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Background: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan., Methods: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum., Results: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA., Conclusions: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis., (© 2024. The Author(s).)

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., (© 2022. Japanese Society of Gastroenterology.)

Background: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions., Methods: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed., Results: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis., Conclusions: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY., Trial Registration Number: UMIN000025215., (© 2022. Japanese Society of Gastroenterology.)

Background: Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan., Methods: We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria., Results: Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1-T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II., Conclusions: Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial., (© 2022. Japanese Society of Gastroenterology.)

Background: The Japanese Society of Gastroenterology (JSGE) published ''Daicho Polyp Shinryo Guideline 2014'' in Japanese and a part of this guideline was published in English as "Evidence-based clinical practice guidelines for management of colorectal polyps" in the Journal of Gastroenterology in 2015. A revised version of the Japanese-language guideline was published in 2020, and here we introduce a part of the contents of revised version., Methods: The guideline committee discussed and drew up a series of clinical questions (CQs). Recommendation statements for the CQs were limited to items with multiple therapeutic options. Items with established conclusions that had 100% agreement with previous guidelines (background questions) and items with no (or old) evidence that are topics for future research (future research questions: FRQs) were given descriptions only. To address the CQs and FRQs, PubMed, ICHUSHI, and other sources were searched for relevant articles published in English from 1983 to October 2018 and articles published in Japanese from 1983 to November 2018. The Japan Medical Library Association was also commissioned to search for relevant materials. Manual searches were performed for questions with insufficient online references., Results: The professional committee created 18 CQs and statements concerning the current concept and diagnosis/treatment of various colorectal polyps, including their epidemiology, screening, pathophysiology, definition and classification, diagnosis, management, practical treatment, complications, and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumors/carcinomas)., Conclusions: After evaluation by the moderators, evidence-based clinical practice guidelines for management of colorectal polyps were proposed for 2020. This report addresses the therapeutic related CQs introduced when formulating these guidelines.

Background: We analyzed the influence of preceding endoscopic submucosal dissection (ESD) on the prognosis of patients with T1 colorectal carcinoma (CRC) after additional surgery using propensity-score matching., Methods: 1638 consecutive patients with T1 CRC were retrospectively identified between January 1998 and December 2016 at the Hiroshima GI Endoscopy Research Group. We assessed 602 patients with 602 T1 CRC who underwent additional surgery after ESD (n = 216) or surgery alone (n = 386). The enrolled patients were treated according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016, and were defined as non-endoscopically curable (non-e-curable) when they did not satisfy its curative criteria. We analyzed the pathological characteristics and the prognosis of non-e-curable patients using propensity-score matching between the additional surgery after ESD and surgery alone groups., Results: There were no cases of recurrence and lymph node metastasis among the e-curable patients. The rate of lymph node metastasis and recurrences in the non-e-curable patients were 10.8% and 2.6%, respectively. After propensity-score matching, there were no significant differences in the 5-year overall survival rates (96.9% vs. 92.0%), 5-year disease-free survival rates (96.7% vs. 96.7%) and 5-year disease-specific survival rates (100% vs. 98.6%) after treatment of T1 CRCs between the 2 groups in non-e-curable patients., Conclusions: Preceding ESD with histological en bloc resection for patients with T1 CRC did not affect their oncologic behavior adversely after additional surgery.

