Biomedical subjects

Hideyuki Mishima

Publications and source records attributed to Hideyuki Mishima.

At least 19 recordsLinked to original sources

PubMed2006

A phase II Study of the global dose and schedule of capecitabine in Japanese patients with metastatic colorectal cancer.

BACKGROUND: Although the standard 3-week capecitabine regimen (1250 mg/m(2) twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m(2) twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC). METHODS: Previously untreated patients with MCRC received oral capecitabine 1250 mg/m(2) twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis. RESULTS: Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23-48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2-6.7 months). The median overall survival was 20.2 months (95% CI, 16.6-27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients. CONCLUSIONS: The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.

Administration, Oral↗

PubMed2006

An icteric type hepatocellular carcinoma with no detectable tumor in the liver: report of a case.

A 70-year-old man was admitted to our hospital with obstructive jaundice. Computed tomography revealed a tumor in the left intrahepatic bile duct extending to the common bile duct without any significant lesions in the liver. Cholangiography showed a filling defect due to an intraductal tumor. Cytology of the bile juice was negative and tumor markers were carcinoembryonic antigen 5.7 ng/ml, carbohydrate antigen 19-9 49 U/ml, alpha-fetoprotein 9 ng/dl, and PIVKA-II 19 200 AU/ml. With a preoperative diagnosis of hilar bile duct carcinoma, a laparotomy was performed. The common bile duct was filled with a tumor and it extended into the bilateral intrahepatic bile ducts. The intraductal tumor was removed together with the extrahepatic bile ducts. An intraoperative histological examination of the tumor showed a well-differentiated hepatocellular carcinoma. No lesions were detected in the liver by ultrasonography, palpation during the operation, or a computed tomography scan after the operation. At 1 year postoperatively, no recurrence has been seen in this patient.

Aged↗

PubMed2006

[FOLFOX].

In metastatic colorectal cancer, a combination of Leucovorin (LV) and fluorouraci (l FU) with oxaliplatin (FOLFOX) is a standard first-line regimen. The two limiting toxicities of FOLFOX are neutropenia and the specific reversible sensory neuropathy of oxaliplatin. The cumulative neurotoxicity often requires therapy to be stopped. Immediate hypersensitive reactions (anaphylaxis) have been noted as often as to 0.6 percent. We should pay sufficient attention to side effects of FOLFOX.

Anaphylaxis↗

PubMed2005

Sequential treatment with irinotecan and doxifluridine: optimal dosing schedule in murine models and in a phase I study for metastatic colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) and doxifluridine (5'-DFUR) are active agents against colorectal cancer. Each drug, however, has the possibility of causing diarrhea. METHODS AND RESULTS: First, we determined the optimal dosing regimen in murine models. CPT-11 (i.v., q2d x 3) and 5'-DFUR (p.o., qd x 14) were administered to mice bearing a human colorectal cancer xenograft model. Diarrhea was stronger in the simultaneously administered schedule but not much stronger in the sequentially administered schedule compared with monotherapies. Both schedules yielded similar antitumor efficacies. Next, we conducted a phase I study combining CPT-11 on days 1 and 15, and 5'-DFUR on days 3-14 and 17-28 every 5 weeks in 19 patients with metastatic colorectal cancer. The doses of CPT-11 ranged from 80 to 150 mg/m2 and those of 5'-DFUR from 800 to 1,200 mg. Diarrhea of grade 3/4 developed in only 1 patient at 100 mg/m2/800-mg doses. Dose-limiting toxicities were hyperbilirubinemia and skipping doses due to fatigue at 150 mg/m2/1,200-mg doses. CONCLUSION: For the phase II study, the recommended dose was set at CPT-11 150 mg/m2 and 5'-DFUR 800 mg.

Adult↗

PubMed2005

[A case of unknown primary squamous cell carcinoma in the neck showing a high response with combined chemotherapy including nedaplatin, adriamycin and 5-fluorouracil].

