[Meningeal carcinomatosis in breast cancer: from diagnosis to treatment]. / Carcinomatosis meningea en el cancer de mama: del diagnostico al tratamiento.

The appearance of meningeal carcinomatosis in breast cancer is an event that is being reported increasingly more frequently in the literature. It seems to be related with the lengthening of the patients' lives, improved sensitivity to diagnostic imaging and impermeability of the blood-brain barrier to the chemotherapeutic agents. It is an evolutionary form that affirms the metastatic invasion of the subarachnoidal space and is correlated with limited survival. Its diagnosis is difficult, due to the lack of specificity of the clinical signs dominated by headaches, cognitive disorders and possible signs and symptoms of progressive focal lesions. Magnetic resonance imaging of the brain and the spinal cord interpreted by a specialist in neuro-oncology is the preferred examination in this indication, in the search for an increase in meningeal enhancement. Biological analysis of the cerebrospinal fluid is an essential element in the diagnosis. In addition to the biochemical study, the presence of neoplastic cells is in itself enough to confirm the diagnosis. False negatives are very common and represent an important diagnostic problem that entails the need to repeat the lumbar punctures. The therapeutic methods are standard, often invasive, dominated by intrathecal chemotherapy and are based on low-level scientific evidence. This study analyses the epidemiology, the prognostic factors, the diagnostic tools, currently available treatments and the possible future therapies of meningeal carcinomatosis in breast cancer.

TITLE: Carcinomatosis meningea en el cancer de mama: del diagnostico al tratamiento.La aparicion de carcinomatosis meningea en el cancer de mama es un suceso cada vez mas comunicado en la bibliografia. Parece relacionarse con el alargamiento de la vida de las pacientes, la mejor sensibilidad al diagnostico por imagen y la impermeabilidad de la barrera hematoencefalica a los agentes quimioterapicos. Es una forma evolutiva que afirma la invasion metastasica del espacio subaracnoideo y se correlaciona con una supervivencia limitada. El diagnostico es dificil, debido a la inespecificidad de los signos clinicos dominados por cefaleas, trastornos cognitivos, y posibles sintomas y signos de lesiones focales progresivas. La resonancia magnetica del cerebro y de la medula espinal interpretada por un especialista en neurooncologia es el examen de eleccion en esta indicacion, en busqueda de un incremento en la captacion meningea. El analisis biologico del liquido cefalorraquideo es un elemento esencial en el diagnostico. Ademas del estudio bioquimico, la presencia de celulas neoplasicas es por si sola suficiente para confirmar el diagnostico. El numero de falsos negativos es muy comun y representa un gran problema diagnostico que requiere una repeticion de las punciones lumbares. Los metodos terapeuticos son estandares, a menudo invasivos, dominados por la quimioterapia intratecal y se basan sobre una evidencia cientifica de bajo nivel. Se analiza la epidemiologia, los factores pronosticos, las herramientas diagnosticas, los tratamientos disponibles en la actualidad y las posibles terapias futuras de la carcinomatosis meningea en el cancer de mama.

Toxic epidermal necrolysis in a female with metastatic breast cancer treated with vinorelbine.

Vinorelbine is an anticancer agent with high clinical efficacy for the treatment of metastatic breast cancer. Toxic epidermal necrolysis is a rare but serious cutaneous adverse reaction associated with drug therapy. We hereby present a case report of a patient with metastatic breast cancer, treated with vinorelbine, who developed toxic epidermal necrolysis. To the best of our knowledge, ours is the second case report describing this exceptional dermatologic emergency associated with vinorelbine. In June 2014, a 33-year-old female was treated for localized breast cancer. In December 2016, a brain magnetic resonance imaging revealed cerebral and cerebellar recurrence of the breast cancer. Whole brain radiation therapy was administered and treatment with vinorelbine was subsequently initiated. On day 3 of the first cycle of chemotherapy, she presented a general malaise and an itchy rash with conjunctivitis, oral ulcers and diffuse alopecia. The clinical diagnosis was toxic epidermal necrolysis due to vinorelbine. The patient was transferred to the burn unit. Treatment with intravenous steroids, topical steroids and desloratadine was initiated. She subsequently developed Staphylococcus aureus bacteremia and died of multi-organ failure. Toxic epidermal necrolysis is an extremely rare, acute hypersensitivity reaction involving the skin and mucous membranes. Features more suggestive of toxic epidermal necrolysis are acute onset and rapid worsening of painful lesions of the skin and mucous membranes. Specific treatment with active interventions should be practiced in the context of an international and multicentre clinical study in order to give sufficient power for such trials in this rare disease.

