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Biomedical subjects

H Iino

Publications and source records attributed to H Iino.

35 records · Page 2Linked to original sources

Morphology of sporadic colorectal cancer with DNA replication errors.

BACKGROUND: Up to 15% of colorectal cancers are characterised by DNA microsatellite instability (MIN), shown by the presence of DNA replication errors (RERs). AIMS: To identify pathological features that are discriminating for colorectal cancer (CRC) showing extensive MIN. SUBJECTS: A prospective series of 303 patients with CRC and no family history of either familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. METHODS: DNA was extracted from fresh tissue samples and the presence of MIN was studied at nine loci that included TGF beta RII, IGFIIR, and BAX. The 61 cases showing RERs were compared with 63 RER negative cases with respect to a comprehensive set of clinical and pathological variables. Predictive utility of the variables was tested by decision tree analysis. RESULTS: Twenty seven patients with CRC showed extensive RERs (three loci or more) (RER+) and 34 had limited RERs only (28 = one locus; 6 = two loci) (RER+/-), yielding a bimodal distribution. RER+ cancers differed from RER- and RER+/-) cases. Tumour type (adenocarcinoma, mucinous carcinoma, and undifferentiated carcinoma) (p = 0.001), tumour infiltrating lymphocytes (p = 0.001), and anatomical site (p = 0.001) were the most significant of the discriminating variables. Algorithms developed by decision tree analysis allowed cases to be assigned to RER+ versus RER- and +/- status with a global sensitivity of 81.5%, specificity of 96%, and overall accuracy of 93%. CONCLUSIONS: Pathological examination of CRC allows assignment of RER+ status; assignment is specific and relatively sensitive. Conversely RER- and RER+/- CRC are indistinguishable.

Adenocarcinoma↗

Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential.

BACKGROUND: The molecular genetic changes associated with colorectal carcinoma are among the best understood of any common human cancer. The genetic changes during the late stages of colorectal carcinomas may be useful in clinical management for determining the metastatic potential of the carcinoma. METHODS: Tumor tissues were evaluated by restriction fragment length polymorphism (RFLP) analysis of chromosomes 5q, 17p, 18q, and 22q (n = 98), by reverse transcription-polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of the DCC gene (deleted in colorectal carcinoma) (n = 27) and by immunohistochemical analysis of p53 protein expression (n = 44). RESULTS: Loss of heterozygosity (LOH) on chromosomes 17p, 18q, and 22q, but not on 5q, was much more frequently detected in advanced carcinomas than in intramucosal carcinomas (P < 0.01). 17p LOH was significantly correlated with vascular invasion (P < 0.001), whereas 18q LOH was correlated with lymphatic invasion and hepatic metastasis (P < 0.01), and 22q LOH was correlated with lymph node metastasis (P < 0.05). LOH on 5q did not show a significant correlation with any factors of tumor invasion or metastasis. DCC expression was not observed in any of five hepatic metastasis or in five of seven advanced carcinomas that were accompanied by hepatic metastasis (10 of 12). However, a similar lack of expression was observed in only 5 of 15 carcinomas without hepatic metastasis (P < 0.05). p53 Expression was found to vary in both primary and metastatic carcinomas by immunohistochemistry. CONCLUSIONS: The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22q and RT-PCR analysis of DCC expression into messenger RNA) can be used to determine the metastatic potential of colorectal carcinomas.

Adult↗

A case of arteriovenous malformation in the submucosal layer of the stomach.

Arteriovenous malformation (AVM) of the stomach is extremely rare. We report a patient with asymptomatic gastric AVM detected during mass screening of the upper gastrointestinal tract. The patient, a 69-year-old female, had no history of gastrointestinal bleeding. Endoscopy revealed a gastric submucosal tumor (3 cm in diameter) at the posterior wall below the esophago-cardiac junction. Endoscopic ultrasonography (EUS) showed a hypoechoic structure in the third layer of the stomach, suggesting gastric AVM in the submucosal layer. Complete resection of the AVM tissue was performed by strip biopsy with surgical resection. Histological examination showed AVM in the submucosal layer. EUS examination was useful for the diagnosis of gastric AVM in this case.

Aged↗

Genetic changes of both p53 alleles associated with the conversion from colorectal adenoma to early carcinoma in familial adenomatous polyposis and non-familial adenomatous polyposis patients.

