, more individuals have been downgraded to lower-risk groups that require less frequent or no surveillance. Furthermore, increased attention has been paid to the surveillance of patients who undergo serrated polyp removal. Previous guidelines in Japan did not clearly outline the risk stratification in post-polypectomy surveillance. However, the new colonoscopy screening and surveillance guidelines presented by the Japan Gastroenterological Endoscopy Society include a risk-stratified post-polypectomy surveillance program. Further discussion and analysis of unresolved issues in this field, such as the optimal follow-up after the first surveillance, the upper age limit for surveillance, and the ideal method for improving adherence to surveillance guidelines, are warranted.

Abstract Objectives Duckbill‐type metal stent (DMS) was the first laser‐cut biliary metal stent with an anti‐reflux valve. Removal of DMS is believed to be difficult and relevant reports are scarce. This study aims to investigate the feasibility of DMS removal. Methods We retrospectively analyzed patients who underwent DMS removal between June 2019 and March 2022 to evaluate success rates and factors affecting outcomes. In addition, six different methods of DMS removal were reproduced in vitro, varying removal devices, angle of applied force, and grasped location. Extraction resistance, the distance of forceps stroke, and stent length after removal were compared. Results Forty patients were enrolled, and DMS removal was successful in 31 cases (78%). No adverse events were observed. Tumor ingrowth was evident in 78% (7/9) of failed cases. Patients receiving biliary metal stents for the first time (naïve cases), long indwelling time, longer stent, and stent tearing during removal were associated with unsuccessful stent removal. In the in vitro study, a larger force was required to remove the stent at an extraction angle of 120° than at 0°. Among cases in which force was applied at 120°, the load tended to be lower when rat‐tooth forceps were applied horizontally across the stent. Conclusions Stent removal was possible in a majority of cases. Deployment of additional stents inside DMS may be preferable to forceful removal in the presence of factors associated with difficult stent removals, such as tumor ingrowth, naïve cases, longer stents, long indwelling time, and stent tearing during removal.

Abstract Red dichromatic imaging is a new image‐enhancement technology that clarifies the differences in blood concentrations and improves the visibility of the bleeding point. A 71‐year‐old man was presented with a common bile duct stone, which was completely removed using electrohydraulic shock wave lithotripsy with peroral cholangioscopy. During peroral cholangioscopy, a nodular lesion was found at the confluence of the cystic duct, and a forceps biopsy was performed. It was difficult to confirm the bleeding point using white‐light imaging because of the pooling of blood. After switching to red dichromatic imaging mode 2 and washing the bile duct with saline solution, the bleeding point was observed in darker yellow than the surrounding blood, allowing the identification of the bleeding point. Red dichromatic imaging can be used in the future to maintain hemostasis during peroral cholangioscopy.

Abstract Background and Aim This study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features. Methods We retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed. Results A total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B‐cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa‐associated lymphoid tissue (MALT) lymphoma (9%), peripheral T‐cell lymphoma‐NOS (2%), monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine. Conclusions Colorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types.

Background/Aims Probe-based confocal laser endomicroscopy (pCLE) requires the administration of intravenous (IV) fluorescein. This study aimed to determine the optimal dose of IV fluorescein for both upper and lower gastrointestinal (GI) tract pCLE. Methods Patients 20 to 79 years old with gastric high-grade dysplasia (HGD) or colorectal neoplasms (CRNs) were enrolled in the study. The dose de-escalation method was employed with five levels. The primary endpoint of the study was the determination of the optimal dose of IV fluorescein for pCLE of the GI tract. The reduced dose was determined based on off-line reviews by three endoscopists. An insufficient dose of fluorescein was defined as the dose of fluorescein with which the pCLE images were not deemed to be visible. If all three endoscopists determined that the tissue structure was visible, the doses were de-escalated. Results A total of 12 patients with gastric HGD and 12 patients with CRNs were enrolled in the study. Doses were de-escalated to 0.5 mg/kg of fluorescein for both non-neoplastic duodenal and colorectal mucosa. All gastric HGD or CRNs were visible with pCLE with IV fluorescein at 0.5 mg/kg. Conclusions In the present study, pCLE with IV fluorescein 0.5 mg/kg was adequate to visualize the magnified structure of both the upper and lower GI tract.

