Background and Aims The technical difficulties inherent in endoscopic submucosal dissection (ESD) for colorectal neoplasms may result in the failure of en bloc resection or perforation. The aim of ...this retrospective study was to assess the predictors of en bloc resection failure or perforation by using preoperatively available factors. Methods Between September 2002 and March 2013, 716 colorectal ESDs in 673 consecutive patients were performed at a tertiary cancer center. Patient characteristics, tumor location, tumor type, colonoscopy-related factors, and endoscopist experience were assessed based on a prospectively recorded institutional ESD database. Logistic regression analysis was performed to identify predictors of failure of en bloc resection or perforations, with subgroup analyses of ESDs performed by endoscopists less experienced in colorectal ESD (<40 cases) and for colonic lesions only. Results On multivariate analysis, independent predictors of failure of en bloc resection or perforations were the presence of fold convergence (odds ratio OR 4.4; 95% confidence interval 95% CI, 1.9-9.9), protruding type (OR 3.6; 95% CI, 1.8-7.1), poor endoscope operability (OR 3.5; 95% CI, 1.8-6.9), right-sided colonic lesions (OR 3.0; 95% CI, 1.5-6.3 vs rectal lesions), left-sided colonic lesions (OR 3.2; 95% CI, 1.7-6.3, vs rectal lesions), the presence of an underlying semilunar fold (OR 2.1; 95% CI, 1.3-3.6), and a less-experienced endoscopist (OR 2.1; 95% CI, 1.3-3.6). Among less-experienced endoscopists, colonic lesions were independent predictors (right-sided colonic lesions 8.1; 95% CI, 2.9-25.1; left-sided colonic lesions 8.1; 95% CI, 2.5-28.3 vs rectal lesions). For colonic lesions, the presence of fold convergence (OR 3.7; 95% CI, 1.6-8.6), poor endoscope operability (OR 3.6; 95% CI, 1.8-7.2), a less-experienced endoscopist (OR 3.0; 95% CI, 1.7-1.8), and the presence of an underlying semilunar fold (OR 2.7; 95% CI, 1.5-4.7) were identified predictors. Conclusion This study successfully identified predictors of en bloc resection failure or perforation. Understanding these indicators could help to accurately stratify lesions according to technical difficulty and to appropriately select endoscopists.
Background Endoscopic resection (ER) has been accepted as minimally invasive treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. It has already ...been determined which lesions in differentiated-type EGC present a negligible risk of lymph node metastasis, and ER is being performed for these lesions. In contrast, no consensus has been reached on which lesions in undifferentiated-type (UD-type) EGC present a negligible risk for lymph node metastasis, nor have indications for ER for UD-type EGC been established. Methods We investigated 3843 patients who had undergone gastrectomy with lymph node dissection for solitary UD-type EGC at the Cancer Institute Hospital, Tokyo, and the National Cancer Center Hospital, Tokyo. Seven clinicopathological factors were assessed for their possible association with lymph node metastasis. Results Of the 3843 patients, 2163 (56.3%) had intramucosal cancers and 1680 (43.7%) had submucosal invasive cancers. Only 105 (4.9%) intramucosal cancers compared with 399 (23.8%) submucosal invasive cancers were associated with lymph node metastases. By multivariate analysis, tumor size 21 mm or more, lymphatic-vascular capillary involvement, and submucosal penetration were independent risk factors for lymph node metastasis (P < 0.001, respectively). None of the 310 intramucosal cancers 20 mm or less in size without lymphatic- vascular capillary involvement and ulcerative findings was associated with lymph node metastases (95% confidence interval, 0-0.96%). Conclusion UD-type intramucosal EGC 20 mm or less in size without lymphatic-vascular capillary involvement and ulcerative findings presents a negligible risk of lymph node metastasis. We propose that in this circumstance ER could be considered.
Lymph node metastasis occurs in as many as 16% of patients with submucosal invasive colorectal carcinoma. We investigated the association between histopathological factors and lymph node metastases ...in 322 consecutive patients with submucosal invasive colorectal carcinoma who had undergone radical colectomy with lymph node dissection to detect patients at high risk of lymph node metastasis without measuring the depth of submucosal invasion. Lymph node metastasis was found in 46 (14.3%) of 322 patients with submucosal invasive colorectal carcinoma. Univariate analysis showed that each of the following histopathological factors had a significant influence on lymph node metastasis: invasion depth, lymphatic invasion, venous invasion, tumor differentiation, growth pattern of the intramucosal tumor component, complete disruption of the muscularis mucosa due to tumor invasion, and tumor budding at the submucosal invasive front. Multivariate analysis showed that lymphatic invasion (P<0.01), tumor differentiation (P<0.01), and tumor budding (P<0.01) were significantly associated with lymph node metastasis. All 46 cases of lymph node metastasis showed at least one of the following findings: lymphatic invasion, moderately or poorly differentiated tumor grade, tumor budding, or complete disruption of the muscularis mucosa due to tumor invasion. Patients with submucosal invasive colorectal carcinoma that show at least one of three factors--lymphatic invasion, moderately or poorly differentiated tumor grade, or tumor budding--are at high risk for lymph node metastasis. All of the patients with lymph node metastasis, who did not have any of these factors, showed a completely disrupted muscularis mucosa.
