Richard Villet

Prognostic value of isolated tumor cells and micrometastases of lymph nodes in early-stage breast cancer: a French sentinel node multicenter cohort study.

To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis.

Characteristics and clinical outcome of T1 breast cancer: a multicenter retrospective cohort study

BACKGROUND A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST). PATIENTS AND METHODS Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized. RESULTS Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors. CONCLUSION Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.BACKGROUND A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST). PATIENTS AND METHODS Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized. RESULTS Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors. CONCLUSION Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.

Survival impact and predictive factors of axillary recurrence after sentinel biopsy.

BACKGROUND The rate of axillary recurrence (AR) after sentinel lymph node biopsy is usually low but few studies investigated its impact on survival. Our aim was to determine the rate and predictive factors of AR in a large cohort of breast cancer patients and its impact on survival. PATIENTS AND METHODS From 1999 to 2013, 14,095 patients who underwent surgery for clinically N0 previously untreated breast cancer and had sentinel lymph node biopsy were analysed. A simplified score predictive of AR was established. RESULTS Median follow-up was 55.2 months. AR was observed in 0.51% of cases, with a median time to onset of 43.4 months. In multivariate analysis, the occurrence of AR was significantly correlated with grade 2 or 3 disease, absence of radiotherapy and tumour subtype (hormonal receptor [HR]- / human estrogen receptor [HER]+). AR rates were 1% for triple-negative tumours, 2.8% for HER2-positive tumours, 0.4% for luminal A tumours, 0.9% for HER2-negative luminal B tumours, and 0.5% for HER2-positive luminal B tumours. A simplified score predictive of the occurrence of AR was established. Patients could be divided into three different score groups (p < 0.0001). In multivariate analysis, overall survival was significantly lower in cases of AR (p < 0.0001), age >50, lymphovascular invasion, grade 3 disease, sentinel node (SN) macrometastases, tumour size >20 mm, absence of chemotherapy and triple-negative phenotype. Survival in patients with AR was significantly lower in case of early-onset (2 years) AR (p = 0.017). CONCLUSIONS Isolated AR is more common in Her2-positive/HR-negative triple-negative tumours with a more severe prognosis in triple-negative and Her2-positive/HR-negative tumours, and represents an independent adverse factor justifying an indication for systemic treatment for AR treatment. However, the benefit of any systemic treatment remains to be proven.

Comparison of Anterior Colporrhaphy versus Bologna Procedure in Women with Genuine Stress Incontinence

Abstract: The aim of the study was to compare the anterior colporrhaphy and the Bologna operation for the treatment of anterior vaginal wall prolapse associated with genuine urinary incontinence (GSI). Sixty-two women undergoing surgery for GSI and concurrent grade 2–3 cystocele were the subjects of the study. Anterior colporraphy was performed on 31 women (group A) and the Bologna operation on another 31 (group B). The mean follow-up was 3 years (range 2–7). Perioperative complications, including urinary tract infections, occurred in 16% of group A versus 42% of group B (P<0.001). Anatomic success regarding the prolapse was, respectively, 92.9% (26/28) and 84.6% (22/26) (P= 0.25). Subjective cure rates of GSI (patient history) were 57.1% in group A (16/28) and 87% in group B (23/26) (P<0.05). Objective cure rates of GSI (negative stress test result) were 53.6% in group A (15/28) and 84.6% in group B (22/26) (P<0.02). We concluded that the Bologna operation was more effective for treating GSI associated with anterior vaginal prolapse than was anterior colporraphy, with an increased rate of morbidity and postoperative urinary retention.

