Search PubMed⌕ Search

Biomedical subjects

H Mitomi

Publications and source records attributed to H Mitomi.

At least 19 recordsLinked to original sources
PubMed2006

New technique of laparoscopic colectomy with the LAP DISC and a 5-mm flexible scope.

PURPOSE: We devised a new method for the safe introduction of the first trocar and induction of pneumoperitoneum for laparoscopic excision of the large intestine. METHODS: With this method, a small laparotomy is first conducted according to the size of the exposed affected intestinal tract or tumor size, prior to the application of a LAP DISC (LD) to the wound and introduction of a 12-mm trocar for the establishment of pneumoperitoneum. The method is advantageous in that organ injury and vessel injury are avoided when the small laparotomy is conducted first, and prompt transition to a conventional laparotomy is possible. The diaphragm of the iris bulb can be controlled in a non-stepwise manner. In addition, trocars, the stapler, and other instruments, can be inserted under the pneumoperitoneum. Furthermore, the use of a 5-mm flexible scope allows surgical maneuvers, except for application of LD, to be conducted via 5-mm trocars. In addition, the 5-mm scope can be inserted through any trocar, allowing multidirectional avoidance of dead space and intraperitoneal observation. When only 5-mm trocars are used, it is not necessary for the sites of trocar puncture to be closed by sutures, and this minimizes the risk of adhesions and port-site herniation. The method is also considered to be excellent from the point of view of esthetics. RESULTS: We employed this surgical approach in 50 patients with colorectal cancer at our hospital. None of the patients developed any traumatic complications associated with the insertion of trocars, and none of the patients, even those with a past history of abdominal operation, required conversion to conventional laparotomy. CONCLUSIONS: Based on these results, this method involving a small laparotomy prior to the application of an LD and introduction of a 12-mm trocar for establishing pneumoperitoneum, with the efficient use of a 5-mm flexible camera, is considered to be safe and useful for laparoscopic excision of the large intestine.

Adult↗
PubMed2003

Endoscopic mucosal resection in the management of gastric carcinoid tumors.

BACKGROUND AND STUDY AIMS: Gastric carcinoid tumors are a rare disease. Previously, total gastrectomy was regarded as the treatment of choice. However, differences in biological malignancy have recently led to the increased use of endoscopic mucosal resection (EMR) for treatment. We studied the outcome of EMR in patients with gastric carcinoids who were treated at our hospital and discuss the indications for endoscopic treatment. PATIENTS AND METHODS: Between 1986 and 1999 we carried out gastric mucosal resection in five patients with gastric carcinoid tumors. The procedure used for EMR was either strip biopsy or endoscopic aspiration mucosectomy. RESULTS: The carcinoid tumors measured 10 mm or less in four of the five patients. Two patients had type A gastritis, and all had hypergastrinemia. There was no evidence of recurrence during follow-up (range 6 - 66 months; mean 32.6 months). CONCLUSION: EMR is useful in the management of type 1 gastric carcinoids as classified by Rindi (hypergastrinemia; tumor diameter of 10 mm or less).

Adult↗
PubMed2001

CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation.

BACKGROUND: Recent studies have suggested a correlation between increased or decreased expression of CD44 variant molecules and tumor metastasis. CD44 expression in gallbladder carcinoma was examined and compared with tumor differentiation. METHODS: Eighty-three samples of gallbladder carcinoma, 17 gallbladder adenoma samples, and 66 normal control mucosa samples were stained immunohistochemically for CD44 standard form (CD44s), variant 3 (CD44v3), and variant 6 (CD44v6). RNA extracted from nine patients with carcinoma also was investigated with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and Southern blot hybridization (SBH) for the CD44 gene. RESULTS: Normal gallbladder mucosa showed strong, membranous staining for CD44s but not for CD44v3 or CD44v6. In gallbladder tumors, CD44s was stained as strongly as it was in normal mucosa, but immunoreactivity for CD44v3 and CD44v6 also was significant. In well differentiated, advanced adenocarcinomas (n = 38), CD44s immunoreactivity was significantly lower in the invasive component than in the intramucosal component of the tumors (P = 0.0048). Immunoreactivity for CD44v3 and CD44v6 in moderately and poorly differentiated areas was significantly higher than in well differentiated areas (P < 0.0001 and P = 0.0378, respectively). RT-PCR and SBH signals for CD44v3 and CD44v6, including exons 7 and 10, were strong in carcinoma samples but weak in normal samples, in line with the results of immunohistochemistry. The prognosis of patients with gallbladder carcinoma was not associated significantly with altered expression of CD44s, CD44v3, or CD44v6. CONCLUSIONS: The current study demonstrated that CD44 variant overexpression in patients with gallbladder carcinoma was linked closely with histologic dedifferentiation rather than clinicopathologic factors, including prognosis.

