Biomedical subjects

Hirotoshi Hasegawa

Publications and source records attributed to Hirotoshi Hasegawa.

17 recordsLinked to original sources

PubMed2003

Chemosensitivity testing--present and future in Japan.

Radical surgery with extended lymph node dissection is the first and only curative treatment of gastrointestinal cancer. Although the combined cancer chemotherapy has achieved 30%-50% response rates, a controversy still remains over the significance of the adjuvant cancer chemotherapy after surgery. To break through this limitation, we have introduced the chemosensitivity test to evaluate the appropriate adjuvant cancer chemotherapy for advanced gastrointestinal cancer. Our plural studies indicated that the chemosensitivity test would be useful in evaluating the appropriated adjuvant chemotherapy by increasing survival in the sensitive group. Recently, the molecular targets have been clarified for the conventionally available antitumor agents, e.g., thymidylate synthetase for 5-fluorouracil, ATP-binding cassette transporters for anthracyclines, glutathione-related detoxification for platins, and topoisomerase I for CPT-11, which will be applied for dinical use in evaluating the appropriate cancer chemotherapy. The chemosensitivity test is approved as "advanced clinical medicine" by the Japanese Ministry of Health, Welfare, and Labor in five institutes at present. Because complete dissection and chemosensitivity test-guided adjuvant chemotherapy will result in a survival benefit for patients with advanced gastrointestinal cancer, this test should be approved as "social insurance" for further wide clinical application.

Antineoplastic Agents↗

PubMed2003

Diffuse cavernous hemangioma of the rectum: report of a case.

Cavernous hemangioma of the rectum (CHR) is an uncommon benign vascular lesion, which mainly affects young adults. The rectosigmoid area is the most common site of cavernous hemangioma in the gastrointestinal tract. CHR is often misdiagnosed due to a lack of knowledge of the clinical features. We report a case of CHR, focusing on the clinical features, diagnostic procedures used, and treatments given. This patient was finally treated effectively with abdominoperineal resection. Thorough preoperative imaging is necessary to confirm the diagnosis and evaluate both the site and extent of the hemangioma. Magnetic resonance imaging (MRI) provides information about the dimensions of the tumor and involvement of the adjacent structures with its high resolution and multiplanar capability, without the use of contrast medium. Moreover, endorectal surface coil MRI depicts the five separate layers of the bowel wall and internal and external sphincter more clearly than the conventional body coil MRI.

Female↗

PubMed2003

Short-term surgical outcomes of laparoscopic colonic surgery in octogenarians: a matched case-control study.

This study was undertaken to evaluate the short-term surgical outcomes of laparoscopic surgery for colonic carcinoma in octogenarians and compare them with those for a younger group of patients who underwent the same surgical procedures. This matched case-control study involved 17 octogenarian patients with colonic carcinoma who underwent laparoscopic surgery between 1996 and 2001. The results were compared with those for 34 matched patients aged 60 years or less who underwent the same surgical procedures during the same period. Both groups were well matched for clinical characteristics. However, the American Society of Anesthesiology status was significantly higher in the octogenarian group (P = 0.001). There were no significant differences between the two groups in terms of the incidence of complications, the interval before resumption of liquid or solid food intake, or length of hospitalization. There were no deaths in either group. Advanced age should not be regarded as a contraindication for laparoscopic colonic surgery.

Adult↗

PubMed2003

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray.

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer.

Antineoplastic Agents↗

PubMed2003

Gene expression in colorectal cancer and in vitro chemosensitivity to 5-fluorouracil: a study of 88 surgical specimens.

