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Biomedical subjects

A Ohtsu

Publications and source records attributed to A Ohtsu.

At least 55 records · Page 3Linked to original sources
PubMed1999

Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus.

PURPOSE: To investigate the efficacy and feasibility of concurrent chemoradiotherapy for locally advanced carcinoma of the esophagus. PATIENTS AND METHODS: Fifty-four patients with clinically T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusion of fluorouracil 400 mg/m(2)/24 hours on days 1 to 5 and 8 to 12, 2-hour infusion of cisplatin 40 mg/m(2) on days 1 and 8, and concurrent radiation therapy at a dose of 30 Gy in 15 fractions over 3 weeks. Filgrastim was prophylactically administered to 35 patients. This schedule was repeated twice every 5 weeks, for a total radiation dose of 60 Gy, followed by two courses of fluorouracil (800 mg/m(2)/24 hours for 5 days) and cisplatin (80 mg/m(2) on day 1). RESULTS: There were 21 patients with T4M0 disease, one with T2M1 LYM, 17 with T3M1 LYM, and 15 withT4M1 LYM. Forty-nine patients (91%) completed at least the chemoradiotherapy segment. The 18 patients (33%) who achieved a complete response included nine (25%) of the 36 with T4 disease and nine (50%) of the 18 with non-T4 disease. Major toxicities were leukocytopenia and esophagitis; there were four (7%) treatment-related deaths. Prophylactic filgrastim reduced the incidence of grade 3 or worse leukopenia without improving dose-intensity or response. With a median follow-up duration of 43 months, median survival time was 9 months. The 3-year survival rate was 23%. CONCLUSION: Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.

Adult↗
PubMed1998

Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). CDHP inhibits dihydropyrimidine dehydrogenase (DPD), an enzyme which degrades 5-FU, and maintains prolonged 5-FU concentrations in the blood and tumours. Oxo is distributed in the gastrointestinal tract at a high concentration after oral administration and alleviates gastrointestinal toxicity due to 5-FU. S-1 improves the tumour-selective toxicity of 5-FU by the actions of two modulators, CDHP and Oxo. We conducted a late phase II clinical trial of S-1 as an open trial in patients with advanced gastric cancer, to confirm its antitumour effect and adverse reactions. 51 patients with advanced gastric cancer were enrolled in the trial. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2/day. One course consisted of consecutive administration for 28 days and 14 days' rest. Administration was repeated over four courses. A complete response was obtained in 1 patient and partial responses in 24 patients, producing a response rate of 49% (25/51) (95% confidence interval (CI) 35.9-62.3%). The incidence of adverse reactions was 78% (40/51) and that of adverse reactions of grades 3 and 4 was 20%. Adverse reactions of grades 3 and 4 included a decrease in the haematocrit, leucopenia, granulocytopenia, diarrhoea, malaise and proteinuria. No serious unexpected adverse reactions were observed. In conclusion, S-1 was effective and well tolerated in patients with advanced gastric cancer.

Administration, Oral↗
PubMed1998

Growth patterns and genetic changes of colorectal carcinoma.

BACKGROUND: Recent Japanese studies have shown that histogenesis of small colorectal carcinomas can be divided into two groups: polypoid growth arising from polypoid neoplasia, and nonpolypoid growth arising from flat or depressed neoplasia. This classification should be verified with genetic as well as morphologic characteristics. SUBJECTS AND METHODS: In order to classify our subject into polypoid growth and nonpolypoid growth types both histologically and endoscopically, we selected 42 colorectal carcinomas < 2 cm in size (35 submucosal and seven more advanced). Clinicopathological findings, presence or absence of Ki-ras gene mutation and overexpression of p53 protein were compared between the two types. RESULTS: Histologically, the cases were divided into 27 of the polypoid growth type and 15 of the nonpolypoid growth type. None of the nonpolypoid growth cases contained adenomatous remnant, wheras this was found in 75% of the polypoid growth cases. No Ki-ras mutation was observed in any of the nonpolypoid growth cases, although it appeared in 44% of the polypoid growth cases. Regarding the overexpression of p53 protein, no significant difference was observed between the two types. The histological and the colonoscopic polypoid growth-nonpolypoid growth classifications correlated well with each other (agreement rate 98%), except for one lesion, which was classified as polypoid growth type endoscopically but as nonpolypoid growth type histologically. CONCLUSIONS: The histologically defined polypoid growth-nonpolypoid growth classification may indicate a difference in pathway of colorectal carcinogenesis. Also, colonoscopic polypoid growth-nonpolypoid growth classification is available for preoperative estimation of the genetic characteristics of small carcinomas.

Adenoma↗
PubMed1998

Diagnostic findings in endoscopic screening of superficial colorectal neoplasia: results from a prospective study.

