Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, ...synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.
Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take nonselective nonsteroidal anti-inflammatory drugs and PPIs simultaneously. We performed a ...randomized, double-blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate nonsteroidal anti-inflammatory drug-induced small bowel injury.
Fifty-seven healthy subjects were randomly assigned groups given the cyclooxygenase (COX) 2 inhibitor celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2 + placebo group, n = 30), or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2 + PPI group, n = 27). The study was performed from October 2012 through September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of celecoxib with rabeprazole or placebo. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination.
A significantly higher proportion of subjects in the COX-2 + PPI group developed small bowel injury (12 of 27 subjects; 44.4%) than in the COX-2 + placebo group (5 of 30 subjects; 16.7%; P = .04). Subjects in the COX-2 + PPI group had a significant increase in risk of small bowel injury compared with the COX-2 + placebo group (relative risk, 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each member of the COX-2 + PPI group was greater than in each member of the COX-2 + placebo group (P = .02). The number of ulcers did not differ between groups. Twenty-six percent of subjects in the COX-2 + PPI group developed mucosal injury in the jejunum, compared with none of the subjects in the COX-2 + placebo group (P = .003); no such trend was found in the ileum.
In a randomized, controlled trial, PPIs increased the risk of short-term nonsteroidal anti-inflammatory drug-induced small bowel injury. UMIN clinical trial registry number: UMIN000008883.
Background
Magnifying endoscopy with narrow-band imaging (NBI) is effective for the diagnosis of early gastric cancer (EGC). However, magnifying endoscopy is not yet popular globally because of the ...required level of skill and lack of availability. To overcome these problems, dual-focus endoscopy (standard- and near-focus (NF) modes) has been developed. In this study, we evaluated the diagnostic performance of NF with second-generation (2G)-NBI (NF-NBI) for the diagnosis of EGC.
Methods
This was a secondary analysis of a multicenter randomized controlled trial of 4523 high-risk patients who underwent gastroscopies at 13 institutions in Japan. Patients were randomly assigned to white-light imaging (WLI) followed by 2G-NBI or to 2G-NBI followed by WLI. Lesions suspicious for EGC, newly detected by non-magnifying WLI or 2G-NBI, were subsequently observed with NF-NBI. All detected lesions were biopsied or resected. The diagnostic performance of NF-NBI was compared with the final histology.
Results
A total of 870 detected lesions (145 EGC, 725 non-EGC) were analyzed. Overall diagnostic performance for EGC using NF-NBI was accuracy 87.7%, sensitivity 60.7%, specificity 93.1%, positive predictive value 63.8%, and negative predictive value 92.2%. There were no significant differences in diagnostic performance between lesions detected by WLI or 2G-NBI. For lesions diagnosed with high (333 lesions) and low (537 lesions) confidences, accuracy was 92.2% and 84.9%, sensitivity was 64.7% and 58.5%, and specificity was 90.5% and 88.8%, respectively.
Conclusion
The diagnostic performance of NF-NBI is good and acceptable for diagnosis of EGC in combination with either WLI or 2G-NBI.
Background
Curative treatment of patients with gastric cancer requires reliable detection of early gastric cancer. Magnifying endoscopy with narrow-band imaging (M-NBI) is useful for the accurate ...preoperative diagnosis of early gastric cancer. However, the role of M-NBI in screening endoscopy has not been established. The aims of this study were to determine the feasibility and limitations of M-NBI in screening endoscopy.
Methods
We conducted a multicenter prospective uncontrolled trial of patients undergoing routine screening endoscopy patients. We determined the diagnostic accuracy, sensitivity and specificity of M-NBI according to the degree of certainty and need for biopsy, as assessed using the VS (vessel plus surface) classification system. We analyzed the endoscopic and histopathological characteristics of both false negative and false positive high confidence M-NBI diagnoses. We then developed a provisional diagnostic strategy based on the diagnostic performance and limitations identified in this study.
