Immunohistochemical Localization of REG Ia Protein in Salivary Gland Tumors

The regenerating gene( Reg) Ia protein has a trophic effect on gastric epithelial cells, and its overexpressionis reported in gastrointestinal cancers. The salivary gland is a component of the digestive system, andtherefore, REG Ia protein may play some role in the pathophysiology of salivary gland tumors. In the presentstudy, we determined the immunohistochemical localization of REG Ia protein in salivary gland tumorsand moreover investigated its relationship to clinicopathological features. Twenty-eight patients with salivarygland tumor were enrolled. The specimens resected by surgery from those patients were examinedusing immunohistochemistry for REG Ia protein and Ki67. Five of the 16 pleomorphic adenomas (31.3%)were positive for REG Ia protein. Regarding salivary gland carcinomas, four of five mucoepidermoid carcinomas(80%), three of five adenoid cystic carcinomas (60%), one of two polymorphous low-grade adenocarcinomas(50%) were also positive for REG Ia protein. However, no relationships were found betweenREG Ia protein expression and clinicopathological features. Regarding the Ki67 expression, strong signalwas observed in the tumor cells of patients with salivary gland adenoma as well as carcinoma. REG Ia proteinis expressed not only in adenocarcinoma but also precancerous adenoma cells proliferating actively,suggesting that REG Ia protein may play a role at least in part in the development of salivary gland tumors

Pathological Approach for Surveillance of Ulcerative Colitis-associated cancer:Usefulness of Immunohistochemistry for p53

The patients with long-standing ulcerative colitis( UC) have a high-risk of neoplastic lesions in the colonicmucosa. The UC-associated neoplastic lesion is difficult to detect by endoscopic examination or diagnosehistologically. In the present study, we aimed to clarify whether immunohistochemistry for p53 is useful todiscriminate the UC-associated neoplasia from inflammed regenerating epithelium. Tissue samples were obtainedfrom colorectomy specimens from 20 patients with long-standing UC (range 6-29 years). The surfaceof microstructure of the tissues was observed by stereomicroscopy, and the sections were examined usingimmunohistochemistry for p53. All of T2-4 carcinomas were detectable by endoscopic examination beforesurgery, whereas considerable number of dysplasias (52.5%), Tis carcinomas (33.3%), and T1 carcinomas(60.0%) were undetectable. Fifty-three of 67 UC-associated neoplastic lesions (79.1%) were of flat-typemacroscopically. The detection rate of flat-type neoplasias( 45.3%) was significantly lower than that of protrudingones (100%). The positivity of p53 overexpression was 0 % in UC-II, 52.5 % in UC-III, and 70.4 %in UC-IV, respectively. UC-II lesions had lower positivity of p53 overexpression than UC-III( P=0.027) or-IV lesions( P=0.003). Immunohistochemical analysis of p53 protein is useful to discriminate the UC-associatedneoplasia from inflammed regenerating epithelium

Localization of Stem Cells in Small Intestinal Epithelium:Strategies for Identifying Small Intestinal Stem Cells

In the small intestine, stem cells are considered to exist at the bottom of the crypt. Actively proliferatingtransitional cells supplied from stem cells are differentiated into two directions upward and downward. Upwardcells are differentiated into absorbing epithelial cells, goblet cells, and endocrine cells, and downwardcells differentiated into Paneth cells. However there are some difficulties to identify the stem cells becauseof their unique characteristics. At first, stem cells occur as actual stem cells and potential stem cells, andsecond, there is diversity in stem cells. Therefore, molecules suitable for a marker of small intestinal stemcells are necessary to distinguish "true" stem cells from others. Energetically searched for in recent years,Musashi-1, type 1A bone morphogenetic protein receptor (BMPR-1A), phospho-phosphatase and tensinhomolog deleted on chromosome ten( phospho-PTEN), doublecortin and calmodulin kinase-like-1( DCAMKL1),ephrin receptors( Eph receptors), integrins, and leucine-rich repeat-containing G protein-coupled receptor5 (Lgr5) are proposed. Among them, Musashi-1 draws attention as one of a candidate marker forsmall intestinal stem cells. We here introduce our reviews about expression of Musashi-1 and Hes1 proteinsin the small intestine, and would like to overview the way to identify the small intestinal stem cells

A Novel Approach to Endoscopic Submucosal Dissection Using Bipolar Current Needle Knife for Colorectal Tumors

