Tomokazu Hisayuki

Immunohistochemical analysis of nestin and c-kit and their significance in pancreatic tumors.

The purpose of the present study was to clarify the difference of expression of two stem cell markers, nestin and c‐kit, among various pancreatic epithelial tumors and evaluate their utility. Immunohistochemistry was done for 99 surgically resected pancreatic tumor specimens, including 20 ductal adenocarcinoma (DAC), two undifferentiated carcinomas (UC), 31 intraductal papillary‐mucinous neoplasms (IPMN), six mucinous cystic neoplasms (MCN), five serous cystadenomas (SCA), six acinar cell carcinomas, two pancreatoblastoma (PB), eight solid‐pseudopapillary neoplasms (SPN), and 19 endocrine neoplasms (EN). Nestin was widely expressed in four SPN, one PB, one SCA, sarcoma areas in two UC, one MCN, and one DAC, and an area of oncocytic component in one IPMN. Some of these SPN, SCA and sarcomatous or oncocytic components in which nestin was expressed, also coexpressed c‐kit. Additionally, partial (scattered) expression of c‐kit was observed in ductal elements of 16 DAC, eight IPMN, five MCN, and one UC, one SCA, and three EN. The eight c‐kit‐positive IPMN included four of 23 adenoma‐to‐border lesions and four of eight non‐invasive‐to‐invasive carcinomas. The three EN were all carcinomas. These indicate that expression of two stem cell markers is different by tumor type, but the utility of judging direction or degree of differentiation and malignant grade on the basis of their expression status is suggested.

Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis.

Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas to be resected endoscopically with negative margins. However, the criteria for curative endoscopic resection remain unclear. We aimed to identify risk factors for nodal metastasis in T1 carcinoma patients and hence establish the indication for additional surgery with lymph node dissection.

Proliferating Potential and Apoptosis in the Development of Secondary Hyperparathyroidism: A Study Based on Ki-67 Immunohistochemical Staining and the Terminal dUTP Nick-End Labeling Assay

Abstract:  Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis (HD) patients. SHPT progresses from initial diffuse hyperplasia (diffuse) to early nodularity (early), then to multinodular hyperplasia (nodular), and finally to a single nodule (single) consisting of uniform parenchymal cells. We analyzed the roles of proliferation and apoptosis in SHPT progression. Seventy‐four parathyroid glands from 36 HD patients with SHPT, and 10 parathyroid glands from 10 non‐HD patients without SHPT were used for analysis. The former were classified as diffuse (N = 17), early (N = 22), nodular (N = 20), and single (N = 15); the latter were classified as normal (N = 10). To analyze proliferating cells we used Ki‐67, and to detect apoptotic cells, we used the terminal deoxynucleotidyl transferase (Tdt)‐mediated dUTP nick‐end labeling (TUNEL) assay. Concerning the Ki‐67 labeling index (LI), the incremental order was single, nodular, early, diffuse, and normal. Oxyphilic cells and around the central portion of each lesion were distinctly stained by Ki‐67. Concerning the TUNEL LI, the incremental order was early, diffuse, nodular, single, and normal. Chief cells and around the peripheral portion of each lesion were distinctly stained by TUNEL. In the progression from early to nodular, for oxyphilic cells, the Ki‐67 LI increased and the TUNEL LI decreased; for chief cells, the Ki‐67 LI decreased and the TUNEL LI showed no significant change. We considered that proliferative activity increases and that the apoptosis rate decreases as SHPT progresses from diffuse to single. Moreover, the specific differences in the rate of proliferation and apoptosis between oxyphilic and chief cells might be associated with SHPT progression.