Abstract Annular pancreas is a congenital abnormality in which part of the pancreatic head completely or partially surrounds the duodenum in a ring‐like manner. The condition is thought to be an abnormality of the ventral pancreatic bud. While pancreatitis is a common complication of the annular pancreas, its recurrence may be prevented by improving the outflow of pancreatic juice. The present case report describes a 23‐year‐old woman who had been referred to our hospital for recurrent pancreatitis since childhood. An endoscopic incision was made on the orifice of the annular pancreas, after which pancreatitis of the annular pancreas did not recur for 6 years. The patient subsequently exhibited pancreatolithiasis in the dorsal pancreatic duct, which was successfully treated with endoscopic treatment. Endoscopic pancreatic sphincterotomy may prevent the recurrence of pancreatitis and avoid further surgical interventions by improving the flow of pancreatic juice.

This systematic review aimed to assess the efficacy of the current approach to tissue traction during the endoscopic submucosal dissection (ESD) of superficial esophageal cancer, early gastric cancer, and colorectal neoplasms. We performed a systematic electronic literature search of articles published in PubMed and selected comparative studies to investigate the treatment outcomes of tractionassisted versus conventional ESD. Using the keywords, we retrieved 381 articles, including five eligible articles on the esophagus, 13 on the stomach, and 12 on the colorectum. A total of seven randomized controlled trials and 23 retrospective studies were identified. Clip line traction and submucosal tunneling were effective in reducing the procedural time during esophageal ESD. The efficacy of traction methods in gastric ESD varied in terms of the devices and strategies used depending on the lesion location and degree of submucosal fibrosis. Several prospective and retrospective studies utilized traction devices without the need to reinsert the colonoscope. When pocket creation is included, the traction devices and methods effectively shorten the procedural time during colorectal ESD. Although the efficacy is dependent on the organ and tumor locations, several traction techniques have been demonstrated to be efficacious in facilitating ESD by maintaining satisfactory traction during dissection.

The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests.

Background: There is limited data on the relationship between hospital volumes and outcomes with respect to cancer survival in Japan. The primary objective of this study was to evaluate the effect of hospital volume on cancer survival rate using a population-based cohort database. Methods: Using the Kanagawa cancer registry, propensity score matching was employed to create a dataset for each cancer type by selecting 1:1 matches for cases from high- and other-volume hospitals. The 5-year survival rate was estimated and the hazard ratio (HR) for hospital volume was calculated using a Cox proportional hazard model. Additional analyses were performed limited to cancer patients who underwent surgical operation, chemotherapy, and other treatments in each tumor stage and at the time of diagnosis. Results: The number of cases with complete data, defined as common cancers (prostate, kidney, bladder, esophagus, stomach, liver, pancreas, colon, breast, and lung), was 181,039. Adjusted HR differed significantly among hospital volume categories for the most common cancers except bladder, and the trends varied according to cancer type. The HR ranged from 0.76 (95%CI, 0.74–0.79) for stomach cancer to 0.85 (0.81–0.90) for colon cancer. Conclusions: This study revealed that a relationship may exist between hospital volume and cancer survival in Japan.

