Encephalitozoon cuniculi (Microspora) genome: physical map and evidence for telomere-associated rDNA units on all chromosomes.

A restriction map of the 2.8-Mb genome of the unicellular eukaryote Encephalitozoon cuniculi (phylum Microspora), a mammal-infecting intracellular parasite, has been constructed using two restriction enzymes with 6 bp recognition sites (Bss HII and Mlu I). The fragments resulting from either single digestions of the whole molecular karyotype or double digestions of 11 individual chromosomes have been separated by two-dimensional pulsed field gel electrophoresis (2D-PFGE) procedures. The average distance between successive restriction sites is approximately 19 kb. The terminal regions of the chromosomes show a common pattern covering approximately 15 kb and including one 16S-23S rDNA unit. Results of hybridisation and molecular combing experiments indicate a palindromic-like orientation of the two subtelomeric rDNA copies on each chromosome. We have also located 67 DNA markers (clones from a partial E. cuniculi genomic library) by hybridisation to restriction fragments. Partial or complete sequencing has revealed homologies with known protein-coding genes for 32 of these clones. Evidence for two homologous chromosomes III, with a size difference (3 kb) related to a subtelomeric deletion/insertion event, argues for diploidy of E.cuniculi. The physical map should be useful for both the whole genome sequencing project and studies on genome plasticity of this widespread parasite.

In-gel DNA radiolabelling and two-dimensional pulsed field gel electrophoresis procedures suitable for fingerprinting and mapping small eukaryotic genomes.

A simple method for complete genome radiolabelling is described, involving long-wave UV exposure of agarose-embedded chromosomal DNA and [alpha-(32)P]dCTP incorporation mediated by the Klenow fragment. Experiments on the budding yeast genome show that the labelling procedure can be coupled with two new two-dimensional pulsed field gel electrophoresis (2D-PFGE) protocols of genome analysis: (i) the KARD (karyotype and restriction display)-PFGE which provides a complete view of the fragments resulting from a single restriction of the whole genome and (ii) the DDIC (double digestion of isolated chromosome)-PFGE which is the eukaryotic counterpart of complete/complete 2D-PFGE in bacterial genomics.

Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study.

OBJECTIVE: Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS: Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS: Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION: The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

Natural history of neck disease in patients with squamous cell carcinoma of oropharynx and pharyngolarynx.

Out of a series of 2040 patients referred to the Institut Curie with squamous cell carcinoma of oropharynx and pharyngolarynx, 1666 cases were evaluated on admission regarding the characteristic metastases patterns to their cervical lymph nodes. Incidence and topographic distribution of lymph nodes are correlated with the anatomic sites of primary lesions. Biological virulence of these tumors is emphasized since the overall incidence of positive neck nodes attains 63% (1048/1666) and advanced disease, stage IV in the UICC classification, 61%. Cervical status is also related to several characteristics of the primary: clinical staging and variety, and histopathological differentiation. Ipsilateral cervical involvement is characterized by the high incidence of metastases in the jugular chain for the whole series, in the submaxillary group for oropharyngeal carcinomas and in the spinal accessory chain for cancer of the pharyngolarynx (pyriform sinus and lateral epilarynx). Preliminary therapeutic implications are derived from this nodal distribution. Comparisons are established between the 1978 UICC and 1976 AJC classifications, showing a good correlation despite multiple differences in staging criteria. It is shown that assessment combining both the multiplicity and the volume of cervical metastases allows to evaluate more accurately the aggressiveness of the primary.

A study of the interaction of alcohol drinking and tobacco smoking among French cases of laryngeal cancer.

