Colorectal tumor is a heterogeneous disease, with varying clinical presentation and prognosis in patients. To establish a platform encompassing this diversity, we generated 55 colorectal tumor ...organoid lines from a range of histological subtypes and clinical stages, including rare subtypes. Each line was defined by gene expression signatures and optimized for organoid culture according to niche factor requirements. In vitro and in xenografts, the organoids reproduced the histopathological grade and differentiation capacity of their parental tumors. Notably, we found that niche-independent growth is predominantly associated with the adenoma-carcinoma transition reflecting accumulation of multiple mutations. For matched pairs of primary and metastatic organoids, which had similar genetic profiles and niche factor requirements, the metastasis-derived organoids exhibited higher metastatic capacity. These observations underscore the importance of genotype-phenotype analyses at a single-patient level and the value of our resource to provide insights into colorectal tumorigenesis and patient-centered therapeutic development.
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•An organoid library with diverse colorectal tumor grades and subtypes was established•A refined culture method improves colorectal tumor organoid establishment efficiency•Tumor organoids faithfully recapitulate clinical phenotypes of patient tumors•Niche factor dependency decreases along with adenoma-carcinoma transition
Fujii et al. generated a comprehensive organoid library from colorectal cancer patients. Each organoid line was characterized by gene expression and as xenografts recapitulating the original clinical phenotype. By optimizing niche factor requirements and derivation efficiency, they were able to encompass a range of clinical stages and rare subtypes and reveal that niche-independent growth is progressively associated with the adenoma-carcinoma transition.
Image-enhanced endoscopy (IEE) allows real-time high-contrast imaging of a targeted lesion without any special equipment. Among various IEE technologies, narrow-band imaging, in which a light of ...shorter wavelength is used, emphasizes the surface and blood vessel patterns on the mucosal surface. This technology has been widely used in endoscopic diagnosis in the gastrointestinal tract. Red dichromatic imaging (RDI) was recently developed; it utilizes lights of longer wavelengths (520–550, 595–610, and 620–640 nm), which have weak light scattering characteristics in contrast to narrow-band imaging. RDI was designed to enhance the visibility of deep-lying blood vessels and areas of bleeding, and it has been installed in the latest Olympus endoscopy system, EVIS X1, as an advanced version of the optical-digital method that was originally developed. Improving the visibility of deep blood vessels allows more accurate evaluation of esophageal varices and the degree of inflammation in ulcerative colitis. Easier identification of a bleeding source makes hemostasis quicker and easier to accomplish during endoscopic resection procedures such as endoscopic submucosal dissection and peroral endoscopic myotomy as well as during treatment of gastrointestinal bleeding from a peptide ulcer or colon diverticulum. The authors herein review the technological development and principles, review the existing literature on RDI, and discuss the utility and effectiveness of this unique IEE technology in gastrointestinal endoscopy.
Background Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, although it is not widely used in the colorectum because of technical ...difficulty. Objective To examine the current status of colorectal ESDs at specialized endoscopic treatment centers. Design and Setting Multicenter cohort study using a prospectively completed database at 10 specialized institutions. Patients and Interventions From June 1998 to February 2008, 1111 colorectal tumors in 1090 patients were treated by ESD. Main Outcome Measurements Tumor size, macroscopic type, histology, procedure time, en bloc and curative resection rates and complications. Results Included in the 1111 tumors were 356 tubular adenomas, 519 intramucosal cancers, 112 superficial submucosal (SM) cancers, 101 SM deep cancers, 18 carcinoid tumors, 1 mucosa-associated lymphoid tissue lymphoma, and 4 serrated lesions. Macroscopic types included 956 laterally spreading tumors, 30 depressed, 62 protruded, 44 recurrent, and 19 SM tumors. The en bloc and curative resection rates were 88% and 89%, respectively. The mean procedure time ± standard deviation was 116 ± 88 minutes with a mean tumor size of 35 ± 18 mm. Perforations occurred in 54 cases (4.9%) with 4 cases of delayed perforation (0.4%) and 17 cases of postoperative bleeding (1.5%). Two immediate perforations with ineffective endoscopic clipping and 3 delayed perforations required emergency surgery. Tumor size of 50 mm or larger was an independent risk factor for complications, whereas a large number of ESDs performed at an institution decreased the risk of complications. Limitations No long-term outcome data. Conclusions ESD performed by experienced endoscopists is an effective alternative treatment to surgery, providing high en bloc and curative resection rates for large superficial colorectal tumors.