We report a case of a 54-year-old man with unknown primary squamous cell carcinoma in the bilateral neck. The patient was treated with chemotherapy and radiation therapy, because his right common carotid artery was invaded by the right neck tumor, and a complete curative operation was not considered possible. We chose instead combination chemotherapy with nedaplatin, adriamycin and 5-fluorouracil (NAF), because it was reported that NAF was available for advanced squamous cell carcinoma of the esophagus. After 3 cycles of NAF chemotherapy, the patient showed a partial response of approximately an 86% decrease in the right neck tumor for over three months. In addition to NAF, radiation therapy was performed. In the CT findings after chemotherapy and radiation therapy, the patient showed a complete response in the bilateral neck tumors. Unknown primary squamous cell carcinoma in the neck has been treated by combination therapy consisting of chemotherapy, radiation therapy and surgery. The regime of 5-fluorouracil and cisplatin is said to be an effective treatment for unknown primary squamous cell carcinoma in the neck. Based on our experience, NAF would be available as chemotherapy for unknown primary squamous cell carcinomas in the neck.

Antibiotics, Antineoplastic↗

PubMed2005

[Clinical outcome of the use of self-expandable metallic stents (SEMS) for palliation of patients with malignant upper GI obstruction caused by incurable gastric cancer].

Ten patients with malignant upper gastrointestinal obstruction caused by incurable gastric cancer underwent an endoscopic placement of self-expandable metallic stents for palliation. There were 6 male and 4 female patients aged 39-98 (median, 65.5). The site of obstruction was the cardia in 2, the pylorus in 4, the duodenum in 1, and surgical anastomosis in 3 patients. All the patients were unable to take food orally. Stent deployment was technically successful in all patients. After the stent insertion, 80% of patients resumed solid diet. The median survival time after the insertion was 129 days. The median length of home stay after the procedure was 54.5 days. Although chemotherapy was added in 5 patients after the insertion, there were no significant differences either in survival time or in home stay between the patients with and without chemotherapy. No procedure-related mortality was observed. Mediastinitis occurred in 1 patient, and the remaining 9 patients had no serious complications. Stent migration was observed in 2 patients, and stent occlusion due to tumor ingrowth occurred in 4 patients.

Adult↗

PubMed2005

[A case of successful resection for recurrent intraductal papillary mucinous adenocarcinoma].

Intraductal papillary-mucinous neoplasms (IPMN) of the pancreas have recently been defined and classified by the World Health Organization. In addition, many cases of IPMN continue to be recognized frequently. We report a case of a 65-year-old female who underwent surgical resection of the pancreas twice within a period of 6 months for primary and recurrent IPMN. We first performed distal pancreatectomy with splenectomy for IPMN in the pacreatic body. A histopathological study revealed invasive adenocarcinoma and the negative margin of the pancreatic duct. A cystic mass in the uncinate process of the gland was identified by CT scan 6 months after the initial surgery. Complete pancreaticoduodenectomy was performed. Recurrent IPMN consisted of adenosquamous cell carcinoma. She currently is alive without evidence of disease at 3 years from the second resection. Recurrent disease in the residual pancreas suggests that a long-term surveillance is critical.

Adenocarcinoma, Mucinous↗

PubMed2004

[A case of metastatic gastrointestinal stromal tumor developing a resistance to STI571 (imatinib mesylate)].

