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Biomedical subjects

A Ochiai

Publications and source records attributed to A Ochiai.

At least 73 records · Page 4Linked to original sources

Heterotopic sebaceous glands in the esophagus: histopathological and immunohistochemical study of a resected esophagus.

A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a congenital anomaly. The present case concerns a 79-year-old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions. Histological examination of these glands, all of which were located in the lamina propria, revealed lobules of cells that showed characteristic sebaceous differentiation. Bulbous nests of proliferating basal cells showing sebaceous differentiation were occasionally observed in the esophageal epithelium. Of the antibodies against six different keratins used, only anti-keratin 14 labeled both the heterotopic sebaceous glands and the bulbous nests. Acquired metaplastic change of the esophageal epithelium is probably the pathogenetic mechanism involved in these unusual lesions.

Aged↗

Paraneoplastic vasculitis associated with esophageal carcinoma.

We report a case of esophageal carcinoma associated with paraneoplastic vasculitis. A 69-year-old man suffered from low-grade fever and numbness of the lower limbs for 3 months before esophageal and gastric carcinomas were detected. Concurrent infection or collagen disease was ruled out following clinical and laboratory examinations. In April 1996, the gastric carcinoma was completely removed by endoscopic mucosal resection, but the symptoms remained. Three weeks later esophagectomy was performed for esophageal carcinoma after which time the fever and numbness disappeared. The esophageal carcinoma was a well-differentiated squamous cell carcinoma invading into the submucosal layer. Twenty-two lymph node metastases were found in 68 resected lymph nodes. Latent thyroid cancer was found. Histologically, vasculitis was detected in the esophagus, stomach and serratus anterior muscle. The distribution and degree of vasculitis were most pronounced in the esophagus. The concurrent onset and spontaneous resolution of fever and numbness after the removal of the esophageal carcinoma suggested a paraneoplastic origin. The majority of patients with malignant neoplasm-associated vasculitis had hematologic neoplasms. Cases of esophageal carcinoma associated with paraneoplastic vasculitis are extremely rare.

Aged↗

Histologic and immunohistochemical analysis of early submucosal invasive carcinoma of the colon and rectum.

To investigate the development and progression of colorectal carcinoma, submucosal invasive carcinoma (SMC) with residual intramucosal neoplasm was studied histopathologically. Intramucosal neoplasm was confirmed by immunohistochemical staining against anti-alpha-smooth muscle actin antibody. Submucosal invasive carcinoma was classified into polypoid growth-type carcinoma (PGC) and non-polypoid growth-type carcinoma (NPGC), depending on the presence of intramucosal tumor proliferation. Tumors were > 15 mm in size in 78.2% of the PGC lesions studied, but the degree of submucosal invasion was minimal (invasion of the upper 500 microm of the submucosal layer) in 52.9% of the PGC lesions. Conversely, 64.4% of NPGC lesions were 15 mm in size and the degree of submucosal invasion was moderate or severe (involving the middle and deeper layer of the submucosa) for 72.9% of NPGC. In other words, lesions of NPGC were significantly smaller in size but showed deeper infiltration than PGC lesions. Furthermore, PGC was derived from intramucosal polypoid carcinoma (including carcinoma with adenoma) and was morphologically identical to polyp cancer as reported previously. However, NPGC was derived from the flat and/or depressed type of intramucosal carcinoma classified not as polyp type, but as the superficial type. Typical NPGC was, therefore, also of the superficial type. In addition, approximately 25% of PGC lesions were identified as having an adenoma-carcinoma sequence. There was no coexistence with adenoma in the NPGC lesions, suggesting de novo development. When the degree of histologic atypia in the two types of intramucosal carcinoma was compared, 74.7% of PGC lesions showed low-grade carcinoma, regardless of tumor size, while 62.7% of NPGC lesions showed high-grade carcinoma in the intramucosal lesion. Approximately 25% of carcinomas with low-grade atypia were positive for p53 (as were the high-grade lesions), but it was not expressed in the adenoma. Therefore, tumor development and the degree of invasion differed significantly between the two types of carcinoma.