To predict the sensitivity of colorectal cancer to 5-fluorouracil (5-FU), we compared the gene expression of surgically obtained colorectal cancer specimens with chemosensitivity to 5-FU as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Eighty-eight patients with advanced and/or metastatic colorectal cancer provided written informed consent and entered the trial from September 2000 to October 2001. Fresh surgical specimens were used for the MTT assay, and sensitivity to 5-FU was evaluated at a cutoff concentration of 50 microg/ml and 48-h incubation time. Frozen samples were stored at - 80 degrees C until mRNA analysis of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), es-nucleoside transporter (NT), and E2F1 by real-time RT-PCR. The correlations between the variables were analyzed, and the predictive value of these mRNAs was assessed statistically using a receiver operating characteristic (ROC) curve. NT and DPD, TP and DPD, and TP and NT mRNA expression levels correlated significantly, while TS and E2F1 showed no correlations. High NT expression was associated with low sensitivity to 5-FU (P < 0.013), as were high DPD and E2F1 expression (P < 0.022 for both). High TP mRNA expression correlated with low sensitivity to 5-FU (P < 0.034), although high TS mRNA expression did not. ROC curves indicated that DPD and NT mRNAs were possible predictors of sensitivity to 5-FU, with cutoff values of 0.6 and 0.4, respectively. The sensitivity of colorectal cancer to 5-FU may be regulated by DPD, the rate-limiting enzyme of catabolism, and NT, an important transmembrane transporter of nucleosides.

Antimetabolites, Antineoplastic↗

PubMed2002

Significance of transforming growth factor beta1 as a new tumor marker for colorectal cancer.

Transforming growth factor beta1 (TGF-beta1) is thought to be involved in cancer growth and progression. TGF-beta1 changes to its active form after being secreted in its latent form. Our aim was to clarify the significance of plasma concentrations of active and total TGF-beta1 of patients with colorectal cancer. Plasma concentrations of active and total TGF-beta1 in 45 patients with colorectal cancer and 23 healthy volunteers were measured using ELISA and the activation rate (ratio of active to total TGF-beta1) was determined. Plasma concentrations of active TGF-beta1 (21.9 +/- 12.8 pg/ml) were significantly higher in patients with colorectal cancer than in healthy volunteers (9.9 +/- 5.9 pg/ml; p < 0.001, Welch's t-test). Concentration of total TGF-beta1 was also significantly higher for patients with colorectal cancer (18.0 +/- 13.0 ng/ml vs. 11.1 +/- 6.4 ng/ml; p < 0.01, Welch's t-test). However, there was no significant difference in the TGF-beta1 activation rate between the 2 groups. There was a correlation between Dukes' stage and plasma concentration of active or total TGF-beta1 (p < 0.01, Spearman's rank correlation test) and on day 7 the active TGF-beta1 levels for patients recovering from curative resection were similar to those of the control group of healthy volunteers. These results suggest that active TGF-beta1 might be used as a tumor marker for colorectal cancer.

Adenocarcinoma↗

PubMed2002

Serrated adenoma developing into advanced colon cancer in 2 years.

We report the case of a 76-year-old woman with a flat elevated lesion (laterally spreading tumor; LST) in the transverse colon that had been identified 2 years before the current presentation. Pathologically, the lesion had been diagnosed as a serrated adenoma with severe dysplasia. The patient had refused endoscopic resection because she was afraid of the risk of colonic perforation; she did not come to follow-up until 2 years after the diagnosis, when she had advanced colon cancer in the transverse colon where the LST had been detected. Histopathological examination confirmed a poorly differentiated adenocarcinoma with no adenomatous component such as had been found in the LST lesion.

Adenocarcinoma↗

PubMed2002

Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer.

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.

Aged↗

PubMed2002

Successful application of laparoscopic surgery to the treatment of Crohn's disease with fistulas.