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract characterized by the expression of a receptor that activates tyrosine kinase called c-kit. Since malignant GISTs are resistant to conventional radiation therapy and chemotherapy, recurrent or malignant GIST has an extremely poor prognosis even after surgical resection. The development of a tyrosine kinase inhibitor, STI571 (imatinib mesylate, Glivec, Gleevec), which inhibits the BCR-ABL, PDGF-R alpha and c-kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastatic disease. We report a patient with GIST and diffused peritoneal metastases, whose tumor initially responded to STI571 and eventually became resistant. A 45-year-old woman underwent partial jejunostomy on September 3, 1998, under a diagnosis of submucosal tumor of the jejunum. Pathological examination of the primary tumor revealed a strong c-kit expression and GIST was diagnosed. The patient underwent an excision of peritoneal recurrences on October 31, 2000; April 17, 2001; and August 28, 2001. A treatment with STI571 (400 mg/day) was initiated on October 15, 2001, and she was free from peritoneal masses for 8 months after the fourth operation. However, the patient herself suspended the STI571 therapy for one month and multiple peritoneal metastases developed. Although the treatment with STI571 was restarted at 400 mg/day, the peritoneal masses did not respond this time. She died of liver, lung, and peritoneal metastases after the seventh cytoreductive operation on February 11, 2004. Several mechanisms of the resistance to STI571 have been identified. Amplification or an overexpression of KIT has been proposed to be involved in the resistance development. Several mutations of KIT were also correlated with the clinical outcome. Her tumors showed mutations in exons 9 or 11 of KIT, which had longer event-free and overall survival times than those tumors that had mutations of exons 13 or 17. In this case, an exon 11 mutation of KIT was initially noted. After the interruption of the treatment, an additional point mutation arose in exon 13 that caused a resistance to STI571. Currently STI571 is the first-line therapy for non-resectable GISTs, but a single-agent therapy often leads to tumor resistance. It is our hope that we will be able to design an alternative treatment to overcome such resistance.

Antineoplastic Agents↗

PubMed2004

[Evaluation of prophylactic hepatic arterial infusion chemotherapy after curative hepatectomy for metastatic colorectal cancer].

We evaluated the effect of hepatic arterial infusion (HAI) chemotherapy after curative resection of liver metastases of colorectal cancer. A total of 161 patients underwent curative resection of liver metastases. Among them, 50 patients underwent HAI of 5-FU, and 111 patients had no HAI therapy. The 50% disease-free survival time (50% DFS) was 758 days and 342 days in the HAI group and the non-HAI group (logrank test, p<0.01), and the 50% overall survival time (50% OS) was 978 days versus 730 days (p<0.05), respectively. Among the 71 patients with multiple resectable metastases (H2 or H3), the HAI group had a significantly superior 50% DFS. HAI therapy seems to be an effective form of adjuvant chemotherapy after hepatic resection of metastatic colorectal cancer.

Antineoplastic Agents↗

PubMed2004

[Effectiveness of chemoradiotherapy for three cases of squamous cell anal carcinoma].

We report three patients with squamous cell anal carcinoma who were treated by chemoradiotherapy. Case 1: A 62-year-old female with squamous cell anal carcinoma invading the vagina underwent a posterior pelvic exenteration. She had paraaortic lymph node metastases. She was treated by chemoradiotherapy with 5-FU/CDDP and external irradiation (50 Gy) as an adjuvant therapy, and survived for 5 years. Case 2: A 74-year-old female with anal squamous cell carcinoma Stage II was treated by chemoradiotherapy with tegafur/uracil, external irradiation (30 Gy) and interstitial irradiation (24 Gy). She is currently living without any signs of recurrence for 3 years and 8 months. Case 3: A 53-year-old female with anal squamous cell carcinoma Stage IIIa was treated by chemoradiotherapy using 5'-DFUR and external irradiation (66 Gy). She is currently living without any signs of recurrence for 1 year and 9 months. The prognosis of anal squamous cell carcinoma that received Cur B or C resection was extremely poor with a median survival time (MST) of 7 or 6 months. Chemoradiotherapy seems to be effective as the first line treatment.

Aged↗

PubMed2004

[A case of disease-free survival of liver and lung metastases of rectal cancer resected for a total of five times].

We report a case of disease-free survival of liver and lung metastases of rectal cancer resected for a total of five times. A 54-year-old female with metastatic liver and lung tumors of rectal cancer was admitted to our hospital. After a radical resection of the original tumor was performed at a previous hospital, liver and lung metastases had been confirmed in 1 year and 9 months and in 2 years and 2 months, respectively, and that both metastases had been resected as well. On admission to our hospital, computed tomography (CT) showed a liver metastasis of 3-cm in diameter in segment 3 and a lung metastasis of 2-cm in diameter in lingular segment. Two surgeries were performed to resect both of them. Because of a recurrent liver metastasis observed in segment 4, we performed a right hepatic lobectomy and partial duodenectomy 2 years later from the surgeries. After the fifth surgery for metastatic lesions, no sign of recurrence has been observed in 2 years and 11 months.