Depressed-Type Colonic Lesions and “De Novo” Cancer in Familial Adenomatous Polyposis: A Colonoscopist’s Viewpoint

Familial adenomatous polyposis (FAP) is the most common inherited polyposis syndrome. Almost all patients with FAP will develop colorectal cancer if their FAP is not identified and treated at an early stage. Although there are many reports about polypoid lesions and colorectal cancers in FAP patients, little information is available concerning depressed lesions in FAP patients. Several reports suggested that depressed-type lesions are characteristic of FAP and important in the light of their rapid growth and high malignancy. Here, we describe the occurrence of depressed-type lesions in FAP patients treated at our institution. Between April 2001 and March 2010, eight of 18 FAP patients had colorectal cancers. Depressed-type colorectal cancer was found in three patients. It should be kept in mind that depressed-type lesions occur even in FAP.

Comparative clinicopathological characteristics of colon and rectal T1 carcinoma

Lymph node metastasis significantly influences the management of patients with colorectal carcinoma. It has been observed that the biology of colorectal carcinoma differs by location. The aim of the current study was to retrospectively compare the clinicopathological characteristics of patients with colon and rectal T1 carcinomas, particularly their rates of lymph node metastasis. Of the 19,864 patients who underwent endoscopic or surgical resection of colorectal neoplasms at Showa University Northern Yokohama Hospital, 557 had T1 surgically resected carcinomas, including 457 patients with colon T1 carcinomas and 100 patients with rectal T1 carcinomas. Analysed clinicopathological features included patient age, gender, tumor size, morphology, tumor budding, invasion depth, vascular invasion, histological grade, lymphatic invasion and lymph node metastasis. Rectal T1 carcinomas were significantly larger than colon T1 carcinomas (mean ± standard deviation: 23.7±13.1 mm vs. 19.9±11.0 mm, P<0.01) and were accompanied by significantly higher rates of vascular invasion (48.0% vs. 30.2%, P<0.01). Significant differences were not observed among any other clinicopathological factors. In conclusion, tumor location itself was not a risk factor for lymph node metastasis in colorectal T1 carcinomas, even though on average, rectal T1 carcinomas were larger and accompanied by a significantly higher rate of vascular invasion than colon T1 carcinomas.

White light-emitting contrast image capsule endoscopy for visualization of small intestine lesions: a pilot study

Background and study aims  Capsule endoscopy (CE) has become a routine means of diagnosing obscure gastrointestinal bleeding (OGIB) in the small intestine. Capsules using novel blue-enhanced white light-emitting diodes are expected to acquire clearer contrast images (CIs) of the small bowel vasculature. We conducted a pilot study to examine whether CIs facilitate visualization of small bowel erosions, ulcers, and areas of angioectasia compared with standard white light images (WLIs). Patients and methods  A total of 24 patients with OGIB were recruited in this study. The main outcome measure was visibility of lesions on CIs compared with WLIs. We also examined the color difference between lesions and normal mucosa (ΔE) with each imaging modality. Results  Three experienced physicians retrospectively evaluated 138 images of small bowel lesions (107 erosions, or ulcers, and 31 areas of angioectasia) obtained from 24 CE examinations. The endoscopists judged that compared with WLIs, CIs afforded easier identification of erosions or ulcers in 29 of 107 cases (27.1 %), were non-inferior in 68 of 107 cases (63.6 %), and were inferior in 10 of 107 cases (9.3 %). Identification of angioectasia was judged to be easier with CIs in 15 of 31 cases (48.4 %), non-inferior in 13 of 31 cases (41.9 %), and inferior in 3 of 31 cases (9.7 %). ΔE was significantly higher for CIs than WLIs, especially for angioectasia, potentially explaining why lesions were easier to visualize. Conclusions  CIs obtained by CE appear to facilitate identification of small bowel erosions, ulcers, and areas of angioectasia compared with WLIs.

