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Alternative splicing, regulated by DEAD‐Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT‐qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56‐knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2‐M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1. We identified DDX56 as a novel oncogene on chromosome 7p and a prognostic biomarker of colorectal cancer (CRC). DDX56 can induce oncogenic splicing abnormalities of the G2‐M cell cycle checkpoint gene WEE1 which contributes to the inhibition of proliferation and cell cycle progression.

BackgroundMucin depletion is one of the histological indicators of clinical relapse among patients with ulcerative colitis (UC). Mucin depletion is evaluated semiquantitatively by pathologists using histological images. Therefore, the interobserver concordance is not extremely high, and an objective evaluation method is needed. This study was conducted to demonstrate that our automated quantitative method using a deep learning-based model is useful in predicting the prognosis of patients with UC.MethodsDeep learning-based models were trained to detect goblet cell mucus area from whole slide images of biopsy specimens. This study involved 114 patients with UC in endoscopic remission with a partial Mayo score of ≤ 1. Biopsy specimens were collected during colonoscopy, and the ratio of goblet cell mucus area to the epithelial cell and goblet cell mucus area was calculated as goblet cell ratio (GCR). The follow-up time was 12 months, and the primary outcome was the relapse rate. Clinical relapse was defined as partial Mayo score of ≥ 3.ResultsSixteen patients (14%) experienced clinical relapse. In the relapsed group, the GCRs of specimens obtained from the cecum, ascending colon, and rectum were significantly lower than those of specimens in the relapse-free group (p = 0.010, p = 0.027, p < 0.01). In the rectum, patients with a GCR of ≤ 12% had a significantly higher relapse rate than those with a GCR of > 12% (45% [10/22] vs. 6.5% [6/92]; p < 0.01).ConclusionsQuantifying goblet cell mucus areas using a deep learning-based model is useful in predicting the clinical relapse in patients with UC in clinical and endoscopic remission.

ObjectiveTo assess whether follow-up colonoscopy after polypectomy at 3 years only, or at 1 and 3 years would effectively detect advanced neoplasia (AN), including nonpolypoid colorectal neoplasms (NP-CRNs).DesignA prospective multicentre randomised controlled trial was conducted in 11 Japanese institutions. The enrolled participants underwent a two-round baseline colonoscopy (interval: 1 year) to remove all neoplastic lesions. Subsequently, they were randomly assigned to undergo follow-up colonoscopy at 1 and 3 years (2-examination group) or at 3 years only (1-examination group). The incidence of AN, defined as lesions with low-grade dysplasia ≥10 mm, high-grade dysplasia or invasive cancer, at follow-up colonoscopy was evaluated.ResultsA total of 3926 patients were enrolled in this study. The mean age was 57.3 (range: 40–69) years, and 2440 (62%) were male. Of these, 2166 patients were assigned to two groups (2-examination: 1087, 1-examination: 1079). Overall, we detected 29 AN in 28 patients at follow-up colonoscopy in both groups. On per-protocol analysis (701 in 2-examination vs 763 in 1-examination group), the incidence of AN was similar between the two groups (1.7% vs 2.1%, p=0.599). The results of the non-inferiority test were significant (p=0.017 in per-protocol, p=0.001 in intention-to-treat analysis). NP-CRNs composed of dominantly of the detected AN (62%, 18/29), and most of them were classified into laterally spreading tumour non-granular type (83%, 15/18).ConclusionAfter a two-round baseline colonoscopy, follow-up colonoscopy at 3 years detected AN, including NP-CRNs, as effectively as follow-up colonoscopies performed after 1 and 3 years.

Conventional endoscopic resection (CER) is a widely accepted treatment for early colorectal neoplasia; however, large colorectal neoplasias remain problematic, as they necessitate piecemeal resection, increasing the risk of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en bloc resection rate. This study aimed to evaluate local recurrence and its associated risk factors after endoscopic resection (ER) for colorectal neoplasias ≥20 mm. A multicenter prospective study at 18 medium- and high-volume specialized institutions was conducted in Japan. Follow-up colonoscopy was performed after 12 months in cases of complete resection and after 3-6 months in cases of incomplete resection. Local recurrence was confirmed by endoscopic findings and/or pathological analysis. Follow-up colonoscopy was performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years; 885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3% (65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and for ESD, respectively. The relative risks of local recurrence were 0.21 (95% confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95% confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER. Significant factors associated with local recurrence were piecemeal resection, laterally spreading tumors of granular type, tumor size ≥40 mm, no pre-treatment magnification, and ≤10 years of experience in CER, and piecemeal resection only in ESD. En bloc ESD reduces the local recurrence rate for large colorectal neoplasias. Piecemeal resection is the most important risk factor for local recurrence regardless of the ER method used.

