Mucosal High-grade Neoplasia Research Articles

MRI features in differentiating mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus.

To evaluate the diagnostic accuracy of unenhanced and contrast-enhanced MRI in the differentiation of mucosal high-grade neoplasia (MHN) from early invasive squamous cell cancer (EISCC) of the esophagus. Between March 2015 and January 2019, 72 study participants with MHN (n = 46) and EISCC (n = 26) of the esophagus were enrolled in this prospective study. Postoperative histopathologic analysis was the reference standard. All participants underwent MRI (T2-multi-shot turbo spin-echo sequence (msTSE), diffusion-weighted imaging (DWI), and 3D gradient-echo-based sequence (3D-GRE)). Two radiologists, blinded to participants' data, independently evaluated MRI and assigned MR features including shape (mucosal thickening or focal mass), signal on T2-msTSE and DWI, enhancement degree (intense or slight), and enhancement pattern (homogeneous, heterogeneous, or heart-shaped). Diagnostic performance of the 5 features was compared using the chi-square test; kappa values were assessed for reader performance. Surgery was performed within 3.6 + 3.5days after MR imaging. Inter-reader agreement on MR features was excellent (kappa value = 0.854, p < 0.001). All 8 mass-like MHN were "heart-shaped" in appearance. The degree of enhancement showed the best diagnosis performance in differentiating between MHN and EISCC of the esophagus. The combination of all 5 features had only borderline improved sensitivity, specificity, and AUC of 100%, 96.2%, and 0.999, respectively, which was not statistically significant compared with the degree of enhancement alone. MRI can differentiate MHN from EISCC in esophagus; the presence of "heart-shaped" appearance favors the diagnosis of MHN. • All 8 mass-like MHN showed a "heart-shaped" enhancement pattern which may help differentiating MHN from EISCC. • Degree of enhancement had the best diagnostic performance in differentiating between MHN and EISCC in esophagus. • The combined 5 features (shape, signal in T2-msTSE and DWI, enhancement degree, and enhancement pattern) provided sensitivity, specificity, and AUC of 100%, 96.2%, and 0.999, respectively, which was not statistically significant than tumor enhancement alone in distinguishing MHN from EISCC.

Can magnifying endoscopy with narrow-band imaging discriminate between carcinomas and low grade adenomas in gastric superficial elevated lesions?

Background and study aims: The aim of this study was to investigate the capability of magnifying endoscopy with narrow-band imaging (ME-NBI) to discriminate between early carcinomas (EC) and low grade adenomas (LGA) in gastric superficial elevated epithelial neoplasias. Patients and methods: We investigated 100 consecutive cases of gastric superficial elevated epithelial neoplasias that were removed using endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification; category 4 (mucosal high grade neoplasia) and category 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, whereas category 3 (mucosal low grade neoplasia) lesions were diagnosed as LGA. The associations between the postoperative pathological diagnoses and the ME-NBI findings were analyzed, and included the shape, specification, and area of irregularity in the microvascular architecture (MV) and the microsurface structure (MS). Results: Seventy-nine EC and 21 LGA cases diagnosed postoperatively were evaluated retrospectively. The lesion size (median; range (mm)) was significantly larger in the EC group (14; 2 – 95) compared to the LGA group (5; 2 – 16) (P < 0.001). Wavy forms in the MV shapes (P = 0.031), extension in the MV specifications (P = 0.035), and area with MV irregularity (P = 0.001) were found to be statistically significant predictive findings for EC. Villous forms in the MS shapes (P = 0.026), enlargement in the MS specifications (P = 0.044), and area with MS irregularity (P = 0.021) were also found to be statistically significant predictive findings for EC. The rates of preoperative sensitivity, specificity, and diagnostic accuracy of ME-NBI for discriminating EC were 86.1 %, 38.9 %, and 75 %, respectively. Conclusions: The present study suggests that ME-NBI is useful for the differential diagnosis of EC and LGA in gastric superficial elevated epithelial neoplasias.Study registration: UMIN000012925.

