Place de l’imagerie dans l’évaluation de l’efficacité des traitements dans le cancer du sein

This paper describes, from the current literature, the role of various imaging methods to assess the response to therapy in breast cancer. Two different clinical situations are considered: neoadjuvant chemotherapy of locally advanced breast cancer and the metastastic breast cancer. Significant clinical data are available for three criteria: the volume of the tumour, the uptake of fluorodeoxyglucose using PET and the perfusion of the tumor evaluated either by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) or by PET using ¹⁵O water. ¹⁸F FDG PET allows prediction of the response after one or two cycles of neoadjuvant chemotherapy. New approaches will offer opportunities to refine the role of imaging in monitoring the response to chemotherapy. PET using thymidine as biomarker is promising in assessing the tissular proliferation. Estrogen analogs could be used to predict hormonally responsive breast cancer. Many other approaches, although less developed, might offer new insights in the response to therapy of breast cancer like magnetic resonance spectroscopy or optical imaging of hemoglobin oxygenation. Imaging also offers potential of monitoring the down-regulation of specialized receptors of the cell membrane in response to treatment: the most studied receptor in preclinical model has been the human epidermal growth factor receptor type 2 (HER2). Integrin, a family of cell adhesion receptor, is also an important target for imaging. Apoptosis, multidrug resistance and hypoxia can also be studied using appropriate biomarkers. To allow reliable multicenter trials of new drugs, these different imaging approaches still require an improved standardization of image acquisition and processing.     

Place de l’embolisation percutanée de la varicocèle dans le traitement de l’infertilité

Objectives

To describe percutaneous embolization of varicocele and to evaluate the effect on fertility disorders.

Materials and methods

One hundred nineteen patients, aged 11 to 48 years, underwent percutaneous embolization for varicocele indicated by a fertility disorder in 23% of cases. Correction of the varicocele and resolution of associated pain, improvement of testicular trophicity and the effect on fertility were studied and a review of the literature was performed.

Results

Percutaneous embolization was performed using neuroleptanalgesia on an outpatient basis. The technique combined venous sclerotherapy and placement of coils in the gonadal vein. The technique was successful in 95% of cases and one complication was observed. At 3 months, the varicocele and related pain had resolved in 98% of treated patients. According to previous reports in the literature, the relations between varicocele and fertility disorders are still unclear, but improvement of fertility (semen quality and conception rates) after varicocele repair has been established.

Conclusion

Although the consequences of varicocele on fertility have not been fully elucidated, treatment of varicocele appears to be beneficial. Percutaneous embolization of varicocele is a safe and effective alternative to surgery. This technique, based on a urological and radiological consensus, is the first-line treatment for varicocele in our institution.     

Importance de l’étape pré-analytique en spermiologie pour le diagnostic et l’évaluation des thérapeutiques

Semen analysis is subject to great variability, partly due to the mechanism of ejaculation. This variability can be reduced by taking certain precautions, such as interviewing the patient to eliminate any external factor of variability, by imposing a 3- to 5-day period of sexual abstinence, by explaining the procedures to avoid bacterial contamination of the sample, by verifying whether the whole semen sample has been collected, by checking that the temperature of the sample is maintained at 37°C and finally, by carefully homogenising the sample to obtain good quality liquefaction.     

Intérêt de l’analyse de la morphologie fine et de la qualité nucléaire des spermatozoïdes dans le cadre des techniques d’AMP

Routine semen examination does not identify minor malformations of the sperm nucleus and chromatin architectural defects, which may be associated with ART outcome and cannot be detected by the embryologist even at 1000x magnification. Recent publications have demonstrated the advantages, compared to routine analysis, of a new method of real-time detailed morphological evaluation of motile spermatozoa: motile sperm organellar morphology examination (MSOME). MSOME is performed with an inverted light microscope equipped with high-power differential interference contrast optics enhanced by digital imaging to achieve a magnification of 10000x. To be considered morphologically normal, a sperm nucleus must have both a normal shape and a normal chromatin content. The aim of the present study was to combine MSOME and sperm DNA fragmentation characteristics to assess reproductive outcome. The study population consisted of the male partners of 52 couples referred for conventional IVF or split cycles (half IVF-half ICSI cycles) and exhibiting normal routine sperm parameters. Spermatozoa were analysed by examining the fine nuclear morphology and DNA integrity using the sperm chromatin dispersion test (SCD test), based on the principle that the deproteinized nuclei of spermatozoa with nonfragmented DNA show extended halos of DNA dispersion that are either absent or only minimally present in sperm nuclei with fragmented DNA. Fertilization rates were significantly lower in the group showing less than 8% of normal spermatozoa according to MSOME criteria, but early embryo development was not affected. Fine sperm morphology correlated with DNA fragmentation rate. These results demonstrate that the assessment of sperm nuclear normality by MSOME analysis and SCD test improves characterization of the semen sample and should be evaluated as a tool for allocating patients to specific assisted reproduction treatments.     

