[Hypofractionated radiotherapy in rectal cancer for elderly patients]. / Radiothérapie hypofractionnée des cancers du rectum chez le sujet âgé.

Rectal cancer is a common pathology in the elderly. The standard for advanced rectal tumors is a chemoradiotherapy regimen combined 50Gy with concomitant chemotherapy followed by a surgery. This treatment induces interruptions of chemoradiotherapy and toxicities G3-4 more important in people over 70 years of age. Hypofractionated radiotherapy 5×5Gy with surgery following week is an alternative. All retrospective studies on this fractionation report an excellent immediate and chronic tolerance. The randomized phase III NACRE trial, comparing these 2 radiotherapy, followed by surgery at 6-8 week, established a standard in the management of the elderly patients.

[Combined radiation therapy and androgen deprivation in the management of prostate cancer: Where do we stand?]. / Association de radiothérapie et d'hormonothérapie dans la prise en charge des cancers localisés de la prostate: où en est-on?

Radiotherapy and androgen deprivation therapy play a major role in the management of prostate cancer. Indeed, radiotherapy and hormone therapy are combined in a neoadjuvant and concomitant setting for intermediate risk cancers but also in an adjuvant setting in high risk or locally advanced prostate cancer. The benefice of this association was suggested by preclinical studies and demonstrated later by several randomized trials. However, as these trials were conducted before the era of dose escalation the role of androgen deprivation therapy in this case is less clear. Moreover, as hormonal therapy can lead to a significant morbidity and a decrement in quality of life its indications must be carefully weighed especially in case of intermediate risk cancer witch represent a heterogeneous group with distinct prognostic subgroups.

Prognostic factors affecting cervical adenocarcinoma: 10 years experience in a single institution.

OBJECTIVES: We performed a population-based study to determine the significance of adenocarcinoma and to evaluate its behavior over the last 10 years among patients treated in the National cancer institute of Morocco. STUDY DESIGN: This is a retrospective study that was conducted in the national cancer institute of Morocco. Over a period of 10 years, we retrieved 350 cases of cervical invasive adenocarcinoma. Survival was analyzed according to the Kaplan-Meier method. A univariate analysis of prognostic factors was performed using the test of log rank. Cox regression model was used for the multivariate analysis of prognostic factors. RESULTS: Mean age at presentation was 46 years. Sixty seven percent of the patients had locally advanced stage. Radiotherapy was prescribed in 73.3 % of the cases. The mean follow-up time for surviving patients was 51 months. The 5-year survival rates according to clinical stages were as follows, 76 and 62 % for stages I and II, respectively, 32 and 9 % for stages III and IV, respectively. Tumor stage, tumor grade, positive lymph nodes status, lymphovascular space involvement and patient's age were significant prognostic factors in a univariate analysis. While only stage and lymph node involvement remained significant independent predictors for survival in the multivariate analysis. CONCLUSION: Although in our country incidence of adenocarcinoma is lower than the ones reported in western countries, in general our results are consistent with those reported in the literature. Better outcomes are observed in both early stages and young patients. Also, we found that FIGO stage, grade and lymph node metastases to be significant prognostic factors for survival in cervical adenocarcinoma.

Impact of cervical cancer on quality of life: beyond the short term (Results from a single institution): Quality of life in long-term cervical cancer survivors: results from a single institution.

BACKGROUND: Cervical cancer (CC) is one of the most widespread gynecological malignancies in women worldwide. Treatment strategies and screening modalities have largely evolved these past years resulting in an improvement of survival. However, treatment modalities are associated with long term side effects that significantly impacts quality of life (QOL) in cervical cancer survivors. The aim of this study is to evaluate QOL (General and sexual QOL) in cervical cancer survivors up to 10 years after the diagnosis. MATERIAL AND METHODS: In a cross-sectional descriptive study design, 110 cervical cancer survivors (CCS) and 80 healthy controls completed questionnaires assessing QOL. RESULTS: Participants were Arabic White, sexually active. The mean age at diagnosis was 34 years and was 43 years at the time of the interview. In our series long term CCS have generally a good global QOL comparable with healthy controls. However, issues concerning emotional functioning were over expressed by CCS. As to the sexual impact of cervical cancer; CCS experienced less sexual functioning and enjoyment and less satisfaction with their body image when compared to healthy controls. In a multivariate analysis, spiritual well-being and social support were the predictor factors that statistically affected QOL among the studied cohort, it accounted for 81 % of the variance in QOL scores. CONCLUSIONS: A better understanding of the complexity of the relationship between QOL and cervical cancer sequelae in one hand and socio-demographic factors in the other hand is necessary to improve QOL among cervical cancer survivors. More efforts should make to inform disease free patients about expected side effects and symptoms to face the physical changes that would affect their QOL and sexual activity.