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.
Most of the esophageal squamous cell carcinomas (ESCCs) and cancers of the head and neck (H&N) region are diagnosed at later stages. To achieve better survival, early detection is necessary. We ...compared the real-time diagnostic yield of superficial cancer in these regions between conventional white light imaging (WLI) and narrow band imaging (NBI) in high-risk patients.
In a multicenter, prospective, randomized controlled trial, 320 patients with ESCC were randomly assigned to primary WLI followed by NBI (n = 162) or primary NBI followed by WLI (n = 158) in a back-to-back fashion. The primary aim was to compare the real-time detection rates of superficial cancer in the H&N region and the esophagus between WLI and NBI. The secondary aim was to evaluate the diagnostic accuracy of these techniques.
NBI detected superficial cancer more frequently than did WLI in both the H&N region and the esophagus (100% v 8%, P < .001; 97% v 55%, P < .001, respectively). The sensitivity of NBI for diagnosis of superficial cancer was 100% and 97.2% in the H&N region and the esophagus, respectively. The accuracy of NBI for diagnosis of superficial cancer was 86.7% and 88.9% in these regions, respectively. The sensitivity and accuracy were significantly higher using NBI than WLI in both regions (P < .001 and P = .02 for the H&N region; P < .001 for both measures for the esophagus, respectively).
NBI could be the standard examination for the early detection of superficial cancer in the H&N region and the esophagus.
Background & Aims Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this ...process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. Methods We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1–9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. Results Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C ( P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C ( P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C ( P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25–0.91; P = .025), whereas smoking abstinence did not. Conclusions Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.
Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have ...clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC.
SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined.
For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m.
These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.
Background
Perioperative treatment is an accepted standard approach for treating locally advanced gastric cancer (LAGC). Histopathological tumor regression with < 10% residual tumor is a globally ...accepted prognosticator in LAGC patients who received neoadjuvant chemotherapy (NAC) and curative surgery. However, despite a response of the primary tumor, a significant percentage of patients dies from recurrence and identification of those at risk for relapse remains challenging. We re-estimated the value of histopathological tumor regression as a prognosticator alongside other factors, especially posttherapy topographical nodal status, ypN-site.
Patients and methods
Individual patient data including clinicopathological variables were used from the four JCOG trials investigating NAC (JCOG0001, JCOG0002, JCOG0210, JCOG0405) for analyzing prognosticators in patients with curative surgery excluding those with type 4 AGC by univariable and multivariable Cox regression analyses.
Results
Among 85 patients, 5-year overall survival (OS) was 46.0% 95% confidence interval (CI) 35.0–56.4 with a median follow-up of 3.2 years. On univariable analysis, histopathological tumor regression with ≥ 10% residual tumor and ypN-site 2–3 were negatively associated with OS
≥
10% residual tumor: hazard ratio (HR) 2.60; 95% CI 1.22–5.54;
P
= 0.014; ypN2–3: HR 3.59; 95% CI 1.60–8.06;
P
= 0.002). On multivariable analysis, only ypN-site 2–3 was predictive of OS (HR 3.67; 95% CI 1.55–8.69;
P
= 0.003), whereas histopathological tumor regression with ≥ 10% residual tumor was not (HR 2.24; 95% CI 0.98–5.10;
P
= 0.055).
Conclusions
ypN-site may have greater impact on OS than histopathological tumor regression in patients who received NAC plus surgery for non-type 4 LAGC.
More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate ...histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥1000 μm (odds ratio (95% confidence interval)=5.56 (2.14-19.10)) and high-grade budding/sprouting (3.14 (1.91-5.21)). Among lesions with a depth of submucosal invasion ≥1000 μm, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion <1000 μm. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥1000 μm and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥1000 μm and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion <1000 μm. These findings revealed that a depth of submucosal invasion ≥1000 μm and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.
The tumorigenesis of non‐ampullary duodenal epithelial tumors (NADETs) might be different between the oral and anal sides of Vater's papilla. We conducted an immunohistological review to elucidate ...the clinicopathological features according to the tumor location and phenotypic classification. A review of an institutional database identified 121 patients with 125 superficial NADETs. NADETs were histologically evaluated and classified into the intestinal or gastric type based on immunohistochemical analysis. Clinicopathological factors were compared based on the tumor location and phenotype. Logistic regression analysis was performed to identify independent predictors for gastric‐type NADETs. According to location analysis, the mucin phenotype was significantly different (oral side, intestinal‐type 64.8%, gastric‐type 35.3%; anal side, intestinal‐type 87.3%, gastric‐type 12.7%; P < 0.01). Although the incidence of adenoma was significantly predominant in the intestinal type (75.3%), most gastric‐type NADETs were cancerous (64.3%). Notably, most gastric‐type NADETs were adenocarcinomas even when the tumor size was ≤0 mm. In multivariate analysis, tumor location on the oral side (odds ratio OR, 4.42), villous structure (OR, 6.44), and low tumor gland density (OR, 9.49) were independent predictors of gastric‐type tumors. Gastric‐type NADETs significantly differ from intestinal‐type NADETs in terms of tumor location, morphology, and biology.
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