Background: We aimed to clarify the long-term outcomes of patients with T1 colorectal carcinoma (CRC) after endoscopic resection (ER) and surgical resection., Methods: We examined T1 CRC patients treated during 1992-2008 and who had ≥5 years of follow-up. Patients who did not meet the curative criteria after ER according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines were defined as "non-endoscopically curable" and classified into three groups: ER alone (Group A: 121 patients), additional surgery after ER (Group B: 238 patients), and surgical resection alone (Group C: 342 patients). Long-term outcomes and predictors of recurrence were analyzed., Results: Of the 882 patients with T1 CRC, 701 were non-endoscopically curable. Among these patients, recurrence and 5-year overall survival (OS) rates were 0.6 and 91.1%, respectively. In Groups A, B, and C, recurrence rates were 5.0, 5.5, and 3.8%, OS rates were 79.3, 92.4, and 91.5% (p < 0.01), and 5-year disease-free survival (DFS) rates were 98.1, 97.9, and 98.5%, respectively. Thirty-two patients experienced local recurrence or distant/lymph node metastasis (Group A: 6; Group B: 13; Group C: 13) and 14 patients died of primary CRC (Group A: 3; Group B: 7; Group C: 4). Age ≥65 years, protruded gross type, positive lymphatic invasion, and high budding grade were significant predictors of recurrence in non-endoscopically curable patients., Conclusions: Our findings supported the JSCCR criteria for endoscopically curable T1 CRC. ER for T1 CRC did not worsen the clinical outcomes of patients who required additional surgical resection.

Background: The risk for lymph node metastasis and the prognostic significance of pedunculated-type T1 colorectal carcinomas (CRCs) require further study. We aimed to assess the validity of the 2014 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines based on long-term outcomes of pedunculated-type T1 CRCs., Methods: In this multicenter retrospective cohort study, we examined 176 patients who underwent resection endoscopically or surgically at 14 institutions between January 1990 and December 2010. Patients meeting the JSCCR curative criteria were defined as "endoscopically curable (e-curable)" and those who did not were "non-e-curable". We evaluated the prognosis of 116 patients (58 e-curable, 58 non-e-curable) who were observed for >5 years after treatment., Results: Overall incidence of lymph node metastasis was 5 % (4/81; 95 % confidence interval 1.4-12 %: three cases of submucosal invasion depth ≥1000 μm [stalk invasion] and lymphatic invasion, one case of head invasion and budding grade 2/3). There was no local or metastatic recurrence in the e-curable patients, but six of them died of another cause (observation period, 80 months). There was no local recurrence in the non-e-curable patients; however, distant metastasis was observed in one patient. Death due to the primary disease was not observed in non-e-curable patients, but six of them died of another cause (observation period, 72 months)., Conclusions: Our data support the validity of the JSCCR curative criteria for pedunculated-type T1 CRCs. Endoscopic resection cannot be considered curative for pedunculated-type T1 CRC with head invasion alone.

Background: KRAS gene mutations are found in 40-50% of colorectal cancer cases, but their functional contribution is not fully understood. To address this issue, we generated genetically engineered mice with colon tumors expressing an oncogenic Kras(G12D) allele in the context of the Adenomatous polyposis coli (Apc) deficiency to compare them to tumors harboring Apc deficiency alone., Methods: CDX2P9.5-G22Cre (referred to as G22Cre) mice showing inducible Cre recombinase transgene expression in the proximal colon controlled under the CDX2 gene promoter were intercrossed with Apc (flox/flox) mice and LSL-Kras (G12D) mice carrying loxP-flanked Apc and Lox-Stop-Lox oncogenic Kras(G12D) alleles, respectively, to generate G22Cre; Apc(flox/flox); Kras(G12D) and G22Cre; Apc(flox/flox); KrasWT mice. Gene expression profiles of the tumors were analyzed using high-density oligonucleotide arrays., Results: Morphologically, minimal difference in proximal colon tumor was observed between the two mouse models. Consistent with previous findings in vitro, Glut1 transcript and protein expression was up-regulated in the tumors of G22Cre;Apc (flox/flox) ; Kras(G12D) mice. Immunohistochemical staining analysis revealed that GLUT1 protein expression correlated with KRAS mutations in human colorectal cancer. Microarray analysis identified 11 candidate genes upregulated more than fivefold and quantitative PCR analysis confirmed that Aqp8, Ttr, Qpct, and Slc26a3 genes were upregulated 3.7- to 30.2-fold in tumors with mutant Kras., Conclusions: These results demonstrated the validity of the G22Cre; Apc(flox/flox) ;Kras (G12D) mice as a new mouse model with oncogenic Kras activation. We believe that this model can facilitate efforts to define novel factors that contribute to the pathogenesis of human colorectal cancer with KRAS mutations.