Frequency and efficacy of additional investigations following incomplete colonoscopies: A population-based analysis

BackgroundLimited data are available on the follow-up of patients with incomplete colonoscopy following positive faecal occult blood testing. Our study aimed to determine the proportion of and reasons for incomplete colonoscopies, the proportion of patients who completed colonic evaluations, the methods used and the subsequent findings. MethodsA total of 9483 colonoscopies performed after positive testing in a colorectal cancer screening programme setting were included. The study was prospective for index colonoscopy findings and partly retrospective for follow-up. ResultsOverall 297 colonoscopies were incomplete (3.2%). A secondary colonic evaluation was deemed necessary in 245 patients, of which 126 underwent an additional examination (51.4%). Radiology was the primary method used for complete colonic evaluation, whereas a repeat colonoscopy was performed in only 6.4%; the examination was normal in 119 patients (94.4%). A mucosal high-grade neoplasia was removed in 1, and multiple (≥3) adenomas were removed in 2 patients. ConclusionsThe present screening programme with biennial faecal occult blood testing revealed a high colonoscopy completion rate, a low rate of secondary colonic evaluation, infrequent use of colonoscopy for completion, and a low detection rate of significant neoplasia.

Natural history of diminutive colorectal polyps: long-term prospective observation by colonoscopy.

Endoscopic removal of colorectal adenomatous polyps effectively prevents cancer. However, the treatment strategy for diminutive polyps (diameter ≤ 5 mm) remains controversial. Understanding the natural history of diminutive polyps is a prerequisite to their effective management. We prospectively examined the natural history of diminutive polyps by long-term surveillance colonoscopy. A total of 207 polyps detected in 112 patients from December 1991 through March 2002 were studied. To avoid potential effects on size and morphological characteristics, all polyps were selected randomly and were followed without biopsy. Polyp size was estimated by comparing the lesion with the diameter of a biopsy forceps. Mean follow up was 7.8 years (SD, 4.8; range, 1.0-18.6; median, 7.5; interquartile range 3.4-11.2). Twenty-four polyps were resected endoscopically, and the histopathological diagnosis was mucosal high-grade neoplasia (Category 4) for one polyp, and mucosal low-grade neoplasia (Category 3) for 23 polyps. Mean linear size of the polyps was 3.2 mm (SD, 1.0; range, 1.3-5.0) at initial colonoscopy and 3.8 mm (SD 1.6; range 1.3-10.0) at final colonoscopy (P<0.01). Left-sided polyps showed a higher growth rate than right-sided polyps, and a type IIIL2 pit pattern was associated with a lower growth rate than a type IIIL1 pattern. We clarified the natural history of diminutive polyps by long-term follow-up colonoscopy. The benign course of diminutive polyps should be considered in the design of treatment strategies.

Clinicopathological features of colorectal polyps: evaluation of the ‘predict, resect and discard’ strategies

'Predict, resect and discard' strategies for diminutive and small colonic polyps are considered to be cost effective for treating colorectal cancers. The aim of this study was to determine, retrospectively, the histological features of colonic polyps resected by endoscopic procedures or surgery using an updated database. We retrospectively analysed the clinicopathological features of colorectal polyps, less than 20 mm in size, which were removed by endoscopy from January 2009 to November 2011 at the National Cancer Center Hospital (NCCH) in Tokyo, Japan. Less than 1% of diminutive polyps (≤ 5 mm) were classified as mucosal high-grade neoplasia (Category 4), and no submucosal invasion by carcinoma (Category 5) lesions were noted. However, 3% of small polyps (6-9 mm) were classified as Category 5; of these, 6% were submucosal deep invasive cancers. Morphologically, depressed components were observed more frequently in carcinomas than in adenomas in both small and large polyps (10-20 mm). In light of the 'predict, resect and discard' strategies for small polyps, we should pay attention to the possible clinical malignancy of small and large polyps. We recommend that these strategies should be applied selectively and that they should be informed by accurate endoscopic evaluations.

