Noritake Tanaka

Estrogen and progesterone receptors in gastric cancer.

Cancerous tissue from 86 patients with primary gastric cancer were examined for the presence of receptors for estrogen (ER) and progesterone (PgR). ER and PgR were present in 8 (15.4%) and 5 (9.6%)respectively, of 52 male patients9 (26.6%) and 7 (20.6%)respectively, of 34 female patients, a total of 17 (19.8%) and 12 (14.0%)respectively. One male patient (1.9%) and 4 female patients (11.8%) had both ER and PgR, and 40 male (76.9%) and 22 female patients (64.7%) showed no ER or PgR. The binding activity ranged from 6 to 200 fmol/mg protein for estradiol and from 5 to 58 fmol/mg protein for progesterone. ER‐ and/or PgR‐positive cases were characterized grossly as Borrmann type 4, and microscopically as diffuse type with scirrhous growth pattern. The presence of ER and/or PgR in some gastric cancers indicates the possibility that sex hormonal factors are involved in these tumors.

Helicobacter pylori infection increases the risk of colorectal adenoma and adenocarcinoma, especially in women

BackgroundRecent reports suggest that Helicobacter pylori infection can potentially increase the risk of colorectal cancer. The purpose of this study was to assess the association between H. pylori infection and the risk of colorectal adenoma and adenocarcinoma, and to evaluate any differences on the basis of sex.MethodsThe subjects were 669 (40- to 80-year-old) patients who underwent both barium enema examination and total colonoscopy, and who were evaluated for H. pylori infection by 13C-urea breath test, urease test, or histological diagnosis of biopsied gastric specimens. There were 142 H. pylori-negative and 527-positive patients. The odds ratios (ORs) for H. pylori-positive patients with colorectal adenoma and adenocarcinoma, and for tumor patients with either adenoma or adenocarcinoma were calculated.ResultsAmong the H. pylori-negative patients, there were 52 patients without tumor, 63 with adenoma, 27 with adenocarcinoma, and 90 with tumor. Among the H. pylori-positive patients, there were 136, 264, 127, and 391 patients respectively. Pooling all subjects, those infected with H. pylori had a significantly increased OR for adenoma, adenocarcinoma, or tumor, compared to H. pylori-free patients (OR, 1.60, 1.80, and 1.66, respectively). For female H. pylori-positive subjects, the risk of having adenocarcinoma or tumor was significantly higher than that for their H. pylori-free counterparts, while for male H. pylori-positive and -negative subjects, there was no such significant difference.ConclusionsThe results therefore suggest that, in patients aged 40–80 years, H. pylori infection increased the risk of colorectal adenoma and adenocarcinoma, with significantly higher risks for female patients.

Immunohistochemical study of intracellular estradiol in human gastric cancer

Tissues from primary human gastric cancers were examined for intracellular estradiol (E2) by using the avidin‐biotin‐peroxidase complex (ABC) immunohistochemical method on formalin‐fixed paraffinembedded sections. Reaction products of E2 were located only in the cytoplasm of the cancer cells, and not detected in noncancerous gastric epithelium. E2‐positive tissues were found in 23 (44.2%) of 52 male patients, seven (20.6%) of 34 female patients and a total of 30 (34.9%) of 86 patients. In male patients, E2‐positive cases occurred without age distinction. In female patients, however, E2 was not found in patients in older age groups, especially patients in the postmenopausal state. Microscopically, E2 was found frequently in intestinal type of cancers in male patients and in cancer with scirrhous growth pattern, in female patients. This is the first report of the demonstration of E2 in gastric cancer. The findings suggest that hormonal factors are involved in gastric cancer, and that the cancers contain endocrinic characteristics.

Immunological Quantitation of DT-Diaphorase in Carcinoma Cell Lines and Clinical Colon Cancers: Advanced Tumors Express Greater Levels of DT-Diaphorase

NAD(P)H:quinone oxidoreductase (DT‐diaphorase; DTD) plays a major role in activating mitomycin C (MMC) in human colon and gastric carcinoma cell lines. Thus, measurement of DTD in clinical tumor samples could be beneficial in designing adjuvant chemotherapy. We explored immunological quantitation of DTD protein using a monoclonal antibody against DTD, demonstrating a close correlation between protein expression and enzyme activity of DTD in colon and gastric carcinoma cell lines and in colorectal tumor samples. This indicates that such immunoblot analysis is a simple alternative method for quantitating DTD in clinically excised samples. In most colorectal tumor samples, the tumors expressed larger amounts of DTD than did the peripheral normal tissues, suggesting a selective toxicity of MMC toward tumor cells. Also tumors with nodal metastases showed significantly higher DTD levels than did tumors without metastasis. These results raise the possibility that DTD expression is related to tumorigenesis and malignant progression of colorectal tumors. Measurement of DTD by the immunological method described here could be beneficial in designing a rational adjuvant chemotherapy with MMC.

