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T Yasutake

Publications and source records attributed to T Yasutake.

At least 55 records · Page 3Linked to original sources

Chromosome arm 20q gains and other genomic alterations in colorectal cancer metastatic to liver, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization.

Comprehensive information about the molecular cytogenetic changes in metastases of colorectal cancer is not yet available. To define such changes in metastases, we measured relative DNA sequence copy numbers by comparative genomic hybridization (CGH). Samples from 27 liver metastases and 6 synchronous primary tumors were analyzed. An average of 9.9 aberrations per tumor was found in the metastases. Gains of chromosome arms 20q (85%), 13q (48%), 7p (44%), and 8q (44%) and losses of chromosome arms 18q (89%), 8p (59%), 1p (56%), and 18p (48%) were detected most frequently. Chromosomes 14 and 15 were lost in 26% and 30% of the metastases, respectively. No consistent differences were observed between primary tumors and synchronous metastases. Fluorescence in situ hybridization (FISH) was used for further characterization of gains of chromosome arm 20q. Touch preparations of 13 tumors that had demonstrated 20q gain with CGH were examined with FISH by use of a set of probes mapping to different parts of 20q. A probe for 20p was used as a reference. FISH showed relative gain of at least one 20q locus in 12 of the tumors. High-level gains were detected in 38% of the tumors, preferentially for probes mapping to band 20q13. Our CGH data indicate that colorectal metastases show chromosomal changes similar to those that have been reported for primary tumors. Chromosomal losses were seen at higher frequency, particularly for chromosomes 14 and 15. By FISH, we identified subregions on chromosome arm 20q that are frequently involved in DNA amplifications in colorectal cancer and that may harbor candidate proto-oncogenes.

Adult↗

Successful transvaginal repair of a rectovaginal fistula developing after double-stapled anastomosis in low anterior resection: report of four cases.

The management of postoperative rectovaginal fistula (RVF) after low anterior resection for rectal cancer is difficult and the results are often unsatisfactory. Among 140 patients with rectal cancer who underwent low anterior resection with a double-stapled anastomosis at our hospital between 1986 and 1996, 4 (2.9%) developed RVF as a postoperative complication. The RVF developed gradually from 9 to 128 days after low anterior resection. We describe herein our technique of using a modified transvaginal approach for RVF repair with a diverting colostomy. In all four patients, the RVFs were completely eradicated with reestablishment of intestinal continuity and did not recur during the mean follow-up period of 29.5 months, ranging from 12 to 67 months. This report serves to demonstrate that emerging RVFs secondary to stapled anastomosis in low anterior resection for rectal cancer must be recognized, and that a modified transvaginal approach provides an effective method of repair.

Adolescent↗

The use of an omental pedicle graft to prevent small-bowel obstruction after restorative proctocolectomy.

Small-bowel obstruction remains one of the most frequent complications after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Of particular concern is small-bowel adhesion to the pelvic dead space that causes afferent limb obstruction, sometimes necessitating laparotomy. In this report, we describe a technique using an omental pedicle graft (OPG) to fill the pelvic dead space to prevent small-bowel obstruction and the resulting afferent limb obstruction after IPAA. The OPG is created from the left half of the omentum, while maintaining the blood supply from the left gastroepiploic vessels. The omentum is placed into the pelvis along the left paracolic gutter from where the colon has been resected. It is then passed over the pelvic brim and placed behind and along the bilateral sides of the ileal pouch, filling the space. This modified technique was employed in the treatment of four patients with chronic ulcerative colitis, none of whom developed any signs of small-bowel obstruction.

Chronic Disease↗

High serum concentrations of sialyl Tn antigen in carcinomas of the biliary tract and pancreas.

Sialyl-Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. In the present study, we compared the serum level of STn antigen in 14 patients with benign diseases of the biliary tract and pancreas, 15 patients with bile duct cancers, and 9 patients with cancer of the pancreas. High levels of serum STn (>45 U/ml) were frequently detected in patients with carcinoma of the biliary tract (53.3%) or pancreas (55.6%), compared with the detection of high levels in those with benign diseases (14.3%; P < 0.05). Serum levels of STn did not correlate with the presence of jaundice, cholangitis, or pancreatitis, or with the level of carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9. In cancer tissues, the expression of STn antigen detected by immunostaining correlated significantly with serum STn (P < 0.05). Our results indicate that measurement of serum STn level may be potentially useful for the diagnosis of carcinomas of the biliary tract and pancreas, particularly when combined with other tumor markers such as CEA or CA19-9.

Adult↗

Higher frequencies of numerical aberrations of chromosome 17 in primary gastric cancers are associated with lymph node metastasis.