Clinical characterization of gastric lesions initially diagnosed as low‐grade adenomas on forceps biopsy

The aim of this study was to elucidate characteristics of gastric lesions that are initially diagnosed as low-grade adenomas and to establish appropriate treatment. We retrospectively reviewed 231 lesions initially diagnosed as gastric adenomas. All forceps biopsy samples were histologically diagnosed as category 3 low-grade adenomas according to the revised Vienna Classification. All patients underwent endoscopic resection with endoscopic findings and post-resection diagnoses evaluated subsequently. Sixty-three lesions were initially diagnosed as depressed adenomas, and 168 lesions were diagnosed as protruding adenomas. The depressed lesions were significantly smaller (11.6 ± 5.0 mm) than the protruding lesions (17.0 ± 10.8 mm) (P < 0.001). Diagnoses reclassified to category 4 mucosal high-grade neoplasia (i.e. high-grade adenoma, adenocarcinoma in adenoma and adenocarcinoma) were more frequent among depressed lesions (52.4%) than among protruding lesions (31.0%) (P = 0.004). Multivariate analysis of all 231 lesions showed that lesion size larger than 20 mm (P < 0.001) and depressed appearance (including central depression) (P < 0.001) were significant independent factors suggesting cancer. For the 168 protruding lesions, lesion size larger than 20 mm (P < 0.001) and central depression (P < 0.001) were significant independent factors suggesting cancer. For the 63 depressed lesions, lesion size larger than 15 mm (P = 0.016) and a moth-eaten appearance (P = 0.017) were significant independent factors in the pre-treatment diagnosis of cancer. Adenocarcinoma lesions were often found in depressed lesions and protruding lesions with central depression. Endoscopic resection for total biopsy is recommended, even if forceps biopsy indicates low-grade adenoma, as pre-treatment biopsy may be inadequate for an accurate histological diagnosis.

Autofluorescence imaging endoscopy for screening of esophageal squamous mucosal high‐grade neoplasia: A phase II study

Few prospective studies examining the efficacy of autofluorescence imaging (AFI) screening for esophageal cancer have been reported. This study aimed to investigate the diagnostic value of AFI endoscopy for the screening of squamous mucosal high-grade neoplasia of the esophagus, performed by experienced and less-experienced endoscopists. Patients with a history of esophageal neoplasia or head and neck cancer underwent AFI endoscopic screening, followed by chromoendoscopy using iodine staining as the reference standard. The primary outcome was the sensitivity of AFI for detecting new squamous mucosal high-grade neoplasias. The secondary outcome was the positive predictive value (PPV) of AFI. Of a total 364 patients who underwent endoscopic examination, 43 new mucosal high-grade neoplasias were detected. The sensitivities of AFI in the experienced and less-experienced endoscopist groups were 71% (95% confidence interval [CI]: 55-87%) and 50% (95% CI: 32-68%), respectively. The PPV of AFI in the experienced and the less-experienced endoscopist groups were 25% (95% CI: 16-34%) and 26% (95% CI: 15-37%), respectively. The sensitivity of AFI in lesions ≤ 10 mm (31%, 5/16 lesions) was significantly lower than that in lesions > 10 mm (78%, 21/27 lesions) (P = 0.003). The sensitivity of AFI for the detection of new squamous mucosal high-grade neoplasias, and its PPV, were both low. Based on these results, a randomized study to compare AFI with standard techniques is not justified.

