[Radiotherapy for ovarian carcinoma management: Literature review]. / Place de la radiothérapie dans le traitement des cancers ovariens : revue de la littérature.

Ovarian cancer is the fifth most common cancer in women in France with 4714 new cases in 2017. More than 70% of patients whose disease is initially locally advanced will present locoregional or distant recurrence. Therapeutic options in this situation are not consensual. They are based on chemotherapy possibly associated with an iterative cytoreductive surgery when it is bearable by the patient. The place of radiotherapy in the management of the disease is hidden in the vast majority of national or international standards. We conducted a general review of the literature to clarify the role of irradiation in the global management of ovarian cancers, particularly in recurrence.

Dosimetric comparison of free-breathing and deep inspiration breath-hold radiotherapy for lung cancer.

PURPOSE: The goal of this work was to evaluate the potential benefit of deep inspiration breath-hold (DIBH) compared to free breathing (FB) radiotherapy in a homogeneous population of patients with lung cancer. METHODS AND MATERIALS: A total of 25 patients with non-small cell lung cancer treated by DIBH underwent an additional FB CT scan. The DIBH and FB treatment plans were compared. Target volume was compared using coverage, homogeneity, and conformal indices. Organs at risk were compared using V(5), V(13), V(20), V(25), V(37), mean dose (D(mean)) for lungs, V(40) and D(mean) for the heart, V(50), D(mean) and maximum dose (D(max)) for the esophagus, and using biological indices, i.e., the equivalent uniform dose (EUD) and the normal tissue complication probability (NTCP). RESULTS: Median age was 62 years. Prescribed total dose was 66 Gy. Conformity index was improved with DIBH (0.67 vs. 0.58, p = 0.046) but coverage and homogeneity indices were not significantly different. Lung dosimetric parameters were improved using DIBH: D(mean) (13 vs. 15 Gy, p = 10(-4)), V(5) (43 vs. 51%, p = 6.10(-5)), V(13) (31 vs. 38%, p = 2.10(-3)), V(20) (25 vs. 31%, p = 0.01), V(25) (22% vs. 27%, p = 0.01) and V(37) (12 vs. 16%, p = 0.03), EUD (8.2 vs. 9.9 Gy, p = 3.10(-4)), and NTCP (1.9 vs. 4.8%, p = 10(-3)). For the heart, D(mean) (14 vs. 17 Gy, p = 0.003), V(40) (12 vs. 17%, p = 0.004), and EUD (19 vs. 22 Gy, p = 6.10(-4)) were reduced with DIBH, whereas V(30) and NTCP were similar. DIBH improved the D(mean) (28 vs. 30 Gy, p = 0.007) and V(50) (25 vs. 30%, p = 0.003) for the esophagus, while EUD, NTCP, and D(max) were not altered. CONCLUSION: DIBH improves the target conformity index and heart and lung dosimetry in lung cancer patients treated with radiotherapy. The clinical implications of these findings should be confirmed.

[Radiotherapy for breast cancer and pacemaker]. / Radiothérapie pour un cancer du sein et stimulateur cardiaque.

