[Informed consent in gastric cancer patients treated with chemotherapy].
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Humans↗
Biomedical subjects
A Ohtsu
Publications and source records attributed to A Ohtsu.
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↗
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↗
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↗
A case of inoperable esophageal carcinoma with hepatic and nodal metastases which showed a long-term survival after chemoradiotherapy including nedaplatin.
We report a case of metastatic esophageal carcinoma successfully treated with chemoradiotherapy. A 61-year-old man, diagnosed as suffering from advanced esophageal carcinoma with liver and lymph node metastases, was treated with a combination of nedaplatin (90 mg/m2/day, 1 h drip infusion, day 1), 5-fluorouracil (800 mg/m2/day, continuous infusion, days 1-5), and radiotherapy (2 Gy/day, days 1-5, 8-12 and 15-19). The cycle was repeated twice every 5 weeks from July 2, 1997. He achieved a complete response 1 month after finishing two courses of chemoradiotherapy followed by an additional three courses of chemotherapy without radiation. Seven months after the completion of radiotherapy, pericardial effusion with negative cytology was recognized. The effusion was treated by pericardiocentesis and drainage for several days. After drainage, the effusion could be easily managed with diuretics. This patient is still alive with no evidence of disease more than 2.5 years after the initiation of the treatment.
Antineoplastic Combined Chemotherapy Protocols↗
Verrucous carcinoma of the esophagus completely resected by endoscopy.
Verrucous carcinoma of the esophagus is a very rare esophageal cancer. We present a case of verrucous carcinoma of the esophagus, the 14th such case reported. In contrast to the previous cases, our patient had no symptoms and did not have a history of severe or repeated injury of the esophagus. The patient was completely resected by endoscopy and was well after 3 yr of follow-up, without recurrence of the disease.
Adult↗
Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.
BACKGROUND: Multiple occurrences of oesophageal dysplasia are frequently observed in head and neck cancer patients, and closely associated with alcohol consumption. Acetaldehyde, the first metabolite of ethanol, is thought to play an important role in the carcinogenesis of the upper aerodigestive tract. AIM: To investigate if genetic polymorphism in alcohol metabolising enzymes (ADH3, alcohol dehydrogenase 3; ALDH2, aldehyde dehydrogenase 2) is associated with oesophageal multiple dysplasia in head and neck cancer patients. METHODS: Thirty one consecutive patients with head and neck cancer were included in the study. Multiple oesophageal dysplasia was detected endoscopically as multiple Lugol voiding lesions (multiple LVL) using the Lugol dye staining method. The ADH3 and ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Among the 31 patients with head and neck cancer, 17 had multiple LVL. Multiple LVL were closely associated with a second primary oesophageal carcinoma in head and neck cancer patients (odds ratio 60.7, 95% CI 5.6-659). Furthermore, the mutant ALDH2 allele was significantly more prevalent in patients with multiple LVL (65% v 29%; p<0.05) whereas no difference was observed in ADH3 polymorphism. CONCLUSIONS: The mutant ALDH2 allele appears to be a risk indicator for multiple LVL in head and neck cancer patients. Accumulation of acetaldehyde due to low ALDH2 activity may play a critical role in cancerous changes throughout the mucosa in the upper aerodigestive tract.
Aged↗
Clinical implications of immunoreactivity of thymidylate synthase and dihydropyrimidine dehydrogenase in gastric cancer treated with oral fluoropyrimidine (S-1). Study Group of S-1 for Gastric Cancer.
Many reports have demonstrated that thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are biomarkers for the response and prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. A newly developed orally administered drug, fluoropyrimidine (S-1), has been developed with clinical efficacy when combined with an inhibitor of DPD. In this study, the relationship between immunoreactivity to TS and DPD in biopsy specimens and the effects of chemotherapy was investigated in 41 patients treated with S-1 therapy for advanced gastric cancer. Response rates were 54% (13/24) in TS(+) and 53% (9/17) in TS(-) patients (p=0.938), and those of DPD(+) and (-) patients were 61% (11/18) and 48% (11/23) (p=0.397), respectively. The median survival time of all the subjects was 253 days. There was no significant difference in median survival time between TS(+) patients (284 days) and (-) patients (189 days: p=0.670). The 18 DPD(+) patients had median survival times slightly longer (338 days) than the 23 patients with DPD(-) (207 days: p=0.206). This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status. Further studies are needed to confirm these results with larger numbers of patients.