Original article: Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists

Narrow-band imaging (NBI) is a novel, noninvasive optical technique that uses reflected light to visualize the organ surface. However, few prospective studies that examine the efficacy of NBI screening for esophageal cancer have been reported. To compare the diagnostic yield of NBI endoscopy for screening of squamous mucosal high-grade neoplasia of the esophagus between experienced and less experienced endoscopists. Patients with a history of esophageal neoplasia or head and neck cancer received NBI endoscopic screening for esophageal neoplasia followed by chromoendoscopy using iodine staining. Biopsy specimens were taken from iodine-unstained lesions and the histological results of mucosal high-grade neoplasias served as the reference standard. The primary outcome was the sensitivity of NBI for detecting new lesions. The secondary outcome was the positive predictive value of NBI and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NBI in a per lesion basis. A total of 350 patients (170 by experienced endoscopists and 180 by less experienced endoscopists) underwent endoscopic examination. A total of 42 new mucosal high-grade neoplastic lesions (25 in the experienced endoscopist group and 17 in the less experienced endoscopist group) were detected. In the per-lesion-based analysis, the sensitivity was significantly higher in the experienced endoscopist group (100%; 25/25) compared with the less experienced endoscopist group (53%; 9/17) (P < 0.001). The positive predictive value of NBI was higher in the experienced endoscopist group than in the less experienced endoscopist group (45%, 25/55 vs. 35%, 9/26), although the difference was not significant (P = 0.50). The sensitivity of NBI in the less experienced endoscopist group was 43% in the former half of patients, and increased to 60% in the latter half of patients. In the per-patient-based analysis, the sensitivity of NBI was significantly higher in the experienced endoscopist group (100%) than in the less experienced endoscopist group (100 vs. 69%, respectively; P = 0.04). The positive predictive values of the experienced endoscopist group and the less experienced endoscopist group were similar, and were 48 and 47%, respectively. In conclusion, compared with the gold standard of chromoendoscopy with iodine staining, the sensitivity of NBI for screening of mucosal high-grade neoplasia was 100% with the experienced endoscopists but was low with the less experienced endoscopists. Electronic chromoendoscopy with NBI is a promising screening tool in these high-risk patients with esophageal mucosal high-grade neoplasia, particularly when performed by endoscopists with experience of using NBI.

Significance of each narrow‐band imaging finding in diagnosing squamous mucosal high‐grade neoplasia of the esophagus

Although narrow-band imaging (NBI) is used increasingly in clinical situations, the significance of each NBI finding has not been investigated. The primary endpoint of the present study was to identify the significant NBI findings to diagnose esophageal mucosal high-grade neoplasia. Between August 2007 and January 2009, we detected 59 new superficial esophageal lesions. The video images of NBI were recorded digitally. NBI findings such as brownish dots (dilated intra-epithelial papillary capillary loop [IPCL]), tortuous IPCL, elongated IPCL, caliber change in IPCL, variety in IPCL shapes, demarcation line, brownish epithelium, and protrusion or depression were evaluated using the video images. The association between each NBI finding and diagnosis of mucosal high-grade neoplasia, and intra- and interobserver agreement was evaluated. In univariate analysis, brownish epithelium, brownish dots, tortuous IPCL, variety in IPCL shapes and demarcation line were associated significantly with diagnosis of mucosal high-grade neoplasia. In multivariate analysis, brownish epithelium and brownish dots were confirmed to be independent factors. Odds ratios were 25.5 (95% confidence interval [CI]: 2.4-268) for brownish epithelium and 19.3 (95% CI: 1.8-207.7) for brownish dots. Intraobserver agreement was substantial for brownish epithelium and brownish dots. Interobserver agreement was moderate in brownish epithelium and brownish dots. Brownish epithelium and brownish dots were confirmed to be significant and reproducible NBI findings in the diagnosis of squamous mucosal high-grade neoplasia of the esophagus. Initial assessment of esophageal lesions should be done based on these findings.

Transnasal endoscopy with narrow-band imaging and Lugol staining to screen patients with head and neck cancer whose condition limits oral intubation with standard endoscope (with video)