PURPOSE: Patients with permanent cardiac pacemakers occasionally require radiotherapy. Therapeutic irradiation may cause pacemakers to malfunction due to the effects of ionizing radiation or electromagnetic interference. We studied the breast cancer patients who needed breast and/or chest wall and lymph node irradiation to assess the feasibility and tolerance in this population of patients. PATIENTS AND METHODS: From November 2008 to December 2009, more than 900 patients received radiotherapy for their breast cancer in our department using megavoltage linear accelerator (X 4-6 MV and electrons). Among them, seven patients were with permanent pacemaker. All patients have been treated to the breast and chest wall and/or lymph nodes. Total dose to breast and/or chest wall was 50 Gy/25 fractions and 46 Gy/23 fractions to lymph nodes. Patients who underwent conserving surgery followed by breast irradiation were boosted when indicated to tumour bed with 16 Gy/8 fractions. All patients were monitored everyday in presence of radiation oncologist to follow the function of their pacemaker. All pacemakers were controlled before and after radiotherapy by the patients' cardiologist. RESULTS: Seven patients were referred in our department for postoperative breast cancer radiotherapy. Among them, only one patient was declined for radiotherapy and underwent mastectomy without radiotherapy. In four cases the pacemaker was repositioned before the beginning of radiotherapy. Six patients, aged between 48 and 84 years underwent irradiation for their breast cancer. Four patients were treated with conserving surgery followed by breast radiotherapy and two with mastectomy followed by chest wall and internal mammary chain, supra- and infra-clavicular lymph node irradiation. The dose to the pacemaker generator was kept below 2 Gy. There was no pacemaker dysfunction observed during the radiotherapy. CONCLUSION: The multidisciplinary work with position change of the pacemaker before radiotherapy and everyday monitoring permitted the safe treatment of our patients. Updated guidelines are definitely needed with more details about acceptable doses at the different parts of the pacemaker.

[Normal tissue tolerance to external beam radiation therapy: eye structures]. / Dose de tolérance à l'irradiation des tissus sains: l'oeil.

The radiation dose received by the eye depends on the pathology, tumour location (ocular globe, orbit, neighboring structures) and the radiation technique. The major complication is the complete loss of vision, which is often multifactorial. This article, based on a literature review, describes the radiation effects and the tolerance doses for all eye structures: cornea, lens, retina, optic nerves, orbit and ocular adnexa.

[Demography of radiation oncology residents in France in 2008: current situation and perspectives for the next three years]. / Démographie des internes en oncologie-radiothérapie en France en 2008: état et perspectives pour les trois prochaines années.

PURPOSE: Although a recent increase in number of young radiation oncologists in training has been observed during the past decade, the general demographic evolution of radiation oncologists covers partially future needs. MATERIAL AND METHOD: During the seven past national annual courses, which were organised and supported by the Société française des jeunes radiothérapeutes oncologues (SFJRO), the Société française de radiothérapie oncologique (SFRO), the Collège national des enseignants de cancérologie (CNEC) and the Institut national du cancer (Inca), different types of surveys were realized in order to analyse demography, quality of training and motivations of French residents in radiation oncology. The latest results were collected during the last national course, which took place in March 2008. Seventy-five young French radiation oncologists ("internes des hopitaux" or residents) out of 110 participants who attended the national course and 75 questionnaires were analysed. RESULTS: Since 2002, the total number of residents increased regularly (50, 75, 103 and 109 residents respectively in 2000, 2005, 2007 and 2008). Men and women are presently 48.5% and 51.5% respectively. Qualitative analysis of practical and theoretical training was performed using a visual analogical scale from zero to 10. Scores of 56 and 61 were respectively observed. Other descriptions of local training in the different universities (clinical skills, clinical cases analysis, bibliography session...) are described. Finally, analysis of the motivations for choosing the radiation oncology speciality demonstrates common interests in both medical practice and technical aspects in oncology. Innovation, technology, imaging and research are also widely mentioned. Sixteen residents will finish their training by the end of 2008, 42 are expected in 2009 and 27 in 2010. Almost all residents believe that a postgraduate position is necessary to complete their training as assistant professor ("chefs de clinique-assistants des hôpitaux") in a university hospital or a cancer centre. Unfortunately, only 36 assistant professor positions are available in France, representing half of the need. Only 21 residents out of 104 already have a position as assistant professor. The availability of such a position remains undetermined for the rest of them. CONCLUSIONS: Despite the recent increase in the number of residents in radiation oncology in France, the need to create new assistant professor positions is crucial to assure quality of training for this both medical and technical speciality. Since 2002, the establishment of SFJRO has facilitated national links among residents, between residents and professors (CNEC), and between the French society (SFRO) and the European society (ESTRO).

A rare gynecological case of paraneoplastic cerebellar degeneration discovered by FDG-PET.

