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Biomedical subjects

M Gignoux

Publications and source records attributed to M Gignoux.

At least 19 recordsLinked to original sources

Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus.

BACKGROUND: We conducted a multicenter, randomized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus. METHODS: The preoperative combined therapy consisted of two one-week courses; each involved radiotherapy, in a dose of 18.5 Gy delivered in five fractions of 3.7 Gy each, and 80 mg of cisplatin per square meter of body-surface area, administered 0 to 2 days before the first day of radiotherapy. The surgical plan included one-stage en bloc esophagectomy and proximal gastrectomy by the abdominal and right thoracic routes, to be performed immediately after randomization in the group assigned to surgery alone and two to four weeks after the completion of preoperative chemoradiotherapy in the group assigned to combined therapy. RESULTS: A total of 297 patients entered the study; 11 were found to be ineligible, and 4 were lost to follow-up. Of the remaining 282, 139 were assigned to surgery alone and 143 to combined therapy. After a median follow-up of 55.2 months, no significant difference in overall survival was observed; the median survival was 18.6 months for both groups. As compared with the group treated with surgery alone, the group treated preoperatively had longer disease-free survival (P=0.003), a longer interval free of local disease (P=0.01), a lower rate of cancer-related deaths (P=0.002), and a higher frequency of curative resection (P=0.017). However, there were more postoperative deaths (P=0.012) in the group treated preoperatively with chemoradiotherapy. Three prognostic factors were found to influence survival in a multivariate analysis: the disease stage, based on computed tomography; the location of the tumor; and whether the surgical resection was curative. CONCLUSIONS: In patients with squamous-cell esophageal cancer, preoperative chemoradiotherapy did not improve overall survival, but it did prolong disease-free survival and survival free of local disease.

Antineoplastic Agents

Oesophageal cancer in France: potential importance of hot alcoholic drinks.

In France, major geographic variation exists in the incidence of oesophageal cancer, the highest incidence being reported in Normandy and Brittany. The role of alcohol in the risk of oesophageal cancer is well established in Western countries. One possible explanation for geographical variation of incidence is that higher incidence of oesophageal cancer is due to specific local alcoholic beverages. The aim of this study was to determine whether different types of alcoholic beverages exert different effects on the risk of oesophageal cancer, and whether the variation of incidence in France is due to variation in local drinking behaviour. We conducted a multicentre case-control study in 3 regions of France (Normandy, Burgundy and Midi-Pyrenees), among which there is a 5-fold variation in incidence. We selected 208 cases and 399 controls, all males. During the interview, the subject's entire alcohol history was reconstituted, noting each type of alcoholic beverage consumed throughout life. The link between the risk of oesophageal cancer and alcohol varies greatly according to the type of alcoholic beverage, with aniseed aperitifs, hot spirits (especially hot Calvados) and beer carrying the highest risk. Consumption of hot Calvados appeared to explain about 2/3 of the inter-regional and urban/rural differences in incidence, whereas total alcohol intake explained less than 1/5. Even after adjustment for all other alcoholic beverages, consumption of hot calvados explained almost half of the peak in incidence of oesophageal cancer in the Northwest of France, as well as half of the urban/rural differences in incidence.

Aged

Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in different human ovarian carcinoma and malignant peritoneal mesothelioma cells.

An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or carboplatin and amphotericin B (AmB) was undertaken on a set of different ovarian carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB-CARP1) cell lines and ascitic cells freshly obtained from ovarian cancer patients so as to investigate the possibility of overcoming their resistance to platinum compounds. Growth-inhibition curves obtained 6 days after a 2-h period of exposure to the drugs showed that AmB at 5-10 mg/l allowed a 5- to 10-fold decrease in the 50% growth-inhibitory concentrations (IC50) of CDDP and carboplatin on either sensitive or resistant cells. Intracellular platinum assays with IGROVI cells showed that AmB acted by increasing dramatically the platinum uptake at a proportion that accounted for the increase in cytotoxicity. In the subline IGROVI-C10, a 10-fold resistant subline of IGROVI, AmB at 10 mg/l allowed recovery to the level of sensitivity seen in the parental cell line in the absence of AmB but not to the level observed in the presence of AmB. Acquisition of resistance mechanisms that are independent of the regulation of platinum uptake might be involved in this cell line. Thus, AmB might act by increasing the intracellular concentration of platinum without modifying the resistance mechanism involved downstream. However, in our models an increase in the intracellular level of platinum was always sufficient for the recovery of chemosensitivity in vitro. We also show that the phosphodiesterase inhibiting methylxanthines act synergistically with AmB. The latter drugs are weakly toxic and could also attenuate the nephrotoxicity of AmB.