Background and Aims Endoscopic biopsy sampling for the diagnosis of duodenal adenocarcinoma is not perfect. We investigated the accuracy of biopsy specimen diagnoses of superficial nonampullary ...duodenal epithelial tumors (NADETs). Methods Clinicopathologic data were retrospectively reviewed for 95 superficial NADETs from 95 patients who underwent endoscopic resection. Preoperative diagnoses based on biopsy specimens were compared with histologic diagnoses of resected specimens. Results Among the 21 lesions with biopsy specimen diagnoses of carcinoma, 12 (57.1%) were histologically diagnosed as adenomas after resection. Among the 74 lesions with biopsy specimen diagnoses of adenoma, 15 (20.3%) were histologically diagnosed as carcinomas after resection. The duodenal biopsy specimen predicted final histologic diagnoses of carcinoma with a sensitivity of 37.5% (95% CI, 18.8-59.4), specificity of 83.1% (95% CI, 72.3-91.0), accuracy of 71.6% (95% CI, 61.4-80.4), positive predictive value of 42.9% (95% CI, 21.8-66.0), and negative predictive value of 79.7% (95% CI, 68.8-88.2). Among 61 cases considered suitable for EMR, treatment modality was converted from EMR to endoscopic submucosal dissection because of the nonlifting sign in 15 cases (24.6%). Conclusions The accuracy of duodenal biopsy sampling was relatively low. Duodenal biopsy sampling may induce unexpected fibrosis. New endoscopic modalities that can improve preoperative diagnosis yield of NADETs are eagerly awaited.
Background and Aims Endoscopic submucosal dissection (ESD) can remove early stage GI tumors of various sizes en bloc; however, success requires reducing the relatively high postprocedure bleeding ...rate. The aim of this study was to assess the safety and efficacy of a novel, fully synthetic, and self-assembled peptide solution that functions as an extracellular matrix scaffold material to facilitate reconstruction of normal tissues in ESD-induced ulcers. Methods Consecutive patients who underwent gastric ESD were prospectively enrolled. Immediately after the resection, the solution was applied to the site with a catheter. Gastric ulcers were evaluated by endoscopy and classified as active, healing, or scarring stages at weeks 1, 4, and 8 after ESD. Results Forty-seven patients with 53 lesions, including 14 (29.8%) previously on antithrombotic therapy and 2 (4.3%) requiring heparin bridge therapy, were analyzed; 2 patients were excluded, 1 with perforations and 1 with persistent coagulopathy. The mean size of the en bloc resected specimens was 36.5 ± 11.3 mm. The rate of post-ESD bleeding was 2.0% (1/51; 95% CI, 0.03–10.3). Transitional rate to the healing stage of ESD-induced ulcers at week 1 was 96% (49/51). Subsequent endoscopies demonstrated the scarring stage in 19% (9/48) and 98% (41/42) at weeks 4 and 8, respectively. No adverse effects related to this solution occurred. Conclusions The use of this novel peptide solution may potentially aid in reducing the delayed bleeding rate by promoting mucosal regeneration and speed of ulcer healing after large endoscopic resections in the stomach. Further studies, particularly randomized controlled studies, are needed to fully evaluate its efficacy. (Clinical trial registration number: 000011548.)
Background and Aim
Although duodenal cancer is rare, no epidemiological research on this disease has been conducted in Asian countries. We aimed to elucidate the incidence and clinical features of ...duodenal cancer in Japan using a large‐scale national database.
Methods
Data of patients with primary duodenal cancer diagnosed from January 1, 2016, to December 31, 2016, were extracted from the Japanese national cancer registry. Excluding malignant neoplasm of the Vater's ampulla, we calculated the incidence among the population as a crude number of patients with duodenal cancer divided by the total Japanese population in 2016. We performed multivariate analyses using logistic regression models to identify risk factors for advanced cancer, defined as metastatic cancer or local invasion to adjacent organs.
Results
Data on 3005 patients were included. The incidence of duodenal cancer was 23.7 per 1 000 000 person‐years. In total, 56.4% of cases were detected at the localized stage. In the localized cancer group, endoscopic resection was more frequently performed (48.0%), whereas in the advanced cancer group, surgery and chemotherapy were the major treatment options (39.3% and 41.5%, respectively). Multivariate analyses identified age ≥80 years (odds ratio OR, 1.489; 95% confidence interval CI, 1.113–1.992; P = 0.007), incidental detection (OR, 2.325; CI, 1.623–3.331; P < 0.0001), and precise examination for symptomatic patients (OR, 10.561; CI, 7.416–15.042; P < 0.0001) as independent risk factors for advanced cancer.
Conclusions
Our study revealed the incidence of duodenal cancer in Japan. However, localized cancer was the major tumor stage at detection, resulting in a high rate of endoscopic resection.
To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period.
Between ...February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes.
The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan–Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47–45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76–37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection.
A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. Clinical Trial Registration Number: UMIN000010136.
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Accurate histologic assessment facilitated by endoscopic submucosal dissection enables stratification of the risk of lymph node metastasis and determines the necessity of additional surgery, which may have led to a good long-term prognosis.
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