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Risk evaluation of lymph node metastasis (LNM) for endoscopically resected submucosal invasive (T1) colorectal cancers (CRC) is critical for determining therapeutic strategies, but interobserver variability for histologic evaluation remains a major problem. To address this issue, we developed a machine-learning model for predicting LNM of T1 CRC without histologic assessment. A total of 783 consecutive T1 CRC cases were randomly split into 548 training and 235 validation cases. First, we trained convolutional neural networks (CNN) to extract cancer tile images from whole-slide images, then re-labeled these cancer tiles with LNM status for re-training. Statistical parameters of the tile images based on the probability of primary endpoints were assembled to predict LNM in cases with a random forest algorithm, and defined its predictive value as random forest score. We evaluated the performance of case-based prediction models for both training and validation datasets with area under the receiver operating characteristic curves (AUC). The accuracy for classifying cancer tiles was 0.980. Among cancer tiles, the accuracy for classifying tiles that were LNM-positive or LNM-negative was 0.740. The AUCs of the prediction models in the training and validation sets were 0.971 and 0.760, respectively. CNN judged the LNM probability by considering histologic tumor grade.

BackgroundDetermining the depth of invasion of early stage colorectal cancer has been emphasized as a means of improving endoscopic diagnostic accuracy. Recent studies have focused on other pathological risk factors for lymph node metastasis (LNM). We investigated the significance of depth of invasion and predictive properties of other endoscopic findings.MethodsWe retrospectively investigated 846 patients with submucosal invasive (T1) colorectal cancer who received an accurate pathological diagnosis and were treated between January 2005 and December 2016. Pathological risk factors associated with LNM were reviewed. We divided patients into groups: low-risk T1 colorectal cancer (LRC; no risk factors) and high-risk T1 colorectal cancer (HRC; exhibiting lymphovascular invasion, tumor budding grade of 2/3, and/or poor differentiation) and studied predictive endoscopic factors for HRC.ResultsSignificant risk factors for LNM in multivariate analysis were lymphovascular invasion [odds ratio (OR) 8.09; 95% confidence interval (CI) 3.84–17.1], tumor budding (OR 1.89; 95% CI 1.09–3.29), and histological differentiation (OR 2.09; 95% CI 1.12–3.89). The LNM-positive rate with only deep submucosal invasion was 1.6%. Significant predictive factors for HRC in multivariate analysis identified rectal tumor location (OR 1.92; 95% CI 1.35 –2.72, depression (OR 2.73; 95% CI 1.96 –3.80), protuberance within the depression (OR 2.58; 95% CI 1.39– 4.78), expansiveness (OR 2.39; 95% CI 1.27– 4.50), and loss of mucosal patterns (OR 1.90; 95% CI 1.20 –3.01) as significant factors.ConclusionsRectal tumor location, depression, protuberance within the depression, expansiveness, and loss of mucosal patterns could be predictive factors for HRC.

BackgroundColorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees’ skill acquisition.MethodsThe differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018).ResultsA total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mm2/min vs. 15.9 mm2/min), en bloc resection rate (100% vs. 90%), and R0 resection rate (96% vs. 83%).ConclusionsThe rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.

BackgroundWe assessed the technical and oncological safety of self-expandable metallic stent (SEMS) insertion followed by laparoscopic colorectal surgery as a bridge to surgery (BTS) for obstructive colorectal cancer (CRC).MethodsA retrospective, single-center study analyzed the short- and long-term outcomes of SEMS insertion followed by laparoscopic colorectal surgery in patients with stage II/III/IV obstructive CRC from 2012 to 2020 at Cancer Institute Hospital.ResultsIn 66 patients, including 28 stage IV patients, the clinical success rates of SEMS insertion were 97%. In laparoscopic surgery, primary anastomosis was performed in 61 patients (92%), and open conversion was required in 2 patients (3%). Postoperative complications were seen in 9 patients (13%); however, there was no anastomotic leakage or mortality. Curative resection was achieved in all 38 stage II/III patients and 15 of 28 (54%) stage IV patients. Stage IV patients had a longer operation time and greater blood loss than stage II/III patients; however, the open conversion and postoperative complication rates were similar between the groups. In stage II/III patients, 3-year disease-free survival and 3-year overall survival [OS] were 87.1 and 89.5%, respectively. The median OS of stage IV patients was 34.9 months, and stage IV patients who underwent R0 resection showed a significantly better OS (P = 0.0011) than those with R2 resection.ConclusionSEMS insertion followed by laparoscopic surgery is a feasible treatment strategy that achieves a high-primary anastomosis rate without severe postoperative complication in not only stage II/III but also stage IV obstructive CRC patients.

