Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1: Diagnostic exploration and staging, surgery, perioperative care, and pathology.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Short text of the French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

[Surgery for advanced stage ovarian cancer: Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Chirurgie des cancers avancés de l'ovaire. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

Debulking surgery is the key step of advanced stage ovarian cancer treatment with chemotherapy. The quality of surgical resection is the main prognosis factor, thus a complete resection must be achieved (grade A) in an expert center (grade B). Surgery for stage IV is possible and has a benefit in case of complete peritoneal resection (LoE3). Pelvic and aortic lymphadenectomies are recommended in case of clinical or radiological suspicious lymph nodes (grade B). In absence of clinical or radiological suspicious lymph nodes and in case of complete peritoneal resection during initial debulking surgery, lymphadenectomy can be omitted because it won't change nor medical treatment nor overall survival (grade B). Neoadjuvant chemotherapy can be proposed in case of: impossibility to perform initial complete surgical resection (grade B) ; alteration of general state or co-morbidities or elderly patient (in order to decrease morbidity and increase quality of life) (grade B); stage IV with multiple intra-hepatic or pulmonary metastasis or important ascites with miliary (grade B). In case of stage III or IV ovarian cancer diagnosed on a biopsy during prior laparotomy, a neoadjuvant chemotherapy and interval debulking surgery should be preferred (gradeC). In case of palliative surgery or peroperative impossibility to perform a complete resection, no data regarding the type of surgery to perform influencing survival or quality of life is available. Peritoneal carcinosis description before resection and residual disease at the end of the surgery should be reported (size, location and reason of non-extirpability) (grade B). A score of peritoneal carcinosis such as Peritoneal Carcinosis Index (PCI) should be used in order to objectively evaluate the tumoral burden (gradeC). A standardized operative report is recommended (gradeC).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

[Part I drafted from the short text of the French Guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Diagnosis management, surgery, perioperative care, and pathological analysis)]. / Partie 1 rédigée sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Explorations diagnostiques et bilan d'extension, chirurgie, soins périopératoires et anatomopathologie).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

Impact of axillary dissection in women with invasive breast cancer who do not fit the Z0011 ACOSOG trial because of three or more metastatic sentinel lymph nodes.

AIM: The objective of this study was to determine the effects of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy alone (SLNB) on the survival of patients with 3 or more metastatic lymph nodes (MLN) in invasive breast cancer. METHODS: Data of 9521 patients with invasive T1-2M0 breast carcinoma and initial treatment with SLNB completed or not by ALND and 3 or more MLN were extracted from the SEER database. Univariate and multivariate analyses were performed. RESULTS: Overall, 9521 patients were included in the study. SLNB-alone compared with ALND did not result in different overall survival (OS) or specific survival (SS) for patients with 3 or more MLN (p = 0.46 and 0.58, respectively). In subgroup analyses, OS was comparable between SLNB-alone and ALND when patients had only 3 or more than 3 MLN. When patients had 3 MLN, the 5-year SS was significantly better for patients with ALND compared with SLNB-alone: 91.5% and 85.1%, respectively (p = 0.02). The Hazard Ratio (HR) for OS comparing SLNB-alone with ALND adjusting for age, adjuvant radiotherapy, tumor size, estrogen receptor status, grade and tumor type resulted in an HR of 1.05 (95% CI, 0.72-1.54, p = 0.77). CONCLUSION: In conclusion, patients with a T1-T2 invasive breast cancer and at least 3 MLN do not benefit from ALND after SLNB for specific and overall survival, thus limiting ALND to a staging procedure. A subgroup of patients with 3 MLN had a better SS with ALND, possibly due to an under-staging of the SLNB-alone group.

Role of robot-assisted laparoscopy in adjuvant surgery for locally advanced cervical cancer.

OBJECTIVE: The aim of this study was to compare the feasibility and efficacy of robot-assisted laparoscopy with traditional laparotomy and conventional laparoscopy in a series of patients with locally advanced cervical cancer managed in our two institutions. METHODS: Twenty-two patients who underwent robot-assisted laparoscopy were compared with 20 patients who underwent adjuvant surgery by laparotomy and 16 who underwent conventional laparoscopy, before the arrival of the Da Vinci surgical system. RESULTS: There was no significant difference between the three groups in terms of body mass index, FIGO stage, or tumor histology. The complication rate was similar in the three groups of patients, although there was a trend towards more lymphatic complications in the robot-assisted subgroup managed medically. There was no significant difference in the recurrence rate between the robot-assisted laparoscopy, conventional laparoscopy and laparotomy groups (27.3%, 29.4% and 30%, respectively). CONCLUSION: Robot-assisted laparoscopy is feasible after concurrent chemoradiation and brachytherapy in cases of locally advanced cervical cancer. This new surgical approach reduces hospital stay, and seems to result in less severe complications than conventional laparotomy without modifying the oncological outcome.

IS911 transpososome assembly as analysed by tethered particle motion.

Initiation of transposition requires formation of a synaptic complex between both transposon ends and the transposase (Tpase), the enzyme which catalyses DNA cleavage and strand transfer and which ensures transposon mobility. We have used a single-molecule approach, tethered particle motion (TPM), to observe binding of a Tpase derivative, OrfAB[149], amputated for its C-terminal catalytic domain, to DNA molecules carrying one or two IS911 ends. Binding of OrfAB[149] to a single IS911 end provoked a small shortening of the DNA. This is consistent with a DNA bend introduced by protein binding to a single end. This was confirmed using a classic gel retardation assay with circularly permuted DNA substrates. When two ends were present on the tethered DNA in their natural, inverted, configuration, Tpase not only provoked the short reduction in length but also generated species with greatly reduce effective length consistent with DNA looping between the ends. Once formed, this 'looped' species was very stable. Kinetic analysis in real-time suggested that passage from the bound unlooped to the looped state could involve another species of intermediate length in which both transposon ends are bound. DNA carrying directly repeated ends also gave rise to the looped species but the level of the intermediate species was significantly enhanced. Its accumulation could reflect a less favourable synapse formation from this configuration than for the inverted ends. This is compatible with a model in which Tpase binds separately to and bends each end (the intermediate species) and protein-protein interactions then lead to synapsis (the looped species).