Actins↗

Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations.

Gastric cancer frequently occurs in family members with hereditary non-polyposis colorectal cancer (HNPCC) and Li-Fraumeni syndrome (LFS) and germline E-cadherin mutations were recently identified in a subset of familial gastric cancers. Thus, families with an aggregation of gastric cancers were recruited by reviewing the genealogical trees of 3632 patients with gastric cancer. The criteria for recruiting such families were the following: at least three relatives should have gastric cancer and one of them should be a first degree relative of the other two; at least two successive generations should be affected; in one of the relatives gastric cancer should be diagnosed before age 50. Thirty-one cases (0.9%) fitted all three of these criteria. There were only gastric cancer patients in 18 of the 31 families and there were no families that fitted clinical criteria of HNPCC or LFS. Paraffin-embedded tissues were available in 29 probands and DNA was successfully isolated for molecular analyses in 13 probands. RER phenotype was detected in three (23%) cases, whereas germline p53 mutations were detected in none of 13 cases. A germline E-cadherin mutation was detected in one of three diffuse types and none of 10 intestinal types, however, a mutation resulting in the replacement of Gly by Val was detected in the precursor sequence. Thus, although familial clustering of gastric cancer occurs in approximately 1% of gastric cancer patients, germline mutations of the DNA mismatch repair, p53 and E-cadherin genes do not significantly contribute to such a clustering.

Adolescent↗

Receptor for hyaluronan-mediated motility and CD44 expressions in colon cancer assessed by quantitative analysis using real-time reverse transcriptase-polymerase chain reaction.

Receptor for hyaluronan (HA)-mediated motility (RHAMM) is a receptor for HA-mediated motility and its expression is correlated with malignancy of ras-transformed cells in that binding of HA to this receptor activates their migratory ability. CD44, a cell surface receptor for HA is also implicated in metastatic behavior of some cancer cells. In this study we examined the relationships of cancer progression with mRNA levels of RHAMM, CD44 (all forms), and exon 6 of CD44 using the real-time reverse transcriptase-polymerase chain reaction method in specimens of colon cancers at different diagnostic stages from 30 patients. Increased mRNA levels of RHAMM were observed in 29 specimens (97%), CD44s (all forms) in 21 specimens (70%), and its exon 6 in 19 specimens (63%) in comparison with those in the corresponding noncancerous tissue specimens. A statistically significant correlation between RHAMM expression and cancerous specimens at any of Dukes' stages A, B, and C was found, and the overexpression of CD44 mRNAs was confirmed in specimens at Dukes' stage C. Thus, our present study for the first time suggests that RHAMM expression may be a clinically useful indicator of colon cancer.

Adult↗

Disruption of E-cadherin-mediated cell adhesion systems in gastric cancers in young patients.

The aim of this study was to elucidate the pathogenetic backgrounds of early-onset gastric cancers. Mutations of the E-cadherin and beta-catenin genes were analyzed by subjecting microdissected cancer cells and corresponding non-cancerous epithelial cells obtained from 9 gastric cancer patients under 35 years old to polymerase chain reaction-single strand conformation polymorphism analysis. Somatic, but no germline, E-cadherin gene mutations were detected in 6 (67%) of the patients. The cancer cells of 2 patients were exon 9-deleted E-cadherin molecule-immunoreactive. Neither somatic nor germline mutations in exon 3 of the beta-catenin gene were observed in any patient. One patient lacked beta-catenin immunoreactivity and the cancer cells of 6 others showed cytoplasmic beta-catenin immunoreactivity. The E-cadherin-mediated cell adhesion system in the cancer cells of all the patients examined appeared to be disrupted, indicating that somatically acquired dysfunction of this system plays an important role in early-onset diffuse-type gastric cancers. Helicobacter pylori infection was observed in 6 (67%) of our 9 patients, an incidence higher than the average in young Japanese individuals. Thus, early-onset gastric cancers may be attributable to environmental factors such as Helicobacter pylori infection.