Safety of Vaginal Mesh Surgery Versus Laparoscopic Mesh Sacropexy for Cystocele Repair: Results of the Prosthetic Pelvic Floor Repair Randomized Controlled Trial

BACKGROUND Laparoscopic mesh sacropexy (LS) or transvaginal mesh repair (TVM) are surgical techniques used to treat cystoceles. Health authorities have highlighted the need for comparative studies to evaluate the safety of surgeries with meshes. OBJECTIVE To compare the rate of complications, and functional and anatomical outcomes between LS and TVM. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized controlled trial from October 2012 to April 2014 in 11 French public hospitals. Women with cystocele stage ≥2 (pelvic organ prolapse quantification), aged 45-75 yr, without previous prolapse surgery. INTERVENTION Synthetic nonabsorbable mesh placed in the vesicovaginal space, sutured to the promontory (LS) or maintained by arms through pelvic ligaments (TVM). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Rate of surgical complications ≥grade II according to the modified Clavien-Dindo classification at 1 yr. Secondary outcomes were reintervention rate, and functional and anatomical results. RESULTS AND LIMITATIONS A total of 130 women were randomized in LS and 132 in TVM; five women withdrew before intervention, leaving 129 in LS and 128 in TVM. The rate of complications ≥grade II was lower after LS than after TVM, but did not meet statistical significance (17% vs 26%, treatment difference 8.6% [95% confidence interval, CI -1.5 to 18]; p=0.088). The rate of complications of grade III or higher was nonetheless significantly lower after LS (LS=0.8%, TVM=9.4%, treatment difference 8.6% [95% CI 3.4%; 15%]; p=0.001). LS was converted to TVM in 6.3%. The total reoperation rate was lower after LS but did not meet statistical significance (LS=4.7%, TVM=10.9%, treatment difference 6.3% [95% CI -0.4 to 13.3]; p=0.060). There was no difference in symptoms, quality of life, improvement, composite definition of success, anatomical results rates between groups except for the vaginal apex and length, and dyspareunia (in favor of LS). CONCLUSIONS LS is a valuable option for primary repair of cystocele in sexually active patients. LS is safer than TVM, but may not be feasible in all cases. Both techniques offer same functional outcomes, success rates, and anatomical outcomes, but sexual function is better preserved by LS. PATIENT SUMMARY Our study demonstrates that laparoscopic sacropexy (LS) is a valuable option for primary repair of cystocele. LS offers equivalent success rates to vaginal mesh procedures, but is safer with a lower rate of complications and reoperations, and sexual function is better preserved.

Eligibility criteria for intraoperative radiotherapy for breast cancer: study employing 12,025 patients treated in two cohorts

BackgroundWe wished to estimate the proportion of patients with breast cancer eligible for an exclusive targeted intraoperative radiotherapy (TARGIT) and to evaluate their survival without local recurrence.MethodsWe undertook a retrospective study examining two cohorts. The first cohort was multicentric (G3S) and contained 7580 patients. The second cohort was monocentric (cohort 2) comprising 4445 patients. All patients underwent conservative surgery followed by external radiotherapy for invasive breast cancer (T0–T3, N0–N1) between 1980 and 2005. Within each cohort, two groups were isolated according to the inclusion criteria of the TARGIT A study (T group) and RIOP trial (R group).In the multicentric cohort (G3S) eligible patients for TARGIT A and RIOP trials were T1E and R1E subgroups, respectively. In cohort number 2, the corresponding subgroups were T2E and R2E. Similarly, non-eligible patients were T1nE, R1nE and T2nE, and R2nE.The eligible groups in the TARGIT A study that were not eligible in the RIOP trial (TE–RE) were also studied. The proportion of patients eligible for TARGIT was calculated according to the criteria of each study. A comparison was made of the 5-year survival without local or locoregional recurrence between the TE versus TnE, RE versus RnE, and RE versus (TE–RE) groups.ResultsIn G3S and cohort 2, the proportion of patients eligible for TARGIT was, respectively, 53.2% and 33.9% according the criteria of the TARGIT A study, and 21% and 8% according the criteria of the RIOP trial. Survival without five-year locoregional recurrence was significantly different between T1E and T1nE groups (97.6% versus 97% [log rank =0.009]), R1E and R1nE groups (98% versus 97.1% [log rank =0.011]), T2E and T2nE groups (96.6% versus 93.1% [log rank <0. 0001]) and R2E and R2nE groups (98.6% versus 94% [log rank =0.001]). In both cohorts, no significant difference was found between RE and (TE–RE) groups.ConclusionsAlmost 50% of T0-2 N0 patients could be eligible for TARGIT.