Background Conventional endoscopic resection (CER) for early colorectal neoplasia (CRN) is widely accepted as a minimally invasive treatment. Endoscopic submucosal dissection (ESD) was developed in Japan to resect larger lesions, but ESD was not covered by the Japanese national health insurance until April 2012. In addition, treatment strategies vary considerably among medical facilities. To evaluate the current situation in Japan regarding endoscopic treatment of CRNs measuring ≥20 mm, we conducted a prospective multicenter study at 18 medium-volume and high-volume specialized facilities in cooperation with the Japan Society for Cancer of the Colon and Rectum (JSCCR). Methods The JSCCR conducted a multicenter, observational study of all patients treated by CER and ESD of CRNs measuring ≥20 mm. Results From October 2007 to December 2010, CERs and ESDs were performed on 1,845 CRNs (CERs 1,029; ESDs 816). Lesions diagnosed as protruded, flat, and depressed totaled 541, 1224, and 48, respectively. En bloc resection rates and mean procedure times for CER/ESD were 56.9 %/94.5 % ( P  < 0.01) and 18 ± 23 min/96 ± 69 min, respectively. The average ESD procedure time was 129 ± 83 min in the ≥40-mm group. As lesion size increased, the CER en bloc resection rate decreased significantly (trend P  < 0.01), but the ESD en bloc resection rate remained over 93 %. Perforation and delayed bleeding rates of CER/ESD were 0.8 %/1.6 % ( P  < 0.05) and 2 %/2.2 % ( P  = 0.3), respectively. Conclusions The en bloc resection rate for ESD was significantly higher than for CER, although complication rates were fairly low. Despite a longer procedure time, safety of colorectal ESD has improved in various facilities in Japan. However, ESD for lesions measuring ≥40 mm must be performed by experienced endoscopists due to the longer procedure time.

Background Novel risk factors for lymph node metastasis (LNM) in T1 colorectal cancer (CRC) have been recently proposed, but most have not been implemented because of the lack of validation. Here we determined the value of poorly differentiated clusters (PDCs) in a multi-institutional cohort of T1 CRC cases. Methods A pathology review involving 30 institutions was conducted for 3556 T1 CRCs. PDC was defined as malignant clusters comprising ≥5 cells and lacking a glandular formation. The ability to identify LNM risk was compared using Akaike’s information criterion (AIC). Results PDC was observed in 1401 tumors (39.4 %), including 94 (17.8 %) with <1000 µm submucosal invasion and 1307 (43.2 %) with ≥1000 µm submucosal invasion ( P  < 0.0001). The incidence of LNM was higher in PDC-positive tumors (17.4 %) than in PDC-negative tumors (6.9 %; P  < 0.0001), and PDCs had an adverse impact on LNM irrespective of the degree of submucosal invasion. Grade 3, vascular invasion, budding, and submucosal invasion depth were also significant factors (all, P  < 0.0001). AIC of risk factor to identify LNM risk was most favorable for vascular invasion (2273.4), followed by PDC (2357.4); submucosal invasion depth (2429.1) was the most unfavorable. Interinstitutional judgment disparities were smaller in PDC (kappa, 0.51) than vascular invasion (0.33) or tumor grade (0.48). Conclusions PDC is a promising new parameter with good ability to identify LNM risk. Use of its appropriate judgment criteria will enable us determine whether an observational policy can be safely applied following local tumor excision in T1 CRC cases.

Objective To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. Design A double-blinded, randomised, placebo-controlled multicentre clinical trial was conducted. Participants 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. Results The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints with an adjusted OR of 0.60 (95% CI 0.36 to 0.98) compared with the subjects in the placebo group. Subgroup analysis revealed that subjects who were non-smokers, defined as those who had smoked in the past or who had never smoked, had a marked reduction in the number of recurrent tumours in the aspirin-treated group. The adjusted OR for aspirin treatment in non-smokers was 0.37 (CI 0.21 to 0.68, p<0.05). Interestingly, the use of aspirin in smokers resulted in an increased risk, with an OR of 3.44. In addition, no severe adverse effects were observed in either group. Conclusions Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. The clinical trial registry website and the clinical trial number http://www.umin.ac.jp (number UMIN000000697).

BackgroundElderly patients are often considered as a high-risk population for major abdominal surgery due to reduced functional reserve and increased comorbidities. The aim of this study was to assess the safety and curability of laparoscopic gastrectomy in elderly patients with gastric cancer compared with short- and long-term outcomes in non-elderly patients.MethodsWe retrospectively investigated 386 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2007 and December 2015 at the Digestive Disease Center, Showa University, Northern Yokohama Hospital. We categorized the patients into two groups by age: the elderly patients (≥ 75 years old) and the non-elderly patients (< 74 years old). Patient characteristics, clinicopathologic and operative findings, and short- and long-term outcomes were investigated and compared between the two groups.ResultsThe elderly group showed a significantly higher rate of comorbidities (73.1 vs. 49.2%, P < 0.001), and American Society of Anesthesiologists (ASA) scores ≥ 2 (76.3 vs. 43.7%, P < 0.001), and using anticoagulant agents (25.8 vs. 7.9%, P < 0.001) than the non-elderly group. The postoperative morbidity and mortality did not differ between the two groups (19.4 vs. 18.8%; P = 0.880, 2.2 vs. 0%; P = 0.058). In the multivariate analysis, male sex was the only risk factor for postoperative morbidity after laparoscopic gastrectomy. However, age was not found to be a risk factor. The 5-year overall survival ratio was significantly lower in the elderly group than in the non-elderly group (67.7 vs. 85.0%; P < 0.001). However, the 5-year disease-specific survival ratio was similar in the two groups (84.8 vs. 89.1%; P = 0.071).ConclusionLaparoscopic gastrectomy for gastric cancer could be safely performed in elderly patients with acceptable postoperative morbidity and curability.