PURPOSE: The role of laparoscopic surgery in patients with Crohn's disease remains to be defined, although increasingly difficult cases are being treated using minimally invasive techniques. We examined technical feasibility in 20 patients with Crohn's disease associated with fistulas. METHODS: Laparoscopic surgery was attempted in 37 patients with stricturing ileal disease or ileocolonic Crohn's disease from 1994 to 2000 after failure of strict nutritional therapy. Twenty of these patients with a total of 31 intestinal fistulas (14 ileoileal, 6 ileocolonic, 5 ileorectal, 2 ileovesical, 2 ileocutaneous, 1 gastrocolic, and 1 ileoduodenal) underwent 25 operations. Fistulas were divided intracorporeally, except for ileoileal fistulas. Fifteen patients underwent ileocecal resection; six underwent strictureplasty; six underwent partial resection of the small intestine; three underwent segmental colonic resection; and one underwent resection of anastomotic recurrence. Median follow-up was 48 (range, 5-77) months. RESULTS: Oral intake was started a median of 1 (range, 1-9) day after operation, and patients were discharged a median of 8 (range, 6-21) days after surgery. Four complications were observed in 25 operations (16 percent), including 1 intestinal obstruction/ileus, 2 wound infections, and 1 intra-abdominal abscess. There were no intraoperative or postoperative deaths. Four of the 5 operations were converted to open surgery (16 percent). Three of the 5 patients (60 percent) who required reoperation for anastomotic recurrence underwent repeated laparoscopic surgery using the same small incision. CONCLUSION: Laparoscopic treatment for Crohn's disease complicated by fistulas is feasible without high complication or conversion rates. Recurrent disease requiring reoperation can also be successfully treated using laparoscopic methods.

Adult↗

PubMed2002

Sentinel node mapping for colorectal cancer with radioactive tracer.

PURPOSE: The aim of this study was to test the feasibility and accuracy of radioactivity-guided mapping of the first lymph nodes found in draining the primary tumor site for colorectal cancer. METHODS: We enrolled 56 consecutive patients with preoperative diagnosis of curatively resectable colorectal cancer. Endoscopic injection of technetium Tc 99m-labeled tin colloid (15 MBq) was performed preoperatively, and radioactive sentinel nodes were identified intraoperatively with a gamma probe. Standard radical resection with lymph node dissection was performed in all patients, and all resected nodes were evaluated by routine histopathologic examination. RESULTS: Radioactivity-guided methods were used to detect sentinel nodes in 51 (91 percent) of 56 patients. The number of lymph nodes resected was 23.9 +/- 15.2 per case. The number of sentinel nodes was 3.5 +/- 2.1 (range, 0-8) per case. In 18 of 22 patients with lymph node metastasis, the sentinel node was positive. The incidence of metastasis in the sentinel node (22 percent) was significantly higher than that in nonsentinel nodes (3 percent, P < 0.01). Diagnostic accuracy according to sentinel node status was 92 percent (47/51). Four false-negative cases in this study were advanced cases with T3 primary tumors. The detection rate and diagnostic accuracy for patients with T1 or T2 primary tumors (29 cases) were 100 percent each. CONCLUSION: Intraoperative radioactivity-guided sentinel node mapping was accurate for patients with colorectal cancer with T1 or T2 tumors. The results suggest that sentinel node mapping and intraoperative biopsy may be a sensitive and specific diagnostic method for detecting metastasis in regional lymph nodes in patients with colorectal cancer.

Adult↗

PubMed2002

Prospective evaluation of laparoscopic surgery for rectosigmoidal and rectal carcinoma.

PURPOSE: This study was designed to examine the short-term results of laparoscopy in the treatment of curative cases of rectosigmoidal and rectal carcinoma. METHODS: A review was performed of a prospective registry of 70 patients who underwent curative laparoscopic resection for rectosigmoidal and rectal carcinoma between July 1993 and April 2001. Before 1997, only patients with early (Tis or T1) cancers located in the rectosigmoid and upper rectum that required bowel resection were candidates for laparoscopy. In 1997, we expanded the application of laparoscopy to include T2 cancers located anywhere in the rectum. Mesorectal transection was performed at least 5 cm below the tumor for rectosigmoidal and upper rectal lesions, and total mesorectal excision was performed for lower tumors. Primary anastomosis was performed by a double-stapling technique, or a handsewn coloanal anastomosis was performed. Patient demographics and outcomes were recorded prospectively. RESULTS: The median follow-up was 23 months. An anastomosis was performed in 92.9 percent of the operations. Oral intake was started on median postoperative Day 1, and the median length of hospitalization was 8 days. Two patients needed conversion to conventional open surgery. A total of 15 postoperative complications occurred in 13 patients (18.6 percent), including anastomotic leakage in 6 (8.6 percent) and bowel obstruction in 3 (4.3 percent). Reoperation was required in six patients. Two patients developed recurrence of cancer at the anastomotic site. The expected 5-year survival and disease-free survival rates were 100 and 92.1 percent, respectively. CONCLUSION: The findings of the present study demonstrate the feasibility and safety of laparoscopic surgery for selected patients with rectal carcinoma. Morbidity and mortality rates and oncologic outcome appear to be comparable with conventional surgery.