Antiangiogenic effect of Octreotide inhibits the growth of human rectal neuroendocrine carcinoma

Background: Somatostatin and its analogues have antitumor effects on foregut and midgut neuroendocrine (NE) tumors, but their effect on hindgut NE tumors is unclear. We examined the effect of the somatostatin analogue, octreotide, on human rectal NE carcinoma. Materials and Methods: Expression of somatostatin receptor (sst) on NE carcinoma was examined by immunohistochemical staining. Octreotide was added in cell culture medium in order to investigate antiproliferative effect toward NE carcinoma in vitro. Octreotide was administered for 6 weeks to nude mice xenografted with NE carcinoma. We investigated the effect of octreotide on the tumor histologically. The plasma levels of VEGF and bFGF were measured. Results: The NE carcinoma and endothelial cells expressed sst. Octreotide induced NE carcinoma to apoptosis in vitro and in vivo. Octreotide-treated tumors had a massive necrotic area (62.7 ± 19.3% treated vs. 39.7 ± 20.34% untreated, p < 0.05). Microvessels in the treated tumor were decreased (264.0 ± 48.2/mm2 treated vs. 341.4 ± 56.6/mm2 untreated, p < 0.05). The plasma levels of VEGF and bFGF were reduced by octreotide. Conclusions: Octreotide induces rectal NE carcinoma to apoptosis and inhibits angiogenesis in the tumor. These result in tumor necrosis. Octreotide has an antitumor effect on rectal NE carcinoma.

A study of histopathological assessment criteria for assessing malignancy of gastrointestinal stromal tumor, from a clinical standpoint.

BackgroundAs no established histopathological criteria exist for assessing the malignant potential of gastrointestinal stromal tumor (GIST), recurrence or metastasis is occasionally observed in lesions diagnosed histopathologically as benign. The present study aimed to clarify the histopathological criteria for assessing the malignancy of GIST, from a clinical standpoint.MethodsThe subjects were 22 patients with GIST expressing CD117 (c-kit) and/or CD34, who were followed up for more than 2 years. Clinically, GIST malignancy was diagnosed if any of the following criteria were met: peripheral invasive growth, lymph node metastasis, metastasis to another organ, peritoneal dissemination, recurrence, or death. GIST was also categorized as either benign or malignant by a new histological malignancy classification system, based on the determination of significant factors indicating malignancy in the clinical classification system above.ResultsSignificant factors for malignancy identified in the clinical malignancy classification were: tumor hemorrhage/necrosis (present vs absent; P = 0.0053), tumor size (<5 cm vs ≥5 cm; P = 0.0022), and Ki-67 labeling index (<3% vs ≥3%; P = 0.0002). A new histological malignancy classification, based on a combination of these three factors, was developed. A significant correlation existed between the clinical system and the new histological malignancy classification system (P = 0.0008). The recurrence-free survival rate was 100% in the histologically benign cases and 37.5% in the histologically malignant cases (P = 0.0012).ConclusionsThe new histological malignancy classification for GIST was demonstrated to be useful from a clinical standpoint.

Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice

Thirty‐two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF‐positive surgical specimens and one (6%) of the 16 EGF‐negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

Myoepithelial hamartoma of the small bowel: Report of a case

Benign small bowel tumors seldom cause symptoms, due to the fluid content and distensibility of the small bowel. We herein present the case of a solitary ileal hamartoma causing melena and abdominal pain in a 24-year-old man. The diagnosis of a submucosal ileal tumor was made after performing small bowel barium studies. Surgical treatment was undertaken, and a histological examination of the excised lesion, which showed a partially ulcerated tumor surface and extended from the submucosa to the subserosa, revealed numerous cystic glands of various sizes together with bundles of proliferating smooth muscle cells. Histochemical and immunohistochemical investigations were performed for differential diagnosis, and the tumor features were consistent with a diagnosis of ileal myoepithelial hamartoma. In the literature, small intestinal myoepithelial hamartomas are quite rare and this is the first report of a myoepithelial hamartoma causing melena.

Contrasting Actions of Estradiol on the Growth of Human Gastric Cancer Xenografts in Nude Mice

The effects of estradiol on the growth of six human gastric xenografts in nude mice were studied and diverse effects were found, including one case of stimulation, two of inhibition and three of unchanged condition. Neither the histological features of the original tumor nor the estrogen‐binding capacity seemed to be related to the response to estradiol. It is concluded that the growth of human gastric cancer can be modulated by estradiol.

The usefulness of conducting investigations on intra-abdominal bacterial contamination in digestive tract operations.

A bacteriological study of 108 cases of gastrointestinal surgery was conducted by analyzing intra-abdominal bacterial contamination (IABC) and postoperative surgical site infections (SSI). We utilized an anaerobic porter to detect intra-abdominal bacterial infection and transport bacteria to the laboratory. The positive IABC rate was 42.9% for gastric cancer surgery, 22.6% for biliary tract surgery, and 85.7% for colorectal cancer surgery. Most cases of SSI were IABC-positive, and isolated bacterial species from the SSI were similar to those from the IABC. In colorectal cancer surgery, a preoperative chemical intestinal preparation and the prophylactic use of antibiotics had a major influence on the sensitivity of bacteria isolated from the SSI. These data suggest that prophylactic antibiotics should be chosen from among those to which bacteria from the IABC are highly sensitive, and that therapeutic antibiotics should be chosen from among those to which bacteria isolated from the SSI are highly sensitive. Finally, the exploration of IABC enables us to predict the incidence of SSI.