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Biomedical subjects

A Ohtsu

Publications and source records attributed to A Ohtsu.

At least 19 recordsLinked to original sources
PubMed2003

Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric cancer.

A dose-escalation study of cisplatin (CDDP) combined with S-1, a new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was given orally at 40 mg m(-2) b.i.d. for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg m(-2) depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg m(-2), because 33.3% of patients (2/6) developed DLTs, mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg m(-2). In the phase II portion, 19 patients including six patients of the RD phase I portion were evaluated. The median administered courses was four (range: 1-8). The incidences of severe (grades 3-4) haematological and nonhaematological toxicities were 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95% confidence interval: 54.9-90.6%), and the median survival day was 383. This regimen is considered to be active against AGC with acceptable toxicity.

Adult↗
PubMed2003

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus.

We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m(-2) 24 h(-1) on days 1-5 and 8-12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m(-2) on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P=0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P=0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.

Adult↗
PubMed2002

[Salvage operation for esophageal cancer after radical chemoradiotherapy].

We reviewed salvage surgery cases for esophageal cancer following radical chemoradiotherapy. From January 1998 through January 2001, 6 patients (4 men, 2 women) underwent salvage operation at our department. Mean age was 56 years (range: 46-66). According to the Japanese Society for Esophageal Diseases localization schema, there was one case in the upper third of the thoracic esophagus, 3 cases in the middle third and 2 cases in the lower third. The histology was squamous cell carcinoma in all cases. Our radical chemoradiotherapy regimen for esophageal cancer was fluorouracil (5-FU) 400 mg/m2/24 hours i.v. on days 1 to 5 and 8 to 12, cisplatin (CDDP) 40 mg/m2/2 hours i.v. on days 1 and 8, and concurrent radiation therapy (2 Gy/day on days 1 to 5, 8 to 12 and 15 to 19). This regimen was repeated in 5 weeks, followed by 5-FU 800 mg/m2/24 hours i.v. on days 1 to 5 and CDDP 80 mg/m2/2 hours i.v. on day 1, which was repeated in 4 weeks. After these chemoradiotherapy, patients who were confirmed to have local recurrence or esophagobronchial fistula underwent salvage operation. Postoperative complications were anastomosis leakage in 1 patient, and anastomosis stenosis in 2 and esophagobronchial fistula in 1. Although no postoperative hospitalized death occurred, 1 patient died because of empyema 3 months after salvage operation. Another patient died due to respiratory failure 15 months later. The salvage operation outcomes are not acceptable. Salvage procedure and indication for salvage intervention need to be changed.

Aged↗
PubMed2001

Combination chemotherapy of irinotecan plus cisplatin for advanced gastric cancer: efficacy and feasibility in clinical practice.

BACKGROUND: A previous phase II study showed that a combination of irinotecan (CPT-11) with cisplatin (CDDP) was effective for advanced gastric cancers, but was associated with substantial neutropenia and diarrhea. The aim of this retrospective study was to evaluate the efficacy and feasibility of the combination in clinical practice. METHODS: The subjects comprised 65 patients with advanced gastric cancer treated with CPT-11 (70mg/m2, day 1, day 15) and CDDP (80mg/m2, day 1) as first-line chemotherapy between April 1993 and March 1999. Patient backgrounds, response rates, response durations, times to progression, and survival rates were investigated retrospectively. RESULTS: The overall response rate and the response rates for measurable metastatic lesions and primary sites were 43% (28/65), 48% (31/64), and 24% (10/42). Leucopenia of grade 4 and diarrhea of grade 3 or 4 were observed in 6 (9%) and 5 (8%) patients, respectively. Among the 19 patients with peritoneal metastasis, leucopenia of grade 4 and diarrhea of grade 3 or 4 were observed in only 1 of the 18 patients who received sufficient oral intake (6%). There were no treatment-related or early deaths within 30 days from the last treatment day. The median survival times of all patients, patients with an intestinal type of adenocarcinoma, and patients with a diffuse type were 365, 472, and 291 days, respectively. Multivariate analysis showed that the histological type of cancer was a significant independent prognostic factor (P = 0.0169). CONCLUSION: This retrospective study confirmed the efficacy and feasibility of this combination therapy in clinical practice.

Adenocarcinoma↗
PubMed2001

Macroscopic typing with wall stricture sign may reflect tumor behaviors of advanced colorectal cancers.