Laryngeal cancer represents an important cause of cancer in France, and the individual effects of alcohol and tobacco on this cancer site are well known. However the problem of the interaction between these agents is less extensively documented, and the role of the high consumptions of alcohol has not been studied frequently. A case-control analysis was undertaken to investigate the joint effect of alcohol and tobacco by comparing 197 glottic and 214 supraglottic cancer cases to 4135 controls representative of the French general population. Heavy drinkers were available from the two groups of cases, the highest alcohol category being equivalent to a consumption of more than 2 litres of wine per day. The relative risks estimated for heavy drinkers and smokers were high, and the results indicated an even stronger effect of alcohol drinking and tobacco smoking on the upper part of the laryngeal region. Additive and multiplicative models were fitted to the data. The multiplicative hypothesis was found to be the most appropriate, implying that the risks associated with alcohol and tobacco multiply when the exposures occur simultaneously. The public health implications of this result and the contribution of heavy drinkers and smokers to the frequency of upper respiratory and digestive tract cancers are discussed.

History of previous nasal diseases and sinonasal cancer: a case-control study.

A case-control study on cancer of the nose and paranasal sinuses, and several risk factors including previous nasal diseases and symptoms, was performed in France from January 1986 through February 1988. The frequency of previous nasal diseases and symptoms was analyzed by histologic type of cancer. Different results were observed for squamous cell carcinomas and adenocarcinomas. In men, there were statistically significant associations between squamous cell carcinomas and sinusitis, bleeding from the nose, polyps, rhinitis, and trauma to the nose; and between adenocarcinomas, bleeding from the nose, and rhinitis. In women, there was an association between squamous cell carcinomas and nasal polyps.

Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head and neck.

One hundred thirty-eight patients, who were followed for a minimum of 5 years, had either surgery and postoperative radiotherapy (48 patients) or radiotherapy only (90 patients) for metastatic epidermoid carcinoma in cervical nodes from an unknown head and neck primary. All received radiotherapy to the presumed occult sites. Forty-five percent presented with a single unilateral adenopathy. Those who were initially operable had a neck recurrence rate of 17% and a survival rate of 53%. Forty-three percent of initially inoperable patients recurred and only 25% survived. Patients with adenopathy which completely regressed or became resectable after irradiation had an 80% locoregional control. Only 4% developed an overt cancer at an occult site within 5 years.

Alcohol and tobacco consumption in cancer of the mouth, pharynx, and larynx: a study of 316 female patients.

Three hundred sixteen female patients with cancer of the larynx, pharynx, and mouth were examined and the following cancer sites were compared with respect to alcohol and tobacco consumption: oropharynx, hypopharynx, larynx, epilarynx, lip, and mouth. The mean daily tobacco consumption of smokers and ex-smokers was not significantly different between cancer locations; however, significant differences between cancer sites were observed with regard to the proportion of nonsmokers. The percentage of nonsmokers was the highest for cancer of the lips and the lowest for cancer of the epilarynx. Cancer locations differed significantly depending on daily alcohol consumption. Consumption was the lowest for patients with cancer of the lips. The percentage of nondrinkers was high for cancers of the lips and larynx and low for cancer of the epilarynx. Examination of the nonsmoking/nondrinking females (27.2%) did not reveal any features specific to this group, except that the patients were older.

Radiation treatment of lateral epilaryngeal cancer. Prognostic factors and results.

Treatment results of epilaryngeal cancer are rarely individualized in the world literature. For this purpose, we have reviewed the records of 167 patients with squamous cell carcinoma of the lateral epilarynx who received radical radiotherapy at the Institut Curie on a megavoltage unit, between 1959-1975. Two-thirds of the lesions were located at the junction of the ary- and pharyngo-epiglottic folds and lateral border of the epiglottis. Forty-four percent of patients had advanced primary lesions (T3, T4) and over 50% had palpable neck nodes at the time of presentation. The absolute survival for the entire patient population at 3 and 5 years was 44% and 32%. Local control for T1 and T2 tumors at 3 years was about 80%. Survival at 5 years for the N0 Stage patient was 40%, whereas it was about 20% for those with clinically palpable nodes. Patients with exophytic tumors and lesions which regressed completely within 8 weeks following irradiation had a significantly better 3-year survival and local control than those with nonexophytic tumors and with tumors which had incompletely regressed after irradiation. Radiotherapy remains the treatment of choice for the small tumors (T1, T2) but the association of radical surgery with pre- or postoperative radiotherapy should be considered for advanced disease.

