[A curious biphasic breast lesion]. / Une curieuse lésion biphasique du sein.

Adenomyoepithelioma represents 0.5% of breast tumors in postmenauposal women. Prognosis is good when the tumor is benign. However, its malignant variant is associated with a poor prognosis with local recurrences and metastatic potential. We present the case of a malignant adenomyoepithelioma, expose the 2019 WHO classification issues and propose a classification in three categories: benign, atypical and malignant adenomyoepitheliomas (in situ and invasive).

Negative Survival Impact of Occult Lymph Node Involvement in Small HER2-Positive Early Breast Cancer Treated by Up-Front Surgery.

(1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5-64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04-5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03-6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients.

Do surgeons overestimate diaphragmatic peritoneal disease in interval debulking surgery of ovarian cancer?

INTRODUCTION: Cytoreductive surgery is a key point in ovarian cancer treatment. Substantial morbidity may be consecutive to this major radical surgery. However, the objective of no residual tumor (CC-0) had demonstrated its clear improvement of prognosis. Could macroscopically-driven interval debulking surgery (IDS) overestimate active cancer cells and be unnecessarily morbid? MATERIALS AND METHODS: This retrospective cohort study was conducted in Center Leon Berard Cancer Center between 2000 and 2018. We included women with advanced epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent an IDS including resection of peritoneal metastases on the diaphragmatic domes. The primary endpoint was the pathological outcome of peritoneal resections of diaphragmatic domes. RESULTS: Peritoneal resections of diaphragmatic domes consisted of 117 patients. 75 patients required resection of nodules from the right cupola only, 2 patients from the left cupola only, and 40 patients bilaterally. Pathological analysis of the diaphragmatic domes found that 84.6% of samples demonstrated the presence of malignant cells, and only 12.8% found no tumor involvement. Pathology analysis could not be performed for 3 patients (2.6%) (vaporization). CONCLUSION: Surgical evaluation after neoadjuvant chemotherapy in ovarian cancer does not often overestimate peritoneal involvement by active carcinomatosis. Potential surgical morbidity due to peritoneal resection in IDS is admissible.

Performance of Indocyanine Green Compared to 99mTc-Nanocolloids for Sentinel Lymph Node Detection in Early Vulvar Cancer.

STUDY OBJECTIVE: The aim of this study was to evaluate the performance of indocyanine green (ICG) compared to that of the gold standard 99mtechnetium (99mTc-nanocolloids) in detecting sentinel lymph nodes (SLN) in early vulvar cancer. MATERIAL AND METHODS: A single-center retrospective cohort study comparing SLN detection by 99mTc-nanocolloids and ICG was performed in patients presenting early vulvar cancer (T1/2), with clinically negative nodes. All SLN showing a radioactive and/or fluorescent signal were resected. The primary endpoints were the sensitivity, positive predictive value (PPV) and false negative (FN) rate of ICG in detecting SLN compared to 99mTc-nanocolloids. RESULTS: Thirty patients were included and 99 SLN were identified in 43 groins. Compared to 99mTc-nanocolloids, ICG had a sensitivity of 80.8% (95% CI [72.6; 88.6%]), a PPV of 96.2% (95% CI [91.8; 100%]) and a FN rate of 19.1% in detecting SLN. Seventeen (17.1%) infiltrated (positive) SLN were identified out of the 99 SLN detected. Compared to 99mTc-nanocolloids, ICG showed a sensitivity of 82.3% (95% CI [73.1; 91.5%]), a PPV of 100% and a FN rate of 17.6% (3/17) in detecting infiltrated SLN. CONCLUSION: Despite its many advantages, ICG cannot be used as the sole tracer for the detection of SLN in early vulvar cancer and should be employed in conjunction with 99mTc-nanocolloids.

Development of a mucinous adenocarcinoma on a sigmoid colpoplasty for vaginal agenesis: About a case report and review of the literature.