[Primary central nervous lymphoma: what is the role for radiotherapy?]. / Lymphome primitif du système nerveux central : quel rôle pour la radiothérapie ?

Primary central nervous system lymphoma is a rare extranodal form of non-Hodgkin lymphoma with an aggressive course and unsatisfactory outcome. Historically, whole-brain radiotherapy was the sole treatment for patients with primary central nervous system lymphoma, with high response rates but typically, this did not result in long-lasting remissions. The addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy has significantly improved patients' outcome, but has resulted in a higher incidence of late neurotoxicity, particularly in elderly patients. To date, the role of consolidation radiotherapy is controversial, and some investigators have developed alternative strategies aiming at avoiding immediate irradiation or using a reduced radiotherapy dose to the whole-brain with promising results.

[Concomitant chemoradiotherapy for muscle-invasive bladder cancer: current knowledge, controversies and future directions]. / Chimioradiothérapie concomitante des tumeurs infiltrantes de la vessie : acquis, controverses et perspectives.

Radical cystectomy with lymphadenectomy is currently the standard of care for muscle-invasive urothelial bladder cancer; however and because of its morbidity and its impact on quality of life, there is a growing tendency for bladder-sparing strategies. Initially reserved for elderly or unfit patients unable to undergo radical cystectomy, chemoradiotherapy became a true alternative to surgery for highly selected patients. Although there are no randomized trials comparing radical cystectomy with bladder preserving approaches, surgery remains the preferred treatment for many clinicians. Furthermore, comparison is even more difficult as modalities of radiotherapy are not consensual and differ between centers with a variability of protocols, volume of irradiation and type of chemotherapy. Several ongoing trials are attempting to optimize chemoradiotherapy and limit its toxicity, especially through techniques of adaptive radiotherapy or targeted therapies.

[Superior vena cava syndrome with malignant causes]. / Syndrome cave supérieur d'origine maligne.

Superior vena cava syndrome comprises various symptoms and signs resulting from the obstruction of the superior vena cava and resulting in reduced blood flow. Superior vena cava may occur secondary to a variety of conditions, but malignant etiologies are the most common. Usually, the diagnosis is based on a quite clear clinical presentation. Patient with acute presentation can develop life-threatening complications such as cerebral or laryngeal edema. In the absence of these two conditions, a histologic diagnosis should be obtained before the initiation of any therapy. Management of superior vena cava syndrome requires a multidisciplinary team. Therapeutic approaches include radiotherapy, chemotherapy and endovascular approach, and the choice of therapy will depend on the severity of the symptoms, the type and the stage of the tumor, but also the patient's general condition.

Is preoperative radiotherapy suitable for all patients with primary soft tissue sarcoma of the limbs?

AIM: To evaluate the indications and results of preoperative radiotherapy (RT) on a series of selected patients treated at our institution with curative intent for a limb sarcoma (STS). PATIENTS AND METHODS: From 05/1993 to 12/2011, 64 STS patients received preoperative RT. RESULTS: RT was delivered as a "limb salvage treatment" prior to surgery for the following reasons: as the preferential induction treatment in 53 patients (83%) or as a second intent (17%) after the failure of neoadjuvant systemic chemotherapy/isolated limb perfusion. Surgery was performed after RT in 54 (84%) patients and final limb salvage was performed in 98%. Musculo-cutaneous flap reconstruction was planned upfront in 44% patients, and 19% had a skin graft. Seven patients (13%) had a postoperative RT boost. Thirteen (20%) patients had grade (G) 3/4 adverse events, one after RT and 12 after surgery. At a median follow-up of 3.5 years, the 3-year actuarial overall survival (OS) and distant relapse (DR) rates were 83% and 31%, respectively. Two patients developed a local relapse and two a local progression (non-operated patients). In the multivariate analysis (MVA), histological subtype (leiomyosarcoma) and grade 3 were predictive of poorer survival. Patients with >3 month delay between the start of RT and surgery at our institution had an increased risk of DR in the MVA. CONCLUSION: Induction RT should be personalised according to histological subtype, tumour site and risks-benefit ratio of preoperative radiotherapy and is best managed by a multidisciplinary surgical and oncology team in a specialist sarcoma centre.

[Small cell neuroendocrine carcinoma of the uterine cervix: Report of six cases and a review of the literature]. / Carcinome neuroendocrine à petites cellules du col utérin : à propos de six cas et revue de la littérature.

Neuroendocrine carcinoma is a rare and aggressive malignant tumour, mainly developing at the expense of the respiratory and of the digestive tract. Gynecological neuroendocrine tumours are rare and small cell neuroendocrine tumours of the uterine cervix represent 2% of cervical cancer. Given their rarity and the lack of randomized trials, the diagnostic and therapeutic management of these tumors is difficult and essentially based on that of pulmonary neuroendocrine tumours. Like the latter, and despite multimodality regimens, the prognosis of these tumours remains poor. Through this series, we report our experience in the management of these particular tumours while comparing our data with those of the literature.

Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level.

Previous studies of the structure of core nanocrystals of ferritin (Ft) in the brains of patients with Alzheimer's disease (AD) have shown differences in the mineral compound in comparison with physiological Ft. Both Ft cores have a polyphasic composition but whereas the major phase in physiological Ft is hexagonal ferric iron oxide (ferrihydrite), the major phases in brain AD Ft are two cubic mixed ferric-ferrous iron oxides (magnetite and wüstite). One of these (wüstite) is similar to what is detected in hemosiderin (Hm) cores in primary hemochromatosis (Quintana, C., Cowley, J.M, Marhic, C., 2004. Electron nanodiffraction and high resolution electron microscopy studies of the structure and composition of physiological and pathological ferritin. J. Struct. Biol. 147, 166-178). We have studied, herein, the distribution of iron, Ft, and Hm in sections of AD hippocampus using analytical microscopy. Iron present in Ft cores was directly mapped in a nanoSIMS microscope and the iron distribution has been correlated with the constituent elements N, P, and S. Ft and Hm cores were visualized at an ultrastructural level in an analytical transmission electron microscope. In senile plaques, Ft was observed in the coronal region associated with a non-beta-amyloid component and in the periphery of plaques, together with Hm, in sulfur-rich dense bodies of dystrophic neurites. Hm was also found in lysosomes and siderosomes of glial cells. Ft was observed in the cytoplasm and nucleus of oligodendrocytes. Ft was particularly abundant in myelinated axons in association with oligodendrocyte processes. These findings provide new arguments to support the hypothesis of a dysfunction of Ft (with eventual degradation to Hm) in AD resulting in an increase of toxic brain ferrous ions that may contribute to the production of free radicals that induce both cellular oxidative stress and aged-related myelin breakdown associated with cognitive decline and AD (Bartzokis, G., 2004. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging 25, 5-18).

[Isolated ptosis in a 58-year-old woman]. / Ptosis isolé apparu chez une femme à l'âge de 58 ans.

A 60-year-old woman who had experienced isolated ptosis for two years was seen when it had been fixed for one year. She had a personal and familial history of stromal corneal dystrophy. The diagnosis of mitochondrial cytopathy was made on the basis of clinical, electrophysiological, biological and histological findings. Surgical repair of the ptosis allowed visual recovery. The relationship between ptosis, corneal dystrophy and mitochondrial cytopathy is discussed.

[Contribution of intravitreal infracyanine green to macular hole and epimacular membrane surgery: preliminary study]. / Apport du vert d'infracyanine intravitréen dans la chirurgie des trous maculaires et des membranes épirétiniennes.

PURPOSE: To evaluate the contribution of intravitreal infracyanine green to macular hole and epimacular membrane surgery. PATIENTS AND METHODS: Twenty-five consecutive patients were operated on for macular hole (seven cases) or epiretinal membrane (18 cases) using intravitreal infracyanine. In most cases, 25mg of infracyanine powder was diluted in 5ml of solvent, then in 5ml of BSS and used within 1 hour. The solution was injected at the end of the vitrectomy and aspirated after 1-2 minutes. The internal limiting membrane was removed in both diseases. All specimens were studied using confocal microscopy or an immunocytochemical preparation. RESULTS: In cases of macular hole, the internal limiting membrane was bright green colored. Opening and peeling were greatly facilitated. In cases of epiretinal membrane, staining was variable: the most frequent aspect was an uncolored central area similar to a geographic map surrounded by a green stained zone. Sometimes the coloration appeared as sparse spots on the posterior pole. Occasionally the staining was homogeneous as in the macular hole cases. After the removal of the membrane, a second injection made it possible to check for the persistence of the internal limiting membrane and proceed to its ablation when necessary. A good correlation was found between surgical and histopathological aspects. CONCLUSION: Intravitreal infracyanine green is very helpful for the removal of internal limiting membrane in macular holes and epiretinal membrane surgery.

[Etiology of enucleations. Apropos of 3,246 cases]. / Etiologie des énucléations. A propos de 3,246 cas.