Facteurs pronostiques des carcinomes lobulaires infiltrants du sein : à propos de 940 cas

OBJECTIVES To assess the prognostic factors of T1 and T2 infiltrating lobular breast cancers, and to investigate predictive factors of axillary lymph node involvement. METHODS This is a retrospective multicentric study, conducted from 1999 to 2008, among 13 french centers. All data concerning patients with breast cancer who underwent a primary surgical treatment including a sentinel lymph node procedure have been collected (tumors was stage T1 or T2). Patients underwent partial or radical mastectomy. Axillary lymph node dissection was done systematically (at the time of sentinel procedure evaluation), or in case of sentinel lymph node involvement. Among all the 8100 patients, 940 cases of lobular infiltrating tumors were extracted. Univariate analysis was done to identify significant prognosis factors, and then a Cox regression was applied. Analysis interested factors that improved disease free survival, overall survival and factors that influenced the chemotherapy indication. Different factors that may be related with lymph node involvement have been tested with univariate than multivariate analysis, to highlight predictive factors of axillary involvement. RESULTS Median age was 60 years (27-89). Most of patients had tumours with a size superior to 10mm (n=676, 72%), with a minority of high SBR grade (n=38, 4%), and a majority of positive hormonal status (n = 880, 93, 6%). The median duration of follow-up was 59 months (1-131). Factors significantly associated with decreased disease free survival was histological grade 3 (hazard ratio [HR]: 3,85, IC 1,21-12,21), tumour size superior to 2cm (HR: 2,85, IC: 1,43-5,68) and macrometastatic lymph node status (HR: 3,11, IC: 1,47-6,58). Concerning overall survival, multivariate analysis demonstrated a significant impact of age less than 50 years (HR: 5,2, IC: 1,39-19,49), histological grade 3 (HR: 5,03, IC: 1,19-21,25), tumour size superior to 2cm (HR: 2,53, IC: 1,13-5,69). Analysis concerning macrometastatic lymph node status nearly reached significance (HR: 2,43, IC: 0,99-5,93). There was no detectable effect of chemotherapy regarding disease free survival (odds ratio [OR] 0,8, IC: 0,35-1,80) and overall survival (OR: 0,72, IC: 0,28-1,82). Disease free survival was similar between no axillary invasion (pN0) and isolated tumor cells (pNi+), or micrometastatic lymph nodes (pNmic). There were no difference neither between one or more than one macromatastatic lymph node. But disease free survival was statistically worse for pN1 compared to other lymph node status (pN0, pNi+ or pNmic). Factors associated with lymph node involvement after logistic regression was: age from 51 to 65 years (OR: 2,1, IC 1,45-3,04), age inferior to 50 years (OR 3,2, IC: 2,05-5,03), Tumour size superior to 2cm (OR 4,4, IC: 3,2-6,14), SBR grading 2 (OR 1,9, IC: 1,30-2,90) and SBR grade 3 (OR 3,5, IC: 1,61-7,75). CONCLUSION The analysis of this series of 940 T1 and T2 lobular invasive breast carcinomas offers several information: factors associated with axillary lymph node involvement are age under 65 years, tumor size greater than 20mm, and a SBR grade 2 or 3. The same factors were significantly associated with the OS and DFS. The macrometastatic lymph node involvement has a significant impact on DFS and OS, which is not true for isolated cells and micrometastases, which seem to have the same prognosis as pN0.

Transvaginal treatment of anterior and apical genital prolapses using an Ultra lightweight mesh: Restorelle® Direct Fix™. A retrospective study on feasibility and morbidity