No appropriate macroscopic classification of advanced colorectal cancers (A-CRC) is available for assessing their tumor behavior. In the present study, A-CRC were classified macroscopically as either stricture or nonstricture type, and the differences in clinicopathological features, mode of recurrence, and prognosis between the two types were investigated. The subjects were 166 patients with A-CRC invading beyond the muscular layer who had undergone curative surgical resection. Fresh resected specimens from these patients were used for the study. The A-CRC were classified as of stricture or nonstricture type according to whether or not they showed marked fold convergence and/or stricture of the intestinal tract (more than 30% wall shrinkage) that had the appearance of a "bow tie". Of the 166 A-CRC, 47 (28%) were classified as stricture type. This type was significantly more frequent in the colon (37%; 37/101) than in the rectum (15%; 10/65) (P = 0.003). The stricture type was more frequently associated with an abundance of fibrosis than the nonstricture type (76%; 28/37 vs 39%; 25/64 in colon; P < 0.001; 100%, 10/10 vs 42%, 23/55 in rectum; P < 0.001). The recurrence rate was also higher in the stricture type than in the non-stricture type in both the colon (51%, 19/37 vs 17%, 11/64; P = 0.003) and rectum (80%, 8/10 vs 38%, 21/55; P = 0.01). The time to recurrence was significantly shorter for the stricture type in both the colon (P < 0.001) and rectum (P = 0.02). These results indicate that the macroscopic typing of A-CRC according to the presence or absence of wall stricture sign may reflect their tumor behavior, although this behavior appears to be complex and related to tumor progression. This classification could be important clinically to assess tumor behavior in a simple way.

Aged↗
PubMed2001

Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer.

BACKGROUND: The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. METHODS: Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2, day 15), repeated at a 28-day interval, and followed by radical surgery. RESULTS: A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. CONCLUSIONS: Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate.

Adenocarcinoma, Scirrhous↗
PubMed2001

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study.

BACKGROUND: Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. METHODS: This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m2, given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m2. Leucovorin 10mg/m2 was administered six times, every 6h, starting 24h after MTX administration. RESULTS: Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. CONCLUSIONS: This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer.

Adult↗
PubMed2001

Phase II trial of paclitaxel by three-hour infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity reactions.

PURPOSE: To determine the antitumor activity and toxicity of paclitaxel administered as a three-hour infusion and to estimate the incidence of hypersensitivity reactions using a short-course prophylaxis regimen in patients with advanced gastric cancer. PATIENTS AND METHODS: Sixty patients with advanced measurable gastric cancer and performance status 0 to 2, who had received at most one prior chemotherapy regimen, were treated with paclitaxel 210 mg/m2 over three hours following a short-course premedication with dexamethasone, diphenhydramine and ranitidine administered 30 min prior to the delivery of paclitaxel. Cycles were repeated every three weeks. Twenty-six patients (43%) had received prior chemotherapy for metastatic disease and six patients had received adjuvant chemotherapy. The response rate to prior chemotherapy was 50% (13 of 26). RESULTS: Objective responses were observed in 14 of 60 patients (23%; 95% confidence interval (95% CI): 13%-36%). Six of twenty-eight (21%) patients with no prior chemotherapy and 7 of 26 (27%) previously treated patients for metastatic disease developed a PR. There were no complete responses. The median duration of response was 152 days. The study treatment was well tolerated. Twenty-two of sixty patients (37%) experienced grade 3 or 4 neutropenia, which was the most common and serious toxicity. Grade 3 peripheral neuropathy occurred in one patient. Hypersensitivity reactions were observed in only nine patients (15%) and were all grade 1. CONCLUSIONS: A three-hour infusion of paclitaxel is both an active and safe treatment for gastric cancer using the short-course premedication schedule. Paclitaxel appears to be non-cross resistant to other active agents for gastric cancer.

Adult↗
PubMed2001

Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy.

BACKGROUND: Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. METHODS: Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. RESULTS: The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 degrees C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. CONCLUSION: Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications.

Adult↗
PubMed2001

Retrospective study of hyponatremia in gastric cancer patients treated with a combination chemotherapy of 5-fluorouracil and cisplatin: a possible warning sign of severe hematological toxicities?