Background: Histopathology can be used to detect ulcerative colitis (UC) relapse, but diagnosis of the disease activity by histopathology requires multiple biopsies to be taken. Magnifying endocytoscopy provides a method for real-time ultra-magnifying imaging. It was recently reported that the endocytoscopy system score (ECSS) correlates well with the histopathology of UC. Here we evaluated the clinical usefulness of endocytoscopy for accurately monitoring UC during remission., Methods: We performed endocytoscopy on 26 patients with UC in remission that had been diagnosed by conventional colonoscopy at our institution between January and April 2013. Endocytoscopy was performed at the area of the rectum where UC had been detected with conventional endoscopy. Biopsies were also taken from the same area and histopathology was evaluated by a single pathologist according to the Matts' grading system. The correlation between the relapse rate of UC and both the ECSS and the Matts' histopathological grade was evaluated., Results: The ECSS of the intestinal mucosa in UC showed a correlation with the Matts' histopathological grade (Spearman's |r| = 0.647). The patients were classified into two groups: those with an ECSS of 0-2 (Grade A, 12 cases) and those with an ECSS of 3-6 (Grade B, 10 cases). To date, three Grade B cases have relapsed and no Grade A cases have relapsed. The average post-endocytoscopy surveillance period was 446 ± 92 days., Conclusions: The ECSS may be a predictive indicator for UC relapse since there was a correlation between the ECSS and the degree of inflammation as determined by histopathology.

Background: Although Japanese guidelines proposed by the Japan Gastroenterological Endoscopy Society for endoscopic submucosal dissection (ESD) for colorectal tumors recommend continued use of low-dose aspirin (LDA), this strategy is controversial. It was our practice to interrupt LDA therapy 5-7 days before ESD until December 2010, when we instituted the new guidelines and performed ESD without interrupting LDA therapy. The aim of the present study was to confirm the validity of the noninterrupted use of LDA inpatients undergoing ESD for colorectal tumors., Methods: We studied 582 consecutive patients with 609 colorectal tumors who underwent ESD at Hiroshima University Hospital between January 2006 and July 2014. The patients comprised three groups: LDA-interrupted group (13 patients with 13 colorectal tumors), LDA-continued group (28 patients with 31 colorectal tumors), and no anticoagulant/antiplatelet group (541 patients with 565 colorectal tumors)., Results: The en bloc resection rate was 100% (13/13) in the LDA-interrupted group and 90.3% (28/31) in the LDA-continued group. Incidences of poor bleeding control during the procedure and bleeding after the procedure were 7.7% (1/13) and 15.4% (2/13) of patients, respectively, in the LDA-interrupted group, and 3.2% (1/31) and 16.1% (5/31) of patients, respectively, in the LDA-continued group. No patients experienced ischemic events in the perioperative period., Conclusions: Our data suggest that continued use of LDA increased the risk of bleeding after ESD for colorectal tumors compared with nonuse of anticoagulant/antiplatelets. No significant difference was seen between the LDA-continued group and the LDA-interrupted group.