Adult↗

PubMed2002

Laparoscopic restorative proctocolectomy for patients with ulcerative colitis.

BACKGROUND: Significant concern continues about the feasibility of laparoscopic restorative proctocolectomy (RP) with an ileal J pouch anal anastomosis in the surgical treatment of patients with ulcerative colitis (UC). The aim of this study was to clarify the feasibility of laparoscopic RP at a single institution where the surgical routine of laparoscopic colorectal surgery has already been established. PATIENTS AND METHODS: Between July 1994 and December 2001, 18 patients with UC underwent laparoscopic RP. The median age was 30 (range, 18-51) years, and the median follow-up was 20 (range, 5-89) months. Five trocars were placed. After the entire colon and rectum were mobilized and the vessels were divided intracorporeally, the rectum was divided with use of a laparoscopic linear stapler. A pouch anal anastomosis was fashioned with use of a double stapling technique. A diverting loop ileostomy was fashioned. RESULTS: There were no conversions to the open procedure. The median operative time and median blood loss were 360 (range, 290-500) minutes and 105 (range, 10-586) mL, respectively. Six postoperative complications occurred (wound sepsis, 2; bowel obstruction, 1; anastomotic stricture, 2; pouchitis, 1). In one patient, a bowel obstruction developed 3 months after the operation, which was managed conservatively. The median length of the hospital stay was 9 (range, 7-21) days. CONCLUSIONS: The laparoscopic RP is safe and feasible in selected patients with UC. New laparoscopic instrumentation, such as a linear stapler, and a more reliable laparoscopic coagulating and dividing tool should be designed, which would make it possible to perform this procedure more frequently in the surgical treatment of UC.

Adult↗

PubMedDate not supplied

Neoadjuvant chemotherapy of irinotecan, 5-fluorouracil and leucovorin in patients with advanced rectal cancer. Report of two cases.

We report on two patients with T3N1 rectal cancer treated with a combination of irinotecan, 5-fluorouracil and leucovorin as neoadjuvant chemotherapy. On days 1, 8 and 15 of this 4-week cycle, leucovorin (250 mg/m2) was administered in a 2-hour intravenous infusion, followed by 5-fluorouracil (500 mg/m2) in a 10-min intravenous bolus, and then irinotecan (80 mg/m2) in a 90-min intravenous infusion. During the chemotherapy, no grade 3-4 toxicities were observed. Two weeks after the completion of 2 cycles of this regimen, both patients underwent surgery without postoperative complications. The responses were one pathological and one macroscopic complete response. Both patients with T3 tumors were down-staged to pT0 and pT2, respectively. As for the N stage, both patients were down-staged to pN0. The combination of irinotecan/5-fluorouracil/leucovorin appears to be feasible and effective, and to have a potential as an optimal neoadjuvant therapy in patients with advanced rectal cancer.

Adenocarcinoma↗

PubMedDate not supplied

Clinical usefulness of chemosensitivity test for advanced colorectal cancer.

We assessed the usefulness of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in the evaluation of appropriate adjuvant cancer chemotherapy for patients with advanced colorectal cancer. We analyzed 405 cases of colorectal cancer treated between January 1990 and August 1999 in terms of the MTT assay and survival outcome. Patients with Dukes' C and D were classified into a "surgery alone" group (n = 53), a "sensitive" group who received drugs that had a greater than 50% inhibition rate by MTT assay (n = 23), or "resistant"" group who were insensitive to the chemotherapy drugs (n = 124). Statistically significant differences in survival outcome were observed between the groups, with the sensitive group showing significantly better survival compared with the resistant group (p = 0.0158) and the surgery-alone group (p = 0.0004). Our results suggest that the MTT assay may be useful in evaluating the optimum adjuvant chemotherapy for patients with advanced colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

A potential important role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed.