Adenocarcinoma↗
PubMed2001

Adenocarcinoma complicating Barrett's esophagus: an analysis of cell proliferation.

In Japan, cases of Barrett's esophagus with concurrent adenocarcinoma are relatively rare. We report herein a case of long-segment Barrett's esophagus-associated adenocarcinoma in a 72-year-old Japanese man. The surgical specimen showed that an ulcerating tumor, measuring 5.5 x 3.9 cm, was present in the lower esophagus adjacent to the esophagogastric junction, the background lower esophagus having an erythematous appearance. Histologically, the ulcerating tumor was a well-to-moderately differentiated tubular adenocarcinoma, with a small area of signet ring cell carcinoma invading the adventitia. In addition, the esophageal epithelium was replaced by columnar epithelium (9.5 cm in length) with multifocal dysplastic changes. Immunohistochemically, the number of Ki-67-positive cells gradually increased, moving from the normal gastric mucosa (mean Ki-67 labeling index [mKLI], 2.6%) through Barrett's epithelium (mKLI, 12.9%), low-grade dysplasia (mKLI, 16.9%), and high-grade dysplasia (mKLI. 23.7%) to invasive carcinoma, in that order, with labeling higher in the invasive tubular adenocarcinoma elements (mKLI, 40.5%) than in areas of signet ring cell carcinoma (mKLI, 20.4%). Findings in our patient suggest that increased cellular proliferation plays an integral part, in the progression of Barrett's metaplasia to adenocarcinoma. The collection of further cases for analysis will be necessary to confirm this hypothesis.

Adenocarcinoma↗
PubMed2001

Alpha-Fetoprotein-producing esophageal adenocarcinoma: report of a case.

Alpha-fetoprotein (AFP)-producing esophageal tumors are extremely rare. We report herein the case of a 51-year-old man found to have an AFP-producing adenocarcinoma arising from esophageal proper mucosa. The patient presented for investigation of dysphagia, and esophagogram and endoscopy revealed a lesion about 2 cm in size with a depressed center surrounded by low nodular protrusions in the lower esophagus. The preoperative serum AFP concentration was elevated to 52.4 ng/ml. A subtotal esophagectomy was performed, and macroscopic examination of the resected specimen revealed a superficial protruding lesion. Histopathological studies showed a poorly differentiated adenocarcinoma with a single lymph node metastasis. The tumor had infiltrated the submucosal layer, but there was no evidence of lymphatic or venous invasion. Immunohistochemical study revealed tumor cells positive for AFP. There were no findings of Barrett's epithelium or any mucosal changes due to reflux esophagitis. An elevated AFP level 2 years after the operation led us to suspect tumor recurrence; however, diagnostic imaging studies showed no evidence of a recurrence or metastases. The serum AFP levels responded well to chemotherapy with transient decreased levels, but continued to rise until finally, 5 years after the operation, adenocarcinoma cells were detected in the pleural effusion. Thus, careful monitoring of the serum AFP levels at regular intervals could be a useful marker to indicate recurrence of esophageal carcinoma.

Adenocarcinoma↗
PubMed2001

Immunohistochemical detection of human gastrointestinal glutathione peroxidase in normal tissues and cultured cells with novel mouse monoclonal antibodies.