[Clinical peculiarities of nasopharyngeal cancers]. / Particularités cliniques des cancers du nasopharynx

Nasopharyngeal carcinomas are very different from other malignancies of the upper digestive and respiratory tracts. Very uncommon in France, mostly undifferenciated, they occur in all decades, even in children or young adults, with a sex-ratio of 3/1, and without connection with alcohol and tobacco. Their insidious onset leads to the first manifestation as cervical metastasis, or evidence of intracranial involvment. The 5 years Survival rate is 30 p. 100: failures are local or distant metastases, principally in the skeleton. Destruction of the base of the skull and supraclavicular nodes yield poor results. Trials on systemic chemotherapy are in progress.

[Chemotherapy of carcinoma of the upper respiratory and digestive tract]. / Chimiothérapie des carcinomes des voies aéro-digestives supérieures.

New regimens of chemotherapy in previously untreated squamous cell head and neck carcinoma yielded a 60 per cent rate of regression in over 50 per cent of patients. Planned radical surgery may be delayed and curative irradiation is often preferred. However, many patients have been excluded for polychemotherapy because of poor general condition. The results of simultaneous perioperative chemotherapy and X-ray therapy are not well known. Adjuvant chemotherapy after initial treatment is difficult to apply and to appreciate for results. Chemotherapy of recurrences is disappointing, even if efficient. Randomised trials are necessary to improve our knowledge in this field.

[Quality of life in ENT cancers]. / Qualité de vie des cancéreux ORL.

Head and neck cancer carcinomas have poor prognosis and their treatment yield heavy sequellae. Specific psychological features enhance difficulties occurring in the improvement of quality of life during and after treatment. Physicians and nurses must inform both patient and his family before treatment. After treatment of advanced tumors, respiration, swallowing are often impaired and cosmetic results in face and neck may be poor. When possible, rehabilitation as acquiring oesophageal speech for laryngectomees improve quality of life. When palliative treatment is only possible, quality of life is deeply damaged: difficulty of medical care, lack of communication, worsening lead to loneliness and sometimes rejection.

[Development of pharyngo-laryngeal surgery after radiotherapy]. / Evolution de la chirurgie pharyngo-laryngée après radiothérapie.

Myo-cutaneous pedicled flap (MCF) had transformed technics and indications for salvage procedures after high doses of radiotherapy in laryngeal and hypopharyngeal carcinomas. Wide field total laryngectomies extended to oropharynx, skin, circular pharyngectomies extended to cervical oesophagus are possible with 3 times less carotid blow-up and rare fistulas. Radical neck dissection is currently performed in the same procedure without major healing problems. The feeding tube is often removed within a month. Systematic use of MCF in patients irradiated over 70 Gy may reduce the post-operative mortality and yield better survival rates, which at present 2 years after salvage surgery, are 36% in hypopharyngeal carcinomas (38/106) and 50% in laryngeal cancers (106/210).

[Carcinomas of the nasopharynx in adults]. / Carcinomes du rhinopharynx de l'adulte.

From 1959 through 1980, 139 MO adult patients (greater than 15 Y.) presenting with nasopharyngeal cancer were treated by definitive radiotherapy: 103 (74%) undifferentiated carcinomas and 36 (26%) squamous cell carcinomas. Chemotherapy was prescribed only in case of failure of treatment. Case distribution is the following according to UICC classification: stages I and II: 12%, stage III: 16%, stage IV: 72%. Survival rate is respectively 70%, 45%, 20%. The overall 3 and 5 year survival rate is 46% and 30%. Almost 80% of the failures occur by the end of the second year. Local control is 95% for T1-T2, 73% for T3 and around 50% for T4 cases. Isolated node failure occurs in 2% and distant metastases in 30%.