Disease-Free Survival↗

PubMed2004

[A case of long-term survival with recurrence leiomyosarcoma of the rectum treated by repeated local resections].

A 47-year-old man was admitted to our hospital for anal pain and diagnosed with submucosal tumor by digital examination. Transsacral resection was performed because the patient refused a stoma. Leiomyoma with highly malignant potential was histologically diagnosed. Surveillance was performed by computed tomography, magnetic resonance imaging and digital examination, but a correct diagnosis was difficult. Due to local tumor increases in the resected region, trans-anal resection was performed 2 years later at the time of local recurrence diagnosis. Over the last 10 years, a total of 8 local resections have been performed since the first surgery. No distant metastases have been confirmed to the patient without a stoma. It appears that a local resection of leimyosarcoma of the rectum with a close surveillance was effective.

Gastrointestinal Stromal Tumors↗

PubMed2003

[Combined determination of urine uracil levels and plasma 5-FU clearance for a simple order-made treatment with anticancer agents of FU derivative].

Individual differences exist in the pharmacodynamics of fluorouracil-derived anticancer agents, with circadian variability even in the same patient probably due to individual differences in the distribution of dihydrophrimidine dehydrogenase (DPD), a decomposing enzyme. Though DPD activity is usually determined in the liver or blood, a more simplified estimation of DPD activity has been recently attempted using urine uracil levels. However, because urine uracil level has the drawback of being easily affected by food ingestion or kidney function, in this study it was determined simultaneously with the determination of plasma 5-FU clearance after sustained instillation of 250 mg 5-FU, in order to estimate DPD activity more accurately. A correlation was observed between urine uracil levels and 5-FU clearance. In cases showing a baseline urine uracil level below 25.1 mumol/g. Creatinine, the blood concentration decreased due to large 5-FU clearance, with a tendency for diminished efficacy of FU-derived anticancer agents. In cases showing a baseline urine uracil level above 99.9 mumol/g. Creatinine, on the other hand, adverse reactions due to FU anticancer agents tended to become more serious. Since urine uracil level can be determined easily, it could be the first choice in screening to detect abnormal metabolism of fluorouracil-derived anticancer agents under present circumstances. By combining determination of urine uracil level with 5-FU clearance, it seems possible to predict adverse effects and the effective rate of these agents more accurately. Under existing circumstances, where genetic analysis remains unavailable as a general practice, the combined determination of urine uracil levels and plasma 5-FU clearance may be beneficial in developing order-made treatments in cancer chemotherapy.

Adult↗

PubMed2003

[Evaluation of arterial infusion chemotherapy for liver metastasis from gastric cancer].

We evaluated the effectiveness of arterial infusion chemotherapy for liver metastasis from gastric cancer. Nineteen patients (9 synchronous cases, 10 metachronous cases) were treated with hepatic arterial infusion chemotherapy (HAIC). The response rate was 26% (CR 3, PR 2, PD 14), and the median survival time was 357 days after the diagnosis of liver metastasis. The treatment was discontinued in 8 patients because of treatment associated complications and disease progression. Absence of extrahepatic lesion, response of HAIC, and hepatectomy did not improve the prognosis. The combination of systemic chemotherapy with HAIC tended to improve the prognosis. It may be necessary to reevaluate HAIC as a treatment modality for liver metastasis from gastric cancer.

Aged↗

PubMed2003

[A case of unresectable liver metastases from rectosigmoid colon cancer with survival for over 3 years after multidisciplinary treatment].

A 61-year-old man underwent curative low anterior resection for rectosigmoid colon cancer. Follow-up ultrasonography revealed unresectable multiple liver metastases at 10 months after surgery. Arterial infusion therapy with 5-fluorouracil (5-FU) was given at 1,500 mg every 2 weeks up to a total dose of 37.5 g, resulting in complete remission (CR) of the liver metastases. However, recurrence was seen 4 months after CR. Following partial hepatectomy and local ablation therapy, he received multidisciplinary treatment including local ablation therapy, arterial infusion of 5-FU and mitomycin C, and systemic chemotherapy with 5-FU/Leucovorin/CPT-11. The patient died of liver failure at 3 years and 7 months after the detection of hepatic metastases. If arterial infusion therapy achieves CR of unresectable hepatic metastases from colorectal cancer, the patient may survive for several years with multidisciplinary treatment including surgery, local ablation therapy, and systemic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

[Support of TS-1, 5-FU preparation containing potent DPD inhibitor by determination of urinary uracil/serum 5-FU clearance].