Early detection of esophageal cancer in patients with head and neck cancers may alter treatment planning and improve survival. However, standard endoscopic screening is not feasible for some patients with tumor-related airway compromise or postirradiation trismus. To evaluate a novel, sequential approach by integrating ultrathin endoscopy with narrow-band imaging and Lugol chromoendoscopy. Cross-sectional study. Single center in Taiwan. Forty-four consecutive patients with transoral difficulty screened for synchronous or metachronous esophageal cancer. Sensitivity, specificity, and accuracy in the detection of mucosal high-grade neoplasia or invasive cancer. Fifty-four endoscopic interpretations were obtained, and 11 mucosal high-grade neoplasia and 7 invasive cancers were confirmed by histology. The mean examination time was 19.4 minutes (range 7.9-35.2 minutes), and all patients tolerated the procedure well. Sensitivity, specificity, and accuracy (with 95% CI) were 55.6% (95% CI, 33.5%-75.6%), 97.2% (95% CI, 85.8%-99.3%), and 83.3% (95% CI, 71.2%-90.9%), respectively, for standard endoscopy; 88.9% (95% CI, 66.9%-96.6%), 97.2% (95% CI, 85.8%-99.3%), and 94.4% (95% CI, 84.9%-97.9%), respectively, with the adjunct of narrow-band imaging; and 88.9% (95% CI, 66.9%-96.6%), 72.2% (95% CI, 55.9%-84.1%), and 77.8% (95% CI, 64.9%-86.8%), respectively, with the adjunct of Lugol chromoendoscopy. When we integrated all interpretations on the basis of the sequential approach, the estimated probability of false-negative findings was 1.2% (95% CI, 0.1%-4.6%). Inherent shortcomings of ultrathin endoscopy, such as its resolution, light source, and lack of magnification. The use of ultrathin endoscopy in a sequential approach for multimodal detection is feasible in patients with transoral difficulty and substantially increases the detection rate of synchronous or metachronous neoplasms.

Classification of gastrointestinal epithelial neoplasia

Use of the terms ‘adenoma’, ‘dysplasia’ and ‘carcinoma’ without classification into clinically relevant categories has resulted in large variations in diagnoses of oesophageal, gastric and colorectal neoplastic lesions, and in discrepancies between biopsy-based and resection-based diagnoses. To overcome these problems, it is recommended that the categories of the revised Vienna classification are used. These are: (1) negative for neoplasia; (2) indefinite for neoplasia; (3) mucosal low-grade neoplasia; (4) mucosal high-grade neoplasia; and (5) submucosal invasion by carcinoma. These categories fit best with current clinical management considerations. The results of a review of both biopsy and resection specimens of 13 gastric neoplastic lesions by 31 pathologists show that neither Western nor Japanese pathologists can distinguish the subcategories of category 4 reproducibly. Moreover, these subcategories are clinically equivalent, as endoscopic or surgical local resection is indicated in all of them. Proper classification into the five main categories should contribute to better communication between pathologists and clinicians, and to a reduction of overtreatment.

Diagnostic criteria for gastrointestinal carcinomas in Japan and Western countries: proposal for a new classification system of gastrointestinal epithelial neoplasia.

Large differences have been found between Western and Japanese pathologists in their diagnosis of adenoma/dysplasia and early carcinoma for gastric, colorectal and oesophageal epithelial neoplastic lesions. Common worldwide terminology based on clinical usefulness, that is, on neoplastic severity and depth of invasion, is needed. Thirty-one pathologists from 12 countries reviewed 35 gastric, 20 colorectal and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. Suspected or definite carcinoma was diagnosed in 17-66% 'of gastric, in 5-40% of colorectal, and in 10-67% of oesophageal slides by pathologists with a Western viewpoint, but in 77-94% of gastric, in 45-75% of colorectal and in 81-100% of oesophageal slides by pathologists with a Japanese viewpoint (from Japan, Germany, Austria and UK). Overall, there was poor agreement between the conventional Western and Japanese diagnoses (kappa values lower than 0.3 for gastric, colorectal and oesophageal lesions). There was much better agreement among the pathologists (kappa values higher than 0.5 for gastric and colorectal lesions) when the original assessments of the slides were regrouped into the five categories of the following classification of GI epithelial neoplasia we hereby propose: C1, negative for neoplasia; C2, indefinite for neoplasia; C3, mucosal low-grade neoplasia (low-grade adenoma/dysplasia); C4, mucosal high-grade neoplasia (high-grade adenoma/dysplasia plus mucosal carcinoma); C5, submucosal invasion of neoplasia. The intercountry differences in the diagnoses of adenoma/dysplasia and early carcinoma can, in large part, be resolved by adopting terminology based on neoplastic severity and depth of invasion. Problems with defining intramucosal invasion are thus avoided. Moreover, grouping high-grade adenoma/dysplasia and mucosal carcinoma together in one category is clinically useful, as patients with small mucosal neoplastic lesions can be cured by endoscopic local resection.