[Occupational cancers: notification, compensation and prevention]. / Cancers professionnels: connaissance, réparation et prévention.

Less than 140 occupational cancers (OC) are compensated every year in France although the incidence is estimated for at least 6,000 new cases, as estimated by the epidemiologists (4% of the mortality by cancers). This situation can be explained by different factors: few compensation claims by the patients or families, frequent lack of interest from medical doctors for relation between cancer and work, occurrence of the OC after retirement, difficulty to distinguish the role of occupational factors from individual comportmental factors in many OC (for ex. a lung cancer hitting a smoker). The consequences of such a situation are multiple: no compensation for more than 95% of patients or relatives, taking for granted that OC is a minor problem, insufficient prevention of the carcinogenic factors on the work place, prevention of cancers restricted to individual comportmental changes. Physicians working in cancerology units have to incite their patients in notifying the OC and help them in compensation claims. They have also to ask for epidemiologic and toxicologic research when clusters of OC are identified in a plant, in order to get better prevention, compensation and regulations.

[Carcinoma of the nasopharynx (cavum) : clinical and developmental aspects]. / Les carcinomes du nasopharynx (cavum): aspects cliniques et évolutifs

Between 1959 and 1974, two hundred and ninety six carcinomas of the nasopharynx were seen at the Institut Gustave-Roussy, in adults. 78% were in man. The most frequently encountered were undifferentiated or poorly differentiated forms, 76% of cases. 38% only of the patients had their birthplace in France. On the first examination 36% of the cases had a T4 tumour, 50% had fixed cervical lymph nodes and 77% had distant metastases. 30% of the cases could not be treated following a protocol attempting complete cure. Since 1970 the Iridium method of irradiation is not used in T1 and T2 cases and all were treated by high voltage methods with eventual complementary surgical treatment for persistent nodes. The survival rate at 5 years is 30% for the whole group and 37% for the determinated group. Failures were encountered by local recurrence present in 58% of those dying of the disease and distant metastases were found in 37%. 20% of the patients died from distant metastases without local and regional lymph node recurrences. Unfavourable prognostic factors are initial involvement in bone and the differentiated histological type. It was noteworthy that associated multiple cancers were rare.

[Chemotherapy of advanced head and neck cancer with a combination of bleomycin, vincristine, methotrexate and hydroxyuree or cis-dichloro-diamino-platinium. Analysis of local and general parameters of prognosis (author's transl)]. / Chimiothérapie des cancers épidermoïdes récidivés des voies aéro-digestives supérieures par une association de bléomycine, vincristine methotrexate et hydroxy-urée ou cis-diamino-dichloro-platinium. Analyse des paramètres généraux et locaux qui constituent le pronostic.

Sixty-six patients with advanced head and neck cancer 57 of whom had failed to respond to prior irradiation, were treated according to two protocols. Group I consisted of 41 patients in relapse who received a monthly combination of bleomycin, vincristin, methotrexate and hydroxyuera. The 16 patients (in relapse) of group II received a monthly combination of bleomycin, vincristin, methotrexate and cis-DDP. Nine patients in group III (patients never treated) received the same combination as in group II. Recurrences were local and/or regional in 37 cases out of 57. Before any chemotherapy, 62 p. 100 of the relapsing patients gave negative responses to delayed hypersensitivity skin tests to recall antigens. Fifty-one p. 100 showed evidence of a nutritional disturbance. Overall objective responses were 31 p. 100 (18/41) in group I and 43 p. 100 (7/16) in group II (this difference was not significant). In group III, 8 patients out of 9 were defined as objective responders. Overall mean survival in group I and II was 5.8 months and showed no difference between the two groups. Response rate and survival were dependent on skin test responses, nutritional status and sites of recurrence. Survival of patients with metastatic recurrence was significantly higher than survival in patients with local recurrence. Toxicity was essentially dependent upon local sequelae of prior irradiation. The results of this trial indicate that despite the effectiveness of such combinations of cytotoxic drugs, the indications for palliative chemotherapy must be discussed in the light of local and general prognostic parameters.