This is the first report to describe the successful detection of human gastrointestinal glutathione peroxidase in normal tissues by Western blotting and immunohistochemical staining techniques. Four hybridoma clones producing monoclonal antibodies (MAbs) against the human gastrointestinal glutathione peroxidase were established from mice immunized with a gastrointestinal glutathione peroxidase-derived peptide. The MAbs did not crossreact with other members of the glutathione peroxidase family, be it cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, or extracellular glutathione peroxidase. Although the MAbs were found to react with a 24-kD protein in a Western blotting assay using gastric carcinoma cell extracts as antigen, they did not react with a B-lymphoblastoid cell extract. Immunohistochemical staining showed gastrointestinal glutathione peroxidase localized in the cytoplasm and in the nucleus of gastric carcinoma cells. Moreover, gastrointestinal glutathione peroxidase was detected in tissue extracts of human stomach, small intestine, large intestine, liver, and gallbladder by Western blotting, and its localization was immunohistochemically confirmed in the mucosal epithelia of the basal area of gastric pits and intestinal crypts.

Aged↗
PubMed2001

p53, but not c-Ki-ras, mutation and down-regulation of p21WAF1/CIP1 and cyclin D1 are associated with malignant transformation in gastric hyperplastic polyps.

To investigate tumorigenesis in the gastric hyperplastic polyp (HP), we evaluated 19 HPs with and 50 HPs without dysplasia (including carcinoma in situ), as compared with normal mucosa and fundic gland polyps. Helicobacter pylori density was highest in HPs without dysplasia. Apoptotic activity and Ki-67 and p53 expression also were higher in dysplasia in HPs than in normal mucosa, fundic gland polyps, or HPs themselves. The p21WAF1/CIP1 and cyclin D1 levels, in contrast, were highest in HPs. In HPs without dysplasia, size was correlated positively with the degree of stromal inflammation and with p53 and cyclin D1 expression. p53 and c-Ki-ras mutations were detected in 41% (8/19) and 5% (1/19) of dysplasia (including carcinoma in situ) in HPs. Our results demonstrate that the HP enlarges with enhanced cell turnover and overexpression of p53, p21WAF1/CIP1, and cyclin D1, associated with H pylori-related inflammation, and that p53 but not c-Ki-ras mutations may have an important role in dysplastic change in HPs.

Adult↗
PubMed2001

Significant correlations of E-cadherin, catenin, and CD44 variant form expression with carcinoma cell differentiation and prognosis of extrahepatic bile duct carcinomas.

To clarify the relation between alteration of expression of cell adhesion molecules and progression of extrahepatic bile duct carcinomas. 55 cases were immunohistochemically examined for E-cadherin, alpha-catenin, beta-catenin, and CD44, with additional reverse transcription-polymerase chain reaction and Southern blotting hybridization (RT-PCR/SBH) assays. Levels of E-cadherin, alpha-catenin, and beta-catenin proteins were lower in carcinomas than in normal mucosa, while CD44 variants 3 and 6 were upregulated. Well-differentiated carcinoma showed higher expression of E-cadherin and alpha-catenin than moderately to poorly differentiated types. Macroscopically papillary lesions had higher expression of E-cadherin than their nonpapillary counterparts. RT-PCR/SBH for CD44 revealed the CD44 variant form to be more prevalent in carcinoma than in normal mucosa, correlating with the immunohistochemical results, and with more exon variety. The Cox proportional hazards test identified histologic type and E-cadherin expression as prognostic factors. Among the examined molecules, E-cadherin was especially related to papillary mass formation and a good prognosis.

Bile Duct Neoplasms↗
PubMed2000

Decreased expression of CD44, alpha-catenin, and deleted colon carcinoma and altered expression of beta-catenin in ulcerative colitis-associated dysplasia and carcinoma, as compared with sporadic colon neoplasms.

BACKGROUND: To clarify the cell adhesion status in ulcerative colitis (UC)-associated colon neoplasm, expression of cell adhesion molecules were investigated and compared with that of sporadic colon neoplasm. METHODS: A total of 14 low grade dysplasias, 16 high grade dysplasias, and 8 adenocarcinomas associated with UC and 17 sporadic adenomas with mild to moderate dysplasia, 22 adenomas with severe dysplasia, and 15 invasive adenocarcinomas were immunohistochemically examined using monoclonal antibodies against CD44, E-cadherin, alpha- and beta-catenin, and deleted colon carcinoma (DCC). RESULTS: CD44, especially its standard form, and DCC expression was stronger in the sporadic colon neoplasms than in the UC-associated lesions. Although E-cadherin did not show significant differences between the two cases, alpha-catenin was more expressed in sporadic colon adenomas with severe dysplasia and carcinomas than in their UC-associated counterparts. Membranous beta-catenin staining was stronger in UC-associated neoplasms, whereas sporadic lesions had greater cytoplasmic and nuclear expression. CONCLUSIONS: The differences in cell adhesion molecule expression suggests that UC-associated and sporadic colon neoplasms arise from different pathways of tumorigenesis.