La vinorelbine est un agent anticancéreux très efficace dans le cancer du sein métastatique. La nécrolyse épidermique toxique est un effet indésirable médicamenteux cutané rare mais grave. Nous présentons le cas d'une patiente avec un cancer du sein métastatique traité par vinorelbine, qui a développé une nécrolyse épidermique toxique. A notre connaissance, c'est le deuxième cas de la nécrolyse épidermique toxique due à la vinorelbine. En juin 2014, une femme de 33 ans a été traitée pour un cancer mammaire localisé. En décembre 2016, elle a présenté des métastases cérébrales et cérébelleuses. Une radiothérapie encéphalique a été administrée puis un traitement par vinorelbine a été initié. Au troisième jour du premier cycle de chimiothérapie, elle a présenté un malaise général et une éruption cutanée avec démangeaisons accompagnée de conjonctivite, d'ulcères buccaux et d'alopécie diffuse. Le diagnostic était en faveur de la nécrolyse épidermique toxique à la vinorelbine. La patiente a été transférée à l'unité de brûlure et a reçu des stéroïdes intraveineux et locaux et la desloratadine. Elle a ensuite développé une bactériémie à Staphylococcus aureus et est décédée d'une défaillance multiviscérale. La nécrolyse épidermique toxique est une réaction d'hypersensibilité aiguë extrêmement rare touchant la peau et les muqueuses. Elle est évoquée devant l'apparition aiguë et l'aggravation rapide de lésions douloureuses de la peau et des muqueuses. Un traitement spécifique avec des interventions actives doit être recherché dans le cadre d'une étude internationale et multicentrique, afin de donner assez de puissance à de tels essais dans cette maladie rare.

[Male breast cancer in Morocco: Epidemiology and prognostic factors. A report of 140 cases]. / Cancer du sein chez l'homme au Maroc : épidémiologie et facteurs pronostiques. À propos de 140 cas.

OBJECTIVES: Male breast cancer is rare; it constitutes 0.2-1.5 % of all malignant tumors in men and 1 % of all breast cancers. METHODS: The goal of this retrospective study is to analyze the epidemiologic, clinic, therapeutic and evolutive profiles of this disease in 140 cases collected at the National Institute of Oncology and military hospital in Rabat, Morocco, between the years 1998 and 2007. RESULTS: The mean age was 61 years. A high incidence of overweight was found. The most frequent clinical presentation was a firm subareolar lump in 83 % of cases. The most common pathological type was an infiltrating ductal carcinoma (93 %). Hormone receptors were positive in 86 % of cases. Eighty-five percent of patients underwent simple mastectomy and axillary dissection, 68 % chest wall irradiation after surgery, 54 % received chemotherapy and 82 % hormonal therapy. Median follow-up was 91.1 months. The estimated 5-year and 10-year overall survival was respectively 68 % and 74 %. CONCLUSION: The management of male and female breast carcinoma is the same, as well as their prognosis at equal stages. Future research for better understanding of this disease are needed to improve the management and prognosis of male patients.

FOLFOX as Perioperative Chemotherapy of localized Gastric Cancer: Efficacy and Tolerance.