BACKGROUND Vaginal mesh safety information is limited, especially concerning single incision techniques using ultra lightweight meshes for the treatment of anterior pelvic organ prolapse (POP). OBJECTIVE To determine the intraoperative and postoperative complication rates after anterior POP repair involving an ultralight mesh (19g/m2): Restorelle® Direct Fix™. METHODS A case series of 218 consecutive patients, operated on between January 2013 and December 2016 in ten tertiary and secondary care centres, was retrospectively analyzed. Eligible patients had POP vaginal repair (recurrent or not) planned with anterior Restorelle® Direct Fix™ mesh (with or without posterior mesh). Surgical complications were graded using the Clavien-Dindo classification. RESULTS Intraoperative complications were bladder wound (0.5%), rectal wound (0.5%), ureteral injuries (0.9%). 98.2% of the patient did not have per operative complications. We observed one fail of procedure. Early complications mainly included urinary retention (8.7%) urinary tract infections (5.5%) and haematoma (2.7%). One haematoma required surgical treatment and another, embolization. 80.7% of the patient did not have complications during hospitalization and 80.3% did not have complication at the follow up visit. None of the analyzed factors (age, body mass index, surgical history, grade of prolapse or concomitant procedure) was significantly associated with the risk of perioperative complications. A total of 2.8% patients had grade III complications according Clavien Dindo. None had grade IV or V. CONCLUSIONS This multicentre case-series on the early experience of the use of anterior Restorelle® Direct Fix™ mesh showed a satisfactory technical feasibility and a low rate of grade III complications according Clavien Dindo. Long term studies are necessary to assess anterior Restorelle® Direct Fix™ mesh performances and to appraise patient satisfaction feedback.

Descending Perineum Associated With Pelvic Organ Prolapse Treated by Sacral Colpoperineopexy and Retrorectal Mesh Fixation: Preliminary Results

Introduction and hypothesis: Descending Perineum Syndrome (DPS) is a coloproctologic disease and the best treatment for it is yet to be defined. DPS is frequently associated with pelvic organ prolapse (POP) and it is reasonable to postulate, that treatment of POP will also have an impact on DPS. We aimed to evaluate the subjective satisfaction and improvement of DPS for patients who have undergone a sacral colpoperineopexy associated with retrorectal mesh for concomitant POP. Methods: This retrospective cohort study, conducted between February 2010 and May 2016 included all women who had undergone surgery to treat POP and DPS. Improvement of POP was assessed clinically and subjective satisfaction was assessed with a survey. Results: Among the 37 operated patients, 31 responded to the questionnaire and 77.4% were satisfied with this surgical procedure. 94.6% were objectively cured for POP. There was a 60% improvement rate for constipation, 63.5 and 68% were cured or improved for ODS and the need for digital maneuvers respectively. Conclusion: Sacral colpoperineopexy associated with retrorectal dorsal mesh appears to objectively and subjectively improve POP associated with DPS.

Surgical Management of Pelvic Organ Prolapsein Women : How to Choose Tee Best Approach

Although benign, pelvic organ prolapse is a real public health problem, affecting mostly women above sixty-five. Eighty-year-old women have an 11.1% lifetime risk of undergoing surgery for prolapse or stress urinary incontinence and 29% will need a second procedure. Surgical approach may be abdominal (sacrocolpopexy by laparotomy, laparoscopy or robot-assisted) or vaginal (autologous, or prosthetic reinforcement). In addition to anatomical correction, surgical objectives include: improvement of the patients quality of life, prolapse symptoms relief, normal urinary, digestive and sexual functions and especially, avoiding iatrogenic sequelae. Thus, the choice of the surgical approach does not only depend upon the site and the severity of the prolapse. Urogynecological surgeons should take into consideration the patients expectations and life style, her age--a determinant factor in deciding upon the best approach -, and her relapse risk factors. They should master both approaches, and the management of surgical complications. Therefore, an apprenticeship in a reference pelviperineology center is a must. In addition, surgeons should be aware of and consider contraindications to each procedure, for instance contraindications to transvaginal prosthesis reinforcement like risk factors of bad healing or infection. Urogynecology specialists have to take into consideration known anatomical and functional results of each technique as cited in the medical literature and act in accordance with international recommendations. The surgerys main objective is to ameliorate the patients discomfort and her quality of life without causing iatrogenic dysfunctional symptoms (urinary, digestive, sexual). The pelvic organ prolapse being a benign pathology, the patients satisfaction is the main marker of the procedure success. In short, regarding the surgical management of pelvic organ prolapse in women the answer to the question How to choose the best approach? is not binary. It depends on several factors, and regardless of the choice, it must