BACKGROUND: PET/CT may be particularly useful to detect the primary cancer in paraneoplastic cerebellar degeneration (PCD) with anti-Yo which is most commonly associated with breast, ovarian and other gynecological cancers. CASE: A 60-year-old woman developed a PCD associated with anti-Yo antibodies in serum and cerebrospinal fluid. Conventional imaging was negative. FDG-PET showed an abnormal hot spot in the right ovarian area associated with lombo aortic lymph nodes. The diagnosis was confirmed by surgery as an ovarian adenocarcinoma. CONCLUSION: In this case report, FDG-PET played a crucial role in detecting the unknown primary tumor in a patient with PCD.

Nicotine, but not cotinine, partially protects dopaminergic neurons against MPTP-induced degeneration in mice.

In order to analyze the putative neuroprotective role of nicotine and cotinine in parkinsonian syndromes, these two compounds were administered in male C57Bl6 mice for 4 weeks. On day 8, four injections of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) were administered. MPTP intoxication induced a 50% loss of dopaminergic neurons in the substantia nigra and a 45% reduction in dopaminergic fibers in the striatum. Administration of cotinine did not affect MPTP toxicity in the nigrostriatal system but chronic nicotine treatment showed a slight protection (15%) of nigrostriatal dopaminergic neurons against MPTP.

Randomized, double-blind, placebo-controlled pilot trial of megestrol acetate in malnourished children with cystic fibrosis.

BACKGROUND: Undernutrition is common in patients with cystic fibrosis (CF). Nutritional rehabilitation has been shown to improve linear growth, pulmonary function, well-being, and resistance to infection in this population. The purpose of this study was to determine whether the administration of megestrol acetate (MA) induces weight gain in malnourished patients with CF, and to assess the composition of weight gain. METHODS: In a randomized, placebo-controlled, double-blind, crossover study, 12 children with CF received MA (10 mg/kg/d) or placebo for 12 weeks, followed by a 12-week washout period, then the alternative treatment. Anthropometrics, caloric intake, and clinical assessment were obtained every 6 weeks; pulmonary function tests, biochemistry, hematology, cortisol, growth hormone, insulin, C-peptide, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and dual-energy x-ray absorptiometry scans were obtained every 12 weeks. RESULTS: Six children did not complete the study, three for reasons unrelated to the study, two because they developed diabetes while receiving MA, and one who had glucose intolerance while receiving the placebo. Average weight gain was 3.05 kg in the MA group and 0.3 kg in the placebo group. The change in weight z score was +0.76 in the MA group and -0.05 in the placebo group. The change in height z score was -0.06 in the MA group and +0.06 in the placebo group. Lean body mass and body fat increased by 1507 g and 1192 g respectively in the MA group. Pulmonary function tests improved in the MA group; serum cortisol levels decreased. Side effects included glucosuria, insomnia, hyperactivity, and irritability. CONCLUSIONS: Weight, body fat, and lean body mass increased and pulmonary function improved in the children with CF given MA. Adrenal suppression, glucose intolerance, and diabetes are side effects.

Enteral nutrition in the pediatric population.

Enteral feeding, the provision of liquid nutrients into the gastrointestinal tract, is an important component of pediatric care. For the infant or child with a functioning or even a partially-functioning GI tract, the use of the enteral route provides a safe and efficient means of delivering nutrition at a time of life when requirements are extremely high. In addition to high nutrient requirements in the early years of life, there are a number of specific pediatric conditions, such as failure to thrive, short bowel syndrome, and congenital heart disease, which place further demands on the growing child. These demands can be met through the careful use of enteral feeds. This article reviews the physiology and practical application of enteral feeding to the pediatric age group.

Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses.