Objective: To completely and safely remove a large colorectal lesion in a single fragment, we have developed an endoscopic electrosurgical knife( B-Knife) for a more effective bipolar cutting adevelopedannd coagulation system.The aim of this study was to evaluate the effectiveness and safety of the B-Knife in patients with large colorectal tumors.Methods:Endoscopic submucosal dissection (ESD) using the B-Knife was performed initially in 3 patients with large colorectal tumors in a pilot study. Subsequently, we examined the clinical outcomes of ESDusing the B-Knife in 25 patients with colorectal tumors.Results:During initial clinical use of the B-Knife, en bloc resection was achieved in all 3 cases, and themean operating time was 43 minutes. All margins of resected material were histologically free of neoplasia.There were no cases of delayed bleeding or perforation. In a series of 25 ESD cases, which consisted of 8adenomas, 15 intramucosal carcinomas, one slightly submucosal invasive carcinoma, and one massive submucosalinvasive carcinoma, the en bloc resection rate was 84% . The mean operation time was 91.6 minutes and the mean size of resected specimens was 36.4 mm (range:19-80 mm). Perforations occurred in one( 4%) case, but delayed bleeding did not occur in any of the cases. Additional surgery was required for2 cases( 8%).Conclusions:ESD using the B-Knife is reliable and safe for the complete resection of select large flat lesions in the colorectum

Diagnostic Validity of DNMT-1 and 3b Immunoreactivity in Non-neoplastic Epithelium of UC Patients with and Without Neoplasia

It is important to improve the efficacy of surveillance in UC patients with neoplasia.In the present study, we assessed the cut-off value of expression of DNMT-1 and DNMT-3b expression in the non-neoplastic rectal epithelium of patients with long-standing and extensive UC. Sixty patients with long-standing and extensive UC participated in this study( 30 with colorectal neoplasia and 30 without). Immunohistochemical analysis was performed to determine the expression of DNMT-1 and 3b in non-neoplasticrectal epithelium of UC patients without neoplasia, and in non-neoplastic rectal epithelium of UC patients with neoplasia. The level of immunoreactive DNMT-1 and DNMT-3b expression was determined as the percentage of positive cells relative to the total number of cells counted under high power magnification.DNMT-1 and 3b expression in non-neoplastic rectal epithelium of UC patients with neoplasia (0.57, range0.53-0.63)(0.32, range 0.18-0.67) was higher than in the non-neoplastic epithelium of UC patients without neoplasia (0.41, range 0.25-0.54, P=.001)(0.0, range 0.0-0.13, P<.001). ROC curve analysis confirmed0.53 and 0.07 as the best DNMT-1 and DNMT-3b cut-off values for identifying individuals at increased risk of neoplasia( area under the curve=0.798 and 0.842, respectively). The cut-off value for DNMT-1 andDNMT-3b expression in non-neoplastic rectal epithelium is therefore an efficient predictor for the increased risk of UC-associated neoplasia

Validation of Pyrosequencing for the Analysis of KRAS Mutations in Colorectal Cancer

The use of antibodies against epidermal growth factor receptor( EGFR) in conjunction with conventionalchemotherapy for metastatic colorectal cancer (CRC) in patients with KRAS wild-type tumors has beenproven to be efficacious. Recently, KRAS testing prior to anti-EGFR therapy has become mandatory formetastatic CRC patients. Although newly developed pyrosequencing is expected to be one of the highthroughput procedures detecting such mutations, the accuracy of the procedure has not been well evaluated.In the present study, we aimed to validate the accuracy, especially the potential for a false-negative result,in detecting KRAS mutations by pyrosequencing using cultured tumor cells. DNA extracted from cultured&igrave;NOZ&icirc; gallbladder cancer cells( known to contain KRAS mutation G12V) at concentrations of 1%, 5%, 10%, and 25%, as well as 2 DNA samples extracted from a resected CRC specimen( known to contain anotherKRAS mutation, G12C) at concentrations of 5% and 25%, were prepared. We analyzed KRAS mutationalstatus and nonexistent and/or nonfunctional mutations of these 6 samples using pyrosequencing. TheKRAS mutation detection rates in the 4 NOZ samples( 1%, 5%, 10%, and 25%) were 0.37%, 2.79%, 5.28%,and 13.85%, respectively. Some artifacts of KRAS mutations unlikely to be present were detected in 1%samples of NOZ at a rate similar to that of the G12V mutation( G12C, 0.29%;G13C, 0.42%). Although theKRAS mutation G12C was detected at rates of 1.26% and 6.49% in samples with 5% and 25% DNA extractedfrom resected CRC specimen, respectively, no other type of KRAS mutation was detected in suchsamples. Pyrosequencing could not detect KRAS mutations correctly in the sample containing 1% DNA.This might cause false negatives. A sample mutated DNA concentration of at least 5% was necessary forprecise analyses by this procedure