Background and study aims Large adenomas are sometimes misidentified as cancers during colonoscopy and are surgically removed. To address this overtreatment, we developed an artificial intelligence (AI) tool that identified cancerous pathology in vivo with high specificity. We evaluated our AI tool under the supervision of a government agency to obtain regulatory approval. Patients and methods The AI tool outputted three pathological class predictions (cancer, adenoma, or non-neoplastic) for endocytoscopic images obtained at 520-fold magnification and previously trained on 68,082 images from six academic centers. A validation test was developed, employing 500 endocytoscopic images taken from various parts of randomly selected 50 large (≥ 20 mm) colorectal lesions (10 images per lesion). An expert board labelled each of the 500 images with a histopathological diagnosis, which was made using endoscopic and histopathological images. The validation test was performed using the AI tool under a controlled environment. The primary outcome measure was the specificity in identifying cancer. Results The validation test consisted of 30 cancers, 15 adenomas, and five non-neoplastic lesions. The AI tool could analyze 83.6 % of the images (418/500): 231 cancers, 152 adenomas, and 35 non-neoplastic lesions. Among the analyzable images, the AI tool identified the three pathological classes with an overall accuracy of 91.9 % (384/418, 95 % confidence interval [CI]: 88.8 %–94.3 %). Its sensitivity and specificity for differentiating cancer was 91.8 % (212/231, 95 % CI: 87.5 %–95.0 %) and 97.3 % (182/187, 95 % CI: 93.9 %–99.1 %), respectively. Conclusions The newly developed AI system designed for endocytoscopy showed excellent specificity in identifying colorectal cancer.

Colorectal tumors with superficial submucosal invasion, which cannot be removed by snaring, are one of the most optimal indications for colorectal endoscopic submucosal dissection (ESD). Therefore, estimation of the invasion depth is the first key to successful colorectal ESD. Although estimation of the invasion depth based on the gross morphology may be useful in selected cases, its diagnostic accuracy could not reach the clinical requirement. The Japan Narrow-band Imaging (NBI) Expert Team (JNET) classification of NBI magnifying endoscopy findings is a useful method for histologic prediction and invasion depth estimation. However, magnifying chromoendoscopy is still necessary for JNET type 2B lesions to reach a satisfactory diagnostic accuracy. Endocytoscopy with artificial intelligence is a promising technology in invasion depth estimation; however, more data are needed for its clinical application.

Background and study aims Linked color imaging (LCI), a newly developed optical modality, enhances mucosal surface contrast. We aimed to evaluate the efficacy and feasibility of insertion-phase LCI in terms of additional benefit of colorectal polyp detection over that obtained with white light imaging (WLI). Patients and methods We consecutively enrolled eligible patients from November 2017 to June 2018. During colonoscopy, LCI or WLI was alternatively applied on scope insertion and LCI was applied on scope withdrawal. Patients were divided into two groups according to the protocolized difference of imaging modality used in the scope insertion phase (LCI and WLI groups). Group differences in clinical outcomes were evaluated. Results A total of 138 patients were enrolled in this study, with equal numbers of patients assigned to the LCI and WLI groups. Most of the lesions located in the proximal colon were detected during the withdrawal phase, without a difference in proportions between the two groups. However, in the LCI group, eight of 49 lesions (16 %) located in the sigmoid and rectosigmoid colon were only detected during the insertion phase, and no such lesions (0 %) were detected during the insertion phase in the WLI group (P = 0.045). Conclusions This study showed the efficacy and feasibility of LCI in improving colorectal polyp detection in the sigmoid colon, especially during insertion. Further studies are warranted to validate the results of our single-center study.

Background and study aims Surgery is the standard treatment for colon tumors associated with diverticulum. Use of endoscopic submucosal dissection (ESD) to treat such tumors is controversial. The aim of this study was to assess the safety and feasibility of ESD in treating superficial colorectal tumors situated near or involving diverticulum. Patients and methods Consecutive patients from two referral centers who had colorectal tumors near or involving diverticulum treated by ESD were retrospectively studied. Clinicopathological characteristics and clinical outcomes were analyzed. Results Of the 12 patients studied, six had tumors near diverticulum and six had tumors involving diverticulum. The overall en-bloc R0 resection rate, median tumor size and procedure time were 67 %, 26.5 mm (range, 15 – 80 mm) and 110 minutes (range, 50 – 220 minutes), respectively. For tumors near diverticulum group, the en-bloc R0 resection rate was 100 % and no adverse events (AEs) or residual/recurrent tumors were observed. In contrast, for intradiverticular tumors group, the en-bloc R0 resection rate was low at 33 %, and one AE (perforation) was observed. The diverticula were ≥ 6 mm in diameter in the patients with incomplete resection. However, all but one diverticulum was unrecognized before ESD. Two residual tumors were detected at the 12-month surveillance and one required surgery. Conclusions This case series indicates that ESD is safe and feasible for treating colorectal tumors near a diverticulum and might be feasible for tumors involving a diverticulum smaller than 6 mm. Selection for smaller diverticulum size may contribute to higher en-bloc R0 resection rates.

