Yusuke Saitoh

Efficacy of high-frequency ultrasound probes for the preoperative staging of invasion depth in flat and depressed colorectal tumors ☆ ☆☆ ★

BACKGROUND Flat and depressed nonpolypoid types of colorectal tumors have drawn much attention. Since endoscopic mucosal resection technique is available, it is of great importance to distinguish intramucosal carcinoma from invasive carcinoma because determination of the invasion depth is essential for choosing this therapy. The usefulness of high-frequency (20 MHz) ultrasound probes for preoperative staging of invasion depth in this type of colorectal tumor was evaluated. METHODS Forty-nine cases of flat and depressed tumors were examined with the ultrasound probe and diagnostic accuracy was confirmed by comparing ultrasonic images with the pathologic findings of the specimens resected either by endoscopic mucosal resection or surgical operation. RESULTS The normal colonic wall was visualized as a nine-layered structure and the muscularis mucosae was depicted in 37 (76%) of 49 cases. Flat and depressed tumors were visualized as hypoechoic lesions and the invasion depth was accurately diagnosed in 43 (88%) of 49 lesions. CONCLUSIONS High-frequency ultrasound probes proved to be useful in determining the invasion depth and therapeutic strategy in flat and depressed colorectal tumors.

JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection

Colorectal endoscopic submucosal dissection (ESD) has become common in recent years. Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also many types of precarcinomatous adenomas. It is important to establish practical guidelines in which the preoperative diagnosis of colorectal neoplasia and the selection of endoscopic treatment procedures are properly outlined, and to ensure that the actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with the guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society has recently compiled a set of colorectal ESD/endoscopic mucosal resection (EMR) guidelines using evidence‐based methods. The guidelines focus on the diagnostic and therapeutic strategies and caveat before, during, and after ESD/EMR and, in this regard, exclude the specific procedures, types and proper use of instruments, devices, and drugs. Although eight areas, ranging from indication to pathology, were originally planned for inclusion in these guidelines, evidence was scarce in each area. Therefore, grades of recommendation were determined largely through expert consensus in these areas.

Invasion depth diagnosis of depressed type early colorectal cancers by combined use of videoendoscopy and chromoendoscopy

BACKGROUND Depressed type early colorectal cancers are found less frequently than other polypoid cancers although they have a higher submucosal invasion rate. Recently videocolonoscopy and chromoendoscopy have become available and precise descriptions of these lesions are now routine. Because endoscopic mucosal resection is designated for intramucosal and focally extended submucosal (m-sm1) cancers, an evaluation of the characteristic findings indicating invasion depth with these modalities is important. METHODS Between January 1991 and March 1996, 64 depressed type early colorectal cancers were detected and treated. When a faint abnormality of the mucosa was suspected by routine videocolonoscopy, 0.1% of indigo carmine solution was sprayed on the mucosal surface (chromoendoscopy). Colonoscopic findings of m-sm1 cancers and moderately and massively extended submucosal (sm2-3) cancers were retrospectively reviewed and compared with confirmed histologic findings. RESULTS Characteristic colonoscopic findings needed for surgical operation were as follows: (1) expansion appearance, (2) deep depression surface, (3) irregular bottom of depression surface, and (4) folds converging toward the tumor. By using these findings, the invasion depth of depressed type early colorectal cancers could be correctly determined in 58 of 64 lesions (91%). CONCLUSIONS Characteristic colonoscopic findings obtained by a combination of videocolonoscopy and chromoendoscopy are useful for determination of the invasion depth of depressed type colorectal cancers, an essential factor in choosing a treatment modality.

Local Recurrence After Endoscopic Resection for Large Colorectal Neoplasia: A Multicenter Prospective Study in Japan

OBJECTIVES: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.