BACKGROUND: Because thymidylate synthetase (TS) is a key enzyme in DNA synthesis, it has been used as a target for cancer chemotherapy. MATERIALS AND METHODS: We investigated the combined antitumor activity of raltitexed, 5-FU and UFT on human tumor xenografts in nude mice and examined changes in TS activity and 5-FU-bound RNA (F-RNA) levels. Human gastric (SC-1-NU) or colon (HT-29) carcinoma xenografts were transplanted subcutaneously into nude mice, and drugs administered intraperitoneally (raltitexed and 5-FU) or perorally (UFT) daily for 5 days, and repeated once after a 2-day interval. RESULTS: The antitumor effects were mostly equivalent between the treatment groups despite the different drugs and sequence orders. TS inhibition rates correlated with the tumor inhibition rate, which was statistically significant, while F-RNA levels did not correlate with antitumor activity. CONCLUSION: Our results indicated that the combination of fluoropyrimidine-related agents should be directed towards increased TS inhibition rather than increased F-RNA levels.

Animals↗

PubMedDate not supplied

The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer.

UNLABELLED: In a previous report we noted that cyclooxygenase-2 (COX-2) expression in clinical colorectal cancer is closely related to liver metastasis and survival. The aim of the present study was to clarify the role of COX-2 in liver metastasis and to examine the potential for a selective COX-2 inhibitor as a novel therapeutic agent in the treatment of colorectal cancer. MATERIALS AND METHODS: COX-2 expression of 6 kinds of human colon cancer cell lines, with various potentials for liver metastasis, were assessed by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). In human tumor xenografts/severe combined immune-deficient (SCID) mouse, we examined the effects of a selective COX-2 inhibitor (JTE-522) on tumor growth or liver metastasis of HT-29, a highly-metastatic cell line, or on COLO205, a non-metastatic cell line. The effect of JTE-522 on vascular endothelial growth factor (VEGF) expression and the activity of matrix metalloproteinases (MMPs) in HT-29 and COLO205 were assessed by enzyme-linked immunosorbent assay (ELISA) and gelatin zymography, respectively. RESULTS: COX-2 was expressed in all metastatic cell lines but not in the non-metastatic lines. JTE-522 prevented the liver metastasis of HT-29, but not the subcutaneous growth of HT-29 and COLO205 in SCID mice. In vitro, JTE-522 suppressed VEGF expression, but did not affect MMP production in HT-29; an inhibitory effect was not found in COLO205. CONCLUSION: A selective COX-2 inhibitor of JTE-522, was found to prevent liver metastases of colon cancer by suppressing VEGF expression, and therefore, COX-2 possibly plays an important role in liver metastasis of human colon cancer via the regulation of VEGF expression.

Animals↗

PubMedDate not supplied

Oncologic outcome of laparoscopic surgery for T1 and T2 colorectal carcinoma.

BACKGROUND/AIMS: Laparoscopic surgery for colorectal carcinoma remains controversial because of the technical difficulties and uncertainty regarding the long-term oncologic outcome after laparoscopic surgery. The objective of this study was to evaluate the feasibility for the laparoscopic surgery in the treatment of pT1 and pT2 colorectal carcinoma. METHODOLOGY: A review was performed of a prospective registry of 226 patients who underwent curative laparoscopic resection for pT1 and pT2 colorectal carcinoma between December, 1992 and December, 2001. Patient demographics and outcomes were recorded prospectively. RESULTS: The median follow-up was 43 months. Three patients (2.0%) in the pT1 group and 3 patients (3.9%) in the pT2 group developed recurrence of carcinoma. The expected five-year survival and disease-free survival rates in the pT1 group were 98.9% and 97.6%, respectively, whereas they were 93.6% and 93.4% in the pT2 group. No patient had port-site or peritoneal recurrence during the follow-up period. CONCLUSIONS: The findings of current study demonstrate that oncologic outcome of laparoscopic surgery for patients with pT1 and pT2 colorectal carcinoma appear to be comparable with conventional surgery. Laparoscopic surgery is oncologically appropriate at least for patients with pT1 and pT2 colorectal carcinoma.

Adult↗