La chimiohyperthermie intrapéritonéale (CHIP) dans les cancers ovariens

RésuméLe cancer de l’ovaire reste, en France, la quatrième cause de décès par cancer chez la femme. Il s’agit d’une maladie souvent diagnostiquée à un stade évolué avec carcinose péritonéale (CP) et dont l’histoire naturelle est marquée par des récidives essentiellement péritonéales et l’acquisition d’un profil de chimiorésistance. Malgré les nombreuses lignes de chimiothérapie systémique et les chirurgies de cytoréduction (CCR), le pronostic de ces récidives reste sombre. Depuis plus de 20ans, plusieurs équipes spécialisées ont développé un traitement combiné des CP, associant une chirurgie de cytoréduction complète à une chimiohyperthermie intrapéritonéale (CHIP). Cette thérapeutique a une large place dans le traitement des CP d’origine non gynécologiques. Le rationnel pour une utilisation de la CHIP dans le traitement des CP d’origine ovarienne est important. D’une part, 3 études prospectives randomisées ont démontré la supériorité de l’utilisation de la chimiothérapie intrapéritonéale (sans hyperthermie) par rapport à la chimiothérapie systémique sur des patientes sélectionnées. D’autre part, des études rétrospectives et cas-témoins évaluant la CHIP font état de données de survie encourageantes, en particulier en cas de récidive chimiorésistante. Néanmoins, la morbidité et la mortalité associées doivent appeler à une sélection rigoureuse des patientes éligibles, et à une prise en charge multidisciplinaire dans des centres spécialisés. L’évaluation de la CHIP doit se faire par le moyen d’études randomisées à différents stades évolutifs : 1re ligne, consolidation, récidives qu’elles soient chimiorésistantes ou chimiosensibles. Plusieurs études européennes sont en cours.SummaryOvarian cancer remains the fourth leading cause of cancer death in women in France. It is all too often diagnosed at an advanced stage with peritoneal carcinomatosis (PC), but remains confined to the peritoneal cavity throughout much of its natural history. Because of cellular selection pressure over time, most tumor recurrences eventually develop resistance to systemic platinum. Options for salvage therapy include alternative systemic chemotherapies and further cytoreductive surgery (CRS), but the prognosis remains poor. Over the past two decades, a new therapeutic approach to PC has been developed that combines CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has already been shown to be effective in non-gynecologic carcinomatosis in numerous reports. There is a strong rationale for the use of HIPEC for PC of ovarian origin. On the one hand, three prospective randomized trials have demonstrated the superiority of intraperitoneal chemotherapy (without hyperthermia) in selected patients compared to systemic chemotherapy. Moreover, retrospective studies and case-control studies of HIPEC have reported encouraging survival data, especially when used to treat chemoresistant recurrence. However, HIPEC has specific morbidity and mortality; this calls for very careful selection of eligible patients by a multidisciplinary team in specialized centers. HIPEC needs to be evaluated by means of randomized trials for ovarian cancer at different developmental stages: as first line therapy, as consolidation, and for chemoresistant recurrence. Several European Phase III studies are currently ongoing

RECENT RESULTS FOR THE DEPENDENCE OF BEAM INSTABILITIES CAUSED BY ELECTRON CLOUDS AT CESRTA DUE TO VARIATIONS IN BUNCH SPACING AND CHROMATICITY*

Abstract At the Cornell Electron-Positron Storage Ring Test Accelerator (CesrTA) experiments have been studying the interaction of the electron cloud (EC) with 2.1 GeV stored electron and positron beams. These experiments are intended to characterize the dependence of beam-EC interactions on various beam parameters, such as bunch spacing and vertical chromaticity. Most experiments were performed with 30 or 45-bunch trains, at a fixed current of 0.75 mA/bunch. Earlier experiments with positrons had varied the bunch spacing between 4 and 56 ns at three different vertical chromaticity settings. More recent measurements have included electron-bunch trains to contrast the build up of EC between electron and positron beams. The dynamics of the stored beam was quantified using: a gated Beam Position Monitor (BPM) and spectrum analyzer to measure the bunch-by-bunch frequency spectrum of the bunch trains; an x-ray beam size monitor to record the bunch-by-bunch, turn-by-turn vertical size of each bunch within the trains. We report on recent observations from these experiments and additional studies, using witness bunches trailing 30 or 45-bunch positron trains, which were used for the generation of the ECs

EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases: Implications for targeted radiotherapy

<p>Abstract</p> <p>Background</p> <p>Proteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.</p> <p>Methods</p> <p>Expression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).</p> <p>Results</p> <p>EGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.</p> <p>Conclusion</p> <p>The EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.</p

The value of mastectomy flap fixation in reducing fluid drainage and seroma formation in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Prolonged and excessive drainage of serous fluid and seroma formation constitute the most common complications after mastectomy for breast carcinoma. Seroma formation delays wound healing, increases susceptibility to infection, skin flap necrosis, persistent pain and prolongs convalescence. For this, several techniques have been investigated to improve primary healing and minimize seroma formation.</p> <p>Materials and methods</p> <p>Between June 2009 and July 2010 forty patients with breast carcinoma, scheduled for modified radical mastectomy, were randomly divided into 2 groups, the study group (20) and the control group (20). In the study group; the mastectomy flaps were fixed to the underlying muscles in raws, at various parts of the flap and at the wound edge using fine absorbable sutures. In the control group; the wound was closed in the conventional method at the edges. Closed suction drains were used in both groups. Patients, tumor characteristics and operative related factors were recorded. The amount and color of drained fluid were recorded daily. The drains were removed when the amount become less than 50 cc. The total amount and duration of drained fluid and the formation of seroma were recorded and the results were compared between the two groups.</p> <p>Results</p> <p>In the flap fixation group, the drain was removed in significantly shorter time compared to the control group (p < 0.001). Also, the total amount of fluid drained was significantly lower in the flap fixation group (p < 0.001). The flap fixation group showed a significantly lower frequency of seroma formation compared to the control group, both clinically (p = 0.028) and ultrasonographically (p = 0.047).</p> <p>Conclusions</p> <p>The mastectomy flap fixation technique is a valuable procedure that significantly decreases the incidence of seroma formation, and reduces the duration and amount of drained fluid. However, it should be tried on a much wider scale to prove its validity.</p

NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment

Spontaneous CD4+ T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4+ T cells in EOC patients with spontaneous immune responses to the antigen are prevalently TH1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer+ cells ex vivo, at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer+ cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25+FOXP3+Treg. Thus, spontaneous CD4+ T-cell responses to ESO in cancer patients are prevalently of TH1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines

Axillary lymph node dissection for breast cancer utilizing Harmonic Focus®

<p>Abstract</p> <p>Background</p> <p>For patients with axillary lymph node metastases from breast cancer, performance of a complete axillary lymph node dissection (ALND) is the standard approach. Due to the rich lymphatic network in the axilla, it is necessary to carefully dissect and identify all lymphatic channels. Traditionally, these lymphatics are sealed with titanium clips or individually sutured. Recently, the Harmonic Focus^®, a hand-held ultrasonic dissector, allows lymphatics to be sealed without the utilization of clips or ties. We hypothesize that ALND performed with the Harmonic Focus^®will decrease operative time and reduce post-operative complications.</p> <p>Methods</p> <p>Retrospective review identified all patients who underwent ALND at a teaching hospital between January of 2005 and December of 2009. Patient demographics, presenting pathology, treatment course, operative time, days to drain removal, and surgical complications were recorded. Comparisons were made to a selected control group of patients who underwent similar surgical procedures along with an ALND performed utilizing hemostatic clips and electrocautery. A total of 41 patients were included in this study.</p> <p>Results</p> <p>Operative time was not improved with the use of ultrasonic dissection, however, there was a decrease in the total number of days that closed suction drainage was required, although this was not statistically significant. Complication rates were similar between the two groups.</p> <p>Conclusion</p> <p>In this case-matched retrospective review, there were fewer required days of closed suction drainage when ALND was performed with ultrasonic dissection versus clips and electrocautery.</p