Results
A total of 1097 patients were enrolled in the study. We analyzed 371 detected lesions (20 cancers and 351 non-cancers). The accuracy, sensitivity and specificity of high confidence M-NBI diagnoses were 98.1, 85.7 and 99.4 %, respectively. The false negative case was a pale mucosal lesion with tissue diagnosis of signet-ring cell carcinoma. Exclusion of pale mucosal lesions increased the accuracy, sensitivity and specificity of high confidence M-NBI diagnoses to 99.4, 100 and 99.4 %, respectively. We therefore propose a practical strategy targeting non-pale mucosal lesions.
Conclusions
With a refined strategy considering its limitations, M-NBI can act as an “optical biopsy” in screening endoscopies.
Background & Aims It is difficult to accurately diagnose patients with depressed gastric mucosal cancer based on conventional white-light imaging (C-WLI) endoscopy. We compared the real-time ...diagnostic yield of C-WLI for small, depressed gastric mucosal cancers with that of magnifying narrow-band imaging (M-NBI). Methods We performed a multicenter, prospective, randomized, controlled trial of patients with undiagnosed depressed lesions ≤10 mm in diameter identified by esophagogastroduodenoscopy. Patients were randomly assigned to groups that were analyzed by C-WLI (n = 176) or M-NBI (n = 177) immediately after detection; the C-WLI group received M-NBI after C-WLI. We compared the diagnostic accuracy, sensitivity, and specificity between C-WLI and M-NBI and assessed the diagnostic yield of M-NBI conducted in conjunction with C-WLI. Results Overall, 40 gastric cancers (20 in each group) were identified. The median diagnostic values for M-NBI and C-WLI were as follows: accuracy, 90.4% and 64.8%; sensitivity, 60.0% and 40.0%; and specificity, 94.3% and 67.9%, respectively. The accuracy and specificity of M-NBI were greater than those of C-WLI ( P < .001); the difference in sensitivity was not significant ( P = .34). The combination of M-NBI with C-WLI significantly enhanced performance compared with C-WLI alone; accuracy increased from (median) 64.8% to 96.6% ( P < .001), sensitivity increased from 40.0% to 95.0% ( P < .001), and specificity increased from 67.9% to 96.8% ( P < .001). Conclusions M-NBI, in conjunction with C-WLI, identifies small, depressed gastric mucosal cancers with 96.6% accuracy, 95.0% sensitivity, and 96.8% specificity. These values are better than for C-WLI or M-NBI alone.
Liquid biopsies enable the detection of circulating tumor DNA (ctDNA). However, the clinical significance of KRAS-mutated ctDNA for pancreatic cancer has been inconsistent with respect to its ...prognostic and predictive potential.
A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS mutation in tissues and KRAS ctDNA levels in plasma were determined by RASKET and droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and for evaluating therapeutic responses to chemotherapy compared with carbohydrate antigen 19-9 (CA19-9). In 67 tumor tissues, discrepancies in point mutations of KRAS were rarely observed among individual patients, implying that one targeted point mutation of KRAS can be determined in tumor tissues prior to longitudinal blood monitoring. One-time blood assessment of KRAS-mutated ctDNA before surgery or chemotherapy was not clearly associated with recurrence and prognosis. Sequential blood monitoring was performed in 39 patients who underwent surgery for potentially resectable tumors. Increased CA19-9 levels were significantly associated with recurrence, but not prognosis (P<0.001, P = 1.0, respectively), whereas emergence of KRAS ctDNA was significantly associated with prognosis (P<0.001) regardless of recurrence. Furthermore, in 39 patients who did not undergo surgery, detection of KRAS ctDNA was a predictive factor for prognosis (P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA was the only independent prognostic factor regardless of tumor resection (hazard ratios = 54.5 for patients who underwent surgery and 10.1 for patients who did not undergo surgery; P<0.001 for both). Patients without emergence of KRAS ctDNA within 1 year after surgery showed significantly better prognosis irrespective of recurrence (P<0.001). No detection or disappearance of KRAS ctDNA within 6 months of treatment was significantly correlated with therapeutic responses to first-line chemotherapy (P<0.001). Changes in KRAS status provided critical information for the prediction of therapeutic responses.
Our study showed for the first time that detection of KRAS ctDNA levels within a short period enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer.
Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the ...prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study.
Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC.
330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %.
Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.
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.
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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