Though FU-derived anticancer agents are metabolized and detoxicated by dihydropyrimidine dehydrogenase (DPD), its wide distribution of activity is concerned primarily in the antitumor effects or side effects of 5-FU. In recent years, it has become possible to predict the metabolism of FU-derived anticancer agents by DPD activity through the determination of urinary uracil levels. In the present study, therefore, we examined whether or not urinary uracil levels could be used as a predictor for as certaining the efficacy and/or side effects of TS-1, which contains a potent DPD inhibitor. Consequently, the following relationship was revealed to exist between urinary uracil levels and clinical effects of TS-1: 1) The effect of TS-1 administration was generally good in patients whose uracil level was within the standard values with no presentation of serious side effects. 2) The administration of TS-1 was also useful even in patients whose uracil levels were below the standard value. 3) Though no side effects were observed when a conventional FU-derived anticancer agent was administered to patients showing an urinary uracil level below the standard value, some side effects appeared when TS-1 was administered. Under present circumstances where understanding of genome diagnosis and establishment of informed consent are rather difficult, this approach of predicting DPD activities through the determination of urinary uracil levels seems to be of help for deciding a therapeutic regimen based on the patient's constitutional features when a cancer chemotherapy with TS-1 is performed.

Adult↗

PubMed2002

Use of microsatellite analysis in young patients with colorectal cancer to identify those with hereditary nonpolyposis colorectal cancer.

BACKGROUND AND OBJECTIVES: The frequency of microsatellite instability (MSI) in young patients with colorectal cancer was evaluated, including reexamination of the medical and family history of each patient, and interviews with the patients to determine any possible new occurrence of hereditary nonpolyposis colorectal cancer (HNPCC) in the patients themselves or their family members. METHODS: Fifty-three young patients (younger than 40 years of age) with colorectal cancer were selected and investigated. DNA was extracted from paraffin sections and microsatellite analysis was performed. RESULTS: The frequency of MSI among the young patients with colorectal cancer was 50.9%, which was significantly higher than the rate of 12-21% noted in older patients with colorectal cancer (P < 0.001). For the 24 young patients with colorectal cancer who did not have MSI, only one case of HNPCC kindred and two cases with a family history of cancer were identified. In contrast, among the 20 young patients with colorectal cancer who had MSI, five cases of HNPCC kindred, two cases with metachronous patients with colorectal cancer, and three cases with a family history of cancer were identified. CONCLUSION: Our results suggest that a defect in the DNA mismatch repair system may play some role in carcinogenesis in young patients with colorectal cancer. Microsatellite analysis and subsequent interviews regarding medical and family history are useful tools for efficiently identifying possible cases of HNPCC among young patients with colorectal cancer.

Adult↗

PubMed2002

[Systemic chemotherapy for advanced colorectal cancer with liver metastasis].

We report the progress of systemic chemotherapy for advanced colorectal cancer with liver metastasis. It must be noted that the purpose of this treatment is to prolong the symptom-free period. Review of hepatic arterial infusion (HAI) compared with systemic chemotherapy for the treatment of unresectable liver metastases from colorectal cancer showed that was attained with HAI a much higher response rate and survival benefit than systemic chemotherapy. However, systemic chemotherapy has shown progress since that time. Regarding administration methods, continuous injection is better than bolus injection for 5-FU. New modulators of 5-FU have also became available, such as leucovorin, CPT-11, and I-OHP. Futhermore, many studies of 5-FU-based combination therapy have shown that the mean survival time (MST) and response rate (RR) are now close to those of HAI. Finally, the combination with HAI with systemic chemotherapy using CPT-11 resulted in the highest RR of 74%. Further trials of such combination therapy will be performed in the future.

Antineoplastic Agents↗