The expression of various matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in 88 primary bronchopulmonary cancers and in 13 neighbouring pulmonary parenchyma samples was quantified by Northern-blot analysis, and morphologically examined by in situ hybridization and immunohistochemistry in order to evaluate the involvement of MMPs in the pathophysiology of these carcinomas and to look for potential markers of aggressivity of lung tumours. Northern-blot analysis showed that the predominantly expressed MMPs in bronchopulmonary cancers were gelatinase A (66%), its activator MT1-MMP (membrane-type-1 matrix metalloproteinase) (56%) and stromelysin-3 (61%). MMP expression frequencies and mRNA levels increased progressively with malignant phenotype, lack of differentiation and TNM stage of the tumours, whereas TIMP expression decreased very early during tumour progression. Moreover, the principal MMPs were significantly co-expressed in primary tumours, suggesting their co-regulation. Morphological studies revealed the expression of MMPs and TIMPs essentially in stromal cells in close contact with tumour clusters. These results indicate that tumour progression in bronchopulmonary carcinomas implies a progressive disruption of the MMP/TIMP balance leading to an excess of several MMPs that act in concert in vivo. Furthermore, the fact that stromal cells are the principal source of MMPs emphasizes the close cooperation between host cells and cancer cells in tumour invasion.

Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers.

Tumor cell-derived collagenase stimulatory factor (TCSF) stimulates in vitro the biosynthesis of various matrix metalloproteinases involved in tumor invasion, such as interstitial collagenase, gelatinase A, and stromelysin 1. The expression of TCSF mRNAs was studied in vivo, using in situ hybridization and Northern blotting analysis, in seven normal tissues and in 22 squamous cell carcinomas of the lung, and in seven benign proliferations and in 22 ductal carcinomas of the mammary gland. By in situ hybridization, TCSF mRNAs were detected in 40 of 44 carcinomas, in pre-invasive and invasive cancer cells of both lung and breast cancers. TCSF mRNAs and gelatinase A mRNAs were both visualized in the same areas in serial sections in breast cancers, and were expressed by different cells, tumor cells, and fibroblasts. The histological results were confirmed by Northern blot analysis, which showed a higher expression of TCSF mRNAs in cancers than in benign and normal tissues. These observations support the hypothesis that TCSF is an important factor in lung and breast tumor progression.

Induction of membrane-type matrix metalloproteinase 1 (MT1-MMP) expression in human fibroblasts by breast adenocarcinoma cells.

Membrane-type matrix metalloproteinase 1 (MT1-MMP) has been recently described as an activator of proMMP-2 (MMP-2) which is involved in tumor invasion. We have shown by in situ hybridization that MT1-MMP is produced by stromal cells in close contact to preinvasive and invasive tumor cells of breast carcinomas. Of particular interest was the observation that some fibroblasts express this enzyme in focal areas in preinvasive lesions, suggesting that particular tumor cells may stimulate fibroblasts to produce MT1-MMP. We have therefore compared the ability of two different breast cancer cell lines, one non-invasive (MCF7) and one invasive (MDA-MB-231) to stimulate MT1-MMP production in human fibroblasts with consequent proMMP-2-activation. The MDA-MB-231 conditioned medium induced MT1-MMP mRNAs in human fibroblasts and a parallel activation of proMMP-2 whereas MCF7 conditioned medium did not have any effect. These results suggest the existence of soluble factor(s) secreted by invasive or some preinvasive breast tumor cells which stimulate fibroblasts to produce and activate MMPs, and emphasize the cooperation between cancer and stromal cells in tumor invasion.

The elastase-induced expression of secretory leukocyte protease inhibitor is decreased in remodelled airway epithelium.

During airway inflammation, proteinases such as human leukocyte elastase are actively secreted. Secretory leukocyte protease inhibitor is a major serine proteinase inhibitor, secreted by bronchial, bronchiolar and lung epithelial cells. We recently identified secretory leukocyte protease inhibitor in human nasal epithelium, exclusively in remodelled areas of the surface epithelium. We now investigated the influence of remodelling and inflammation of the nasal tissue on the in vitro capacity of these cells to respond to human leukocyte elastase. Primary cultures of surface epithelial cells were established from various nasal polyp samples. At confluency, cell cultures were exposed to different human leukocyte elastase concentrations. The secretory leukocyte protease inhibitor immunocytolocalisation, expression and secretion were then investigated. Immunocytochemistry, showed a human leukocyte elastase dose-dependent increase of secretory leukocyte protease inhibitor containing cells and a basal extracellular localization of secretory leukocyte protease inhibitor after incubation with 100 microg/ml human leukocyte elastase. The relative amount of secretory leukocyte protease inhibitor mRNA transcripts increased with respect to the human leukocyte elastase concentration. Nevertheless, the potential stimulation of secretory leukocyte protease inhibitor secretion by human leukocyte elastase was lower in the more remodelled and inflamed tissue. Our results suggest that the contribution of the surface epithelial cells of poorly remodelled tissues to the protection against the deleterious effect of neutrophil proteinases is severely decreased in highly remodelled and inflamed tissues.