BACKGROUND: Some anti-neoplastic agents induce hyponatremia. The relationship between hyponatremia and other toxicities in gastric cancer patients treated with 5-fluorouracil and cisplatin (FP) was investigated retrospectively to clarify its clinical significance. METHODS: The subjects were 50 advanced gastric cancer patients treated with FP. Patients' performance status, oral intake, nausea/vomiting, diarrhea, fever, urine volume, presence of ascites or pleural effusion, laboratory data and administration of diuretics, corticosteroid and contents and volume of hydration before and during the first 5 days after chemotherapy were reviewed. RESULTS: The serum sodium level decreased after initiation of chemotherapy in all patients and the lowest level (nadir) was most frequently observed on day 8 (range, days 2-14), which preceded hematological toxicities. In 10 patients (20%) the nadir of serum sodium was lower than 125 mEq/l. We classified these 10 patients as a low-sodium group and the others into a normal-sodium group. Six (60%) and seven (70%) of the 10 patients in the low-sodium group had complications with grade 3 or 4 leukopenia and thrombocytopenia, whereas only one (3%) and two (5%) were seen in the normal-sodium group (p < 0.0001). Stomatitis and diarrhea were also slightly more severe in the former than the latter group. With respect to sensitivity and probability, receiver operating characteristic curves showed the nadir ((> or = ) or <125 mEq/l) of the serum sodium level was the best marker for both leukopenia and thrombocytopenia. CONCLUSION: Hyponatremia after initiation of chemotherapy with FP may be a warning sign of subsequent severe hematological toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Discrepancies between the gene expression, protein expression, and enzymatic activity of thymidylate synthase and dihydropyrimidine dehydrogenase in human gastrointestinal cancers and adjacent normal mucosa.

The relationships between gene expression, protein expression, and enzymatic activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have not been clarified in tumor and non-tumor tissues of human. In this study, we compared three different parameters by evaluating TS and DPD levels, mRNA expression assessed by RT-PCR, protein expression evaluated by immunohistochemical examination, and enzymatic activity measured by biochemical assay, in the tumor tissue and adjacent normal mucosa of 43 patients with gastrointestinal cancer. TS enzymatic activity in the tumor tissue was significantly higher than in normal tissue in both the stomach (median activity: 81.0 and 38.0 pmol/mg protein, respectively, p=0.012) and the colorectum (49.8 and 30.8, respectively, p=0.023). Similarly, TS mRNA expression in the tumor tissue was significantly higher than in normal tissue in both the stomach (median TS/GAPDH ratio: 6.0 and 2.0, respectively, p=0.009) and the colorectum (3.20 and 0.91, respectively, p=0.001). But no significant differences in DPD activity were observed between the tumor and normal tissue in either stomach (median activity: 41.3 and 41.6 pmol/min/mg protein, respectively) or colorectum (34.9 and 49.0, respectively). On the other hand, DPD mRNA levels in normal tissue were significantly higher than in tumor tissue only in the colorectum (DPD/GAPDH ratio: 0.83 and 0.20, respectively, p=0.003). No linear relationships were found between the enzymatic activity and mRNA expression of TS or DPD either in tumor or normal tissue. Nor were any correlations found between protein expression and either mRNA expression or enzymatic activity for either TS or DPD. These results suggest that tissue TS and DPD levels may vary with differences in the methods used to measure them. These discrepancies must be taken into account when interpreting correlation between TS and DPD levels and clinical outcome.

Aged↗
PubMed2001

Routine endoscopy using electronic endoscopes for gastric cancer diagnosis: retrospective study of inconsistencies between endoscopic and biopsy diagnoses.

To clarify the actual conditions and problems encountered in the diagnosis of gastric cancer during routine endoscopic examinations using electronic endoscopes, a retrospective study of cases that had shown inconsistencies between the endoscopic and biopsy diagnoses was conducted. The subjects were 5,640 patients who had undergone gastric biopsies. They were selected from among 18,248 patients in whom upper gastrointestinal endoscopy had been performed between July 1992 and July 1997 at the National Cancer Center Hospital East. The study was conducted focusing on macroscopic type, size, location, and pathologic findings of the lesions. Cases showing inconsistencies between the endoscopic and biopsy diagnoses comprised 2.7% of all biopsy cases (150 of 5,640). Most of these inconsistently diagnosed lesions were less than 20 mm in diameter. The frequency of inaccurate diagnosis for depressed lesions in the areas of upper and middle thirds of the stomach from the lesser curvature to the posterior wall was significantly higher in the inconsistent group, compared with the accurate diagnoses from the control group. In diagnostic reviews of depressed lesions, 46.0% (46 of 100) were diagnosed accurately, but cases with fewer malignant indices were recognized. These results indicate that diagnostic accuracy must be enhanced through objective biopsy-implementation standards and the use of image processing in using diagnostic methods that employ electronic endoscopes.