Adult↗
New drugs for colorectal cancer based on Japanese experience.
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Antineoplastic Agents↗
[Correlation between response and survival].
The true endpoints of cancer chemotherapy have to be prolongation of survival, palliation of symptoms, or improvement of quality of life in cancer patients, while the response rate is considered to be a surrogate endpoint. When conducting a phase III trial, not only the response rate but also data on survivals in the phase II study should be taken into consideration. New response evaluation criteria and various objective markers in analyzing survival have been developed recently. Our data on chemotherapy for gastrointestinal malignancies reveal correlations between CR cases and survival prolongation among esophageal cancer patients treated with chemoradiotherapy, and between responder and survival prolongation in gastric cancer patients treated with chemotherapy. A review of the literature might reveal a correlation between response and survival prolongation in colorectal chemotherapy patients, though our data did not support such a correlation. At present, it is necessary to recognize that "evidence" should be based on the results of randomized phase III trials with large sample sizes and good quality assurance other than the response rates in phase II trials.
Antineoplastic Agents↗
[Concurrent chemoradiotherapy for T4 and/or M1 LYM squamous cell carcinoma of the esophagus].
A phase II study was conducted to investigate the efficacy and feasibility of chemoradiotherapy for locally advanced carcinoma of the esophagus. Fifty-four patients with clinical T4 and/or M1 LYM squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusions of fluorouracil 400 mg/m2/24 hours on days 1 to 5 and 8 to 12, 2-hour infusions of cisplatin 40 mg/m2 on days 1 and 8, and concurrent radiotherapy 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/m2/24 hours for 5 days) and cisplatin (80 mg/m2 on day 1). There were 36 patients with T4 disease and 33 with M1 LYM. Forty-nine patients (91%) completed 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 leukopenia 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%. Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.
Adult↗
[Latest progress on chemotherapy for advanced gastric cancer].
Although recent phase II studies have demonstrated high antitumor activity in the treatment of advanced gastric cancer, no significant survival benefit has been clearly demonstrated yet, when compared with 5-FU alone. More recently, a number of new agents including irinotecan and S-1 have demonstrated significant activity against gastric cancer as single agent or in combination with other chemotherapeutic agents. A phase III trial of 5-FU alone versus irinotecan plus cisplatin versus S-1 alone in advanced gastric cancer patients will be initiated in Japan Clinical Oncology Group (JCOG) within a few months. These new regimens have a potential becoming a new standard chemotherapy for the treatment of gastric cancer. The patients with peritoneal dissemination has usually not yet evaluated and explored from clinical study because of risk of toxicity and having no measurable disease. A next randomized phase III trial comparing 5-FU alone with sequential methotrexate and 5-fluorouracil in patients with peritoneal metastasis will be initiated in JCOG next year. The development of molecular biology has demonstrated the molecular mechanisms of chemoresistance or chemosensitivity, as well as a number of molecular targets against cancer cells. To date, many molecular targeted agents are being evaluated in various stages of clinical testing. These advances may provide a possibility of tailor made treatment.
Antimetabolites, Antineoplastic↗
Concurrent chemoradiotherapy for esophageal carcinoma patients with malignant fistulae.