BACKGROUND: A prospective study was carried out to clarify the efficacy of an endoscopic screening program for detecting superficial colorectal neoplasias by color changes such as faint redness or discoloration, which have been described as a key finding of these lesions in the literature. METHODS: We enrolled 716 consecutive cases in this study, but more than half of them did not reveal any abnormalities colonoscopically. RESULTS: Of the 716 cases, 48 (7%) were examined by magnifying colonoscopy with a dye spraying technique, following the detection of superficial color changes. Sixteen neoplastic lesions (in 16 cases) were detected among the 48 cases and the detection rate was calculated as 2.2% (16/716) in the total number of cases and 33% (16/48) in those showing color abnormalities. Histologically, all of the 16 were adenomas. These neoplastic lesions were most frequent (52%; 11/21) in those showing faint redness in an oval shape, whereas 14 (94%) of the 15 lesions were non-specific in those showing faint redness with unclear margin. CONCLUSIONS: These results may confirm the diagnostic utility of color abnormality, particularly faint redness in an oval shape, for endoscopic screening of superficial colorectal neoplasias.

Adenoma↗
PubMed1998

An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.

The purpose of this study was to evaluate the feasibility and efficacy of 3-hour infusional paclitaxel for the treatment of advanced gastric cancer with measurable metastatic diseases. Eligibility criteria included no more than one regimen of prior chemotherapy. Paclitaxel was administered as an intravenous infusion over 3 hours at a dose of 210 mg/m2 every 3 weeks. Premedication of dexamethazone, ranitidine, and diphenhydramine were given to all patients. Sixteen patients were registered in the study. One patient did not receive paclitaxel because of gastrointestinal bleeding before the initiation of drug's administration. Thirteen of the 15 patients had a prior history of chemotherapy. Although 10 patients (67%) developed grade 4 neutropenia, no serious infections occurred during the study. Nonhematologic toxicities were generally mild. Three (20%) patients who showed evidences of resistance to the previous intensive regimen achieved a partial response. In conclusion, a 3-hour infusion of paclitaxel is a safe and promising treatment for advanced gastric cancer. Paclitaxel appears to be non-cross resistant to other agents that are commonly used for gastric cancer. A large-scale phase II study is now underway.

Adult↗
PubMed1998

Peroral pancreatoscopy for the diagnosis of pancreatic diseases.

The efficacy associated with peroral pancreatoscopy to diagnose and differentiate pancreatic diseases is herein reviewed and clarified, and problems with this modality are discussed. Three types of pancreatoscopes are presently available: (a) a thin fiberscope with a diameter of 3.3 or 4.5 mm, which has an angulation system and a forceps channel; (b) an ultrathin pancreatoscope with a diameter of 0.75 or 0.8 mm, which can be inserted via an ordinary endoscopic retrograde cholangiopancreatography (ERCP) cannula without endoscopic sphincterotomy; and (c) an ultrathin pancreatoscope combined with a catheter that has an outer diameter of 1.67 mm. Peroral pancreatoscopy facilitates the detection of small lesions of the duct in malignancy or chronic pancreatitis. In particular, it is quite useful in differentiating pancreatic cancer from chronic pancreatitis in cases with local stenosis or elevated lesions of the main pancreatic duct. Among patients with a mucus-producing tumor of the pancreas, pancreatoscopy is also very useful, especially in determining lesion extent. Despite some unresolved problems, we predict that pancreatoscopy will retain a limited or specific and definite role in diagnostic and therapeutic endoscopy for pancreatic diseases.

Endoscopy, Digestive System↗
PubMed1998

[Current status of combined modality therapy for esophageal cancer: from the standpoint of medical oncology].

Surgery is considered to be a standard therapy for stage III or the earlier stage of esophageal cancer. However, the standard therapy is changing because of the recent advances in the non-surgical approach, especially chemoradiotherapy. Various obstacles remain to estimate the outcomes of combined modality therapy, while the consensus of the treatment for such stage excluding T4 diseases are as follows: 1) Concurrent chemoradiotherapy has a superior outcome to radiation alone in patients with squamous cell carcinoma. 2) Recent chemoradiotherapy without surgery achieves results comparable to surgery alone. 3) Preoperative chemoradiotherapy can achieve better results than surgery alone in patients with adenocarcinoma. 4) Preoperative chemotherapy is still experimental. Our preliminary results of chemoradiotherapy for esophageal cancer also showed comparable data to extended surgery in terms of survival. Some significant points to be elucidated regarding combined modalities in stage III or earlier are: 1) the comparison of definitive chemoradiotherapy with Japanese extended surgery, and 2) evaluation of efficacy of surgery after chemoradiotherapy. However, these studies require randomized trials comparing surgery with non-surgical treatment, which appears to present significant obstacles. Critical estimation for each study should be recommended based on accurate clinical staging, biological behavior, and intention-to-treat.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