Adenoma↗
PubMed2000

Acetaldehyde production by non-pathogenic Neisseria in human oral microflora: implications for carcinogenesis in upper aerodigestive tract.

Many epidemiological studies have identified chronic alcohol consumption as a significant risk factor for cancer of the upper aerodigestive tract (UAT) in human. Although acetaldehyde, the first metabolite from ethanol by alcohol dehydrogenase (ADH), is regarded as a carcinogen, how systemic production of acetaldehyde particularly affects the UAT remains unclear. In our study, we searched for the regional source of acetaldehyde in UAT, especially the involvement of bacteria in the human normal oral microflora. Here we demonstrate that, among the bacterial species identified from the human oral cavity, genus Neisseria had extremely high ADH activity and produced significant amounts of acetaldehyde when cultured with medium containing ethanol in vitro. The ability to produce acetaldehyde was more than 100-fold higher than that produced by any other genera we studied. Furthermore, alcohol ingestion influences the bacterial composition of the oral microflora, resulting in an increased proportion of Neisseria. Although Neisseria present in normal oral microflora is generally non-pathogenic, these findings suggest that this microbe can be a regional source of carcinogenic acetaldehyde and thus potentially play an important role in alcohol-related carcinogenesis in human UAT.

Acetaldehyde↗
PubMed2000

Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group.

This study set out to evaluate, in patients with metastatic colorectal carcinoma, the efficacy and toxicity of S-1, which contains tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate, based on a biochemical modulation of 5-fluorouracil (5-FU) targeted at inhibition of dihydropyrimidine dehydrogenase (DPD). Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled into the study. None of the patients had received prior chemotherapy except for adjuvant setting. S-1 was administered orally twice daily at a standard dose of 80 mg m(-2) day(-1) for 28 days followed by a 14-day rest. This agent is continued until disease progression, unaccepted toxicity, or patient refusal. Twenty-two (35%) of the 62 eligible patients achieved PR with a 95% confidence interval of 25-48%. Five of the 10 patients with a history of adjuvant chemotherapy achieved partial remission. The median survival time was 12 months. Major adverse reactions included myelosuppressive and gastrointestinal toxicities, though their incidence of grade 3 or 4 being 13% in neutropenia and less than 10% in the others. None of the 53 patients treated as outpatients required hospitalization due to adverse reactions: These results suggest that S-1 achieves similar responses to those of infusional 5-FU plus leucovorin and shows the potential of another biochemical modulation with easily manageable toxicity.

Administration, Oral↗
PubMed2000

Recurrence after endoscopic mucosal resection for superficial esophageal cancer.

BACKGROUND AND STUDY AIMS: We present the results of endoscopic mucosal resection (EMR) for superficial esophageal cancer in patients treated at the National Cancer Center Hospital East since March 1993, and discuss the factors involved in local recurrence. PATIENTS AND METHODS: The study consisted of 51 patients with a total of 57 superficial esophageal cancers which were treated by EMR at the National Cancer Center Hospital East between March 1993 and March 1998. EMR was performed with a two-channel fiberscope or with the assistance of the endoscopic esophageal mucosal resection tube. Follow-up examinations by means of endoscopy with iodine staining and biopsy were repeated every 3-6 months. RESULTS: A total of 19 patients had double cancers; 12 had head and neck cancers (HNC), six had stomach cancers, and one had lung cancer. The patients with HNC tended to have multiple iodine-unstained areas, and multiple cancers in the esophagus. Local recurrence was detected in two out of five patients (40%) with multiple esophageal cancers, and in two out of 46 patients (4%) with solitary cancer (P=0.0433). There was no difference in the rate of local recurrence between patients with HNC and those without HNC. Three out of four patients with recurrent cancers were given additional treatment, EMR for two and radiotherapy alone for one; no further recurrence occurred except in the patient who underwent radiotherapy alone. CONCLUSIONS: Multiplicity of cancer is a risk factor for local recurrence. Appropriate additional treatment should be indicated for recurrent lesions.

Aged↗