Mutation and loss of heterozygosity (LOH) in the p53 gene were analyzed in 274 colorectal tumors of 4 histopathological grades. Among 160 tumors from 40 familial adenomatous polyposis patients, none of 58 adenomas with moderate dysplasia had p53 mutations, whereas 8% (3 of 37) of severe adenomas, 15% (6 of 40) of intramucosal carcinomas, and 40% (10 of 25) of invasive carcinomas had p53 mutations. Only 3% (1 of 33) of severe adenomas showed both mutation and LOH, while 25% (6 of 24) of intramucosal carcinomas and 40% (10 of 25) of invasive carcinomas had both mutation and LOH. All intramucosal and invasive carcinomas that had mutations lost the other allele of the p53 gene. In 114 tumors from 86 non-familial adenomatous polyposis patients, similar results were obtained; no adenoma showed both mutation and LOH, but both alterations occurred in intramucosal and invasive carcinoma. As regards specificity in 56 mutations detected in the present study, the frequently affected codons were codons 175, 238, 245, 248, 273, and 282, 4 of these amino acids being arginine, and 72% (39 of 54) of all mutations were GC to AT transition. Although expression into p53 polyadenylated RNA was high in every invasive carcinoma irrespective of the presence of mutation or LOH, there was a correlation between mutation and protein level; immunostaining of p53 protein was negative in almost all adenomas, but it was positive in 86% of invasive carcinomas exhibiting p53 mutation. These data suggest that genetic changes on both alleles of the p53 gene through mutation and LOH, which result in abnormal protein accumulation, are involved in the conversion of adenoma to early carcinoma. Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.

Adenoma↗

Relative effect of steroid hormone receptors on the prognosis of patients with operable breast cancer. A univariate and multivariate analysis of 3089 Japanese patients with breast cancer from the Study Group for the Japanese Breast Cancer Society on Hormone Receptors and Prognosis in Breast Cancer.

In a retrospective multicenter study to investigate the correlation between estrogen (ER) and/or progesterone receptors (PgR) in primary breast cancer with patient prognosis, 3118 patients with operable breast cancer (International Union Against Cancer Stages I, II, and III) were investigated from ten hospitals in Japan who underwent surgery from October 1972 to December 1982; 3089 were evaluable. The ER-positive and PgR-positive cancers were found in 56% and 34% of patients, respectively. The positivities decreased as the tumor size increased but were independent on lymph node metastasis. There were no significant differences in relapse-free survival (RFS) in relation to receptor status (median follow-up, 89 months [ER], 84 months [PgR]). However, in patients with four or more positive nodes, those with PgR-positive cancer had a longer RFS. The patients with ER-positive cancer survived significantly longer than ER-negative ones, with the greatest difference seen in those with four or more positive nodes. There was a significantly longer postrelapse survival (PRS) for patients with ER-positive cancer because of the different distribution of the major metastasis and better responses to first-line and subsequent treatments. Cox's multivariate analysis showed that overall survival but not PRS was affected by ER (and more weakly by PgR) because of the longer PRS in patients with ER-positive cancer.

Adult↗

Tetrasomy 8 in acute myelomonocytic leukemia developing after a gastric cancer operation.

A 70 year-old-Japanese man underwent gastrectomy for early gastric cancer with preoperative hypocellular marrow. Three weeks later, acute myelomonocytic leukemia developed with tetrasomy for chromosome 8 (48,XY,+8,+8). The patient died of leukemia on the 33rd postoperative day. Whether or not the operation triggered the leukemia remains unknown.

Adenocarcinoma↗

[A serous cystadenoma of the ovary of borderline malignancy with a fifteen-year history. A case report].

A case of a serous cystadenoma of a ovary of borderline malignancy is reported. Sixteen years earlier, the patient had undergone an exploratory laparotomy because of ovarian tumor, and the histologic diagnosis had been a serous cystadenocarcinoma. Postoperative chemotherapy was not effective and drainage of the tumor fluid had been performed for 15 years, with the estimated drainage volume estimated to have reached, 1,000 1. Gradual malnutrition and marked tumor growth then become apparent. A reevaluation of the initial histologic slides and her clinical course strongly suggested a serous cystadenoma of borderline malignancy. Thus a tumor resection, a bilateral salpingo-oophorectomy, and a hysterectomy was performed. A histologic diagnosis of a resected specimen confirmed a serous cystadenoma of borderline malignancy and the histologic features were quite similar to those of the initial biopsy specimens. The patient is living well postoperatively for 8 months without postoperative chemotherapy.

Adult↗

[Surgical management of pulmonary metastasis from carcinoma of the uterine cervix].

The present study was designed to evaluate the efficacy of surgical management of pulmonary metastasis from carcinoma of the uterine cervix. We saw 609 cases of carcinoma of the uterine cervix from 1979 to 1987, and during the same period also saw 110 cases of recurrent carcinoma of the uterine cervix. Fourteen of these 110 cases were identified as having pulmonary metastasis, and in 11 of 14 cases the recurrent tumors were limited to the lung. Seven of these 11 cases underwent pulmonary resection. Six of the 7 survived more than 2 years after pulmonary resection. Among them, 1 patient has survived more than 4 years, and 1 patient more than 8 years. The tumor cells were thought to metastasize to the lung through the vertebral venous plexus (Batson's plexus) which was suggested as a metastatic route by Thomford et al. in their report on recurrent colon cancer. As a result of this study, if the recurrent tumor is clinically limited to the lung in patients with recurrent carcinoma of the uterine cervix, they should be treated by surgical resection of the pulmonary tumor.