Cadherins↗
PubMed2000

Benign esophageal schwannoma: report of a case.

We report herein the case of an otherwise asymptomatic 62-year-old woman who was found to have an incidental esophageal lesion during endoscopic follow-up of an unrelated disorder. An esophageal submucosal tumor was diagnosed, and the patient was subsequently monitored on a regular yearly basis. As the diameter of the tumor doubled over a 4-year period, the possibility of a malignant lesion could not be excluded, and she was admitted to our hospital for further investigations. Esophagography, endoscopy, endoscopic ultrasonography, and computed tomography confirmed a submucosal tumor, 35 mm in length, in the thoracic midesophagus. A leiomyoma or leiomyosarcoma was suspected based on the known incidence of such tumors, and tumor enucleation was performed. Gross inspection revealed a solid tumor arising from the wall of the esophagus. Histopathologic examination showed intertwined bundles of spindle cells with spiral-like proliferation, and immunohistochemical studies were positive for S-100 protein, whereby a diagnosis of esophageal schwannoma was established. The patient experienced no postoperative complications, and her clinical course to date has been satisfactory. To date, 2 years 8 months after surgery, she has shown no sign of tumor recurrence and remains in good health.

Esophageal Neoplasms↗
PubMed2000

Cyclin D2 overexpression and lack of p27 correlate positively and cyclin E inversely with a poor prognosis in gastric cancer cases.

G1 cyclins and cyclin-dependent kinase (CDK) complexes play important roles in G1 cell cycle transition, and their overexpression is implicated for neoplasia. The p27 protein (p27) negatively regulates G1 progression by binding to G1 cyclins/CDK complexes and inhibits their activity, resulting in inhibition of entry to the cell cycle. We investigated overexpression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), CDK2, and CDK4, in addition to p27, in 260 gastric cancer cases on the basis of Western blots, reverse transcriptase-polymerase chain reaction Southern blots, and immunohistochemistry to clarify the roles of these proteins in tumor progression and prognosis. Examination of 20 cases of fresh cancer and matched normal tissues demonstrated a clear tendency for increased mRNA synthesis to be more frequent than expected from protein levels, and a direct correlation between p27 protein and mRNA was not found. Immunohistochemistry demonstrated 21. 5%, 34.2%, 30.4%, 44.2%, and 48.0% positivity for CCND1, CCND2, CCNE, CDK2, and CDK4, respectively, in the 260 gastric cancer cases. Overexpression of CCND2 and CDK4 significantly correlated with tumor progression. Moreover, CCND2 cytoplasmic staining (26.2%) appeared to be strictly linked with progression, whereas nuclear staining (7. 8%) demonstrated an inverse correlation. Survival curves showed CCND2 (especially cytoplasmic staining) and CDK4 positivity to be associated with a poor prognosis and CCNE positivity with a better prognosis. Tumors with high p27 labeling indices (LIs) were well differentiated, with low levels of invasion and lymph node metastasis. p27-negative cases (37.3%) demonstrated a poor prognosis. Multivariate analysis revealed positivity for CCND2 and negativity for p27 to be independent prognostic factors. There were no direct links among CCND2, CCNE, CDK4, and p27. The results indicate that CCND2 cytoplasmic localization might reflect an important physiological role in tumor progression, whereas CCNE overexpression correlates with differentiation and a good prognosis, possibly because of accumulation of inactive forms of CCNE-CDK2 complexes. Loss of p27 caused by degradation activity may affect tumor cell growth in the presence of an altered extracellular matrix, facilitating metastasis. Cell-cycle-regulatory proteins appear to work independently.

Adenocarcinoma↗
PubMed2000

Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities.

To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.

Adenocarcinoma↗
PubMed2000

Gastric adenomas and superficial adenocarcinomas display distinct patterns of mucin carbohydrate and core protein expression.

