[Targeted therapy in thyroid cancer: Towards a treatment card]. / Les thérapies ciblées dans le cancer de la thyroïde: vers un traitement personnalisé?

Thyroid cancer is an uncommon cancer. Molecular biology plays a vital role in its development. Chemotherapy showed unsatisfactory results in advanced stages where surgery and iodine therapy are not appropriate. These last ten years have been marked by a major advance in understanding the molecular features of this cancer and therapeutic correlations, moreover, clinical trials have focused on the treatment of this disease on metastatic stages and led to a significant therapeutic panel targeting angiogenesis, mutations frequently found in cervical cancer: RET, BRAF, RAS... these are the motesanib, axitinib, sunitinib, pazopanib, vandetanib, cabozotinib and sorafenib. The last three molecules have already the autorisation of FDA and EMA. In this review, we will put the item on oncogenetic characteristics of thyroid carcinoma as well as new targeted therapies in patients refractory to conventional treatment.

Diagnosis of Cholecysto-Colonic Fistula Using Gadoxetic Acid - Magnetic Resonance Cholangiography.

We report the demonstration (for the first time to our knowledge) of a cholecysto-colonic fistula using Primovist® enhanced MRCP in a 74-year-old patient. We discuss the advantage of this newly emerged technique over traditional T2-weighted MRCP in this indication.

[Targeted therapies in digestive oncology]. / Les thérapies ciblées dans la cancérologie digestive.

Targeted therapies have an increasing importance in digestive oncology. These new treatments have been authorized in colon cancer, gastric cancer, pancreatic cancer, endocrine cancer and gastrointestinal stromal tumors. The oncologist should develop high abilities to use these therapies especially concerning the indications, response's biomarkers, toxicities and evaluation methods.

[Predictive factors of response to anthracyclines neoadjuvant chemotherapy in breast cancer]. / Chimiothérapie néoadjuvante par anthracyclines dans le cancer du sein : facteurs prédictifs de réponse.

OBJECTIVES: Anthracyclines chemotherapy remains primordial and impossible to circumvent in the treatment of breast cancer, in the adjuvant, metastatic and neoadjuvant setting. But some breast invasive tumors are resistant to anthracyclines. The neoadjuvant model is ideal to test the chemosensibility by selecting the well-responder patients and identifying the predictive factors of this response. PATIENTS AND METHODS: We report a retrospective study of 126 patients treated at our institute during 2 years (January 2003-December 2004) for a breast cancer with primary chemotherapy. All the patients received anthracyclines according to protocol AC60 (doxorubicine plus cyclophosphamide). RESULTS: The clinical objective response rate (RO) was 67 % with a complete clinical response (RC) of 11 %. We found a pathological complete response (pCR) in seven patients (5,6 %) of the 126 cases. The statistical study identifies only two clinical factors as predictive of RC and pCR: tumoral size T2-T3 and clinical nodal status N0-N1, while the SBR grading and the hormonal receptors were not correlated. DISCUSSION AND CONCLUSION: Some clinical and histological factors are recognized as predictive for the benefit of anthracyclines neoadjuvant chemotherapy, and correlated to the pCR; we discuss our results through those of the literature, by exposing the current data.

[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.

Treatment for metastatic nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis, especially for locally advanced stages (IIB - IVB) and metastasis, remains poor: more than third of cases will present local and/or metastatic recurrence. Overall 5-year survival for all NPC stages ranges from 50% to 70%. The role of chemotherapy in metastasis is well established, and remains an important palliative treatment, although no randomized trial has been reported comparing the different chemotherapy regimens. As 1(st)-line treatment, platin-based regimens seems optimal; in 2(nd) line and after progression under platins, there is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or taxanes has been the most widely tested, with acceptable results. Future trials should integrate targeted therapy, in the light of overexpression of EGFR1 and C-kit in NPC. The present study presents a review of the literature concerning the various studies of metastatic NPC.