BACKGROUND: It remains controversial whether chemotherapy and/or radiotherapy are/is contraindicated for esophageal carcinoma patients with malignant fistulae. In some case reports, closure of fistulae by chemotherapy or radiotherapy has been reported. The current study investigated chemoradiotherapy for these patients using various primary treatments to manage the pulmonary complications. The aim of this study was to evaluate the efficacy and feasibility of chemoradiotherapy for patients with locally advanced esophageal carcinoma with malignant fistulae. METHODS: Patients with endoscopically or radiologically confirmed fistulae were treated with concomitant chemoradiotherapy. Closure of fistulae was assessed by esophagography or endoscopy. Oral food intake also was assessed before and after treatment. RESULTS: Of 202 esophageal carcinoma patients treated at National Cancer Center Hospital East between July 1992 and May 1998, 24 patients (11.9%) developed malignant fistulae. Twelve patients developed fistulae before treatment and the remaining patients developed fistulae during treatment. Closure of the fistulae after chemoradiotherapy was observed in 17 of these patients (70.8%), and 16 of these 17 patients (94.1%) had oral alimentation restored after successful treatment. The median survival time from the diagnosis of the fistula for all patients with fistulae was 198 days; in the patients whose fistulae were present before chemoradiotherapy, the median survival time was 238 days. CONCLUSIONS: These results suggest that the presence of malignant fistulae does not contraindicate chemoradiotherapy. Once the inflammation due to the fistula has been controlled, chemoradiotherapy should be utilized because it may provide the best chance for survival and palliation of severe dysphagia.
Adult↗
The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging.
BACKGROUND AND STUDY AIMS: The reason for the difference in fluorescence between normal and diseased tissues (carcinoma and adenoma) in the colon observed on autofluorescence endoscopy is unclear, flavins, NADPH and collagen being regarded as possible major sources of fluorescence. The purpose of this study was to identify the reason for this difference in fluorescence. PATIENTS AND METHODS: Samples of human colonic tissues (adenoma: n = 6, cancer: n = 11, normal: n = 11) were obtained from resected specimens. The flavin content of human colonic tissue was measured by high performance liquid chromatography. Fluorescence microscopy under blue light excitation (400-440 nm) was performed using frozen sections of normal, adenomatous and cancerous tissues, and examining them for the presence and characteristics of fluorescence. RESULTS: The flavin content of normal and diseased tissue was not significantly different. Fluorescence microscopy of normal colonic tissue revealed strong fluorescence in the submucosal layer, which corresponded to collagen. Tissue fluorescence did not decrease in reducing agent or acid solution. No difference in fluorescence was detected in normal mucosa, adenoma or cancerous tissue on fluorescence microscopy. These findings indicate that flavins and NADPH do not affect tissue fluorescence, and that submucosal collagen is the main source of tissue fluorescence in the colon. CONCLUSION: The reason for the decreased fluorescence in diseased tissues appears to be a decrease in collagen fluorescence due to the screening effect of mucosal thickening or replacement of submucosa by cancer cells.
Adenoma↗
Clinical significance of magnetic resonance cholangiopancreatography for the diagnosis of cystic tumor of the pancreas compared with endoscopic retrograde cholangiopancreatography and computed tomography.
BACKGROUND: Cystic tumor of the pancreas has been investigated by a variety of imaging techniques. Magnetic resonance cholangiopancreatography (MRCP) is being widely used as a non-invasive diagnostic modality for investigation of the biliary tree and pancreatic duct system. The purpose of this study was to compare MRCP images with those of endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) in order to clarify the diagnostic efficacy of MRCP for cystic tumor of the pancreas. METHODS: We retrospectively studied 15 patients with cystic tumor of the pancreas that had been surgically resected and histopathologically confirmed. There were five cases of intraductal papillary adenocarcinoma, five of intraductal papillary adenoma, two of serous cyst adenoma, two of retention cyst associated with invasive ductal adenocarcinoma and one of solid cystic tumor. RESULTS: In all cases MRCP correctly identified the main pancreatic duct (MPD) and showed the entire cystic tumor and the communication between the tumor and the MPD. On the other hand, the detection rate by ERCP of the cystic tumor and the communication between the cystic tumor and the MPD was only 60%. Although the detection rates by CT for the septum and solid components inside the cystic tumor were 100 and 90.0%, respectively, those of MRCP for each were 58.3 and 20.0%. CONCLUSION: MRCP is capable of providing diagnostic information superior to ERCP for the diagnosis of cystic tumor of the pancreas. Although MRCP may provide complementary information about the whole lesion of interest, the characteristic internal features of cystic tumor of the pancrease should be carefully diagnosed in combination with CT.
Adenocarcinoma↗
Computed tomography under endoscopic retrograde pancreatography (ERP-CT) to investigate the drainage area of the pancreatic head.