Adenocarcinoma

Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption, mean intake and current and former consumption.

Numerous epidemiological studies have shown that alcohol and tobacco consumption are the main risk factors for oesophageal cancer in Western countries. In these studies, the consumption of both alcohol and tobacco has almost always been measured as current mean intake. The present case-control study investigates the association between alcohol and tobacco consumption and the risk of oesophageal cancer by assessing exposure as total lifetime intake, mean weekly intake, duration of consumption and former and current consumption. Between 1991 and 1994, 208 cases and 399 control subjects were selected from three French university hospitals (Caen, Dijon and Toulouse). Eligible cases were men aged less than 85 years admitted to one of these hospitals with histologically proven squamous cell carcinoma of the oesophagus. During the interview, complete tobacco and alcohol consumption histories were recorded. Our findings suggest that alcohol consumption and tobacco consumption influence the risk of oesophageal cancer in different ways. In the case of alcohol, the relationship between the odds ratio and mean weekly intake was linear, the risk depending solely on mean weekly intake, with former and current consumption having similar effects. With regard to tobacco, the relationship between the odds ratio and mean weekly intake was log-linear; the risk depended mainly on the duration of consumption and former consumption had a lesser effect than current consumption. Our study suggests that total lifetime intake is not a correct measure of exposure for either alcohol or tobacco: for a given lifetime consumption of tobacco, a moderate intake during a long period carries a higher risk than a high intake during a shorter period and, conversely, for a given lifetime consumption of alcohol, a high intake during a shorter period carries a higher risk than a moderate intake during a longer period. Our results confirm the very low risk associated with a low alcohol intake, even over long periods. In contrast, there is a steep increase in the risk associated with smoking at even low mean intakes if these are continued over long periods. Our findings also suggest that even heavy smokers may benefit from quitting.

Adolescent

Factors affecting compliance with colorectal cancer screening in France: differences between intention to participate and actual participation.

This study aimed to identify the social, cultural and psychological characteristics influencing behaviour in a cancer mass screening campaign in a French population. The intention to take a screening test and actually doing it was studied, in particular. A self reported-questionnaire was mailed in December 1992 to a random sample of people living in Caen (western France), and aged from 45-74 years. The sample was formed by random selection from electoral registers. The study was population based, in the Caen area, department of Calvados, France. The questionnaire comprised 26 open and close questions. Starting in February 1993, the occult blood screening test (haemoccult IIR) for colorectal cancer was offered by general practitioners (GPs), occupational health doctors and pharmacists in the Caen area to all those aged 45-74 years. From 1 February 1993 to 30 June 1994, the data on the mass screening campaign were centralized and the study population divided into those who took the screening test and those who did not. Of the 1,129 persons contacted, 645 (57.1%) returned the questionnaire. After exclusions, 585 questionnaires were used for analysis. The results show that whether a person will actually take a screening test cannot be predicted from their intention to do so. The sociodemographic and cultural characteristics influencing the intention to take the test differ from those influencing execution of the test. Among the variables tested here, the following four sociodemographic and cultural characteristics were independently predictive of actually taking the screening test for colorectal cancer: compliance with the health insurer's advice; low or medium sociodemographic status, living with a partner (or widowhood); and not knowing someone with cancer. The analysis of the quantitative and qualitative differences between the intention to take the test and actually doing it could elucidate the reasons underlying refusal. Poor screening compliance has multiple causes. A record of intention to take a screening test alone is not appropriate. This type of study should no longer be carried out to determine the mechanisms underlying behaviour towards secondary prevention.