Decreased expression of the CFTR protein in remodeled human nasal epithelium from non-cystic fibrosis patients.

BACKGROUND: In normal adult pseudostratified human nasal surface epithelium, the cystic fibrosis transmembrane conductance regulator (CFTR) is localized to the apical domain of the ciliated cells, whereas in cystic fibrosis (CF), the mutated delta F 508 CFTR exhibits an abnormal cytoplasmic localization. Frequent airway injuries either in CF or non-CF patients may induce a remodeling of the surface epithelium characterized by a change in the morphological structure from normal columnar pseudostratified epithelium to either basal cell hyperplasia, mucous cell hyperplasia, or squamous metaplasia. EXPERIMENTAL DESIGN: The localization of CFTR parallel to markers of cell differentiation, such as cytokeratin 14 (CK14, a marker of basal cells), cytokeratin 18 (CK 18, a marker of ciliated and mucous cells), cytokeratin 13 (CK13, a marker of squamous metaplasia cells), and desmoplakins (DP) 1 and 2 (markers of desmosomes) was analyzed by indirect immunofluorescence. RESULTS: In normal pseudostratified epithelium, CFTR was detected at the apical plasma membrane of the ciliated cells, CK14 was identified in basal cells of focal areas, CK18 was localized in both ciliated and mucous cells, CK 13 was detected in all basal cells, and DP 1 and 2 were preferentially detected at the interface between columnar and basal cells. In basal cell hyperplasia, CFTR was poorly expressed in the cytoplasm of the more superficial cells, CK14 and CK13 were localized in basal cell multilayers, CK18 labeling was present in the more superficial cell layers, and DP 1 and 2 were preferentially detected at the interface between the more basal cells. In squamous metaplasia, CFTR labeling was either very low or even undetectable, CK14 was found in focal areas of the more basal cell layers, CK18 labeling was either very low or undetectable, CK13 expression was restricted to the flattened cells toward the epithelial surface, and DP 1&2 were intensively present between all the epithelial cells. CONCLUSIONS: These results suggest that the localization of CFTR in human nasal surface epithelium is related to the differentiation state of this epithelium. Abnormally low expression of the CFTR protein may not only be caused by CFTR gene mutations but can also be associated with airway surface epithelium dedifferentiation and remodeling.

Identification of antileucoprotease in remodelled human adult nasal surface epithelium.

Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells, and plays a major role in the defence of the respiratory tract against proteolytic damage. Nevertheless, several studies have identified ALP in bronchial and bronchiolar surface epithelial cells, and also an increased number of ALP-containing cells in bronchiolar tissue during the development of pulmonary diseases. In order to define more clearly whether the surface epithelium might be involved in the defence of the respiratory mucosa, we have investigated the expression of ALP by cells of the nasal surface epithelium. Indirect immunocytochemistry and in situ hybridization for ALP were performed on human nasal polyp sections. The height of the surface epithelium, its morphology, and the degree of local inflammation were assessed in parallel. Surface epithelium morphology was highly heterogeneous. ALP-containing cells were identified, but only in remodelled areas of the surface epithelium (foldings, basal cell and/or mucous cell hyperplasia), with no association to the degree of inflammation. These results demonstrate that the surface epithelial cells of the human adult nasal mucosa can express ALP in remodelled surface epithelium, and may be actively involved in the biochemical defence of the airways.