We investigated the correlation between the frequency of numerical aberrations of chromosome 17 and clinicopathological features of gastric cancer. The copy number of chromosome 17 was examined with fluorescence in-situ hybridization (FISH) in frozen specimens from 100 primary gastric cancers. Chromosomal numerical aberrations were diagnosed as chromosomal loss (single signal) or gain (triple or more signals), in each cell. The frequency of numerical aberrations of chromosome 17 correlated significantly with the depth of invasion (P < 0.01), lymph node metastasis (P < 0.0001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.01). Numerical aberrations of chromosome 17 were associated with lymph node metastasis in 32 early gastric cancers. Multiple regression analysis identified the depth of invasion and numerical aberrations of chromosome 17 as independent significant determinants of lymph node metastasis. Our findings suggest that alterations in chromosome 17 may be linked with tumor progression in primary gastric cancer. Our results also indicate that numerical aberrations of chromosome 17 detected by FISH provide important information about the malignant potential (in particular, lymph node metastasis) of primary gastric cancer.

Adult↗

Expression of multidrug resistance protein in metastatic colorectal carcinomas.

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.

ATP-Binding Cassette Transporters↗

Proliferation of hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection.

In this study, we determined the proliferation indices of liver metastatic tumours originating from colorectal carcinomas using Ki67 and argyrophil nucleolar organizer region associated proteins (AgNOR) stain. We examined the primary and metastatic tumours in 27 patients with liver metastasis and eight cases with non-metastatic colorectal carcinoma as a control.The number of AgNOR dots in metastatic tumours was significantly higher than in the respective primary tumours of the metastasis group or in non-metastatic colorectal carcinomas. The Ki67 labelling index was similar in all groups. The Ki67 labelling index and AgNOR counts did not correlate with each other. There was no significant relationship between proliferation indices and the duration of the disease-free period following hepatic resection for metastases or with prognosis after hepatectomy. We conclude that Ki67 and AgNOR are not useful indicators of prognosis in patients who undergo operation for liver metastasis of colorectal carcinomas.

Adult↗

Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection.

BACKGROUND: Adhesion molecules are closely involved in the development and growth of metastatic tumours. METHODS: We examined the expression of two adhesion molecules in liver metastatic tumours originating from colorectal carcinomas and correlated the expression of E-cadherin (EC) and CD44 variant exon 6 (v6) in these tumours with prognosis after hepatic resection. We examined 39 primary colorectal and 44 liver metastatic tumours obtained from 39 patients and 30 non-metastatic colorectal carcinomas as controls. The expression of EC in primary colorectal carcinomas of the metastasis group was significantly lower than in the non-metastasis group (P < 0.05). The expression of EC was low in metastatic liver tumours. RESULTS: The expression of CD44v6 in primary colorectal carcinomas of the metastasis group was significantly higher than in the non-metastasis group (P < 0.01). Expression of CD44v6 was high in metastatic liver tumours. However, there was no correlation between the expression of EC and CD44v6 or between each of these molecules and clinicopathological features of primary and metastatic tumours. Negative expression of EC and CD44v6 was a poor prognostic factor for survival after hepatic resection. CONCLUSIONS: Our results indicate that the lack of expression of EC and CD44v6 in liver metastases of colorectal cancer is associated with poor survival after surgery.

Aged↗

Tremor induced by toluene misuse successfully treated by a Vim thalamotomy.

A 22 year old man developed a vigorous tremor of 5 Hz in his right hand, after a 7 year history of toluene misuse. T2 Weighted MRI depicted marked decreases in the signal intensity of the basal ganglia, red nucleus, and thalamus on both sides. The stereotactic coagulation of the left nucleus ventrointermedius (Vim) of the thalamus abolished the tremors in his right hand. This patient clearly exhibited the pathological involvement of rubral lesions in generation of a toluene induced tremor on MRI. Toluene induced tremor is an irreversible symptom which persists even after stopping toluene misuse, therefore in medically intractable cases, it should be positively treated by a Vim thalamotomy.

Adult↗

Physiologic stress responses to laparoscopic cholecystectomy. A comparison of the gasless and pneumoperitoneal procedures.

BACKGROUND: Differences in the physiological stress response to pneumoperitoneal (PP) and gasless abdominal wall-lifting (AWL) procedures used for laparoscopic cholecystectomy have not been properly evaluated. METHODS: We compared leukocyte count, interleukin-6 (IL-6) levels, arterial blood gases, creatinine clearance, plasma renin activity, cardiothoracic ratio, and clinical outcome in 27 patients without systemic complications who underwent laparoscopic cholecystectomy, including 11 by AWL and 16 by PP. RESULTS: Transient leukocytosis and high IL-6 levels were observed at POD 1 (postoperative day) in both groups, but both values returned to baseline by POD 2. IL-6 levels correlated significantly with operation time (p < 0.01). Changes in blood gases, creatinine clearance, plasma renin activity, and cardiothoracic ratio were not different for the two groups. The clinical outcome was similar for both groups. CONCLUSIONS: Our results indicate that both PP and AWL are appropriate for patients without serious complications.