Selection of Postoperative Systemic Chemotherapy for Advanced Gastric Cancer Patients with Hepatic Metastasis Using the Histoculture Drug Response Assay

The usefulness of histoculture drug response assay (HDRA) before the start of antitumor chemotherapy was explored to predict the antitumor response of chemotherapy for progressive gastric cancer patients with hepatic metastasis. Cancer tissue was collected from 6 advanced gastric cancer patients with hepatic metastasis, to assess whether the tumor is sensitive to chemotherapeutic agents of 5-fluorouracil (5-FU), mitomycin C (MMC), docetaxel hydrate (TXT), and cisplatin (CDDP) by the HDRA method. The size of hepatic tumor was measured by CT scan 3 and 6 months after the start of the chemotherapy and examined the relationship between the selected chemotherapy and antitumor response. Of 6 patients investigated in the present study, 3 patients received monotherapy with TS-1[○!R], which was found to be effective in 2 patients (66.7%). In the patient who received MMC monotherapy, the HDRA showed the cancer tissue to be less sensitive to any of antitumor agents tested, resultantly indicating no antitumor response. In the remaining 2 patients with combination therapy with TS-1[○!R] and MMC, the selected chemotherapeutic agents showed anti-tumor effect. The HDRA is useful to predict the antitumor response of postoperative adjunctive chemotherapy for advanced gastric cancer patients with hepatic metastasis, and plays an important role in selection of antitumor agents

ガン ノ ビョウリ

腫瘍tumorは,新生物を指す用語として用いられ,細胞の自律性増殖によって形成される不可逆的な病変として定義される.本稿の主題である「癌」は悪性腫瘍一般(癌腫と肉腫を含む)をさすこともあるが,悪性上皮性腫瘍として捉えられる事が多い.本来,腫瘍の良悪性は,形態変化ではなく,その病変が浸潤・転移をきたすか否かというような生物学的性質により区別されるものである.しかし,病院業務のなかでは,形態学的診断の重要性も高い.腫瘍の良悪性の鑑別には,1)細胞異型,2)細胞増殖活性,3)浸潤,4)転移,といった項目が重要である.また,形態変化のみからは診断困難な癌も少なくなく,そのような症例では免疫組織化学や遺伝子工学的検索の結果が応用される.The term tumor was originally applied to the swelling caused by inflammation, but now equated with neoplasm. In general, neoplasms are irreversible, and their growth is autonomous. In common usage, the terms benign and malignant refer to the overall biological behavior of a tumor, rather than to its morphological characteristics. However, morphological assessment of the tumor is important from a practical point of view. Some of the morphological features that favor malignancy include the following points, 1) anaplasia or cellular atypia, 2) mitotic activity, 3) invasion, and 4) metastasis. There are some exceptions from the above criteria for malignancy, for instance, so-called low-grade cancer (carcinoma with low grade atypia). Immunohistochemical and molecular examination are expected to be helpfulness for the pathological diagnosis of the carcinoma in morphologically exceptional cases

ホンガク ニオケル シンリョウ サンカガタ リンショウ ジッシュウ ニ カンスル コウサツ : モデル・コア・カリキュラム ノ ドウニュウ ト シンリョウ サンカガタ リンショウ ジッシュウ ノ アリカタ

獨協医科大学では,医学教育モデル・コア・カリキュラムに準じた診療参加型臨床実習を実施する予定である.平成16年度以降の臨床実習形式は46週と従来より長くなり,診療参加型となる.これを円滑に導入するためには,臨床実習開始以前から学生の準備教育を充実させ,コ・メディカルを含めた実習にかかわるすべてのスタッフに,臨床実習の意義を徹底させることが必要である.現実的な問題点として,現状では実習教育にたずさわる教員数の絶対的な不足が挙げられ,マンパワーの補充を目的とした組織的な対応を早急に検討することが望まれる.(本論文は,第8回医学教育ワークショップCグループの発表内容を中心に加筆検討を加えたものである.)In introducing clinical clerkship incorporating a core curriculum at Dokkyo University School of Medicine, its problems and concrete plans were evaluated. For smooth introduction of this plan, improving the preliminary education of students before the beginning of clinical training and assuring the understanding of all the staff members involved in clinical training including co - medicals about its significance were considered to be necessary. As a practical problem, a lack of instructors who can be involved in clinical training was raised, and prompt evaluation of systematic measures to increase the staff was strongly recommended