We report a case of mucinous adenocarcinoma developed on sigmoid colpoplasty, performed for a congenital agenesis vaginal. The cancer development of neovagina remains exceptional. Its management consists, in the majority of cases, in surgery for a complete excision. Adjuvant treatments are associated according to the pathological results and the neovagina reconstruction technique performed.

Robotic Nipple-Sparing Mastectomy and Immediate Breast Reconstruction With Robotic Latissimus Dorsi Flap Harvest: Technique and Results.

Introduction. Only few cases of robotic latissimus dorsi flap reconstruction (RLDFR) have been reported in indication of reconstruction for breast cancer (BC). We report our experience of combined robotic nipple-sparing mastectomy (R-NSM) and RLDFR, and analyze technique, indications, and reproducibility. Methods. All patients with R-NSM and RLDFR from November 2016 to August 2, 2018, were analyzed, and technics have been described. Complication rate with Clavien-Dindo grading and postoperative hospitalization length (days) are reported. Results. Thirty-five R-NSM with RLDFR were performed in 22 cases for primitive BC and 13 for local recurrence. In 12 patients, another surgical procedure was performed during the same time (axillary lymph node dissection or contralateral breast surgery). R-NSM was realized through a short axillar incision, with inside-only installation for 12 patients (34.3%): 18 nonautologous and 17 autologous RLDFR associated with implant in 9 patients. In logistic regression, mastectomy weight >330 g was significantly associated with the use of implant (odds ratio [OR] = 17, P = .015), and significant factor of the time of anesthesia ≥380 minutes was 2 installations (OR = 10.4, P = .049). The median duration of hospitalization stay was 4 days. Complications rates were 51.4% (18/35; 9 grade-1, 2 grade-2, and 7 grade-3). In logistic regression, associated other surgical procedure was predictive of grade-3 complications (OR = 6.87, P = .053). Conclusion. We confirmed the reproducibility and safety of R-NSM and RLDFR with a decreased complication rate. NSM was performed in 42.8% of our patients after previous radiotherapy. We observed an increase of grade-3 complications when R-NSM and RLDFR was combined to another surgical procedure.

Fertility and prognosis of borderline ovarian tumor after conservative management: Results of the multicentric OPTIBOT study by the GINECO & TMRG group.

OBJECTIVES: Description of fertility and prognosis of patients with borderline ovarian tumor (BOT) treated by fertility-sparing surgery through a longitudinal study from the French national cancer network. METHODS: All consecutive patients diagnosed with BOT from the French National Network dedicated to Ovarian Malignant Rare Tumors from 2010 and 2017 were selected. In 2018, an update was made by sending a questionnaire regarding recurrence and fertility to patients aged under 43 years at diagnosis and treated conservatively. We compared the characteristics of the patients with/without recurrence and with/without live birth. RESULTS: Fifty-two patients aged 18 to 42 years presented a desire of pregnancy. Thirty patients (58%) presented a FIGO IA tumor, and 20 patients were treated by bilateral cystectomies (38%). We observed at least one live birth for 33 patients (63%) and local recurrences in 20 patients (38%). Both recurrence and live birth in 17 patients (33%) were reported, with recurrence occurring before pregnancy, after a second fertility-sparing treatment, in half of the cases. No factors associated with recurrence or live birth in this study were identified. Moreover, in this population, both recurrence and live birth were independent of age, with a linear risk along time. Disease-free survival was worse for patients treated with bilateral cystectomy (n = 20, 38%), with no difference in terms of fertility. CONCLUSION: Two third of the patients experienced life birth after conservation surgery. We did not highlight an age/time from surgery for which the risk of recurrence outweighs the chance of pregnancy and to radicalize surgery. Moreover, almost a quarter of the live birth occurred after recurrence, with no more further event to date in these patients. The results encourage to consider a second fertility-sparing surgery after local borderline recurrence in the case of pregnancy desire. All these decisions must be discussed in specialized multidisciplinary boards.

Skin sparing mastectomy and robotic latissimus dorsi-flap reconstruction through a single incision.