Adult↗

Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?

BACKGROUND: There is a difference in the location of colorectal mucosal lesions and invasive cancers. AIMS: To ascertain whether the location of colorectal neoplasms reflects the carcinogenesis pathway. METHODS: The subject material consisted of 4147 neoplastic lesions that had been resected endoscopically or surgically from 5025 patients. Mucosal lesions and submucosal cancers were classified into depressed and non-depressed types endoscopically or histologically. The relations between macroscopic type, size, histology, and location were investigated. RESULTS: (a) Non-depressed type. A total of 1774 of 3454 (51%) mucosal lesions were located in the right colon, 1212 (35%) in the left colon, and 468 (14%) in the rectum. The incidence of mucosal lesions larger than 10 mm was 10% (185/1774) in the right colon, 21% (254/1212) in the left colon, and 27% (127/468) in the rectum. The incidence of mucosal lesions with villous components was 2% (32/1774) in the right colon, 5% (63/1212) in the left colon, and 13% (62/468) in the rectum. The ratio of submucosal cancers to mucosal lesions was significantly higher in the rectum (0.064, 30/469) than in the left (0.034, 43/1279) or right (0.010, 18/1857) colon. (b) Depressed type. The incidences of depressed type mucosal lesions and submucosal cancers were 5% (83/1857) and 17% (3/18) in the right colon, 5% (67/1279) and 5% (2/43) in the left colon, and 0.2% (1/469) and 0% (0/30) in the rectum, respectively. CONCLUSION: There may be some mechanisms that promote the progression of mucosal lesions to invasive cancers in the left colon and rectum, whereas a de novo pathway from depressed type lesions may be implicated in some cancers of the right colon.

Adenoma↗

Clinical implications of lymph node micrometastases in patients with colorectal cancers. A case control study.

There is no unanimity about the prognostic significance of lymph node micrometastases from colorectal cancer. A case-control study of patients with recurrent and nonrecurrent colorectal cancer who were closely matched for the Dukes stage, extent of lymph node dissection, tumor size, tumor location, number of resected lymph nodes, age and gender was performed. The presence of micrometastases in a total of 1,633 lymph nodes from 44 patients (22 with and 22 without recurrence) were examined by immunohistochemistry using antibodies for cytokeratin (KL-1) and p53 (RSP53). Immunostaining with KL-1 revealed micrometastases in 15/22 patients [68%; 82/820 lymph nodes (10%)] and 15/22 patients [68%; 45/813 lymph nodes (6%)] in the recurrent and nonrecurrent groups, respectively. Immunohistochemical analysis, using RSP53, of 18 paired patients with p53-positive primary tumor revealed micrometastases in 4/9 patients [44%; (7/265 lymph nodes (2.6%)] and 4/9 patients [44%; 6/257 lymph nodes (2.3%)] with and without recurrence, respectively. Neither the micrometastatic frequencies of the patients nor the resected lymph nodes of the recurrent and nonrecurrent groups differed significantly. Micrometastases in regional lymph nodes are an interesting phenomenon, but do not influence patients' prognoses if the involved lymph nodes are removed.

Adult↗

Comparative morphometric study of bladder detrusor between patients with benign prostatic hyperplasia and controls.