Background and aim The depth of tumor invasion is currently the only reliable predictive risk factor for lymph node metastasis before endoscopic treatment for colorectal cancer. However, the most important factor to predict lymph node metastasis has been suggested to be lymphovascular invasion rather than the depth of invasion. Thus, the aim of this study was to investigate the predictive relevance of lymphovascular invasion before endoscopic treatment. Methods The data on pT1 colorectal cancers that were resected endoscopically or surgically from 2007 to 2015 were retrospectively reviewed. The cases were categorized into two groups: positive or negative for lymphovascular invasion. The following factors were evaluated by univariate and multivariate analyses: age and sex of the patients; location, size, and morphology of the lesion; and depth of invasion. Results The positive and negative groups included 229 and 457 cases, respectively. Younger age (P 65 years, OR, 1.81; 95 %CI, 1.29 – 2.53), presence of depression (OR, 1.97; CI, 1.40 – 2.77), non-LST features (OR, 1.50; CI, 1.04 – 2.15), and pT1b (OR, 3.08; CI, 1.91 – 4.97) were associated with lymphovascular invasion. Conclusion Younger age, presence of depression, T1b, and non-LST are associated with lymphovascular invasion. Therefore, careful pathological diagnosis and surveillance are necessary for lesions demonstrating any of these four factors.

Background and study aims Magnifying narrow-band imaging (M-NBI) enables detailed observation of microvascular architecture and can be used in endoscopic diagnosis of colorectal lesion. However, in clinical practice, differential diagnosis and estimation of invasion depth of colorectal lesions based on M-NBI findings require experience. Therefore, developing computer-aided diagnosis (CAD) for M-NBI would be beneficial for clinical practice. The aim of this study was to evaluate the effectiveness of software for CAD of colorectal lesions. Materials and methods In collaboration with Yamaguchi University, we developed novel software that enables CAD of colorectal lesions using M-NBI images. This software for CAD further specifically divides original Sano’s colorectal M-NBI classification into 3 groups (group A, capillary pattern [CP] type I; group B, CP type II + CP type IIIA; group C, CP type IIIB), which describe hyperplastic polyps (HPs), adenoma/adenocarcinoma (intramucosal [IM] to submucosal [SM]-superficial) lesions, and SM-deep lesions, respectively. We retrospectively reviewed 121 lesions evaluated using M-NBI. Results The 121 reviewed lesions included 21 HP, 80 adenoma/adenocarcinoma (IM to SM-superficial), and 20 SM-deep lesions. The concordance rate between the CAD and the diagnosis of the experienced endoscopists was 90.9 %. The sensitivity, specificity, positive and negative predictive values, and accuracy of the CAD for neoplastic lesions were 83.9 %, 82.6 %, 53.1 %, 95.6 %, and 82.8 %, respectively. The values for SM-deep lesions were 83.9 %, 82.6 %, 53.1 %, 95.6 %, and 82.8 %, respectively. Conclusion Relatively high diagnostic values were obtained using CAD. This software for CAD could possibly lead to a wider use of M-NBI in the endoscopic diagnosis of colorectal lesions.