The concept of ‘Semi‑clean colon’ using the pit pattern classification system has the potential to be acceptable in combination with a <3‑year surveillance colonoscopy

Histological features of colorectal lesions are currently evaluated via a magnifying chromoendoscopy [pit pattern (PIT) classification]. Advanced histological features are rarely observed in diminutive (≤5 mm) adenomatous polyps (DAPs). The Japanese guidelines indicate that diminutive neoplastic lesions without carcinomatous findings may be left untreated and followed up. At the present institution, DAPs with type IIIL PIT are left untreated in various cases, whereas lesions with type III, IV or V PIT are typically resected via routine colonoscopy. This retrospective study aimed to assess the management of DAPs using PIT classification. The participants of the study included patients <30 years previously referred for an initial colonoscopy, then reobserved for <3 years following the procedure. Participants were classified into three groups: Group A, Patients with type IIIL PIT DAP left untreated (semi-clean colon group); group B, patients with all neoplastic polyps, including DAPs, resected (clean colon group); and group C, patients without any adenomatous polyps (internal control group). The cumulative incidence of the index lesions (ILs) at the follow-up colonoscopy was analysed among the three groups. A total of 4,313 patients were enrolled in the study, with categorization as follows: Group A, 1,246; group B, 1,205; and group C, 1,862 patients. ILs were detected in group A, 100 (8.0%); group B, 104 (8.6%); and group C, 29 (1.6%) patients. There was no significant difference observed between groups A and B. It was verified that removing the type IIIL PIT DAPs did not decrease the incidence of ILs within a 3-year time period. Therefore, these polyps may be left untreated in combination with patient reobservation at an appropriate time interval, potentially one equal to that suggested following a polypectomy.

In vivo detection of desmoplastic reaction using endocytoscopy: A new diagnostic marker of submucosal or more extensive invasion in colorectal carcinoma

The pathological determination of desmoplastic reaction (DR) in colorectal carcinoma is useful for predicting extensive submucosal invasion. The aim of the present study was to determine the usefulness of endocytoscopy (EC) in detecting DR. A total of 72 cases of colorectal cancer with submucosal invasion (EC classification, EC3b) were evaluated. The utility of fine granular structure (FGS) observed via EC for the prediction of the presence of DR in the most superficial tumor layers was assessed. Of the 72 lesions, 26 were positive for FGS, and the majority of these lesions (23/26, 88.5%) exhibited a DR, indicating a significant association. The overall accuracy of the identification of FGS via EC that was predictive of a DR was 87.3%. The presence of FGS detected by EC was significantly associated with the presence of a DR, suggesting the clinical usefulness of EC in planning treatment for colon cancer with submucosal invasion.

Retrospective analysis of large bowel obstruction or perforation caused by oral preparation for colonoscopy

Background and study aims  Patients undergoing bowel preparation for colonoscopy are at risk of potentially severe adverse events such as large-bowel obstruction (LBO) and perforation. These patients usually need emergency surgery and the consequences may be fatal. Little is known about the risk factors for LBO and perforation in these circumstances. We sought to establish the natural history of LBO and perforation caused by oral preparation for colonoscopy. Patients and methods  We retrospectively analyzed data from 20 patients with LBO or perforation associated with oral preparation for colonoscopy. All patients were treated at the Showa University Northern Yokohama Hospital (SUNYH) between April 2001 and December 2015. Drugs used for bowel preparation, age, sex, indication for colonoscopy, pathogenesis and treatment were recorded. Results  Eighteen of the patients had LBO and 2 had perforation. Fourteen events occurred at SUNYH, which accounted for 0.016 % of patients who underwent bowel preparation during this period. Seventeen patients were symptomatic when the decision to undertake colonoscopy was made (including 7 who complained of constipation and 4 who complained of abdominal pain; 3e were asymptomatic). Nineteen patients ultimately required surgery, 13 within 3 days of presentation. Eleven patients ultimately required colostomy. There was no perioperative mortality in our cases. Conclusion  Large bowel obstruction and perforation are rare events associated with oral preparation for colonoscopy, but frequently require surgery. Exacerbation of constipation might be a risk factor for LBO or perforation. Potentially catastrophic situations can be avoided by early detection and treatment.