PURPOSE: We determined the change in the amount of connective tissue of the detrusor in patients with benign prostatic hyperplasia (BPH) in relation to the degree of bladder hypertrophy by ultrasound estimated bladder weight. The ratio of connective tissue-to-smooth muscle between controls and BPH cases was compared. MATERIALS AND METHODS: For normal controls we used cadaver bladders excised at autopsy from 13 men with no urinary tract diseases. Bladder wall samples were also obtained at subcapsular prostatectomy for BPH in 26 patients. On thin sections stained with Masson trichrome, the ratio of connective tissue-to-smooth muscle was measured using a computer assisted color image analysis. This ratio was compared in BPH cases with estimated bladder weight, which was measured preoperatively using transabdominal ultrasonography. RESULTS: A connective tissue-to-smooth muscle ratio ranged from 19.8 to 28.2% (mean plus or minus standard deviation 24.7+/-2.4) and from 12.9 to 53.3% (27.3+/-9.9) in control and BPH cases, respectively. In BPH cases a significant correlation was noted between estimated bladder weight and connective tissue-to-smooth muscle ratio (r=0.788, p <0.0001). Interestingly, in BPH cases with an estimated bladder weight of less than 60 gm. the ratio ranged from 12.9 to 30.4% (22.8+/-4.9), which was not significantly different compared to control cases. In contrast, in all BPH cases with an estimated bladder weight of 60 gm. or more connective tissue-to-smooth muscle ratio increased significantly to more than 30% (range 33.4 to 53.3%, mean 42.2+/-13.6%). CONCLUSIONS: These results suggest that abnormal increase of connective tissue in addition to smooth muscle hypertrophy and/or hyperplasia could contribute to advanced bladder hypertrophy caused by infravesical obstruction.

Aged↗

Reduction of integrin beta4 and enhanced migration on laminin in association with intraepithelial spreading of urinary bladder carcinomas.

PURPOSE: The aim of the present study was to investigate the biological and molecular basis of intraepithelial spreading (IES) of carcinomas in situ (CIS) of the urinary bladder, which were considered to be precursors of nodular invasive carcinomas. MATERIALS AND METHODS: The propensity for IES of human transitional carcinoma cells was examined by inoculation into murine renal pelvis and urinary bladder, and the biological character of the cells with a high propensity for IES was explored in vitro. RESULTS: Three of 6 cell lines exhibited a high propensity for IES. When cultured on laminin, these IES cells scattered, whereas 3 non-IES cells and 2 immortalized transitional epithelial cells did not. IES cells showed strong adhesiveness, haptotaxis and enhanced migration on laminin compared with both non-IES and immortalized transitional epithelial cells. In IES cells, expression of the integrin beta4 subunit was markedly reduced and the integrin alpha6beta1 complex was predominant compared with the integrin alpha6beta4 complex. Transfection of IES cells with integrin beta4 subunit cDNA inhibited their ability to migrate on laminin and their propensity for IES. In addition, expression of the integrin beta4 subunit was reduced in surgically resected specimens of CIS of the urinary bladder. CONCLUSION: The results indicate that a reduction in integrin beta4 plays a role in IES of CIS of the urinary bladder through enhanced migration on laminin.

Antigens, CD↗

[Dysfunction of cadherin cell adhesion system in cancer invasion and metastasis].

Dysfunction of the cadherin-mediated cell adhesion system involved in cancer metastasis occurs by several mechanisms: alterations of E-cadherin, alpha- and beta-catenin genes, CpG methylation of the promoter region of E-cadherin, and aberrant tyrosine phosphorylation of beta-catenin. In addition to the cell adhesion function, beta-catenin, which is an intracytoplasmic cadherin binding molecule and thought to be a regulator of cadherin-mediated cell adhesion function, has been proven to associate with both the growth factor receptors, including c-erbB-2, EGF receptor and k-sam and APC tumor suppressor gene product. These data indicate that the cadherin-mediated cell adhesion system plays important roles not only in cancer metastasis but in carcinogenesis.

Adenocarcinoma↗

The clinicopathologic significance of small areas unstained by Lugol's iodine in the mucosa surrounding resected esophageal carcinoma: an analysis of 147 cases.