AIMS: To investigate the histogenetic relationship between gastric epithelial neoplasms we studied differences in expression of mucin carbohydrate antigens and mucin core protein, in normal and metaplastic gastric mucosa, and in gastric adenomas and superficial adenocarcinomas. METHODS AND RESULTS: We generated four monoclonal antibodies, including HGM72/75 against human gastric mucin and HCM14/21 against human colonic mucin, and investigated immunoreactivities of these antibodies and MUC2 protein expression in normal and metaplastic gastric mucosa, adenomas (15 samples) and superficial adenocarcinomas (intestinal-type, 77; diffuse-type, 59 samples). HGM72 reacted with mucous neck cells of the fundic glands and with pyloric glandular cells whereas HGM75 stained foveolar cells and metaplastic goblet cells. Weak binding of HCM14/21 and strong staining with MUC2 were found in metaplastic goblet cells. Binding of HGM75, HCM14, MUC2, but not HGM72 was high in adenomas. An equivalent staining with HGM72 and HGM75 with low expression of MUC2 and HCM14 was shown in intestinal-type carcinomas while the diffuse-type demonstrated more strong reactivity with HGM75 than with HGM72, MUC2 and HCM14. Little binding of HCM21 was observed in any specimens. CONCLUSIONS: This study demonstrates that adenomas predominantly have a intestinal phenotype, but both types of adenocarcinomas retain some cells with a gastric phenotype during the early steps of neoplastic development.

Adenocarcinoma↗
PubMed2000

Possible association of active gastritis, featuring accelerated cell turnover and p53 overexpression, with cancer development at anastomoses after gastrojejunostomy. Comparison with gastroduodenostomy.

To cast light on tumorigenesis in the remnant stomach after distal gastrectomy for peptic ulcer or gastric cancer, 45 cases in gastroduodenostomy (Billroth I, 17 cases) and gastrojejunostomy (Billroth II, 28 cases) groups were compared for a series of parameters. Cancers in Billroth II were significantly more predominant in the anastomosis area and more frequently associated with Epstein-Barr virus infection. Active gastritis, accelerated epithelial cell turnover (as assessed by measurements of apoptosis and cell proliferation), DNA damage, and foveolar cell hyperplasia were all greater in anastomotic areas after Billroth II than in proximal areas after Billroth II or either area after Billroth I. K-ras mutations were rare, but Epstein-Barr virus infection in cancers was seen frequently in anastomosis cases. In conclusion, active gastritis, possibly induced by enterogastric reflux, is linked to tumorigenesis in anastomosis sites in Billroth II cases.

Adult↗
PubMed1999

Markedly elevated cell turnover is characteristic of small, deeply invasive carcinomas of the colorectum.

BACKGROUND: Small, deeply invasive carcinomas invading the muscularis propria or deeper and measuring < or = 2 cm in greatest dimension (S-ADV) are rare in comparison with their larger counterparts (NS-ADV), and their clinicopathologic features are obscure. METHODS: S-ADV and NS-ADV cases as well as cases of submucosal carcinoma (SM-CA) were comparatively assessed for: 1) clinicopathologic findings; 2) Ki-67, mitotic, and apoptotic indices; 3) cathepsin G, p53, and bcl-2 immunoreactivities; and 4) c-Ki-ras mutations. RESULTS: S-ADV and SM-CA, which both are significantly smaller than NS-ADV, did not differ in size, but the frequency of moderately and poorly differentiated carcinoma elements at the leading edges was observed to be higher than in the central cores only in S-ADV, as was tumor "budding" of small clusters of undifferentiated carcinoma cells. The frequency of severe lymphatic involvement in S-ADV was as high as in NS-ADV, and significantly greater than in SM-CA. The Ki-67, mitotic, and apoptotic indices for S-ADV were significantly increased compared with those for NS-ADV and/or SM-CA. Expression of cathepsin G in S-ADV tumor and stromal cells was significantly decreased compared with NS-ADV and/or SM-CA cases. No significant differences in the expression of either p53 or bcl-2 or the incidence of c-Ki-ras mutations were observed among the three groups. CONCLUSIONS: S-ADV can be considered a distinct type of deeply invasive carcinoma, presenting with poor tumor differentiation at the leading edge, and with increased tumor cell proliferation despite its small size.

Biomarkers, Tumor↗