Background Polymerase proofreading‐associated polyposis (PPAP) is a rare autosomal dominant hereditary syndrome caused by germline pathogenic variants in the POLE or POLD1 genes. It is clinically similar to familial adenomatous polyposis (FAP) and Lynch syndrome, making diagnosis difficult. Although the number of reported cases is increasing globally, PPAP remains underrecognized, particularly in Japan. Accurate diagnosis often requires comprehensive genetic testing, including multi‐gene panel analysis and variant reinterpretation. Case Presentation We report a rare case of PPAP in a 50‐year‐old woman with a complex clinical history involving multiple primary malignancies. The patient developed ovarian cancer in her 20s, followed by endometrial and contralateral ovarian cancers in her 30s. She was also diagnosed with early‐stage colorectal cancer and polyposis, for which she underwent total colectomy with ileorectal anastomosis. Initially, she was suspected to have FAP or Lynch syndrome, but genetic testing revealed no pathogenic variants in APC, MUTYH, or mismatch repair genes. Subsequent multi‐gene panel testing identified a POLE variant of uncertain significance (VUS), which was later reclassified as likely pathogenic. Based on this reinterpretation and her clinical phenotype, a diagnosis of PPAP was made. Her disease course included recurrent rectal polyps and carcinoma after colectomy, as well as breast cancer. No upper gastrointestinal polyposis was observed. Conclusion This case represents one of the few reported instances of PPAP in Japan and illustrates the diagnostic complexity of hereditary polyposis syndromes. It highlights the critical role of multi‐gene panel testing and the importance of variant reinterpretation in establishing a definitive diagnosis. Continued surveillance and multidisciplinary care are essential for managing patients with PPAP.

BackgroundColorectal endoscopic submucosal dissection (ESD) is technically demanding while ensuring safety, especially in cases with fibrosis and/or poor maneuverability. To overcome such difficulties, we developed a novel method called the pocket-creation method with a traction device (PCM with TD). We then evaluated the effectiveness and safety of PCM with TD in colorectal ESD compared to other conventional methods.MethodsIn total, 324 colorectal lesions treated with ESD from July 2018 to June 2019 were included. The following three treatment strategies were used: conventional ESD (CE), CE with TD, and PCM with TD. Patient backgrounds and treatment outcomes were retrospectively compared and analyzed.ResultsAs ESD methods, CE, CE with TD, and PCM with TD account for 58% (187/324), 24% (78/324), and 18% (59/324), respectively. No significant difference was observed among the three groups in en bloc and R0 resection rates or adverse events. The rate of lesions with fibrosis and poor maneuverability was significantly higher in the PCM with TD group (CE group vs CE with TD group vs PCM with TD group: fibrosis, 24% vs 47% vs 64%, p < 0.001; poor maneuverability, 5.3% vs 13% vs 20%, p = 0.002). Dissection speed was significantly higher in the PCM with TD than in the CE with TD group (p = 0.003).ConclusionsPCM with TD can achieve a stable en bloc resection rate and R0 dissection rate without adverse events even in the hands of trainees, irrespective of the size and location of the lesion, presence of fibrosis, and under poor maneuverability conditions.

High-grade tumor budding is an adverse prognostic factor for submucosal invasive (T1) colorectal cancer used to predict the risk for lymph node metastasis in endoscopically resected specimens. Cytokeratin immunohistochemistry is a potential option for evaluating tumor budding. The optimal cut-off value between low- and high-grade budding has not yet been determined, however, and the high inter-observer variability in selecting budding foci remains problematic. We explored the optimal cut-off value for predicting lymph node metastasis using cytokeratin immunohistochemistry, and developed a novel computer-assisted semiautomatic quantification method to reduce inter-observer variability. A retrospective single-institution study of 463 T1 colorectal cancer cases was conducted. Cases were split into derivation and validation datasets. Tumor budding foci were counted manually and semiautomatically using Image J software on cytokeratin immunohistochemistry-stained specimens. We determined the cut-off values and compared inter-observer variability among pathologists between the two methods. Univariate and multivariate analyses of the derivation dataset were performed to select the risk factors for lymph node metastasis. Predictive simulation for the validation dataset was conducted. The optimal cut-off values for the manual and semiautomatic methods were ≥10 and ≥12, respectively. For both methods, multivariate analyses revealed that venous invasion, lymphatic invasion, and high-grade tumor budding were independent risk factors for lymph node metastasis. The semiautomatic method provided significantly better inter-observer agreement. The predictive and observed lymph node metastasis frequencies were highly correlated in the validation dataset.