Background and study aims Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by the presence of more than 100 adenomatous polyps in the colorectum. The upper gastrointestinal tract is an extracolonic site for malignancy in patients with FAP. The frequency of death in Japanese patients with FAP because of gastric cancer is 2.8 % and that because of colon cancer is 60.6 %. Few studies have reported upper gastrointestinal diseases in patients with FAP. In the present study, we investigated the clinical outcomes of patients with FAP diagnosed with gastric neoplasms. Patients and methods We enrolled 80 patients with FAP who underwent esophagogastroduodenoscopy from October 1997 to December 2011. We investigated patient characteristics, endoscopic findings of gastric lesions, treatment outcomes, and long-term courses. Results Fundic gland polyposis was observed in 51 patients (64 %) and gastric neoplasms in 22 patients (28 %), including 20 with non-invasive and 2 with invasive neoplasm. Of the 26 neoplasms, 11 were treated by endoscopic resection (ER) and 4 by surgical resection. Metachronous gastric neoplasms were observed in 7 patients (15 lesions) and treated by ER, except for in 1 patient. No patients died of gastric lesions during a median follow-up period of 6.5 years (range, 0 – 14). Conclusion Because gastric lesions including gastric cancers in patients with FAP did not cause any deaths, they can be considered to have favorable prognoses. Early detection of gastric neoplasms through an appropriate follow-up interval may have contributed to these good outcomes.

To date, few reports focused primarily on detecting colorectal laterally spreading tumors (LSTs) have been published. The aim of this study was to determine the visibility of LSTs on computed tomographic colonography (CTC) compared with that on colonoscopy as a standard. We retrospectively reviewed and matched data on endoscopic and CTC reports in 157 patients (161 LSTs) who received a multidetector CT scan using contrast media immediately after total colonoscopy at the National Cancer Center Hospital in Tokyo, Japan, between December 2005 and August 2010. The results of the total colonoscopy were known at the time of the CTC procedure and reading. Of the 161 LSTs detected on colonoscopy, 138 were observed and matched by CTC (86%). Of the 91 granular type LSTs (LST-Gs), 88 (97%) were observed and matched, while of the 70 non-granular type LSTs (LST-NGs), 50 (71%) were observed and matched by CTC (p < 0.0001). CTC enabled observation of 73% (22/30) of 20–29 mm, 83% (35/42) of 30–39 mm, 88% (49/56) of 40–59 mm, and 97% (32/33) of ≥60 mm tumors. The rate of observed LSTs by CTC was 86% (97% of LST-G, 71% of LST-NG) of the LSTs found during total colonoscopy.

Background and study aims: Five-aminolevulinic acid (5-ALA) is being increasingly used for photodynamic diagnosis and therapy of various types of tumors including brain, urologic, and other neoplasias. The use of 5-ALA to treat Barrett’s carcinomas has been documented, but its clinical effectiveness for diagnosis of gastrointestinal tumors, particularly early cancers, remains unknown. Patients and methods: The aim of our feasibility study was to evaluate the visibility of colorectal tumors using endoscopic fluorescence imaging (EFI) after oral administration of 5-ALA. The lesions identified by direct visualization and by the spectrums produced using EFI modality with 5-ALA were compared to the clinicopathologic features of resected specimens. Results: Twenty-three patients with a total of 27 known colorectal lesions were enrolled in the study. The median tumor size was 30 mm (range 10 – 75). Eleven of the lesions were flat or depressed lesions and 16 were sessile. Red fluorescence was observed in 22 out of 27 lesions. Red fluorescence was negative in 4 out of 11 flat or depressed lesions. In comparison with histopathologic findings, the rates of red fluorescence visibility were 62.5 % in low-grade intraepithelial neoplasia, 77.8 % in high-grade neoplasia, and 100 % in submucosal carcinoma. Red fluorescence visibility increased with the degree of dysplasia. There were no significant adverse events identified in this study. Conclusions: This feasibility study using EFI with 5-ALA demonstrated high visibility of superficial colorectal neoplasia. EFI with 5-ALA appears to be a novel, safe technique for improving real-time colorectal tumor imaging.