BACKGROUND: Use of perioperative chemotherapy had significantly improved prognosis of localized gastric cancer. Two studies have validated this approach using cisplatin based chemotherapy despite important toxicities. We conducted this study with the aim to evaluate efficacy and toxicity of FOLFOX regimen in this setting. MATERIAL AND METHODS: This is a retrospective study including patients followed for gastric cancer in the Oncology Department of the military hospital Mohamed V in Rabat, Morocco over a period of 7 years from 2007 to 2013. Patients received 4 cycles of mFOLFOX as perioperative regimen. Assessment of tumor response after completion of preoperative chemotherapy was granted by comparative CT scan, tumor markers measurements and R0 surgery rate.Adverse events were graded according to classification of the National Cancer Institute Common Toxicity Criteria version 4.0. RESULTS: Thirty-one patients were included in this study. Use of preoperative chemotherapy showed partial response in fourteen patients (45.1%), stabilization in fifteen patients (48.4%). Tumor markers CEA and CA 19- 9 were significantly decreased. R0 resection rate was 83.87%. Only 2 (6.45%) cases of grade 3/4 hematologic toxicity were reported in our study. Achieving programmed postoperative chemotherapy was possible in 72.41% of patients. CONCLUSIONS: Our study is limited by the retrospective design and small sample size but FOLFOX chemotherapy seems effective and well tolerated in this setting and its place deserves to be studied in a larger study.

Endometrial stromal sarcoma: prognostic factors and impact of adjuvant therapy in early stages.

BACKGROUND AND OBJECTIVES: Endometrial stromal sarcomas (ESS) are rare uterine neoplasms. surgery remains the cornerstone of treatment for early stages and consists of an abdominal hysterectomy with bilateral salpingo-oopherectomy. Despite appropriate surgical treatment, relapse rates are high (18% to 45%) and the value of adjuvant therapies is not clear. We evaluated prognostic factors and the impact of adjuvant treatment on localized ESS (stages I and II). DESIGN AND SETTING: Retrospective, case-control study conducted at the National Institute Of Oncology in Rabat, Morocco over 10 years from 2000 to 2009. PATIENTS AND METHODS: twenty-one cases of localized ESS were included in the analysis. RESULTS: standard surgery was performed in 71.4% of our patients. Myometrial invasion was noted in 57.1% of cases. Mitotic activity was considered high in five patients. Adjuvant treatment was given to 52.3% of patients: endocrine therapy in five patients and radiotherapy in six. Survival was significantly longer in the group of patients who underwent standard surgical treatment (P=.0007), in the absence of deep myometrial invasion (P=.0248) in cases with a low mitotic index (P<.0001) and in patients who received adjuvant therapy (hormone or radiotherapy) (P=.0048). In a multivariate analysis independent risk factors for monitoring were inadequate surgical treatment and absence of adjuvant treatment. CONCLUSIONS: Myometrial invasion and mitotic index appear to be important prognostic factors. the reference surgery is hysterectomy with bilateral salpingo-oopherectomy. Lymph node dissection does not appear to provide a benefit. finally adjuvant treatment may carry a significant survival benefit.

[Pleomorphic carcinoma of the lung: a case report]. / Le carcinome pléomorphe du poumon. À propos d'un cas.

Pleomorphic carcinoma is a rare malignancy belonging to the family of nonsmall cell lung cancers. A 40-year-old man, a smoker, was hospitalized for thoracic pain and dry cough with a deteriorating general condition. The imaging showed a "drop ball" of both lungs. The pathological evidence was obtained by lung biopsy under scanographic control. The presence of supraclavicular and abdominal nodes classified the tumour as stage IV. The patient received six cycles of first-line chemotherapy associating cisplatin and vinorelbine. However, the disease continued to progress and distant metastases were observed. The patient died 6 months after the diagnosis. Pleomorphic carcinoma is identified by purely histological criteria: the concomitant presence of malignant epithelial and homologous sarcomatoid spindle-cell components. Like the other nonsmall cell lung cancers, the treatment is primarily surgical, and the invasive nature of this tumour makes it very difficult. Pleomorphic carcinoma has a poorer prognosis than conventional nonsmall cell lung cancers despite surgery, irradiation and chemotherapy, because relapse occurs early.

