Fabrice Lecuru

Bilateral Negative Sentinel Nodes Accurately Predict Absence of Lymph Node Metastasis in Early Cervical Cancer: Results of the SENTICOL Study

PURPOSE Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy. PATIENTS AND METHODS Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes. RESULTS One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally. CONCLUSION Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally.

Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings and is there a way of making a correct diagnosis

To determine which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings, and to determine if the use of logistic regression models for calculation of individual risk of malignancy would improve the diagnostic accuracy in difficult tumors.

Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure

OBJECTIVE Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis. DESIGN AND METHODS We performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center. RESULTS Seventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turners syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1. CONCLUSION A genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.

Blue dye injection in the arm in order to conserve the lymphatic drainage of the arm in breast cancer patients requiring an axillary dissection.

BackgroundDespite the widespread use of the sentinel lymph node biopsy technique, many patients with invasive breast cancer still undergo an axillary lymph node dissection and are at risk of arm lymphedema. With the new awareness of lymphatic spread in the axillary nodes, it should be possible to define a new surgical approach between sentinel lymph node biopsy and complete axillary dissection, a procedure preserving specifically lymph nodes in relation to the arm.MethodsTwenty-one patients with an operable breast cancer requiring an axillary dissection underwent surgery with an attempt to separate nodes related to the breast from specific nodes related to the arm. After an injection of blue dye in the arm, the surgeon performed the axillary dissection trying to identify blue nodes and ducts in order to preserve lymphatic arm drainage (LAD). If the blue nodes were located in the normal axillary dissection, they were removed separately.ResultsIn 15 of 21 patients (71%), blue nodes in relation with LAD were identified. In 10 (47%) patients, it was possible to dissect the LAD with the preservation lymphatic ducts. In 10 patients, the LAD nodes were removed: none of them contained metastases, despite the fact that the non-LAD axillary nodes contained metastases in 7 of 10 cases.ConclusionsIdentifying the LAD with blue dye injection in the arm is possible. A subsequent study can now begin to determine if this procedure is safe for patients and able to prevent lymphedema of the arm.

Guidelines for the management of ovarian cancer during pregnancy

Adnexal masses may be detected during prenatal ultrasound, and ovarian cancer may be suspected during pregnancy. Even though such masses are rarely malignant (1/10,000 to 1/50,000 pregnancies), the possibility of borderline tumour or cancer must be considered. It is a common assumption by both patients and physicians that if an ovarian cancer is diagnosed during pregnancy, treatment necessitates sacrificing the well-being of the fetus. However, in most cases, it is possible to offer appropriate treatment to the mother without placing the fetus at serious risk. The care of a pregnant woman with cancer involves evaluation of sometimes competing maternal and fetal risks and benefits. These recommendations attempt to balance these risks and benefits; however, they should be considered advisory and should not replace specific interdisciplinary consultation with specialists in maternal-fetal medicine, gynecologic oncology and pediatrics, as well as imaging and pathology, as needed. Second level ultrasound including Doppler is needed. MRI is not often necessary, and CA 125 is of low contribution. We suggest surgery be performed after 15 weeks gestation for ovarian masses which (1) persist into the second trimester, (2) are greater than 5-10 cm in diameter, or (3) have solid or mixed solid and cystic ultrasound characteristics. During the antepartum period surgical staging and debulking, unilateral salpingo-oophorectomy on the side with the tumour, peritoneal cytology and exploration are necessary. Women found to have advanced stage epithelial ovarian cancer should consider having completion of the debulking of the reproductive organs at the conclusion of the pregnancy. If chemotherapy is indicated, we recommend delaying administration, if possible, until after the delivery or at least after 20 weeks in order to minimize the potential fetal toxicity.

Hypoxia Down-regulates CCAAT/Enhancer Binding Protein-α Expression in Breast Cancer Cells

The transcription factor CCAAT/enhancer binding protein-alpha (C/EBP alpha) is involved in the control of cell differentiation and proliferation, and has been suggested to act as a tumor suppressor in several cancers. By using microarray analysis, we have previously shown that hypoxia and estrogen down-regulate C/EBP alpha mRNA in T-47D breast cancer cells. Here, we have examined the mechanism by which the down-regulation by hypoxia takes place. Using the specific RNA polymerase II inhibitor 5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside, the mRNA stability was analyzed under normoxia or hypoxia by quantitative reverse transcription-PCR. Hypoxia reduced the half-life of C/EBP alpha mRNA by approximately 30%. C/EBP alpha gene promoter studies indicated that hypoxia also repressed the transcription of the gene and identified a hypoxia-responsive element (-522; -527 bp), which binds to hypoxia-inducible factor (HIF)-1 alpha, as essential for down-regulation of C/EBP alpha transcription in hypoxia. Immunocytochemical analysis showed that C/EBP alpha was localized in the nucleus at 21% O(2), but was mostly cytoplasmic under 1% O(2). Knockdown of HIF-1 alpha by RNAi restored C/EBP alpha to normal levels under hypoxic conditions. Immunohistochemical studies of 10 tumor samples did not show any colocalization of C/EBP alpha and glucose transporter 1 (used as a marker for hypoxia). Taken together, these results show that hypoxia down-regulates C/EBP alpha expression in breast cancer cells by several mechanisms, including transcriptional and posttranscriptional effects. The down-regulation of C/EBP alpha in hypoxia is mediated by HIF-1.