Background and study aims: Although endoscopic resection is widely used for the treatment of superficial colorectal neoplasms, the rate of local recurrence of lesions with a positive or indeterminate lateral margin on histologic evaluation is unclear. We aimed to demonstrate the relationship between lateral margin status and local recurrence after the endoscopic resection of intramucosal colorectal neoplasms. Patients and methods: We retrospectively collected the clinical and pathologic data for 844 endoscopically resected colorectal intramucosal neoplasms with a size of 10 mm or larger. We investigated the relationship between the local recurrence rate and the lateral margin status (categorized as LM0 [negative], LM1 [positive], or LMX [indeterminate]). Results: In total, 389 lesions were evaluated as LM0 and showed no local recurrence. Of the 455 lesions evaluated as LMX or LM1, 30 showed local recurrence within a median period of 6.3 months (range, 1.7 – 48.1) from the initial endoscopic resection. The local recurrence rate of the en bloc-LMX group (2.2 %) was significantly lower than that of the piecemeal-LMX group (15.2 %). Of the 30 cases of recurrence, 28 were successfully treated with a second endoscopic resection. Of the two lesions that showed further recurrence, one was treated with a third endoscopic resection, whereas the other – which was a piecemeal-LMX lesion – was eventually diagnosed as invasive cancer and treated with surgery. Conclusions: The local recurrence rate was lower in the en bloc-LMX group than in the piecemeal-LMX group. Thus, we believe that en bloc-LMX lesions that are completely and confidently resected endoscopically can be treated as en bloc-LM0 lesions.

Laterally spreading tumors may sometimes evade detection by colonoscopy. This study aimed to evaluate the use of image-enhanced endoscopy for visualizing laterally spreading tumors of the nongranular type. We reviewed consecutive patients with 47 non-granular-type laterally spreading tumors that had been examined using white-light imaging, autofluorescence imaging, narrow-band imaging, and chromoendoscopy with indigo carmine. The quality of visualization was evaluated using a 5-point scale by less- and more-experienced endoscopists. Autofluorescence imaging provided significantly better visualization than white-light imaging for both less-experienced and experienced endoscopists. On the other hand, no significant differences were observed between the quality of visualization provided by white-light imaging and narrow-band imaging for less-experienced endoscopists. Autofluorescence imaging provides high-quality visualization of non-granular-type laterally spreading tumors on still images. Multicenter trials should be conducted to confirm the usefulness of autofluorescence imaging in detecting laterally spreading colorectal tumors.

Introduction. In Japan, the cost-effectiveness of total colonoscopy (TCS) for primary screening of colorectal cancer (CRC) is unclear. We compared the cost of identifying a patient with CRC using two primary screening strategies: TCS (strategy 1) and the immunochemical fecal test (FIT) (strategy 2). Materials and Methods. We retrospectively analyzed the TCS screening database at our institution from February 2004 to August 2010 (strategy 1, 𝑛=15,348) and the Japanese nationwide survey of CRC screening in 2008 (strategy 2, 𝑛=5,267,443). Results. 112 and 6,838 CRC cases were detected in strategies 1 and 2, costing 2,124,000 JPY and 1,629,000 JPY, respectively. The rate of earlier-stage CRC was higher in strategy 1. Conclusions. The cost was higher using TCS as a primary screening procedure. However, the difference was not excessive, and considering the increased rate of detecting earlier CRC, the use of TCS as a primary screening tool may be cost-effective.

Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the "fetal gene program". Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3'UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload.

Endoscopic submucosal (sm) dissection (ESD) is a recently used technique that enables en-bloc resection of large colorectal tumors allowing a more precise histopathological analysis of the resected specimen. However, it has not been widely adopted even in Japan mainly due to its technical difficulty and increased risk of perforation. Herein, we present an ESD-treated lesion with deep sm invasion removed without complications, such as bleeding or perforation, from a patient at high-risk for surgical intervention. A successful ESD was achieved although the sm invasion was greater than 1000 μm from the muscularis mucosae, and the nonlifting sign was positive. It is our belief that this procedure should be performed at least in patients at high-risk for surgical intervention. At present, we have removed 16 lesions with deep sm invasion by ESD without complications, demonstrating that deep sm cancer can be successfully resected by this technique as a local resection. Herein, we report on one of these cases

Background/Aims: Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated. Methods: Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed. Results: A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8. Conclusions: LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy. [ABSTRACT FROM AUTHOR]