[Prevalence of elevated serum CA 15-3 at time of metastatic relapse of breast cancer and correlation with hormone receptor status]. / Prévalence de l'élévation du CA 15-3 lors de la rechute métastatique des cancers du sein: corrélation avec l'expression des récepteurs hormonaux et de Her2.

CA15-3, a peptide derived from MUC-1, an hormonally-regulated protein, is the most widely used serum marker of breast cancer. CA15-3 level increases at the metastatic phase in 50-80% breast cancer patients. Although rise of CA15-3 precede symptoms of metastasis by a mean time of 2-9 months, current international guidelines do not recommend its routine use for screening for metastases because of moderate sensitivity and absence of clinical impact. We conducted a retrospective study among all patients with metastatic breast cancer seen by three senior breast oncologists during a 4-month period. We evaluated correlation of CA15-3 level at the time of metastatic relapse with ER, PgR and Her2 expressions, tumor type, size and nodal status at initial diagnosis, and sites of metastases. CA15-3 was increased in 168/272 patients (62%) at diagnosis of metastases. ER/PgR positivity was strongly correlated with elevated CA15-3 at this time (P < 0.0001). CA 15-3 was elevated in 69% of the cases of HR+ Her2- primary tumors at time of metastatic relapse. It was elevated in 56% of HR+ Her2+++, 46% of HR- Her2+++ cases and only in 41% of triple-negative cases (P = 0.003). these data confirm that CA 15-3 is very variably elevated at time of metastatic relapse of breast cancer, and this is dependant on HR status.

Optimization of preservatives in a topical formulation using experimental design.

Optimizing the preservative regime for a preparation requires the antimicrobial effectiveness of several preservative combinations to be determined. In this study, three preservatives were tested: benzoic acid, sorbic acid and benzylic alcohol. Their preservative effects were evaluated using the antimicrobial preservative efficacy test (challenge-test) of the European Pharmacopeia (EP). A D-optimal mixture design was used to provide a maximum of information from a limited number of experiments. The results of this study were analysed with the help of the Design Expert software and enabled us to formulate emulsions satisfying both requirements A and B of the EP.

The lyophilization of dispersed systems: influence of freezing process, freezing time, freezing temperature and RBCs concentration on RBCs hemolysis.

In this work, we studied the influence of different parameters controlling cooling stage on biological dispersed system injury. The human red blood cell (RBCs) was chosen as work model. The study examined the influence of two freezing processes on RBCs hemolysis, one process producing big crystals, the other producing small crystals. Using both processes, we examined the effect of freezing temperature, freezing time, and RBCs concentration on injuries to RBCs. Freezing damage was assessed by the hematocrite measure before freezing and after thawing. The process producing a small number of big ice crystals (Pa) seems--in relation to the one producing a large number of small ice crystals (Pb)--to be less traumatic for the RBC, although the two are not statistically different. Freezing temperature and freezing time influence the preservation of RBCs. At 0 and -20 degrees C there were high preservation and total hemolysis, respectively. At -5 degrees C and -10 degrees C, the RBC hemolysis depends on freezing temperature and freezing time. The RBCs hemolysis rates increases when freezing time increases and when freezing temperature decreases. The rates of RBCs preserved decreases with RBCs concentration some with either the freezing process used (Pa or Pb). More, an accentuation of the difference between the two used freezing processes on RBCs hemolysis was retrieved. The analysis of the conductivity evolution within the RBCs suspension frozen showed that the destruction of the RBCs is had essentially to the solution effects. When the crystallization eutectic takes place, the RBCs are already completely destroyed.

Freeze-drying of emulsions--influence of congealing on granulometry research of a cryoprotective agent.

Emulsions of three different size distributions and five oil/water ratios of the finest of these distributions were congealed according to three different congealing processes before the freeze-drying operation. The influence of the various cryoprotective agents added was studied and the size change of the dispersed phase after congealing was examined.