Rôle de la TEP FDG dans l’évaluation de l’extension locorégionale et à distance du mélanome

FDG PET/CT is a relevant examination for patients with high-risk melanoma. For early stages with thickness ≥ 1 mm, lymph node ultrasound, and when negative, lymphoscintigraphy for determination of sentinel lymph node, remain necessary. For more advanced stages, FDG PET can map the lesions and guide the therapeutic strategy, either with surgical management, or systemic therapy (or sometimes both). In patients with high-risk melanoma, it allows to detect relapses early, including in asymptomatic patients, with a potential impact on therapeutic decisions. Beside the detection of classical secondary localizations, FDG PET has the advantage of allowing whole-body imaging, the identification of soft tissue lesions, frequent in melanomas, as well as rarer sites of involvement, such as those of the gastro-intestinal tract. For the assessment of cerebral and leptomeningeal involvement, MRI remains mandatory. Evolutions in the therapeutic management of advanced melanomas, and the search for biomarkers to guide the therapeutic strategy, ask for more refined analyses of PET, with metabolic tumour volume analysis and radiomics. The combination of metabolic imaging data with biological and molecular data, and the development of new PET tracers may improve the assessment of prognosis and the prediction of response to therapies, in order to tailor the therapeutic strategy to each patient. Further studies are needed to consolidate the role of PET/CT in this disease for which numerous therapeutic innovations are emerging.     

Criblage de nouveaux gènes cibles des récepteurs nucléairesdes oxystérols LXRs impliqués dans le maintien de l’épithélium épididymaire et la maturation des spermatozoïdes dans l’épididyme

Liver X receptors (LXRs) are involved in cholesterol homeostasis and lipid metabolism.Ixr knock-out mice for the two isoformsIxra andIxrb exhibit severe disruption of the structure of caput epididymidis segment 1 and 2 epithelium and increased sperm fragility. These defects generate infertility in 10-month-old male mice. The role of LXRs in the epididymis have not yet been investigated. A cell line obtained from mouse caput epididymidis (B2 cells) was used to screen for LXR epididymal target genesin vitro. The presence of one isoform of LXR (LXRα) was detected by immunocytochemistry and the capacity of B2 cells to respond to a synthetic agonist of LXRs (T0901317) was verified. These results validated the use of B2 cells as a model. Bidimensional electrophoresis was performed on B2 cells treated with T0901317. Eight proteins up-regulated by LXRs were isolated. Only one protein has been identified: polyubiquitin, which has already been reported to be involved in cellular cholesterol homeostasis.     

Méthodes d’évaluation des érections automatiques nocturnes dans les dysfonctions érectiles

For more than 25 years, the study of nocturnal penile tumescence (NPT) has been a basic element in the investigation of erectile dysfunction. Numerous methods have been proposed; always non-invasive, generally not very onerous and easily achieved. They require little more than a basic understanding of physiology, and knowledge of the qualitative and quantitative criteria for assessing NPT, in order to avoid any incorrect or dangerous interpretation. Based on more than 8000 nights of recordings, it is possible to separate the advantages, inconveniences and operating costs of the major instrumentation options. Although rather unsatisfactory, plethysmography and rigidometry of NPT have become the cornerstone for investigating erectile dysfunction. Always necessary, sometimes these examinations alone are sufficient, for example when they are normal and allow confirmation of a psychogenic aetiology of impotence. In other situations they must be supplemented with other complementary examinations, in which case the results show an 80% correlation with NPT. A revival of interest in the study of NPT will occur once we have achieved the impossible: the availability of a cheap instrument allowing recording of turgidity, rigidity and REM sleep, without discomfort and in the patient’s home.     

Historique des études sur le paléolithique de l’Archipel du Japon

Paleolithic studies on the Japanese Archipelago started from the excavation of the Iwajuku Site in 1949. In 2000, research efforts were damaged by a forgery incident, which was concerned with the Lower/Middle Paleolithic period. After completing the investigation on the incident, the presence of the Lower/Middle Paleolithic remains unsolved. However, we have entered a new stage of research on the Upper Paleolithic for which over ten thousand sites were discovered. The new research framework places, at the heart, tephra-based lithic chronology, site structure analysis that investigates a site's formation process through conjoined pieces and parent rock analysis, and obsidian archaeology in which diachronic research is conducted on obsidian source exploitation and circulation range. Now unique characteristics of Japanese Paleolithic culture are coming to light, beginning with the migration from the neighboring continent, connecting East Asia through the Paleolithic Cultural Corridor around the Sea of Japan and the Obsidian Road, and nurturing the unique traditions of lithic production.     