Age Factors

Contribution of cervical ultrasound and ultrasound fine-needle aspiration biopsy to the staging of thoracic oesophageal carcinoma.

This study was performed to evaluate the use of cervical ultrasonography and ultrasound-guided fine-needle aspiration for pretherapeutic staging of oesophageal cancer. 50 patients with a thoracic-oesophageal cancer (upper third = 8, middle = 36, lower = 6), previously untreated, underwent cervical ultrasonography to detect supraclavicular lymph node metastases (LN). An ultrasound fine-needle aspiration biopsy was attempted in 12 cases of suspected LN. 26 patients were operated on, of which 13 had surgical exploration of the neck. All patients were followed after treatment with special attention to the supraclavicular area. 14 patients (28%) were ultrasonography positive, 5 of 8 in the upper third, 9 of 42 in the two other thirds. Of the 12 patients where a fine-needle biopsy was attempted, 9 showed neoplastic cells (75%). 5 patients had cervical metastatic LN at surgery, and 5 other patients demonstrated supraclavicular LN metastases during the follow-up. There was one false positive and six false negatives from cervical ultrasonography and two false negatives of UGFAB (ultrasound-guided fine-needle aspiration biopsy). The sensitivity and the specificity of the cervical ultrasonography were 68 and 97%, respectively. The pretherapeutic staging was modified: 7 patients initially stage II-III were regraded to stage IV. Cervical ultrasonography is a reliable method of assessment of supraclavicular LN in thoracic oesophageal carcinoma.

Biopsy, Needle

[Mass screening for colorectal cancer in France. Experience in 165,000 people in the department of Calvados].

OBJECTIVES: Screening for colorectal cancer is a major public health problem in France as in most developed countries. Several controlled trials are on-going in Europe. The aim of the study was to determine requirements for success of mass-screening for colorectal cancer in France. METHODS: A mass-screening program has been conducted between April 1991 and June 1994 in the department of Calvados for 164,364 people aged 45-74 years. The screening test was first proposed by general practitioners and occupational doctors during appointments. Secondly, a postal invitation to obtain the test, free of charge, by doctor or chemist, was sent. RESULTS: Global participation rate was 43.4%; 40.2% of tests were distributed during the first phase, 47.1% during the second phase and 12.7% were distributed by a private health institute. Participation was higher for females (47.1%) than males (39.2%) and for urban districts (46.5%) than rural districts (24.4%). In case of positive test, colonoscopy has been more frequently achieved in urban districts and when test has been distributed by a physician. Positivity rate was 2.8%. Positive predictive value was 8.0% for a cancer and 13.5% for an adenoma larger than 1 cm. Because both positivity rate and positive predictive value were higher for males than females and increased with age, rate of cancer or large adenoma screened was almost three times higher for males than females and markedly increased with age. CONCLUSIONS: In France, different recruitment methods have to be used to reach a satisfactory participation to a mass-screening campaign. Such a program requires involvement of general practitioners and close coordination between practitioners and health care insurance agencies.

Adenoma

[Contribution of cancer registries to the evaluation of cancer treatment: on the example of rectal cancer].

Improvement of health care policy requires an assessment of health care practices. In France, morbidity registries might be the best tool for such an assessment. This study shows how the treatment of rectal cancer can be assessed by French cancer registries. Two studies were conducted: a cross-sectional study on data from 7 cancer registries in 1990 and a longitudinal study on data from 2 digestive cancer registries (departments of Calvados and Côte d'Or) between 1978 and 1990. Finally, we conducted a regional audit concerning quality control in rectal resection for cancer in Lower Normandy between 1988 and 1993. In 1990 the mean resection rate was 77.8%. The sphincter preservation rate was also significantly increased to 53.9% in 1990. The use of adjuvant radiotherapy significantly increased between 1978 and 1990, more rapidly in university centres. In more recent years, the use of radiotherapy concerned 50% of resected rectal cancers with no differences between the various types of health care centres. However, in 1990, major geographical variations were observed for the use of adjuvant radiotherapy. Similar geographical variations were observed for the use of chemotherapy which did not increase with time. Rectal cancers were not diagnosed earlier from 1978 to 1990 in the two departments of Calvados and Côte d'Or. The use of reproducible quality criteria (length of distal excision, number of nodes examined and histological status of lateral margins) showed a global deficiency and marked variations between the various types of health care centres and levels of surgical training. The french network of French cancer registries (FRANCIM) provides accurate and reliable knowledge on medical practices, geographical variations, trends and quality control. The potential of cancer registries has not been clearly determined, although such information is required to plan health care policy.