Adult↗

Chromosome instability evaluated by fluorescence in situ hybridization in hereditary non-polyposis colorectal cancer.

Numerical aberrations of chromosome 17 and nuclear DNA content were compared in patients with hereditary non-polyposis colorectal cancer (HNPCC) and those with sporadic colorectal cancer (SCRC). During a period of 22 years, 30 cases (3.2%) from 28 families satisfied the Japanese clinical criteria of HNPCC. Using freshly frozen tissue samples, we investigated chromosomal aberration with fluorescence in situ hybridization with alpha satellite DNA probe for chromosome 17. Flow cytometric quantification of nuclear DNA content showed DNA aneuploidy in 9 of 15 patients (60.0%) with HNPCC and in 160 of 234 patients (68.4%) with SCRC, there was no significant difference between HNPCC and SCRC. The mean proportion of nuclei with aneusomy 17 (numerical chromosome aberration index: NCAI) in 14 patients with HNPCC was significantly higher than that in 42 patients with SCRC (46.8 +/- 5.0% vs 39.0 +/- 10.3%, P < 0.01). NCAI increased in proportion with the progression of the disease in SCRC (26.1% in stage I, 33.3% in stage II, 38.8% in stage IIIa, 42.7% in stage IIIb, and 46.2% in stage IV, P < 0.01), whereas NCAI in HNPCC was high in all stages (43.5%-49.2%). The proportion of patients with multiple numerical aberration of chromosome 17 was significantly higher in HNPCC (9/14) than among SCRC (11/42). Our data suggest that chromosome 17 is present in an unstable condition in HNPCC.

Adenocarcinoma↗

Importance of cytogenetic markers for multiple primary carcinomas in colorectal cancer: chromosome 17 and p53 locus translocation.

The incidence of non-familial multiple primary cancer in colorectal cancer patients has increased in recent years in Japan. To clarify the characteristic genetic aberrations in such multiple cancers, we examined structural chromosomal aberrations by fluorescence in situ hybridization, using chromosome 17-specific and p53 cosmid DNA probes. We established short-term cultures of 78 surgical specimens and were able to obtain observable metaphase spreads in 23 single colorectal cancer specimens and in 6 colorectal cancer specimens from patients with double primary cancers. The frequency of chromosome 17 and/or p53 locus translocation was significantly greater in tumors with double cancer than in single colorectal cancers (P < 0.05 and P < 0.01, respectively). These aberrations in double cancers frequently appeared even at an early Dukes' stage (A and B) of colorectal carcinoma. Our results suggest that translocation of chromosome 17 and the p53 locus may be specific genetic events probably associated with carcinogenesis of multiple primary cancers in colorectal cancer.

Biomarkers, Tumor↗

Immunohistochemical expression of ABH/Lewis-related antigens in primary breast carcinomas and metastatic lymph node lesions.

The expression of blood group antigens A, B, and H, as well as sialylated and nonsialylated forms of Lewis(a) and Lewis(x), was studied using immunohistochemical methods in normal and tumor tissues in the following cohort of patients: 51 patients with primary breast carcinoma, 13 with metastatic lymph node lesions, and 16 with benign tumors of the breast. As a control, normal tissue was obtained from a similar group of 22 patients with breast cancer. The noncancerous tissues expressed the same A/B/H antigens as the patients' red blood cells and also usually expressed Lewis-related antigens. Seventy-six percent of primary carcinomas failed to express the appropriate A/B/H antigens, and in one blood group A patient the tumor tissue expressed B antigen. In the metastatic lesions, Lewis(a)/sialyl Lewis(a) expression was reduced when compared with the primary tumors, but Lewis(x)/sialyl Lewis(x) antigens were still expressed. These results suggest a possible relationship between the metastatic behavior of the tumor and expression of the blood group antigens.

Antigens, Tumor-Associated, Carbohydrate↗

Evaluation of the topical delivery of a prednisolone derivative based upon percutaneous penetration kinetic analysis.

Prednisolone (PN) and an esterified derivative (PND) were evaluated in pharmacological and pharmacokinetic studies. The pharmacological study was performed using a rat croton-oil induced ear edema model. The results for the topical effect in skin and the systemic effect through multiple topical applications showed that PN and PND were equally potent in suppressing edema, and that PN caused a reduction in thymus weight, whereas PND had little effect. The concentration of these steroids in hairless mouse skin was estimated from an in vitro percutaneous absorption study using the computer simulation program MULTI(FILT). PND was found to be poorly absorbed. In fact, the PND concentration in the viable skin remained low (0.79 microg/cm2), even after 7 d. However, the estimated concentration of PND in the viable skin appears to be in excess of the threshold for effective topical effect during the pharmacological evaluation. In contrast, in the case of PN, the estimated PN concentration increased gradually after application and reached a level of 10.22 microg/cm2 at day 7, suggesting that this increase in PN concentration in the viable skin could result in a systemic effect. The difference between PN and PND concentration in the skin during the time course could be due to the metabolism of PND to PN in the viable skin. Consequently, the difference between the pharmacological study is reflected from the results of the pharmacokinetics of PN and PND in the skin.