Multi-Center Evaluation of Post-Operative Morbidity and Mortality after Optimal Cytoreductive Surgery for Advanced Ovarian Cancer

Purpose While optimal cytoreduction is the standard of care for advanced ovarian cancer, the related post-operative morbidity has not been clearly documented outside pioneering centers. Indeed most of the studies are monocentric with inclusions over several years inducing heterogeneity in techniques and goals of surgery. We assessed the morbidity of optimal cytoreduction surgery for advanced ovarian cancer within a short inclusion period in 6 referral centers dedicated to achieve complete cytoreduction. Patients and Methods The 30 last optimal debulking surgeries of 6 cancer centers were included. Inclusion criteria included: stage IIIc- IV ovarian cancer and optimal surgery performed at the site of inclusion. All post-operative complications within 30 days of surgery were recorded and graded using the Memorial secondary events grading system. Student-t, Chi2 and non-parametric statistical tests were performed. Results 180 patients were included. There was no demographic differences between the centers. 63 patients underwent surgery including intestinal resections (58 recto-sigmoid resection), 24 diaphragmatic resections, 17 splenectomies. 61 patients presented complications; One patient died post-operatively. Major (grade 3–5) complications requiring subsequent surgeries occurred in 21 patients (11.5%). 76% of patients with a major complication had undergone an ultraradical surgery (P = 0.004). Conclusion While ultraradical surgery may result in complete resection of peritoneal disease in advanced ovarian cancer, the associated complication rate is not negligible. Patients should be carefully evaluated and the timing of their surgery optimized in order to avoid major complications.

Gynecologic Cancer InterGroup (GCIG) consensus review for ovarian tumors of low malignant potential (borderline ovarian tumors).

Abstract Since the early 1970s, the World Health Organization and the International Federation of Gynecology and Obstetrics have classified borderline ovarian tumors as an independent group of ovarian epithelial tumors. A consensus statement of the Gynecologic Cancer Intergroup is reported.

Robotically assisted para-aortic lymphadenectomy: Surgical results: A cohort study of 487 patients

Objectives The aim of this study was to evaluate perioperative outcomes of robotic-assisted laparoscopic para-aortic lymphadenectomy (PAL) in patients with gynecologic cancers during the learning phases of robotic surgery programs and to compare results of extraperitoneal versus transperitoneal approaches of PAL. Materials and Methods This study is a retrospective multicentric study of patients who underwent robotically assisted laparoscopic PAL (N = 487). Eleven European centers and 1 US center participated in the study. Abstracted data included age, body mass index, indication, type of surgical approach (transperitoneal or extraperitoneal), associated surgical procedures, operative time, estimated blood loss, lymph node count, hospital length of stay (LOS), and complications. Para-aortic lymphadenectomy was performed by an extraperitoneal approach in 58 cases (12%) and transperitoneal in 429 cases (88%). Results The mean (SD) para-aortic lymph node count was 12.6 (8.1), operative time was 217 (85) minutes, estimated blood loss was 105 (110) mL, and LOS was 2.8 (3.2) days. Four (0.8%) conversions to open and 2 (0.4%) conversions to laparoscopy were described. There were 32 lymphocysts (6.6%), 3 deep venous thromboses (0.6%), and 10 transfusions (2.1%). For transperitoneal approach, the average number of lymph nodes removed was higher in isolated PAL group than the hysterectomy combined group (report node counts 95% confidence interval, −7.29 to −3.52, P = 1.5 × 10−6). For isolated PAL, the LOS was shorter in the extraperitoneal group than in the transperitoneal group (report data 95% CI, −1.35 to −0.35, P = 0.001). Conclusions Robotic-assisted PAL seems safe and feasible. More lymph nodes were removed during an isolated transperitoneal PAL dissection compared with a combined procedure with hysterectomy. Extraperitoneal approach seems attractive relative to transperitoneal dissection, but the superiority of one or the other way is not demonstrated by our study.

Role of video-assisted thoracoscopy in patients with ovarian cancer and pleural effusion.

Objectives: To evaluate the feasibility of video-assisted thoracoscopy (VAT) for staging advanced ovarian cancer, to measure the performance of preoperative computed tomography (CT) for diagnosing pleural metastases, to assess the correlation between pleural and abdominal involvement, and to measure the impact of VAT on patient management. Methods: We retrospectively evaluated 16 VAT procedures in 15 patients with advanced ovarian malignancies and pleural effusions. The reason for VAT was either to evaluate unilateral or bilateral pleural effusions (n = 15) or to evaluate pleural metastases after neoadjuvant chemotherapy (n = 1). Preoperative CT was performed routinely, and findings were compared with those of VAT. The rates of involvement of the hepatic pedicle, mesentery, and right side of the diaphragm were compared with the rate of pleural involvement. Results: The right side of the chest was examined 12 times; and the left side, 4 times. There were no complications; 1 procedure was stopped because of ventilatory intolerance. Video-assisted thoracoscopy identified metastases smaller than 1 cm in 5 patients and larger than 1 cm in 2 additional patients; there was no evidence of pleural involvement in 6 patients. Computed tomography had 14% sensitivity and 25% specificity for pleural status determination, using VAT biopsy as the reference standard. Pleural involvement did not correlate with involvement of the hepatic pedicle, mesentery, or right side of the diaphragm. Conclusions: Video-assisted thoracoscopy performs better than CT for evaluating pleural involvement in ovarian cancer. Video-assisted thoracoscopy supplies accurate data on thoracic involvement, which does not seem predictable from the peritoneal involvement. Video-assisted thoracoscopy may impact patient management.