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:We recently reported the results of a prospective multicenter randomised controlled trial comparing pancolonic observation using a newly developed NBI (CF-HQ290I) and panchromoendoscopy (PCE) for surveillance colonoscopy in UC patients. The results revealed that the NBI observation was not inferior to PCE for the detection of both neoplastic lesions (13.4% vs 9.0%; P = 0.33) and colitis-associated dysplasia or cancer (CC/D) (6.3% vs 4.9%; P = 0.86). Moreover, the total examination time of NBI (15.0 min) was significantly shorter than that of PCE (19.8 min) (P < 0.01). This sub-analysis aimed to evaluate the relevant factors or NBI findings of the background mucosa of CC/D in the preceding Navigator Study (UMIN000013527).METHODS:In total, 263 patients were randomised to the PCE group (n = 130) and the NBI group (n = 133). Surveillance colonoscopy in both groups was performed mainly with targeted biopsy. The pathological diagnoses were made by 2 expert pathologists who performed including immunohistochemical staining (p53, Ki-67) while being blinded to clinical information.RESULTS:A total of 21 sporadic adenoma, 3 traditional serrated adenoma, 2 sessile serrated adenoma/polyp, 10 indefinite for dysplasia, 9 low grade dysplsisadysplasia, and 7 high grade dysplasia or cancer cases were detected. There was no statistical difference for in the contents of these detected lesions between the 2 groups (P = 0.91). The median number of biopsy samples was not different between the 2 groups (1.80/case in NBI, 1.85/case in PCE; P = 0.88). Multivariate analysis demonstrated that age (OR 1.05, 95% CI 1.02–1.08, P < 0.01) and past history of CC/D (OR 4.26, 95% CI 1.29–14.05, P = 0.02) were the relevant factors for the detection of neoplastic lesions, and past history of CC/D (OR 5.70, 95% CI 1.33–24.50, P = 0.02) was the relevant factor for the detection of CC/D. CC/D was significantly more frequently detected than sporadic adenoma in cases in which the background mucosa had an obscure vascular pattern or scar rather than a fair view of the vascular pattern or out of range for inflammation (OR 25.0, 95% CI 3.80–164.4, P < 0.01).CONCLUSION(S):In the Navigator Study, a past history of endoscopic resection or detection of dysplasia on random biopsy was the relevant factor for the detection of CC/D. The NBI findings of the background mucosa were useful in differentiating CC/D and sporadic adenoma.

Purpose Previous studies have yielded conflicting results on the colonic polyp detection rate with narrow-band imaging (NBI) compared with white-light imaging (WLI). We compared the mean number of colonic polyps detected per patient for NBI versus WLI using a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems) used with standard-definition (SD) colonoscopy and wide-angle (WA) colonoscopy. Methods Design: this study is a 2 × 2 factorial, prospective, multicenter randomized controlled trial. Setting: this study was conducted at five academic centers in Japan. Interventions: patients were allocated to one of four groups: (1) WLI with SD colonoscopy (H260AZI), (2) NBI with SD colonoscopy (H260AZI), (3) WLI with WA colonoscopy (CF-HQ290), and (4) NBI with WA colonoscopy (CF-HQ290). Main outcome: the mean numbers of polyps detected per patient were compared between the four groups: WLI with/without WA colonoscopy and NBI with/without WA colonoscopy. Results Of the 454 patients recruited, 431 patients were enrolled. The total numbers of polyps detected by WLI with SD, NBI with SD, WLI with WA, and NBI with WA were 164, 176, 188, and 241, respectively. The mean number of polyps detected per patient was significantly higher in the NBI group than in the WLI group (2.01 vs 1.56; P  = 0.032). The rate was not higher in the WA group than in the SD group (1.97 vs 1.61; P  = 0.089). Conclusions Although WA colonoscopy did not improve the polyp detection, next-generation NBI colonoscopy represents a significant improvement in the detection of colonic polyps.