Adult↗
PubMed1997

Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: The authors previously found specific mutations of the K-ras gene at codon 12 in the pancreatic juice of 67% of patients (6 of 9) with pancreatic ductal carcinoma, and the detection of these mutations was useful for diagnosis. This study was performed to detect and evaluate K-ras mutations in pancreatic juice from patients with intraductal papillary mucinous tumor of the pancreas, which is considered a low grade malignancy. The results were interpreted from the viewpoint of clinical significance. METHODS: K-ras mutations were examined using seminested polymerase chain reaction analysis combined with restriction enzyme digestion, followed by nonradioisotopic single strand DNA conformation polymorphism. RESULTS: Twelve of thirteen cases (92%) of intraductal papillary mucinous tumor of the pancreas, confirmed histologically (9 adenomas and 4 carcinomas), and 26 of 43 cases (60%) of ductal carcinoma showed specific K-ras gene mutations in the pancreatic juice. Furthermore, 4 of 22 patients (18%) with chronic pancreatitis, followed for more than 1 year without a sign of pancreatic tumor, showed K-ras mutations. In contrast, no mutations of the K-ras gene were detected in the pancreatic juice from 28 normal controls. CONCLUSIONS: K-ras mutations were found in the pancreatic juice of all but one patient with intraductal papillary mucinous tumor of the pancreas, but they were not useful for distinguishing carcinoma from adenoma. The authors concluded that K-ras mutations are not a specific marker for pancreatic neoplasms because similar mutations were detected in the pancreatic juice from patients with chronic pancreatitis. At the present time, the detection of K-ras mutations in pancreatic juice should be used clinically as an adjunct diagnostic modality for pancreatic diseases.

Adenocarcinoma, Mucinous↗
PubMed1997

Fluorescent diagnosis of experimental gastric cancer using a tumor-localizing photosensitizer.

To clarify the usefulness of fluorescent diagnosis for gastric cancer, we assessed the sensitivity and specificity of the tumor-localizing photochlorine photosensitizer ATX-S10 in combination with a new fluorescence diagnostic system. Into the submucosa of the stomachs of five rabbits, VX-2 tumor cells originating from squamous cell carcinoma were injected. After 3 weeks, three rabbits (Group I) were sacrificed 3 h after intravenous injection of ATX-S10 at a dose of 20 mg/kg, and their stomachs were observed by the Hg-lamp-induced fluorescence diagnostic system. The other two rabbits (Group II) were also sacrificed without injection of ATX-S10 and observed by the same method. In all cases in Groups I and II, gastric cancers that were invaded from the submucosa to the serosa were recognized histologically. The concentration of ATX-S10 examined by high-performance liquid chromatography (HPLC) in the gastric cancer was significantly higher than in the normal stomach. Fluorescent spectroscopy could detect 630 nm fluorescence selectively, consistent with the cancerous tissue of Group I. Moreover, fluorescent images were detected in only the exposed area of cancerous tissue and were undetected in the surrounding normal mucosa. Conversely, no fluorescent images could be detected in the stomachs of Group II. It is suggested that a fluorescence diagnostic system using ATX-S10 may become useful for the diagnosis of the existence or extension of carcinoma of the gastrointestinal tract.

Animals↗
PubMed1997

Clinicopathological studies on coexisting gastric malignant lymphoma and gastric adenocarcinoma: report of four cases and review of the Japanese literature.

Among 121 cases of primary gastric malignant lymphoma from 1962 to 1994 at the National Cancer Center Hospital, Tokyo, we found four cases (three males and one female) of adenocarcinoma coexisting in the stomach. The incidence of gastric malignant lymphoma together with gastric adenocarcinoma was 3.3%, suggesting that patients with lymphoma may have an increased incidence of gastric adenocarcinoma. A review of the Japanese literature revealed an additional 62 patients who developed coexisting gastric malignant lymphoma and adenocarcinoma. In the total series of 66 patients whose age and sex were recorded, there were 48 males with a mean age of 63.8 years and 18 females with a mean age of 58.6 years. Most adenocarcinomas were macroscopically early (76%) and of histologically differentiated type (75%). Conversely, 71% of lymphomas were of the advanced type macroscopically. The correct preoperative diagnoses were made in only 27% (16/59) of cases, when both tumors were located independently.

Adenocarcinoma↗
PubMed1997

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗
PubMed1997

A histological investigation on tissue responses to titanium implants in cortical bone of the rat femur.

