Masayuki Itabashi

The Vienna classification of gastrointestinal epithelial neoplasia

BACKGROUND Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS 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. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Differences in diagnostic criteria for gastric carcinoma between Japanese and Western pathologists

BACKGROUND There have been many studies on gastric carcinoma in populations with contrasting cancer risks. We aimed to find out whether the criteria for the histological diagnosis of early gastric carcinoma were comparable in Western countries and Japan. METHODS Eight pathologists from Japan, North America, and Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and 18 endoscopic mucosal resections taken from 17 Japanese patients with lesions ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The pathologists were given a list of pathological criteria and a form on which they were asked to indicate the criteria on which they based each diagnosis. FINDINGS For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia, whereas the Japanese diagnosed definite carcinoma in four slides, suspected carcinoma in one, and adenoma in only two. Of 12 slides with high-grade adenoma/dysplasia according to most Western pathologists the Japanese gave the diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing high-grade adenoma/dysplasia with suspected carcinoma according to most Western pathologists the Japanese diagnosed definite carcinoma in all. There were no major differences in the diagnoses of three slides showing reactive epithelium and seven slides with clearly invasive carcinoma. When the opinion of the majority of the pathologists was taken as the final diagnosis there was agreement between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95% CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion for most Western pathologists whereas for the Japanese nuclear features and glandular structures were more important. INTERPRETATION In Japan, gastric carcinoma is diagnosed on nuclear and structural criteria even when invasion is absent according to the Western viewpoint. This diagnostic practice results in almost no discrepancy between the diagnosis of a superficial biopsy sample and that of the final resection specimen. This may also contribute to the relatively high incidence and good prognosis of gastric carcinoma in Japan when compared with Western countries.

Relationship between Development of Diarrhea and the Concentration of SN-38, an Active Metabolite of CPT-11, in the Intestine and the Blood Plasma of Athymic Mice Following Intraperitoneal Administration of CPT-11

Severe diarrhea occurred during daily intraperitoneal administration of 7‐ethyl‐10‐[4‐(l‐piperidino)‐l‐piperidino]carbonyloxycamptothecin (CPT‐11) at a dose of 50 mg/kg in athymic mouse. Serial determination of CPT‐11 and 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), with the use of an on‐line solid extraction HPLC system, demonstrated that much higher levels of the compounds are retained in the intestine and the blood plasma after five consecutive daily injections than after a single injection. Histologic examination of the gastrointestinal tract showed hemorrhagic colitis on day 7 and later after five consecutive daily injections of CPT‐11. The direct cause of diarrhea associated with CPT‐11 administration is considered to be enterocolitis caused by high levels of SN‐38 and/or CPT‐11 retained for a long period in the intestine.

Differences in the diagnostic criteria used by japanese and western pathologists to diagnose colorectal carcinoma

In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries.

Superficial esophageal carcinoma: Surgical treatment and the results

We report 92 patients treated with esophagectomy for superficial esophageal carcinoma (SEC; 9.1% of all resected esophageal cancers at our institution). the operative mortality rate was 5.4%. in 24 cases, cancer invasion was limited to the mucosa, and in 68 to the submucosa. Twenty‐three patients in the former group had no lymph node involvement, whereas 24 patients (35.3%) of the latter group had lymph node metastases. the 5‐year survival rate after surgery for patients with SEC limited to the mucosa was 83.5%, which was significantly better than that for carcinoma invading the submucosa (54.9%). No recurrent disease occurred in patients with lesions limited to the mucosa. in conclusion, an esophagectomy with wide lymphadenectomy is necessary to provide a better prognosis for SEC invading the submucosa, whereas a less extensive treatment may be considered for SEC limited to the mucosa.

Hepatoid adenocarcinoma of the stomach

Although gastric cancer occurs frequently in Japan, few cases of hepatoid adenocarcinoma, a cancer with an extremely poor prognosis, have been reported. Here, we describe a 67-year-old Japanese man referred to our hospital with suspected gastric cancer. Gastrointestinal fiberscopy revealed an elevated lesion with a central depression on the lesser curvature, extending from the antrum to the body of the stomach. On the preoperative examinations, abdominal computed tomography scan, magnetic resonance imaging, and abdominal ultrasonography revealed multiple metastases to the liver and no cirrhotic change. The serum level of alpha-fetoprotein (AFP) was markedly elevated (10,084 ng/ml). After a diagnosis of AFP-producing gastric cancer with multiple liver metastases was made, total gastrectomy, without liver resection, was performed. Microscopically, the tumor showed two main histological features. The main part of the tumor resembled moderately differentiated hepatocellular carcinoma, and the rest showed fetal-type adenocarcinoma. Some parts of the hepatoma-like lesion showed periodic acid-Schiff (PAS)-positive granules. Furthermore, the tumor showed diffuse immunohistochemical positivity for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. According to these histopathological findings, the tumor was diagnosed as hepatoid adenocarcinoma of the stomach. Although anastomotic leakage occurred postoperatively and the liver metastases have increased in size, the patient remains alive 11 months after the operation. Because of the poor prognosis for this histological type of tumor, accurate diagnosis of hepatoid adenocarcinoma is important, and long-term follow-up is required. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

Differences in diagnostic criteria for esophageal squamous cell carcinoma between Japanese and Western pathologists.