Quantitative analysis for human glucocorticoid receptor α/β mRNA in IBD ☆

We have previously reported that in peripheral blood mononuclear cells (PBMC), the augmented expression of the β isoform of the human glucocorticoid receptor (hGRβ), as a putative dominant negative regulator of glucocorticoid action, is associated with glucocorticoid (GC) unresponsiveness of UC patients. In this study, we quantified the levels and serial changes of hGR transcripts in PBMC of IBD patients by a real-time fluorescence monitoring of PCR. As results, relative hGRβ mRNA expression was significantly higher in the active stage of UC than in inactive periods of UC or CD patients. Longitudinal analysis revealed that hGRβ mRNA expression in UC was increased after the relapse of inflammation, suggesting that the overproduction of cytokines during inflammation may be responsible. In in vitro culture experiments of human lymphoid cell (CEM) and human PBMC, IL-7, and IL-18 increased hGRβ mRNA expression in these cells but GC itself did not. Through these analyses, it is indicated that the inflammatory cytokines altered the splicing condition of the primary transcript of hGR gene in IBD patients.

Minute findings by magnifying colonoscopy are useful for the evaluation of ulcerative colitis

BACKGROUND Colonoscopy has an important role in the diagnosis of ulcerative colitis. However, colonoscopic findings are inadequate for the prediction of relapse without histologic examination. In this study, the role of magnifying colonoscopy in ulcerative colitis was evaluated. METHODS One hundred sixteen magnifying colonoscopy observations were made in 61 patients with ulcerative colitis between January 1994 and October 1998. A simple classification of magnifying colonoscopic findings into 5 categories was devised as follows: regularly arranged crypt openings, villous-like, minute defects of epithelium, small yellowish spots, and coral reef-like appearance. The colonoscopic findings by classification were compared with histopathologic findings, and the usefulness of the classification for predicting relapse was prospectively analyzed in 18 patients. RESULTS Compared with grade as determined by conventional colonoscopy, there was a better correlation between the classification of findings by magnifying colonoscopy and histopathologic findings (r(2) = 0.665, 0.807, respectively). Of 18 patients studied prospectively, 7 of 9 with minute defects of epithelium relapsed within 6 months, and the cumulative nonrelapsing rate was significantly lower in patients with minute defects of epithelium compared with those without minute defects of epithelium (p = 0.0059). Moreover, minute defects of epithelium was found to be a significant independent predictive factor for relapse (multivariate analysis, Cox proportional hazards model; p = 0.0203). CONCLUSIONS Our proposed classification of magnifying colonoscopic findings in patients with ulcerative colitis is useful for the evaluation of disease activity and for the prediction of periods of remission.

Evidence-based clinical practice guidelines for management of colorectal polyps

BackgroundRecently in Japan, the morbidity of colorectal polyp has been increasing. As a result, a large number of cases of colorectal polyps that are diagnosed and treated using colonoscopy has now increased, and clinical guidelines are needed for endoscopic management and surveillance after treatment.MethodsThree committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Ten specialists for colorectal polyp management extracted the specific clinical statements from articles published between 1983 and September 2011 obtained from PubMed and a secondary database, and developed the CQs and statements. Basically, statements were made according to the GRADE system. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid.ResultsThe professional committee created 91CQs and statements for the current concept and diagnosis/treatment of various colorectal polyps including epidemiology, screening, pathophysiology, definition and classification, diagnosis, treatment/management, practical treatment, complications and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumor/carcinoma).ConclusionsAfter evaluation by the moderators, evidence-based clinical guidelines for management of colorectal polyps have been proposed for 2014.

The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma.

BACKGROUND AND STUDY AIMS Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps. PATIENTS AND METHODS This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method. RESULTS A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1 % to 86.1 % and 84.7 %, respectively. CONCLUSIONS Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.

Multicentric development of pancreatic intraductal carcinoma through atypical papillary hyperplasia

We report a case of multiple intraductal carcinomas of the pancreas associated with diffuse atypical papillary hyperplasia. A 67-year-old Japanese man with a complaint of epigastric pain was examined by endoscopic retrograde pancreatography, which demonstrated multiple dilated branches of the pancreatic duct in the body and tail of the pancreas. Histologic examination on the resected pancreas showed diffuse atypical papillary hyperplasia in multiple dilated ducts associated with multiple intraductal carcinomas. Histologic features are described and multicentric carcinogenesis through atypical papillary hyperplasia is discussed.

Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis.

Abstract Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.