Benjamin Merlot

Epithelial–mesenchymal transition in ovarian cancer

Ovarian cancer is a highly metastatic disease and the leading cause of death from gynecologic malignancy. Hence, and understanding of the molecular changes associated with ovarian cancer metastasis could lead to the identification of targets for novel therapeutic interventions. The conversion of an epithelial cell to a mesenchymal cell plays a key role both in the embryonic development and cancer invasion and metastasis. Cells undergoing epithelial-mesenchymal transition (EMT) lose their epithelial morphology, reorganize their cytoskeleton and acquire a motile phenotype through the up- and down-regulation of several molecules including tight and adherent junctions proteins and mesenchymal markers. EMT is believed to be governed by signals from the neoplastic microenvironment including a variety of cytokines and growth factors. In ovarian cancer EMT is induced by transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and endothelin-1 (ET-1). Alterations in these cellular pathways candidate them as useful target for ovarian cancer treatment.

Breast cancer during pregnancy

Breast cancer in pregnancy is an uncommon situation but poses dilemmas for patients and their physicians. There is a paucity of prospective studies regarding diagnosis and treatment of breast cancer during pregnancy. Women diagnosed with breast cancer during pregnancy have similar disease characteristics to age-matched controls. Current evidence suggests that diagnosis may be carried out with limitations regarding staging. Surgical treatment may be performed as for non-pregnant women. Radiotherapy and endocrine or antibody treatment should be postponed until after delivery. Chemotherapy is allowed after the first trimester. Physicians should be aggressive in the workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment without delay.

Implications of a two-step procedure in surgical management of patients with early-stage endometrioid endometrial cancer

Objective Since European Society for Medical Oncology (ESMO) recommendations and French guidelines, pelvic lymphadenectomy should not be systematically performed for women with early-stage endometrioid endometrial cancer (EEC) preoperatively assessed at presumed low- or intermediate-risk. The aim of our study was to evaluate the change of our surgical practices after ESMO recommendations, and to evaluate the rate and morbidity of second surgical procedure in case of understaging after the first surgery. Methods This retrospective single-center study included women with EEC preoperatively assessed at presumed low- or intermediate-risk who had surgery between 2006 and 2013. Two periods were defined the times before and after ESMO recommendations. Demographics characteristics, surgical management, operative morbidity, and rate of understaging were compared. The rate of second surgical procedure required for lymph node resection during the second period and its morbidity were also studied. Results Sixty-one and sixty-two patients were operated for EEC preoperatively assessed at presumed low-or intermediate-risk before and after ESMO recommendations, respectively. Although immediate pelvic lymphadenectomy was performed more frequently during the first period than the second period (88.5% vs. 19.4%; p<0.001), the rate of postoperative risk-elevating or upstaging were comparable between the two periods (31.1% vs. 27.4%; p=0.71). Among the patients requiring second surgical procedure during the second period (21.0%), 30.8% did not undergo the second surgery due to their comorbidity or old age. For the patients who underwent second surgical procedure, mean operative time of the second procedure was 246.1±117.8 minutes. Third operation was required in 33.3% of them because of postoperative complications. Conclusion Since ESMO recommendations, second surgical procedure for lymph node resection is often required for women with EEC presumed at low- or intermediate-risk. This reoperation is not always performed due to age/comorbidity of the patients, and presents a significant morbidity.

Chemotherapy Drug Extravasation in Totally Implantable Venous Access Port Systems: How Effective is Early Surgical Lavage?:

Purpose Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL). Methods Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively. Results Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft. Conclusions CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.

Laser interstitial thermotherapy application for breast surgery: Current situation and new trends

While breast specialists debate on therapeutic de-escalation in breast cancer, the treatment of benign lesions is also discussed in relation to new percutaneous ablation techniques. The purpose of these innovations is to minimize potential morbidity. Laser Interstitial ThermoTherapy (LITT) is an option for the ablation of targeted nodules. This review evaluated the scientific publications investigating the LITT approach in malignant and benign breast disease. Three preclinical studies and eight clinical studies (2 studies including fibroadenomas and 6 studies including breast cancers) were reviewed. Although the feasibility and safety of LITT have been confirmed in a phase I trial, heterogeneous inclusion criteria and methods seem to be the main reason for LITT not being yet an extensively used treatment option. In conclusion, further development is necessary before this technique can be used in daily practice.

Minimally invasive surgical management of early-stage cervical cancer: an analysis of the risk factors of surgical complications and of oncologic outcomes.

Objectives The objective of this study was to evaluate the morbidity and the oncologic outcomes of laparoscopic radical hysterectomy in treating early-stage cervical cancer. Methods We included all patients with early-stage cervical cancer (IA, IB1, IIA1, and IIB), as assessed by the Federation International of Gynecology and Obstetrics staging criteria, undergoing laparoscopic radical hysterectomy from January 1999 to December 2013 in our center. Morbidity was classified according to the Clavien and Dindo classification. Results A total of 170 patients were included in which 7 patients were in stage IA2, 150 in IB1, 2 in IIA, and 7 in IIB. The mean operation time was 256 minutes (67–495 minutes). Fourteen severe perioperative complications (8.2%) occurred, in which 5 patients (2.9%) required conversion to an open procedure: 3 bowel injuries, 3 hemorrhages, 2 ureteral injuries, 3 bladder injuries, 2 severe adhesions, and 1 intolerance to the Trendelenburg position. Fourteen patients (8.2%) presented with 1 severe postoperative complication (grade III or more). Two factors appeared as independent risk factors for perioperative and/or postoperative complications: the tumor size (odds ratio, 1.128; 95% confidence interval, 1.054–1.207) and operative time (odds ratio, 1.0116; 95% confidence interval, 1.003–1.020). In a median follow-up of 47.7 months, the 5-year overall survival was 94.1% (range, 88.1%–97.3%), and the 5-year disease-free survival was 88.8% (range, 81.0%–92.6%). Conclusions The laparoscopic approach was favorable for both perioperative and postoperative morbidity. With the advantage of minimal invasiveness, laparoscopic treatment by experienced surgeons is an alternative for early-stage cervical cancer with correct long-term survival outcomes. Mini-invasive surgery could be the standard in early-stage cervical cancer.