The aim of this study was to evaluate the drainage area of the pancreatic head with computed tomography under endoscopic retrograde pancreatography (ERP-CT). ERP-CT was performed in 26 patients without lesions of the pancreatic head. By comparing ERP-CT images with ERP images, we evaluated the drainage area of the inferior branch of the pancreatic head. In 77% of these cases, the drainage function of Santorini's duct system (including the accessory papilla) was impaired. In 13 cases with the normal duct pattern, all inferior branches from Santorini's duct drained the anterior inferior area and all inferior branches from Wirsung's duct drained the posterior inferior area. In six cases with an ansa-type duct pattern, all inferior branches from Wirsung's duct drained the posterior inferior area, and inferior branches from Santorini's duct were divided into branches draining the anterior inferior area and branches draining the posterior inferior area. ERP-CT is a useful method for evaluating the three-dimensional anatomic variations of the pancreatic duct.
Aged↗
Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?
BACKGROUND: There is a difference in the location of colorectal mucosal lesions and invasive cancers. AIMS: To ascertain whether the location of colorectal neoplasms reflects the carcinogenesis pathway. METHODS: The subject material consisted of 4147 neoplastic lesions that had been resected endoscopically or surgically from 5025 patients. Mucosal lesions and submucosal cancers were classified into depressed and non-depressed types endoscopically or histologically. The relations between macroscopic type, size, histology, and location were investigated. RESULTS: (a) Non-depressed type. A total of 1774 of 3454 (51%) mucosal lesions were located in the right colon, 1212 (35%) in the left colon, and 468 (14%) in the rectum. The incidence of mucosal lesions larger than 10 mm was 10% (185/1774) in the right colon, 21% (254/1212) in the left colon, and 27% (127/468) in the rectum. The incidence of mucosal lesions with villous components was 2% (32/1774) in the right colon, 5% (63/1212) in the left colon, and 13% (62/468) in the rectum. The ratio of submucosal cancers to mucosal lesions was significantly higher in the rectum (0.064, 30/469) than in the left (0.034, 43/1279) or right (0.010, 18/1857) colon. (b) Depressed type. The incidences of depressed type mucosal lesions and submucosal cancers were 5% (83/1857) and 17% (3/18) in the right colon, 5% (67/1279) and 5% (2/43) in the left colon, and 0.2% (1/469) and 0% (0/30) in the rectum, respectively. CONCLUSION: There may be some mechanisms that promote the progression of mucosal lesions to invasive cancers in the left colon and rectum, whereas a de novo pathway from depressed type lesions may be implicated in some cancers of the right colon.
Adenoma↗
Phase II study of a combination of irinotecan and cisplatin against metastatic gastric cancer.
PURPOSE: A phase II study of a combination chemotherapy regimen of cisplatin (CDDP) and irinotecan (CPT-11) was conducted to assess its efficacy and feasibility in patients with metastatic gastric cancer. PATIENTS AND METHODS: Eligibility criteria included the following: (1) histologically proven gastric cancer with measurable metastatic lesions, (2) performance status of 2 or less, (3) age of 75 years or younger, (4) one or no prior chemotherapy regimens, (5) adequate bone marrow, liver, renal, and cardiac functions, and (6) written informed consent. The treatment consisted of CPT-11 (70 mg/m2) on day 1 and day 15 and CDDP (80 mg/m2) on day 1, repeated every 4 weeks. RESULTS: Forty-four patients were entered onto the study. The overall response rate was 48% (21 of 44 patients, 95% confidence interval [CI], 33% to 63%) and included one complete remission (2%). The response rate of the patients who had not received prior chemotherapy was 59% (17 of 29 patients, 95% CI, 39% to 77%). The median survival time was 272 days for all patients and 322 days for the 29 patients who had not received prior chemotherapy. Grade 4 neutropenia was observed in 25 patients (57%), and grade 3 or 4 diarrhea was observed in nine patients (20%). Other adverse reactions were mild. No treatment-related deaths occurred. CONCLUSION: This combination chemotherapy regimen is active and well tolerated. It may be an appropriate regimen for future phase III trials.
Adenocarcinoma↗