[Cardiac safety of trastuzumab in adjuvant: a review across 53 observations]. / Tolérance cardiaque du trastuzumab en adjuvant: revue à travers 53 observations.

Trastuzumab has been a revolution in the treatment of breast cancer overexpressing HER. Its use as an adjuvant for a period of 1 year is currently an international standard. Its major toxicity is cardiac, where the systematic monitoring of the LVEF before and during treatment. To evaluate the cardiac safety for our patients, we conducted this retrospective case-control study. The average in LVEF before the start of trastuzumab was 62.5% (51-80), and at the end of treatment 60.55 (40-77), a decrease in absolute value by 2%. This difference is statistically significant with P<0.001. Eighty-three percent of our patients have completed treatment, of whom 26.4% with a provisional arrest because of a regressive fall in LVEF. A final arrest has been made in 17% cases due to either a nonregressive reduction in LVEF or the appearance of symptomatic heart failure found in two patients. Analysis of risk factors toxicity found in this group of patients with a cardiotoxicity persisting an average age and average number of treatments received anthracyclines higher than the rest of our sample, and diminished baseline LVEF. But all these differences were not statistically significants. During the period of monitoring of these patients, six (67%) had spontaneous recovery of their LFEV 5 months ± 2.01 after discontinuation of trastuzumab. For two cases of symptomatic heart failure, they had a clinical improvement under medical treatment in February but is still less than 40%. The cardiac safety in our study seems comparable with the literature data but located in the upper range of levels of toxicity. The lack of statistical power of our study does not exclude a greater cardiac toxicity of trastuzumab among Moroccan women and should prompt a more cautious use of this drug and the achievement of larger studies that could answer this question.

Intérêt des marqueurs tumoraux sériques dans les cancers digestifs

Les marqueurs tumoraux sont des composés produits par les cellules cancéreuses ou leur environnement se retrouvant en quantité suffisante dans le sang, les urines et les liquides d'effusion. Les marqueurs les plus utilisés en pathologie digestive sont l'antigène carcino-embryonnaire (ACE), l'alpha foetoproteine (_FP) et le CA19-19. Le but de notre travail est de discuter l'intérêt de ces trois marqueurs dans le dépistage, le suivi et le pronostic des cancers gastriques, pancréatiques, colorectaux et hépatiques.La faible sensibilité et l'existence de faux positifs rendent parfois ces marqueurs impropres à une stratégie de dépistage. Par contre, seul l'_FP a une valeur diagnostique dans les hépato carcinomes pour les populations à haut risque. L'ACE et le CA19-9 ont une bonne sensibilité et une spécificité relative qui leur permettent de suivre l'évolution des cancers digestifs en particulier les cancers colorectaux. Ils constituent les meilleurs marqueurs pour évaluer le pronostic, l'efficacité thérapeutique et pour dépister les récidives de façon précoce. Leur association est justifiée et permet d'atteindre 91% de spécificité et 76% de sensibilité.Devant la place occupée par la biologie dans le diagnostic, le pronostic et le suivi des cancers digestifs par le dosage des marqueurs tumoraux, nous nous devons que de reconnaître tant leurs performances que leurs limites

[Sacrum histoplasmosis 10 years after NHL of the sacrum: a case report]. / Histoplasmose sacrée dix ans après un lymphome non hodgkinien du sacrum: à propos d'un cas.