Intérêt de la TEP dans le bilan d’extension et l’évaluation de la maladie résiduelle des séminomes testiculaires : étude rétrospective

AimsTo evaluate the value of PET/CT comparatively to CT in staging and restaging after chemotherapy of testicular seminoma, to assess quantitative methods and prognostic value of PET in post-chemotherapy residual masses.MethodsThirty-two patients and a maximum of 65 targeted lesions visualized on PET-CT and CT performed for staging and therapeutic response assessment were analysed and compared. Each lesion was quantified according to miscellaneous SUV normalized methods. Optimal threshold of SUV for prediction of residual disease was obtained (ROC method). The prognostic value of PET/CT at the completion of treatment was determined with progression free survival study (Kaplan-Meier method).ResultsPET/CT exhibited higher accuracy than CT in the initial staging and assessment of therapeutic response, respectively 98% versus 83.3% and 95.1% versus 75.6%. Quantification, whichever method, was not more efficient than visual reading for prediction of residual disease. Progression-free survival was higher with negative than with positive PET/CT (P = 0.0033).ConclusionOur work demonstrates that PET/CT exhibits better accuracy than CT in both staging and restaging at the end of treatment. Quantification methods do not improve accuracy of PET/CT for prediction of viable residual disease. The prognostic value of PET/CT appears very promising and needs to be confirmed by large prospective studies. PET/CT appears to be a relevant method of prognostic stratification of the risk of relapse in seminoma.     

Rôle de la TEP au 18F-FDG dans l’évaluation des volumes cibles chez des patients atteints de CBNPC traités par radiochimiothérapie

Currently ¹⁸F-FDG-PET is the gold standard to evaluate tumor response after chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC). PET can also determine the volumes to be treated by radiotherapy, in inoperable patients. The aim of our mixed (prospective and retrospective) study concerned 28 patients with NSCLC, was to quantify the variation of the metabolic activity of lesions and their volumes after chemotherapy. We also studied the impact of change of these volumes on the definition of radiotherapy target volumes. Patients with stage II–IV and inoperable NSCLC were included. Two PET scans were performed: before treatment (PET1), then after two to six courses of chemotherapy (PET2). Of the 28 patients included, we observed complete metabolic response in six patients (21%), partial metabolic response in 13 patients (46%), stable disease in seven patients (25%), and progressive metabolic disease in two patients (7%), according to the PERCIST criteria. We observed significant variation (P < 0.001) of metabolic activity (estimated by SULpeak or SUVmax) for primary tumor as well as for overall lesions between the two PET scans. Thus, the target volumes of radiotherapy decreased significantly (P < 0.01) in PET2. Our results confirm that ¹⁸F-FDG-PET is not only a powerful technique for treatment evaluation but also a useful tool for radiotherapy planning after chemotherapy, in the context of personalized treatments.     

Place de la prostaglandine E1 intra urétrale dans le traitement de l’impuissance érectile

Transurethral alprostadil (Muse) is an effective and safe treatment of erectile dysfunction. Nevertheless, the result after its exit on the US market two years ago were not as good as the investigational studies which claimed aroud 60% of sccess rate. In the litterature success rate were between 35% and 40% all together. The Muse had a better acceptance than the intra-cavernous injection despite a lower success rate (40 % v.s 75 %). Since Sildenafil came on the market, it seems that the place of Muse is reduced because comparative studies give better results for Sildenafil than Muse (70 % v.s 40 %) and of course with a better acceptance. Nevertheless there are absolute and relative counter-indications to the Sildenafil which could benefit to the treatment by Muse. All the comparative studies, IIC, v.s Muse and sildenafil v.s Muse will be studied in this article. In conclusion Muse should be used as an alternative and should remain an effective tool that must be available to all physicians dealing with erectile dysfunction, perhaps using new formula with a combination of alprostadil with an alpha-blocker.     

Quelques perspectives concernant le traitement des lymphomes par Zevalin® à partir de l’évaluation de l’expérience niçoise

Zevalin^® (yttrium-90 ibritumomab-tiuxetan) is the first radioimmunotherapy authorized in France for non-Hodgkin's lymphoma (NHL) treatment. It is indicated for clinical use in adults for recurrent or refractory follicular NHL including those refractory to rituximab. Treatment responses are between 70 and 80%. Since three years, 13 patients were treated in Nice by Zevalin^®. From this retrospective study, we discuss the various perspectives of this treatment. The majority of our patients in this study were evaluated by 18-FDG–PET and we also evaluated our results in this regard. Even if our follow-up is short, our experience confirms the efficacy and tolerance of Zevalin^® treatment in multirecurrent follicular NHL including those refractory to rituximab. The treatment is of interest in elderly patients and in case of autologous stem cell transplant. The proposed « Autorisation de Mise sur le Marché » (AMM) indication is probably not the best one since efficacy seems better in smaller tumour volumes and when used earlier in the therapeutic course. Zevalin^® will probably be more beneficial in first line treatment, for immunochemotherapy consolidation and for autologous stem cell transplant conditioning. We pointed out the prognostic value of FDG–PET for early post-treatment evaluation, one to two months after Zevalin^® administration. However, larger scale studies are necessary to confirm these findings.     