Cross-Sectional Studies

Participants' characteristics in a French colorectal cancer mass screening campaign.

BACKGROUND: Participation by the target population is clearly a key element in the success of mass screening programs for colorectal cancer. In France, involvement of general practitioners in test distribution is essential to reach a satisfactory participation rate, but other forms of recruitment also have to be organized. The aim of this study was to determine the influence of demographic characteristics such as sex, age, and place of residence on the participation rate in a French mass screening according to different recruitment methods. METHODS: The Hemoccult IIR test was proposed in three consecutive ways: spontaneously by general practitioners and occupational doctors during appointments (phase 1), by postal invitation (phase 2), and finally by direct mailing of the test (phase 3). The target population consisted of 11,947 people between 45 and 74 years of age, living in a district of the French county of Calvados, between March 1991 and April 1993. RESULTS: The overall participation rate was 51.3%. Forty-nine percent of all the tests were done during phase 1, 31% during phase 2, and 20% during phase 3. The overall participation rate varied essentially according to the place of residence, from 65.5% in urban areas and 48.9% in intermediate areas to 27.7% in rural areas. The overall participation rate was also higher for females (57%) than for males (45%) and for those 60 years and older (53.9%) than for those below this age (49.2%). The proportion of tests done during phase 1 was lowest among the youngest and the oldest age groups (37.5% in the 45- to 49-year class and 45.2% in the 70- to 74-year class) and among people living in the rural environment (respectively 55.3%, 45.5%, and 35.9% in urban, intermediate, and rural areas). CONCLUSIONS: This study shows that place of residence strongly influences the global participation rate in mass screening for colorectal cancer in France, whereas sex and age have little influence. Recruitment methods complementary to distribution by general practitioners must be organized, especially for the youngest and oldest age groups (45-49 years and 70-74 years) and above all for people living in rural areas. The social, cultural, and psychological reasons for these differences remain to be investigated, with the aim of adapting mass screening strategies to the different population groups.

Aged

Prognostic factors in resectable gastric cancer: results of EORTC study no. 40813 on FAM adjuvant chemotherapy.

BACKGROUND: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. METHODS: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. RESULTS: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p = 0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage and "adequacy" of surgery. The multivariate analysis retained preoperative Hb level, T, N, and "adequacy" of surgery for time of survival; and T, N, "adequacy" of surgery and adjuvant chemotherapy for recurrence time. CONCLUSIONS: Disease stage is the most important prognostic factor. "Adequate" surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.

Adenocarcinoma

[Epidemiology and prognosis of gastric carcinomas at the province of Calvados. A 10-year study].

OBJECTIVES: The aim of this study was to determine trends in incidence and survival for gastric cancer in the department of Calvados over a ten-year period. METHODS: Between 1978 and 1987, 999 patients with gastric cancer were registered by the Registry of digestive tumours of Calvados. Standardized incidence rates were calculated for males and females and for each site of the tumour in two consecutive 5-year periods: period I: 1978-1982; period II: 1983-1987. Then prognostic factors were determined with univariate and multivariate methods. RESULTS: Global incidence rates were 15.7/100,000 in men, and 6.7/100,000 in women. Incidence rates of antropyloric carcinomas significantly decreased in women (period I: 3.6/100,000, period II: 2.1/100,000; P < 0.01). The incidence rate of cancer of the cardia did not change in men (period I: 2.7/100,000, period II: 2.9/100,000; NS) nor in women (period I: 0.6/100,000, period II: 0.3/100,000; NS). The ratio of early gastric cancer was respectively 8% and 9.2% (NS). The frequency of "signet ring" cells carcinomas increased from 20% during period I, to 34% during period II (P < 0.05). Overall 5-year survival rate was 16%; it was 26.3% after resection, without significant change between the two periods (27% versus 24.4%). The multivariate study in gastric cancer after resection pointed out 5 prognostic factors: age over 75 years, invaded resection margins, lymph node involvement, metastases and parietal wall involvement. CONCLUSIONS: The results of this epidemiologic study in the department of Calvados indicate that a) the global prognosis of gastric cancer was poor and did not change over the 10 years of the study; b) incidence rates of antropyloric carcinomas slightly decreased in women; c) rates of early gastric cancers did not increase.