Implant materials are placed under various sites-including cortical bone, spongy bone, and bone marrow-at the same time according to the depth at implantation. Although cortical bone is an important site for the prognosis of implantation, detailed reports on tissue responses to implantation have been meager. The present study aims to reveal tissue responses to pure titanium implantation in rat femoris cortical bone. The rats received titanium bars surgically in their femurs and were sacrificed 1 day to 40 weeks post-implantation. The prepared tissue specimens were processed for light and transmission electron microscopy (TEM). Further histochemical detections were performed. One day post-implantation, empty osteocytic lacunae indicating degeneration of osteocytes were found in pre-existing cortical bone around the implant. Such pre-existing bone was replaced by new bone, but remained in part even 40 weeks post-implantation. Light microscopy showed that direct contact between the implant and new bone was identified 12 weeks post-implantation. Chronological and ultrastructural observation showed that new bone deposition appeared to proceed toward the implant, and that the intervening layer at the interface was derived from the degenerated debris of multinucleated giant cells and/or osteoblasts. Furthermore, it seemed that the width of intervening layer varied in relation to the distance from the blood vessels. The cells showing tartrate resistant acid phosphatase activity possessed cytological features of osteoclasts under TEM; they were frequently observed in perivascular sites near the implants even after osseointegration, suggesting that bone remodeling took place steadily around the implant.

Acid Phosphatase↗
PubMed1996

The effect of pH, hydrogen peroxide and temperature on the stability of human monoclonal antibody.

The stability of human monoclonal antibody (C23), which is being developed as a passive immunotherapeutic agent against human cytomegalovirus, was investigated. C23 (about 2 mg ml-1) was incubated under sterile conditions for 14 days in buffers with different pH values (ranging from 4-10), in hydrogen peroxide solutions with different concentrations (0.01% or 0.1%), and in saline at 8 degrees C or 37 degrees C. Samples were collected on days 0, 3, 7 and 14, and various physicochemical or biological methods were used to determine the changes in in C23. These methods included turbidity (absorbance at 408 nm and transmittance at 580 nm), pH, size-exclusion high performance liquid chromatography (HPLC), hydroxyapatite HPLC, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and virus neutralization assay. Using these methods, the possible degradation processes of C23 were initially characterized. Deamidation, oxidation, fragmentation, covalent cross-links and aggregation were observed as major degradation routes. These results gave useful information for the manufacturing process and quality control of C23.

Antibodies, Monoclonal↗
PubMed1996

Diagnostic utility of endoscopic ultrasonography for preoperative rectal cancer staging estimation.

The preoperative staging accuracy of endoscopic ultrasonography (EUS) was assessed in 38 rectal cancer patients who underwent rectal EUS and curative surgery from July 1992 to September 1994. We used a GF-UM20 instrument with both 12- and 7.5-MHz transducers. Compared with the histological findings, the diagnostic accuracy rate for EUS was 76% (29/38) for the invasion depth and 85% (sensitivity) and 72% (specificity) for level one lymph node metastasis, resulting in an overall preoperative staging accuracy of 74% (28/38). The diagnostic accuracy of invasion depth was poor (only 45%: 5/11) in cases shown histologically to be a1 (tumor invasion through muscularis propria into parietal fat), but ranged from 90 to 100% when the a1 cases were excluded. The diagnostic accuracy for level one lymph node metastasis was proportional to the nodal size. The size of lymph nodes that had been diagnosed as metastatic and non-metastatic (P < 0.05) differed significantly. Eighteen (86%) of the 21 metastatic nodes with histologically massive invasion were detected preoperatively by EUS. Eight of the 11 undetected metastatic nodes were either less than 4 mm in diameter or showed only slight invasion. Most (81%) of the level one metastatic nodes larger than 5 mm were found. The worst preoperative staging diagnostic accuracy was for stage II cases (63%: 5/8), and in four of the 10 misdiagnosed cases, the stage was underestimated due to slight nodal invasion or skip metastasis (2 cases each). Although it was difficult to diagnose nodal metastasis correctly in these cases, preoperative staging using EUS was considered useful for diagnosing almost 80% of our rectal cancer cases.

Humans↗
PubMed1996

An early phase II study of etoposide (VP-16) in advanced gastric cancer.

An early phase II study was conducted to evaluate the anti-tumor effects and toxicity of etoposide in patients with unresectable or relapsed advanced gastric cancer. From April 1991 to December 1992, 13 patients were enrolled into this study; one was subsequently considered ineligible. Before enrollment, all the patients had been treated with chemotherapy which did not include etoposide. Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120 min for five consecutive days and was repeated every four weeks. Seven patients received one course of this therapy and the remaining five received two. No patient showed a complete or a partial response. No change and progressive disease were observed in three and nine patients, respectively. The clinical toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in 50, 42, and 42% of the patients, respectively. We conclude that this dose of etoposide administered according to the present schedule is ineffective in previously treated patients with advanced gastric cancer.

Adenocarcinoma↗