Background: Previous studies have yielded conflicting results on the adenoma detection rate with narrow band imaging (NBI) compared with white light imaging (WLI). To overcome the confounding factors of these studies, we aimed to evaluate the colonic adenoma detection rate with primary NBI versus that with primary WLI by using consistent NBI system, endoscope, and imaging settings, and experienced colonoscopists., Methods: In this multicenter prospective trial, 813 patients were randomized to undergo high-definition, tandem colonoscopy in the right colon with either NBI followed by WLI (NBI-WLI group) or WLI followed by NBI (WLI-NBI group). The NBI settings were fixed at surface structure enhancement level A-5 and adaptive index of hemoglobin color enhancement level 3. All detected polyps were resected or biopsied for histopathological analysis. The primary and secondary outcome measures were the adenoma detection rates and miss rates, respectively, with primary imaging., Results: The NBI-WLI and WLI-NBI groups comprised 389 and 393 patients, respectively, who met the inclusion criteria. The groups did not differ significantly in age, gender, institution, indication for colonoscopy, bowel preparation, or observation time. The adenoma detection rates of primary NBI and WLI were 42.3 and 42.5 %, respectively [difference not significant (NS)]. The adenoma miss rate was significantly less with primary NBI than with primary WLI (21.3 vs. 27.8 %; p = 0.03)., Conclusions: NBI does not improve the adenoma detection rate during primary colonoscopy; however, it has a lower miss rate for adenoma lesions in the proximal colon than WLI.

Background: Various surface mucosal pit patterns, as recognized by endoscopists, correlate with the histologic features of colorectal cancers. We investigated whether magnified endoscopy images of these pit patterns could be analyzed quantitatively and thus facilitate computer-aided diagnosis of colorectal lesions., Methods: We applied both texture analysis and scale-invariant feature transform (SIFT) descriptors and discriminant analysis to magnified endoscopy images of 165 neoplastic colorectal lesions (pit patterns: type III(L)/IV, n = 44; type V(I)-mildly irregular, n = 36; type V(I)-severely irregular, n = 45; type V(N), n = 40) [histologic findings: tubular adenoma (TA), n = 56; carcinoma with intramucosal or even scant submucosal invasion (M/SM-s), n = 52, carcinoma with massive submucosal invasion (SM-m), n = 57]. We analyzed differences in pit pattern values and corresponding histologic values to determine whether the values were diagnostically meaningful., Results: Gray-level difference matrix (GLDM) inverse difference moment and spatial gray-level dependence matrix (SGLDM) local homogeneity values differed significantly between type III(L)/IV and type V(N) pit patterns. Values differed significantly for each analyzed feature between type III(L)/IV and type V(I)-severely irregular patterns and were high but descending for type III(L)/IV, type V(I)-mildly irregular, and type V(I)-severely irregular pit patterns (in that order). Similarly, texture analysis yielded high but descending values for TA, M/SM-s, and SM-m (in that order). Furthermore, SIFT descriptors and discriminant analysis yielded differences that were superior to those obtained by texture analyses., Conclusions: Computer analysis of magnified endoscopy images for the diagnosis of colorectal lesions appears feasible. We anticipate further developments in the computer-aided diagnosis of pit patterns on magnified endoscopy images.

Endoscopic submucosal dissection (ESD) allows en bloc resection of a lesion, irrespective of the size of the lesion. ESD has been established as a standard method for the endoscopic ablation of malignant tumors in the upper gastrointestinal (GI) tract in Japan. Although the use of ESD for colorectal lesions has been studied via clinical research, ESD is not yet established as a standard therapeutic method for colorectal lesions because colorectal carcinoma has unique pathological, organ specific characteristics that differ radically from those of the esophagus and stomach, and scope handling and control is more difficult in the colorectum than in the upper GI tract. Depending on the efficacy of endoscopic mucosal resection (EMR) and the clinicopathological characteristics of the colorectal tumor, the proposed indications for colorectal ESD are as follows: (1) lesions difficult to remove en bloc with a snare EMR, such as nongranular laterally spreading tumors (particularly the pseudo depressed type), lesions showing a type VI: pit pattern, and large lesions of the protruded type suspected to be carcinoma; (2) lesions with fibrosis due to biopsy or peristasis; (3) sporadic localized lesions in chronic inflammation such as ulcerative colitis; and (4) local residual carcinoma after EMR. Colorectal ESD is currently in the development stage, and a standard protocol will be available in the near future. We hope that colorectal tumors will be efficiently treated by a treatment method appropriately selected from among EMR, ESD, and surgical resection after precise preoperative diagnosis based on techniques such as magnifying colonoscopy.