BACKGROUND: Small areas unstained with Lugol's iodine are often observed in the mucosa surrounding esophageal carcinomas. METHODS: For light microscopic evaluation, the histologic features of 131 small areas unstained by Lugol's iodine in 12 selected cases were investigated. For clinicopathologic evaluation, the numbers of small areas unstained by Lugol's iodine in the mucosa surrounding 147 consecutively resected esophageal carcinomas, including these 12 cases, were counted. The relation between the incidence of such areas and the development of multiple primary cancers in the upper aerodigestive tract was examined together with data on the patients' tobacco and alcohol consumption. RESULTS: Ninety-two percent (131) of the small areas unstained by Lugol's iodine contained dysplastic lesions. Seventeen (12%) of the 147 resected specimens contained fewer than 5 small unstained areas, whereas 52 (35%) had 6-10 and 78 (53%) had more than 11 such areas. The incidence of multicentric cancer in the upper aerodigestive tract and the average alcohol index scores were significantly higher for patients who had more than 11 unstained areas than for patients who had fewer than 5 such areas (P < 0.01). CONCLUSIONS: Lugol's iodine staining method is useful for detecting groups at high risk of multicentric cancer in the upper aerodigestive tract.

Adult↗

Microparticle resins as a potential nasal drug delivery system for insulin.

The application of various resins for the nasal delivery of insulin was examined in rabbits. Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase. The blood glucose level decreased from 118.8 +/- 18.5 mg/dl to 65.8 +/- 13.8 mg/dl at 45 min after administration. These results were superior to those obtained with the unfractionated resin. Styrene-divinylbenzene copolymer (a nonionic resin; 20-45 microns fraction) showed similar enhancement of nasal insulin absorption. In contrast, polyacrylester (a nonionic resin; 20-45 microns fraction) and cholestyramine (a cationic resin) did not promote insulin absorption. These results suggest that some resins may be useful for nasal delivery of insulin.

Administration, Intranasal↗

DNA hypermethylation at the D17S5 locus is associated with gastric carcinogenesis.

The aim of this study was to elucidate the significance of aberrant DNA methylation in gastric carcinogenesis. The DNA methylation status at the D17S5 locus, at which a candidate tumor suppressor gene, HIC-1, was identified, of gastric cancers and non-cancerous gastric mucosae from 42 gastric cancer patients was examined by Southern blotting using a methylation-sensitive restriction enzyme. DNA hypermethylation was observed in 15, 13, 25 and 45% of the tissues showing no remarkable histological findings, chronic gastritis without intestinal metaplasia, intestinal metaplasia and gastric cancer, respectively. The incidence of DNA hypermethylation was significantly higher in gastric cancers than in non-cancerous gastric mucosae (P < 0.05). DNA hypermethylation was often accompanied by allelic loss at the same locus in gastric cancers. DNA hypermethylation at the D17S5 locus, which was even detected in precancerous conditions, including intestinal metaplasia, may play a role in gastric carcinogenesis.

Adult↗

Correlation of ultrasound-estimated bladder weight with ultrasound appearance of the prostate and postvoid residual urine in men with lower urinary tract symptoms.

OBJECTIVES: To reveal the possible relationship of urodynamic tests and transrectal sonography (TRS) of the prostate with bladder hypertrophy as evaluated by ultrasound-estimated bladder weight (UEBW) in men with lower urinary tract symptoms. METHODS: In a total of 234 men aged 50 years or more with a normal prostate or benign prostatic hyperplasia (BPH) as determined by TRS, UEBW was correlated with age, the American Urological Association (AUA) symptom score, postvoid residual urine, maximum flow rate, and transrectal ultrasound planimetry such as prostatic volume and presumed circle area ratio (PCAR). RESULTS: In a simple regression analysis there was a statistically significant correlation between UEBW and the AUA symptom score (R = 0.282, P <0.0001), postvoid residual urine (R = 0.490, P <0.0001), prostatic volume (R = 0.358, P <0.0001), and PCAR (R = 0.468, P <0.0001). A multiple regression analysis demonstrated postvoid residual urine and PCAR to be significant independent determinants of UEBW. The frequency of abnormal UEBW (35.0 g or more) increased significantly with postvoid residual urine (P <0.0001) and PCAR (P <0.0001). CONCLUSIONS: Postvoid residual urine and PCAR were useful parameters for the evaluation of the severity of BPH in terms of bladder hypertrophy probably due to infravesical obstruction.