Adenocarcinoma↗

Clinical studies on dissolution of gallstones using ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA), 7beta hydroxy epimer of chenodeoxycholic acid (CDCA), has been used as a choleretica for 20 years in Japan. Recent report showing increased excretion of UDCA in bile after CDCA administration may suggest the possibility that UDCA has similar effects to CDCA on bile cholesterol unsaturation and on gallstone dissolution. The present paper describes the clinical usefulness of UDCA for gallstone patients during the past two years. Seventy-four gallstone patients with functioning gall-bladders, 19 men and 55 women with a mean age of 48 years, have been treated for 6 months or more. UDCA, supplied in tablets (Ursosan), was given 450 mg per day. The disappearance or the reduction of stone size or number, or both (dissolution effect) was recognized in 32 out of 74 patients (43%). In case of radiolucent stones, the overall effective rate was estimated for 24 of 46 patients (52%). There may be no significant difference in dissolution effect between CDCA and UDCA treatment, however, the merit of UDCA treatment seems to have its few side effects.

Adult↗

[Lymphography].

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Adult↗

Evaluation of apoptosis as a factor affecting the growth of non-polypoid colorectal adenomas.

Some colorectal adenomas show non-polypoid features endoscopically, e.g. nodule-aggregation or lateral spreading. To understand the developmental mechanism of non-polypoid adenomas better, we evaluated apoptosis indices in the upper and lower parts of 26 colorectal adenomas of non-polypoid appearance using TUNEL or single-stranded DNA (ssDNA) immunohistochemical staining. Regression analysis showed an extremely strong positive correlation between the apoptosis index (AI) values generated using each method. The AI of the lower section of lesion (4.54 +/- 1.86) was significantly higher than that of the upper part (1.21 +/- 1.47). In conclusion, ssDNA immunostaining is as useful as the TUNEL method in the evaluation of apoptosis in colorectal adenomas. It seems that vertical growth in non-polypoid adenomas is inhibited by apoptosis allowing horizontal growth to dominate and resulting in the characteristic, laterally spreading morphology.

Apoptosis↗

Clinicopathological characteristics in large, non-polypoid colorectal adenomas with granule-aggregating appearance.

Endoscopically, most large, non-polypoid colorectal adenomas have a granule-aggregating appearance, made up of elevations of small, flat lesions projecting above the surrounding mucosa. In this study we investigated the clinicopathological characteristics in 26 cases of such tumours and proposed the term 'granule-aggregating tumour' (GAT). Patients with GATs (16 men and 10 women) had a mean age of 64.3 years (range, 38-83 years). The mean diameter of the GATs was 28 mm (range, 12-62 mm). Histologically, GATs were diagnosed as tubular (15 cases) or tubulovillous (11 cases) adenomas without submucosal invasion. These tumours had a surface morphology comprised mainly of small, flat elevations or granular structures, measuring 1.2 +/- 0.3 mm in diameter. Of the 26 patients with GATs, 19 (73.1%) were asymptomatic and 11 of these 19 cases (57.9%) were detected by a faecal occult blood test. In nine of the 26 patients (34.6%) GATs were accompanied by colorectal cancers arising at other sites. GATs show typical endoscopic features, often lack symptoms and are frequently accompanied by other cancers in other organs. An awareness of the existence of GATs should assist in the screening, prevention and therapy of colorectal tumours.

Adenoma↗

Low frequency of bcl-2 expression in large non-polypoid colonic neoplasms.

Large non-polypoid colorectal adenomas that spread over the mucosa and morphologically flat lesions are included in a group called granule-aggregating tumours. These are uncommon in the West. We aimed to clarify the biological differences between granule-aggregating tumours and colorectal polypoid adenomas. We evaluated the extent of apoptotic cell loss and expression of bcl-2 and p53 oncoproteins in 26 granule-aggregating tumours and 19 polypoid adenomas. The mean apoptosis index value of granule-aggregating tumours was significantly higher than that of polypoid adenomas. Only two (7.7%) granule-aggregating tumours and 13 (68.4%) polypoid colorectal adenomas expressed bcl-2, while 12 (46.2%) granule-aggregating tumours and six (31.6%) polypoid colorectal adenomas were p53-positive. Our results show that the higher apoptosis index and frequent expression of bcl-2 oncoprotein differentiates granule-aggregating tumours from polypoid colorectal adenomas. We propose that large non-polypoid granule-aggregating tumours of the colorectum are a biologically distinct entity.

Adenoma↗