The location of bone histoplasmosis is rare. It is a parasitic infection caused by Histoplasma capsulatum, affecting especially the immunocompromised. Diagnosis is difficult, requiring the use of mycological and histopathological studies. Through this observation, we report a rare sequence of the development of sacrum histoplasmosis in a patient treated 10 years ago for a malignant non-Hodgkin lymphoma of the sacrum with complete remission. The clinical and radiological investigations suggested a lymphomatous relapse but the pathological study showed histoplasmosis. Antifungal treatment was started with an encouraging evolution.

[Primary adenoid cystic carcinoma in breast]. / Carcinome adénoïde kystique primitif du sein.

Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm. We report two observations occurring in female patients, 54 and 65 years old, who consulted for a mastodynia. Clinical examination showed limited painful breast nodules. On ultrasound and mammography they are well-limited bulky mass without microcalcifications. Diagnosis was based on final histopathological exam completed by immunohistochemistry or after slides review. The two patients were treated by mammectomy plus adjuvant radiotherapy and remain alive in remission with a follow-up of 29 and 36 months.

Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox.

Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.

[Nutritional workshops for cancer patients: a pilot approach]. / Les ateliers de nutrition en oncologie médicale: une expérience pilote.

The authors describe an original experience with 3 years of a nutritional workshop for cancer patients. This intervention combine an information about nutritional aspects of cancer with psychosocial support, to buffer psychological and nutritional consequences of cancer. The workshop, leaded by two specialized teams, one in medical oncology, the other in public health, is proposed to patients during and after a specific treatment. In one day, it provided information about nutrition and cancer, diet education and psychosocial support with supportive-expressive group. At this day, the evaluation of this intervention is only subjective. Fifty-six patients participated in at least one workshop, with majority of women (91%). Nineteen workshops were leaded with average participant number of 7 per workshop the third year. The authors believe that nutritional workshops are of great help for cancer patients, by enhancing social reinsertion, giving opportunity of emotional expression and humanizing the treatment. Our experience show it is possible to propose psychosocial intervention in institution in the context of Mediterranean country. We are leading currently a study that will permit a more systematic evaluation of the effects of this intervention.

Assessment of urinary hydroxypyridinium cross-links measurement in osteoarthritis.

The aim of this study is to re-evaluate urinary collagen cross-links, previously proposed as markers of osteoarthritis (OA). The urinary excretion of collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), was measured using high-performance liquid chromatography (HPLC) in 114 patients with OA, 19 patients with rheumatoid arthritis (RA) and 40 healthy subjects. An increase in PYD and DPD, expressed per millimole of creatinine, was confirmed in RA. However, PYD and DPD in patients with hip OA, knee OA and polyOA were similar, and did not differ from controls. In patients with radiographic end-stage OA, PYD and DPD were significantly higher than in patients with an early OA, but not significantly higher than in controls. The PYD/DPD ratio did not vary with the OA stage. Thus, urinary collagen cross-links are not elevated in OA, but could reflect bone sclerosis and/or erosion in late OA.

Genetic diversity of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis revealed by restriction fragment length polymorphism of the rRNA gene region.

The restriction fragment length polymorphism patterns of rDNAs from Pseudomonas aeruginosa strains isolated from the respiratory tracts of patients suffering from cystic fibrosis were obtained to evaluate the genetic polymorphism of this population of strains. Eighty-seven P. aeruginosa strains isolated from 87 patients from diverse areas of France and the ATCC 10145 strain were examined. Four restriction enzymes were used: BamHI, ClaI, EcoRI, and PstI. Forty-nine strains (56%) were in the three most frequent ribotypes (ribotypes R1 to R3). In addition, hierarchical clustering analysis of the data showed that 71 of the 88 strains (81%) clustered at a distance of less than one-third of the greatest distance observed in the total population. This indicates that clinical isolates implicated in the pathology of cystic fibrosis present a low degree of heterogeneity of rRNA operons, in contrast to the heterogeneity of strains of P. aeruginosa isolated from patients with various other pathologies. This relative homogeneity of rRNA genes was observed independently of the clinical status of the patient and the colony morphology.