Apport de l’iode 131 dans le traitement de la maladie de Basedow dans le service de médecine nucléaire de l’hôpital Ibn Sina de Rabat

One hundred and twenty-nine Grave's Basedow diseases in any gender and variable age patients, coming from several cities of Morocco, were randomized in a study of radio-iodine treatment who took place at the nuclear medicine department of Ibn Sina Hospital (Rabat, Morocco) during the period (from January 2001 to December 2008). The radio-iodine treatment was a first, second or third option and radio-iodine activities delivered varied (from 222 to 555 MBq 6 to 15 mCi) according to the age, the thyroid volume, the degree of hyperthyroidism and socio-economical situation. The high amounts of ¹³¹I were reserved especially to the patients who live far and whose socio-economic level is low with an aim of quickly obtaining an easily controllable state of hypothyroidism by a substitute treatment. The results showed that: (1) 57.36% of patients reverted to euthyroïdism (n = 74) with a patient having received two ¹³¹I cures. The second cure was justified by recurrence of hyperthyroidism after the first cure; (2) 34.88% passed in hypothyroidism (n = 45) with three patients having received two cures of ¹³¹I, the second cure was justified by recurrence of hyperthyroidism after the first cure in two patients and by the persistence of the hyperthyroidism after the first cure for the third patient. The average time of passage in hypothyroidism was 4.5 months; (3) 7.76% had remained in hyperthyroidism after the radioactive iodine treatment. Finally, 92.24% of our patients treated by radioactive iodine had passed in euthyroïdism or hypothyroidism against 7.76% whose hyperthyroidism had persisted or occurred.     

Intérêt du dosage de l’inhibine B et de l’AMH dans le plasma séminal: étude préliminaire

Objectives

The aim of this study was to establish reference values for seminal inhibin B and AMH concentrations in patients with normal and abnormal sperm parameters. Preliminary analysis was performed to evaluate the predictive value of these markers for retrieving testicular sperm in non-obstructive azoospermic men.

Methods

Seminal inhibin B and AMH concentrations were assayed by an enzyme-linked immunoassay in three groups of men: 47 patients with normal sperm parameters, 28 oligospermic men and 68 patients with azoospermia.

Results

Inhibin B and AMH concentrations varied considerably in the three groups, but were significantly higher in normospermic men (inhibin B: 714.36±522.66 ng/l, AMH: 97.08±135.15 pmol/l) than in oligospermic men (inhibin B: 417.5±386.9 ng/l, AMH: 62.02±93.33 pmol/l) and azoospermic men (59.61±2.65 ng/l et 13.12±31.94 pmol/l, respectively) (p<0.001). A significant correlation (p=0.0054) was observed between seminal inhibin B concentration and sperm production. Testicular biopsy allowed sperm retrieval in 11 out of 21 patients (52.3%). The predictive value of seminal inhibin B was analyzed using receiver operating characteristics (ROC) curve analysis. The best discriminating inhibin B concentration was 30 ng/l with an area under the curve (AUC) of 0.63.

Conclusion

This study confirms the correlation between seminal inhibin B and AMH concentrations and spermatogenesis. However, the significance of these two markers as predictors of the presence of testicular sperm in men with non-obstructive azoospermia is limited. This analysis shows that AMH and inhibin B, either alone or in combination with serum FSH, fail to predict the presence of sperm in men with non-obstructive azoospermia undergoing testicular sperm extraction.     

Apport de l’exploration cytogénétique et ultrastructurale dans le pronostic de fertilité des sujets globozoospermiques

Globozoospermia is a severe form of teratozoospermia characterized by round-headed sperms with absence or presence of a rudimentary acrosome. The objective of this study is to analyze sperm from six patients with globozoospermia syndrome and report the results of 11 intracytoplasmic sperm injection (ICSI) attempts. The investigation of these issues was carried out by studying the sperm aneuploidy rate by fluorescent in situ hybridization (sperm-FISH) for chromosomes X, Yand 18. The rate of DNA fragmentation was studied by using the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) technique and a detailed ultrastructural morphology study of the sperm using transmission electron microscopy. Eleven ICSI attempts were performed in patients with low fertilization rate, (9.37%) and pregnancy did not occur. This study confirmed the variability of sperm phenotypes observed in this syndrome and the low fertilization rates after IVF-ICSI regardless of the phenotype.