Adenocarcinoma

[Objectives and means of screening of colorectal cancer].

Despite numerous publications on the subject, the debate over the merits of the various methods available for screening for colorectal cancer is continuing. Choice of the method depends on the patient being treated. In the present state of our knowledge, mass screening by Hemoccult, which is of low cost but of poor sensitivity and only fairly well accepted, cannot be used routinely but must be further evaluated and developed. In persons willing to undergo regular examinations, an annual or biannual Hemoccult examination associated with rectosigmoidoscopy every 5 years appears appropriate. In subjects having a familial history in first-degree relatives, colonoscopic examination every 5 years is adequate. Lastly, in patients with a personal history of cancer or adenoma, screening consists of colonoscopic follow-up adapted to the individual case.

Colonoscopy

[Antibiotic prophylaxis in surgery of the esophagus].

Surgery of oesophagus carcinoma is a long and major procedure. Perioperative radiochemotherapy is often required. Therefore many factors favour the occurrence of local and general postoperative infection, justifying an antibiotic prophylaxis directed against oesophageal and gastric flora. In case of oesophageal stenosis, the oesophageal floral often switches to the fecal type. Antimicrobial agents diffuse to the surgical site and reach there high concentrations for the time of surgery. We recommend, just prior the induction of anaesthesia the intravenous administration of a single dose of a third generation cephalosporin (ceftriaxone 2 g) and nitroimidazole (ornidazole 1 g). The long half-life of these agents allows sufficient concentrations at surgical site to be obtained and the efficacy of this regimen has been demonstrated. Selective decontamination of the digestive tract with systemic antibiotherapy is another approach for the prevention of postoperative complications of surgery of oesophagus carcinoma.

Anti-Bacterial Agents

Changing pattern of oesophageal cancer incidence in France.

BACKGROUND: Data from several Western countries suggest a rapid increase in the incidence of adenocarcinoma of the oesophagus, as well as variations in the sex ratio and the subsite distribution of oesophageal cancer. Although France has a high incidence rate of oesophageal cancer in males, no information was available on trends in its occurrence. The purpose of this study was to report changes in the pattern of oesophageal cancer incidence in three regions of France. METHODS: Data from the three population-based cancer registries of Calvados, Côte d'Or and Haute-Garonne were used to study time trends of oesophageal cancer by sex, age, subsite and histological type between 1978 and 1987. Annual incidence rates have been standardized by the direct method using the world standard population. To test the trend in cancer incidence, either an exponential curve of the form y = aekt was fitted to the annual incidence rates by means of a regression technique, or incidence rates were compared between two 5-year periods after age standardization by Mantel-Haenszel test. RESULTS: The mean annual variation of oesophageal cancer in males was -2.9% in Calvados (P < 0.05), + 0.5% in Côte d'Or (NS) and + 12.4% in Haute-Garonne (P < 0.05). The corresponding figures in females were + 7.9% (NS), + 19.6% (P < 0.05) and + 50.7% (NS). The significant variations in males (decrease in Calvados and increase in Haute-Garonne) were confined to the oldest age group (> or = 65 years). With regard to subsite, incidence in males increased in Haute-Garonne for the upper and the middle third, while there was a significant decrease in Calvados only for the middle third. For histological type, no increase in adenocarcinoma was noticed in males while there was a slight increase in incidence in females (statistically significant in Calvados). CONCLUSIONS: In France, the incidence of oesophageal cancer has decreased in the high-risk region (Calvados) in males, while there was a slight increase in the three studied regions in females. The important rise in incidence of oesophageal adenocarcinomas observed in some Western countries has yet to be seen in France.

Adenocarcinoma