[Standards, options and recommendations (SOR) for clinical care of squamous cell carcinoma of the oropharynx. Groupe de travail SOR]. / Standards, Options et Recommandations pour la prise en charge des patients atteints de cancer épidermoïde de l'oropharynx.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of squamous carcinoma of the oropharynx. METHODS: Data have been identified by literature search using Medline (1991-1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for squamous cell carcinoma of the oropharynx management are that: 1) diagnosis and initial assessment should be based on appropriate clinical and radiological findings; 2) the therapeutic strategy is based on surgery, radiotherapy, bradytherapy and chemotherapy; 3) in limited tumours, the recommended strategy involved the use of one of these modality; 4) a multimodality approach is recommended for the treatment of extended resectable tumours. Following results of recent meta-analyses, use of neo-adjuvant chemotherapy is not recommended. The same studies have shown that association of chemotherapy and radiotherapy either in sequence or in combination significantly improve survival of extended curable tumours. These associations are recommended within the framework of clinical trials; 5) follow-up of squamous carcinoma of the oropharynx should involve physical examination of the upper aerodigestive tract and the lymph nodes areas every three months during the first year, every six months during the second year and then every year. An annual chest x-ray is recommended. Other investigations should be performed as indicated by symptoms and clinical manifestations.

[Sinonasal cancer and occupation: a multicenter case-control study]. / Cancers naso-sinusiens et profession: une étude cas-témoins multicentrique.

A case-control study was conducted to examine occupational risk factors for sinonasal cancer. 207 cases and 409 controls (323 cancer hospital controls and 86 controls selected from lists provided by the cases) were included in the study. All cases and controls were interviewed by specially trained physicians. Detailed information on occupational history was collected, in addition to other potential risk factors for nasal cancer. Results are presented for two histologic types: adenocarcinoma and squamous cell carcinoma. Among males, the risk of adenocarcinoma was significantly elevated for carpenter and joiners (OR = 17.7) and other woodworkers (OR = 26.9). A significant increase in risk of squamous cell cancer (OR = 2.5) and a moderate increase in risk of adenocarcinoma (OR = 1.7; NS) were noted for construction workers. Among females, an excess risk of squamous cell carcinoma was associated with employment in textile industry (OR = 2.9). Elevated risks of squamous cell cancer were observed for farm workers of both sexes (males: OR = 2.2; females OR = 4.9).

[Cancers of the soft palate. Results of repeat surgery]. / Cancers du voile du palais. Résultats de la chirurgie de rattrapage.

Between 1960 and 1983, 270 patients were treated at the CURIE Institute for a carcinoma of the soft palate, including 260 by radiotherapy (mean dose: 69 Gy). Most of these tumours were T1 T2 (201 cases, 76%). There was a high frequency of a past history of carcinoma (38 cases, 14%) as well as of simultaneous carcinomas (44 cases, 16%). Two months after radiotherapy, a velar tumor persisted in 29 patients whilst 1 patient had deep necrosis. 15 of these 30 patients underwent secondary surgical excision. This surgical series included 25 of 27 recurrences seen secondarily and 6 patients operated on for second velar carcinoma appearing in the irradiated zone (mean dose: 68 Gy). 45 of the 46 excisions were carried out by a buccal approach. Overall survival after surgery was 32% at 3 years. The 11 patients operated on for an extensive T3 T4 tumour died before 12 months. These poor results were related to the frequency of local recurrences (12 loco-regional failures amongst 36 deaths) as well as the number of deaths due to second carcinomas (11 deaths amongst the surgical patients). Later carcinomas were particularly frequent during the course of tumours of this site (69 cases out of 270), the problem of multiple malignant tumours finally affecting 122 patients out of 270, i.e. 45%.