PURPOSE: An epidemiological study of the aetiology of enucleation was conducted in patients seen at the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris. The enucleated globes were systematically sent to the laboratory for histological examination. METHODS AND MATERIALS: Histological results of the cases from the register of Anatomo-Pathology section of the laboratory of the C.H.N.O. des Quinze-Vingts, over a 70-year period from 1925-1995 were used; 3,246 globes were examined, that is, 32.83% of all histological examinations. RESULTS: In our series, malignant tumours were the most frequent cause of enucleation (32%), followed by trauma (18%), glaucoma (16%), atrophies-dystrophies (16%) and inflammatory causes (12%). Globes without histological pathology were rare (0.12%). The majority of ophthamic tumours with histological confirmation were melanomas (65.2%) in old age and retinoblastomas (32.5%) in the newborn and early infancy. Our results are compared with those of other authors. CONCLUSION: Great improvements in medicine and diagnostic techniques have taken place, these last decades, and with the possibilities of early diagnosis, enucleation has become rare as it is being replaced by conservative management.

Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial with prognostic factor analysis.

Combined chemotherapy has demonstrated a degree of efficacy in gastric carcinoma. As 5-fluorouracil (5FU) and cisplatinum are two of the most active drugs, we have tested the efficacy of combined 5FU and cisplatinum in a prospective phase II trial. Cycles were administered every 4 weeks and consisted of 5FU 1000 mg/m2/day 5 days continuous intravenous (i.v.) infusion and cisplatinum 100 mg/m2 on day 2. Cycles were repeated according to tolerance and efficacy. 87 patients entered the study, 57 with metastatic or recurrent tumour (M) and 30 with locally advanced gastric cancer (LAGC). The response rate for the 83 evaluable patients was 43% [95% confidence interval (CI) 30-56%]. There were four complete responses (5%), 32 partial responses (39%), 34 cases of stable disease and 13 cases of progressive disease. Responses were more frequent in patients with a good performance status (P = 0.02), with their primary located in the cardia (P = 0.003), with a non-linitis plastica tumour form (P = 0.003) or a tumour containing less than 50% of independent cells (P = 0.016). Median survival was 9 months for the total population. It was better in patients with a good performance status (P = 0.01), and those who did not have linitis plastica (P = 0.005). Toxicity was acceptable, although grade 3-4 neutropenia was reported in 22% of the cycles, mucositis in 14% and 3 patients died of septic complications. The combination of 5FU and cisplatinum is effective in terms of tumour response in advanced gastric cancer and warrants testing with the other active regimens.

Neoadjuvant chemotherapy in locally advanced gastric carcinoma--a phase II trial with combined continuous intravenous 5-fluorouracil and bolus cisplatinum.

Locally advanced gastric adenocarcinomas (LAGC) have a poor prognosis, particularly when tumours are bulky, located in the cardia or in the event of locoregional lymph node involvement. Patients bearing these tumours were entered in a phase II trial of neoadjuvant chemotherapy, combining continuous intravenous 5-fluorouracil (5FU) (1000 mg/m2 for 5 days) and cisplatinum (CDDP) (100 mg/m2 on day 2) repeated every 4 weeks, for one to six cycles according to response and tolerance. 30 patients have been entered, 26 after clinical evaluation (CAT scan and upper gastrointestinal endoscopy) and 4 with unresectable tumours at prior laparotomy. Median age was 60 years, 15/30 patients had a tumour of the cardia, 15/30 had enlarged lymph nodes and 7/30 had linitis plastica (diffuse type). A mean number of three cycles was administered (range 1-6). 27 of the 30 patients were evaluable for response. One patient achieved a complete response (CR) and 14 a partial response (56%; 95% confidence interval 38-74%). No patient had tumour progression, and only 1/6 with linitis plastica responded. 28 patients underwent surgery, and 23 had a macroscopically complete resection (77% of the 30 entered patients); RO resections were performed in 60% of the cases, mainly after an objective response (13/15 versus 4/12 in nonresponders). No pathological CR were seen. Grade 4 neutropenia was observed in eight cycles (5 patients), with five septic complications and one death due to toxicity. Four postoperative complications were observed: 2 cases of severe pneumonia and 2 subphrenic abscesses. One postoperative death, due to intravascular disseminated coagulation, was observed at day 30. Median survival was 16 months and the 1-, 2- and 3-year survival was 67, 42 and 38%, respectively. Patients with linitis plastica had a significantly shorter survival (P < 0.002). We conclude that neodjuvant chemotherapy is feasible in LAGC, although randomised trials are warranted to demonstrate its efficacy on survival and resection rates.

Conjunctival biopsy in Sjögren's syndrome: correlations between histological and immunohistochemical features.

We have examined conjunctival biopsies from nine primary and two secondary cases of Sjögren's syndrome. In all cases histopathological examination revealed metaplasia of the conjunctival epithelium associated with a reduced number of goblet cells and a polymorphic inflammatory cell infiltrate of the stroma. Using monoclonal antibodies with texture analysis of stained preparations we have shown that in all cases the lymphocytic infiltrate was predominantly T-cell but with substantial numbers of IgA and IgG secretory B-cells in three cases. The number of Langerhans cells present was reduced in biopsies showing the most marked degree of epithelial metaplasia.