Large discrepancies have been found between Western and Japanese pathologists in the diagnosis of adenoma/dysplasia versus carcinoma for gastric and colorectal glandular lesions. It is important to determine whether similar differences exist in the diagnosis of esophageal squamous lesions.

A pathologic study of benign breast diseases in Tokyo and New York

Two hundred thirty‐two biopsies of benign breast conditions from the National Cancer Center Hospital in Tokyo and 263 comparable biopsies from Memorial Hospital in New York City were reviewed. The component lesions of benign breast disease were identified and evaluated according to their relative frequency for different ages. Apocrine cysts, apocrine hyperplasia, intraductal hyperplasia, sclerosing adenosis, blunt duct hyperplasia, and atypical lobular hyperplasia were at least twice as common in biopsies from American women. Solitary papillomas were twice as common among biopsies from Japanese patients and tended to show more epithelial proliferation and sclerosing papillomatosis than did Americans. No major differences were found in the frequency of cysts, duct stasis, periductal mastitis, sclerosing intraductal papillomatosis, fibroadenomatoid mastopathy or fibroadenomas. Assuming intraductal hyperplasia and atypical lobular hyperplasia may represent premalignant epithelial changes, the high frequency of these lesions in New York biopsies when compared to Tokyo biopsies correlates well with the higher rate of breast cancer in the United States as compared to Japan. The greater frequency of lobular proliferative lesions and apocrine disease in New York suggests that these lesions may be produced by factors which also predispose American women toward breast cancer. Cancer 50:1899‐1903, 1982.

Overexpression of MDM2 oncoprotein correlates with possession of estrogen receptor alpha and lack of MDM2 mRNA splice variants in human breast cancer.

To evaluate the significance of murine double minute 2 (MDM2) oncoprotein in human breast cancer as a nuclear-cytoplasmic shuttling protein, an estrogen receptor (ER) alpha regulator, and a prognostic marker and to study how MDM2 is overexpressed, we investigated its status in tissue samples and examined the correlation between overexpression and MDM2 gene abnormalities, status, and clinicopathological parameters. We detected MDM2 oncoprotein in both nucleus and cytoplasm by frozen-section immunohistochemistry. There was a significant correlation between MDM2 overexpression and low-grade nuclear atypia, absence of lymph node involvement, and increased levels of ER alpha protein. Our molecular assays found no point mutations in Ser17, but there was a correlation between MDM2 overexpression and the lack of splice variant mRNAs. These results suggest that the distribution of MDM2 reflects its nuclear-cytoplasmic shuttling ability; that interaction between p53 and MDM2 for tumor progression is not enhanced by point mutations at codon 17; and that the expression of MDM2 splice variants is a reason for the lack of its overexpression. MDM2 overexpression correlates with favorable prognostic parameters. A decreased level of MDM2 will lead to a deviation from the ER alpha signaling pathway.

Solitary schwannoma of the colon: report of two cases.

Abstract Some patients with gastrointestinal schwannoma (GIS) have been previously reported in the literature. However, GIS of the colon is quite rare. In addition, it is sometimes difficult to differentiate neurogenic tumors from other soft tissue tumors. We herein describe two cases of schwannoma of the colon, while also reviewing the relevant Japanese literature. The first case, a 73-year-old woman underwent a sigmoidectomy with lymph node dissection following the diagnosis of submucosal tumor. In the second case, a submucosal tumor was located in the cecum of a 44-year-old man. An endoscopic tumor resection was performed in the second case. The resected tumors measured 3.6 and 1.0 cm in maximal diameter, respectively. Microscopically, the tumors consisted predominantly of spindle-shaped cells that proliferated in an interlaced fashion. Mitosis was rarely seen in these tumors. Immunohistochemically, the tumor cells were strongly positive for S-100 protein, weakly positive for glial fibrillary acidic protein, and negative for CD34, α-smooth-muscle actin, and cytokeratin (CAM 5.2) in both cases. The tumors in the two cases were both diagnosed to be benign schwannoma of the colon. In general, schwannoma of the gastrointestinal tract is considered to be benign and should therefore be distinguished from other spindle-cell tumors or malignancies. Once diagnosed as schwannoma, extensive surgery should be avoided. Actually, such patients tend to show a good postoperative course with no evidence of recurrence.