BACKGROUND: Robotic latissimus dorsi-flap reconstruction (RLDFR) after skin-sparing mastectomy (SSM) for breast cancer (BC) has been performed through a single nipple incision. We report results of SSM with RLDFR, mainly with analysis of feasibility, morbidity, indications, and technique standardization. METHODS: We determined characteristics of patients, previous treatment of BC, and type of reconstruction. Surgical technique, duration of surgery, and complication rate were reported according to three successive periods: P1-3. RESULTS: Forty RLDFR, with breast implant for 16 patients, with previous breast radiotherapy in 30% had been performed. In logistic regression, factors significantly associated with duration of surgery ≥ 300 min were P2 (OR 0.024, p = 0.004) and P3 (OR 0.012, p = 0.004) versus P1. The median mastectomy weight was 330 g and 460 g for BMI < and ≥ 23.5 (p = 0.025). Length of hospitalization was 4 days. Total complication rate was 20% (8/40): seven breast complications (four re-operations) and one RLDF complication with re-operation. Periods were significantly predictive of complications (p = 0.045). CONCLUSION: SSM with RLDFR is feasible, safe, and reproducible. We reported a decrease of duration of surgery, length of post-operative hospitalization, and complication rate.

Robotic breast and reconstructive surgery: 100 procedures in 2-years for 80 patients.

OBJECTIVE: To analyze results of the first 100 robotic breast surgeries: feasibility, morbidity, indications and standardization of patient positioning and operative technique. BACKGROUND: Robotic breast surgery is an emergent procedure. METHODS: A prospective cohort of patients undergoing robotic latissimus dorsi-flap reconstruction (RLDFR) and or robotic mastectomy, over a period of 24 months was analyzed. We analyzed patient's characteristics, previous treatment for breast cancer, primitive breast cancer or local recurrence, immediate or delayed breast reconstruction and type of reconstruction. Surgical techniques and duration of surgery were reported according to three successive periods. RESULTS: 46.2% of patients (37/80) had previous breast radiotherapy and 26.2% (21/80) had received neo-adjuvant chemotherapy. Surgical procedure and patient position are described. Surgical incision used for RLDFR was: 37 axillar (50.7%), 20 (27.4%) areolar, 7 (9.6%) central breast, 10 (13.7%) previous incision. Number of surgical procedures was >2 for 35 patients. In logistic regression, factors significantly associated with duration of surgery ≥305mn were: P2 with decreased operative duration (OR: 0.077, p = 0.002) and P3 (OR: 0.015, p < 0.0001) versus P1; and number of surgical procedures: 4 surgical procedures (OR: 15.60, p = 0.048) versus 1. Median hospital stay was 4 days. Total complication rate was 57.5% (46 patients) with 6 grade 2, 9 grade 3 and 1 grade 4 complication. For RLDFR we reported 1 grade 3 (1.3%) and 29 grade 1 (39.7%) complications consisting in dorsal seromas. CONCLUSION: RLDFR is a safe and reproducible procedure that allows breast reconstruction through a single incision, without dorsal scar. A decrease in surgery duration was observed with technique standardization and throughout the learning curve.

Transperitoneal para-aortic lymphadenectomy by robot assisted laparoscopy in 10 steps.

OBJECTIVE: Para-aortic lymphadenectomy was the cornerstone of gynecologic oncology surgery. In endometrial cancer, the quality of para-aortic lymphadenectomy had direct impact on survival of patient. The launch of robot assisted laparoscopy started in 2005 in France, and in 2008 a transperitoneal para-aortic lymphadenectomy was described [1]. With the increase of robots, the robot assisted laparoscopy became more and more popular, hence the need of video tutorial to help less experienced surgeon in this surgical procedure [2]. METHODS: We proposed a description in 10 key steps, of a transperitoneal para-aortic lymphadenectomy by robot assisted laparoscopy (Da Vinci® Si or Xi Robot Surgical System; Intuitive Surgical Inc., Sunnyvale, CA, USA), without other surgical procedure. RESULTS: The 10 steps are: Step 1: port placement and Da Vinci robot positioning Step 2: identification of the right ureter Step 3: identification of the left renal vein Step 4: latero-caval and aorto-caval lymph nodes dissection Step 5: identification of the left ureter Step 6: creation of peritoneal tent Step 7: identification of the inferior mesenteric artery Step 8: latero-aortal lymph nodes dissection Step 9: pre-sacral lymph nodes dissection Step 10: extraction of bags with specimen and surgical textile. CONCLUSION: A standardization of transperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy is the basis of teaching and learning process. Also it increases the quality of surgery, and consequently decreases the risk of complications.

Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function.

Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors such as aging and obesity tends to become a public health issue. However, its immune environment has been less characterized than in other tumors such as breast cancers. NK cells are cytotoxic innate lymphoid cells that are considered as a major anti-tumoral effector cell type which function is drastically altered in tumors which participates to tumor progression. Here we characterize tumor NK cells both phenotypically and functionally in the tumor microenvironment of endometrial cancer. For that, we gathered endometrial tumors, tumor adjacent healthy tissue, blood from matching patients and healthy donor blood to perform comparative analysis of NK cells. First we found that NK cells were impoverished in the tumor infiltrate. We then compared the phenotype of NK cells in the tumor and found that tumor resident CD103+ NK cells exhibited more co-inhibitory molecules such as Tigit, and TIM-3 compared to recruited CD103- NK cells and that the expression of these molecules increased with the severity of the disease. We showed that both chemokines (CXCL12, IP-10, and CCL27) and cytokines profiles (IL-1ß and IL-6) were altered in the tumor microenvironment and might reduce NK cell function and recruitment to the tumor site. This led to hypothesize that the tumor microenvironment reduces resident NK cells cytotoxicity which we confirmed by measuring cytotoxic effector production and degranulation. Taken together, our results show that the tumor microenvironment reshapes NK cell phenotype and function to promote tumor progression.

Positive or close margins: reoperation rate and second conservative resection or total mastectomy?

INTRODUCTION: Reoperation after breast-conserving surgery (BCS) could be proposed for positive or close margins. Reoperation type, re-excision or mastectomy, depends on several factors in relation to patient's and tumor's characteristics. We have analyzed our breast cancer (BC) database in order to determine second and third attempts for BCS and mastectomy rates, as well as associated factors for type of surgery. METHODS: All patients with BCS between 1995 and 2017 were included. Patient's characteristics, pathologic results, and treatments were analyzed. Reoperation rate, type of reoperation, second reoperation, and associated factors of reoperation, mastectomy, and third intervention were determined. Three periods were determined: P1-P3. RESULTS: We analyzed 10,761 patients: 1,161 with ductal carcinoma in situ (DCIS) and 9,600 with invasive BC. The reoperation rate was 41.4% for DCIS and 28.0% for invasive BC. Using multivariate analysis, we identified tumor size >20 mm as being a risk factor for reoperation, whereas age >50 years, P2-3, and some localization decreased reoperation rates. For invasive BC, age >40 years, triple-negative tumors, neoadjuvant chemotherapy, and noncentral tumors decreased reoperation rates and lobular tumor, multifocal tumors, lymphovascular invasion, DCIS component, and Her2-positive tumors increased reoperation rates. For patients requiring reoperation, re-excision was performed in 48.1% (1,523/3,168) and mastectomy was required after first re-excision in 13.46% (205/1,523). For DCIS, mastectomy rates were higher for grade 2 and tumor ≥20 mm. For invasive BC, mastectomy rates were higher for lobular, multifocal, ≥20 mm, Her2-positive tumors and diffuse positive margins and lower for age >50 years and during the last period. Even if interval time between surgery and adjuvant treatments was higher for patients with reoperation, survival rates were not different between patients with and without reoperation. CONCLUSION: A decrease in reoperation and mastectomy rates had been reported with several associated factors. A third intervention with mastectomy was required in 13.5% of patients. This information should be done in case of reoperation.

Breast cancer in young women: Pathologic features and molecular phenotype.

PURPOSE: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications. METHODS: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected. RESULTS: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01). CONCLUSION: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.