Age Factors↗

Intraobserver and interobserver variance in the measurement of ultrasound-estimated bladder weight.

Recently, we reported that ultrasound-estimated bladder weight (UEBW) could be used as a noninvasive tool in evaluating the degree of bladder hypertrophy. This study was designed to test the reproducibility of its measurement. The overall mean UEBW of the initial measurement and that of the second one by one observer in 36 cases was 42.8 +/- 22.6 g and 42.9 +/- 22.6 g, respectively. The paired differences between two measurements ranged from -3.4 to 2.7 g, with a mean difference of only -0.1 g. The interobserver variance was also slight. The paired differences between UEBW measurements derived from the two observers in 32 cases ranged from -6.0 to 7.9 g, with a mean difference of only 0.1 g. The Cochran's test statistic of the measurements of UEBW was 0.142 for one observer and 0.130 for two, which were less than its 5% critical value. Due to these favorable characteristics, UEBW could be reliable tool for the investigation of bladder hypertrophy with a sufficient reproducibility.

Adult↗

Anastomotic recurrence of oesophageal squamous cell carcinoma after transthoracic oesophagectomy.

OBJECTIVE: To assess the incidence of anastomotic recurrence of oesophageal carcinoma and its relationship with proximal surgical margin invaded by tumour. DESIGN: Retrospective study. SETTING: National Cancer Center, Tokyo. SUBJECTS: 463 patients with thoracic oesophageal squamous carcinoma who underwent transthoracic oesophagectomy with a minimal follow-up of three years. MAIN OUTCOME MEASURES: Proximal surgical margin, anastomotic recurrence rate, prognosis. RESULTS: Anastomotic recurrence developed in 12 of the 463 patients (3%), 10 of whom had histologically clear surgical margins. Sixteen patients had histologically invaded surgical margins, 13 of whom developed recurrent disease, 2 (13%) at the anastomosis. These 2 patients died of other diseases after treatment for their recurrent tumours. Two patients with anastomotic recurrence lived for over 5 years without signs of disease after excision of the recurrent tumour. Necropsy of 47 patients with recurrent tumors showed that only one (2%) was at the anastomosis. CONCLUSIONS: Anastomotic recurrence was not inevitable and was rarely fatal in patients with invaded proximal surgical margins at transthoracic oesophagectomy. However, although infrequent, it did occur, even in patients with a cancer-free surgical margin. Resection may be indicated for patients with anastomotic recurrence and no other signs of metastases.

Anastomosis, Surgical↗

Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer.

Liver metastasis is the gravest prognostic factor in colorectal cancer. To identify a reliable indicator for liver metastasis, we evaluated macroscopic features and seven established histopathological findings at the cut section containing the deepest penetration using univariate and multivariate analyses in 417 colorectal cancers. Macroscopic features were divided into two types, streak type and non-streak type, according to the presence or absence of white streak(s) at the advancing margin of tumor invasion. Streak type was observed in 109 patients (26%). The frequency of liver metastasis in streak type tumors (56%) was significantly higher than that in non-streak type tumors (13%) (p < 0.001). The white streak corresponded histologically with cancer cells showing focal dedifferentiation with marked stromal and perivascular fibrosis extending towards the serosa or adventitia. In 343 curatively treated patients, univariate analysis showed that recurrent liver metastasis was significantly associated with macroscopic features, venous invasion, focal dedifferentiation and lymph node metastasis. Multivariate analysis disclosed that macroscopic features and lymph node metastasis were independent indicators of liver metastasis. These macroscopic features, corresponding histologically to stromal behavior against invading cancer cells, are a simple and useful indicator of liver metastasis of colorectal cancer.

Colonic Neoplasms↗