Administration, Topical↗

Differences in spatial localization and chromatin pattern during different phases of cell cycle between normal and cancer cells.

We studied differences in chromatin patterns and the spatial localization of centromeres of chromosome 11 during the cell cycle between normal peripheral blood lymphocytes (PBL) and human promyelocytic leukemia cells (HL-60) using fluorescence in situ hybridization. The pericentromeres in both cells were located at the periphery during Gq (quiescent) phase, but moved towards the nuclear center in G1 and mid-S phase. During G2, the pericentromeres of PBL continued to move towards the nuclear center whereas those of HL-60 returned to the periphery. The angle defining the spatial location of two pericentromeres, in reference to the center of the nucleus, increased in PBL cells from a mean of 67 degrees during Gq phase to 106 degrees during G1 phase (P < 0.01), and the two pericentromeres remained wide apart throughout the entire cell cycle. In HL-60, the angle also increased during G1, but then decreased during mid-S and G2 phases. Both cells exhibited pericentromeric signals during Gq that were round and compact, and the entire chromatin was loosely condensed. The signal became more loose and dispersed during the G1 and mid-S phases. The pericentromere signal varied during G2 and was generally rod-like or bipartite with condensation of the entire chromatin or chromosome-like. Our results suggest that subtle but important differences in spatial localization of pericentromeres are present during the interphase between normal PBL and HL-60 cells.

Cell Cycle↗

Different expressions of sialyl Tn antigen between polypoid and flat-type early colorectal cancers.

PURPOSE: Sialyl Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. We compared the proportion of specimens of flat-type colorectal cancers expressing STn with that of polypoid cancers, by examining the immunohistochemical reactivity of STn in various morphologic types of early and advanced colorectal cancers. METHODS: A total of 111 biopsies from the colorectal area were examined for STn expression, including 11 adenomas, 58 early cancers, and 42 advanced cancers. Each section was stained immunohistochemically for STn antigen. In each section, we examined STn expression in the cancer area, adjacent mucosa, and normal epithelium. RESULTS: STn expression was detected in 90.9 percent of adenomas, 36.2 percent of early cancers (T1), 64.3 percent of advanced cancers (>T1), and 52 percent of mucosa adjacent to cancer. The morphology of cancer tissue did not influence the number of specimens exhibiting STn antigen expression in mucosa adjacent to cancer cells. STn antigen was rarely expressed in flat or depressed-type early cancers (T1; 7.1 percent), and the expression was higher in moderately than in well-differentiated adenocarcinomas. In advanced cancers (>T1), a similar proportion of protruding and small ulcerative cancers expressed STn. CONCLUSION: Our results suggest that the low expression of STn antigen in flat-type cancers may be the result of different mechanisms of cellular transformation during carcinogenesis from the usual adenoma-carcinoma sequence in colorectal neoplasms.

Adenocarcinoma↗

Analysis of p53 gene deletions in colorectal cancers using fluorescence in situ hybridization.

To examine the relationship between the incidence of p53 gene deletion in each nucleus and the clinicopathological features in colorectal cancers, we performed a cytogenetic study using fluorescence in situ hybridization (FISH). FISH was performed on 5 adenomas and 38 colorectal cancers that had been resected surgically. The nucleus, in which the copy number of the p53 signal was lower than that of chromosome 17, was determined as a deletion of the p53 gene. The mean frequency of the deletion of p53 in adenomas and cancers were 7.8% +/- 3.0% and 57.0% +/- 19.0%, respectively. Numerical aberrations of chromosome 17 or a deletion of p53 were also detected in DNA diploidy. The mean frequency of the deletion of p53 in 32 cases with aneusomy of chromosome 17 (65.7% +/- 14.5%) was significantly higher than that in cases of disomy (51.1% +/- 19.3%, P < 0.05). Even though this frequency was high in the early stage, it was not associated with any specific histopathological features. This frequency was also higher in double primary cancers (70.4% +/- 16.7%) compared with single colorectal cancers (53.4% +/- 18.1%) (P < 0.05). Using FISH, our results demonstrated that the clonal deletion of the p53 locus is an early genetic event of colorectal cancers and that a high incidence of p53 deletion may influence the occurrence of double primary cancers.

Adenoma↗