Evolution of synchronous female bilateral breast cancers and response to treatment.

Synchronous bilateral breast cancer (sBBC) occurs after both breasts have been affected by the same germline genetics and environmental exposures. Little evidence exists regarding immune infiltration and response to treatment in sBBCs. Here we show that the impact of the subtype of breast cancer on levels of tumor infiltrating lymphocytes (TILs, n = 277) and on pathologic complete response (pCR) rates (n = 140) differed according to the concordant or discordant subtype of breast cancer of the contralateral tumor: luminal breast tumors with a discordant contralateral tumor had higher TIL levels and higher pCR rates than those with a concordant contralateral tumor. Tumor sequencing revealed that left and right tumors (n = 20) were independent regarding somatic mutations, copy number alterations and clonal phylogeny, whereas primary tumor and residual disease were closely related both from the somatic mutation and from the transcriptomic point of view. Our study indicates that tumor-intrinsic characteristics may have a role in the association of tumor immunity and pCR and demonstrates that the characteristics of the contralateral tumor are also associated with immune infiltration and response to treatment.

Use of fluorescence to guide surgical resection in vulvo-vaginal neoplasia: Two case reports.

We report hereby two cases of fluorescence-guided surgical resection with Indocyanine green in vulvo-vaginal neoplasia. The first case was a 86-year old patient who had a high-grade squamous intraepithelial lesion of the left small lip and on the vulvar fork. After a first incomplete surgery, a second fluorescence-guided vulvectomy was performed with ICG injected intravenously to determine intraoperatively surgical margins. At final pathologic examination, surgical margins were free of disease and postoperative course was uneventful. The second case was a 44-year old patient who had a clear cell carcinoma of the upper vagina. She underwent a fluorescence-guided colpo-hysterectomy with pelvic lymphadenectomy. ICG was injected one centimeter around the tumor and highlighted intraoperatively the limits of the vaginal resection. On the specimens, surgical margins were also negative. Peritumoral or intravenous injection of ICG are promising techniques for the intraoperative identification of surgical margins in gynecologic malignancies.

Outcomes of robotic surgery for endometrial cancer in elderly women.

INTRODUCTION: Few data have been reported on robot-assisted surgery in elderly. The objectives were to compare feasibility, complication data, and survival of patients under and upper the age of 70 who are managed for endometrial cancer by robot-assisted laparoscopy. MATERIALS AND METHODS: This is a retrospective comparative single-center study including patients treated between January 2007 and December 2016. Patients were divided into 2 groups: less than 70 years and greater than or equal to 70 years. The primary endpoint was the rate of complications. The secondary endpoints were conversion rate and follow-up. RESULTS: 148 patients were included: 86 under 70 (group A) and 62 aged 70 and over (group B). More adhesiolysis was performed in group B (p < .01); the pelvic and para-aortic lymph node dissection rates were not different between both groups (p = .2 and p = .9). The operating times were significantly longer in group B (220.1 vs. 234.4 min, p = .02). The conversion rate was similar between the 2 groups (p = .7). The tumors were endometrioid adenocarcinomas for 77.9 and 66.7% respectively (p = .2), with grade 3 tumors more represented in older patients (24.4% vs. 48.4%, p < .01). There were more tumors at high risk of recurrence after 70 years (33.7 vs. 45.2%, p = .04). No significant difference was found for postoperative complications. There was no difference in overall survival (p = .7) or progression-free survival (p = .2). Undertreated women rate was similar in both groups (p = .1). CONCLUSION: Robotic surgery appears feasible and reproducible and could bring a benefit and allow optimal surgery without increasing the morbidity in the management of endometrial cancers whatever the age is.

Haemodynamic management during hyperthermic intraperitoneal chemotherapy: A systematic review.

CONTEXT: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a surgical technique for peritoneal carcinomatosis combining cytoreduction surgery and peritoneal irrigation of cytotoxic agents responsible for haemodynamics and fluid homeostasis alterations. To this day, no guidelines exist concerning intraoperative management. OBJECTIVES: To review data on haemodynamic monitoring and management of patients undergoing HIPEC and to help design a standardised anaesthetic protocol. DATA SOURCES: MEDLINE, EMBASE and Cochrane library were searched using the following. STUDY SELECTION: Original articles and case-reports. Letters to editors and reviews were excluded. DATA EXTRACTION: Data on haemodynamic management, morbidity and mortality. DATA SYNTHESIS: Haemodynamic management during HIPEC is highly variable and depends on local protocols. Only one randomised controlled trial evaluated the benefit of goal-directed fluid administration (GDFA). GDFA guided by advanced haemodynamic monitoring resulted in significantly less complication, shorter length of stay and less mortality compared to standard fluid administration. Renal protection protocol did not decrease the risk of acute kidney injury (AKI). CONCLUSION: Our review reveals that fluid administration guided by advanced monitoring seems to be associated with less postoperative morbidity and mortality after HIPEC. Nevertheless, the literature review shows that intraoperative haemodynamic management is highly variable for this surgery. The use of renal protection strategy does not decrease the prevalence of AKI. Further prospective trials comparing different fluid management and haemodynamic monitoring strategies are urgently needed (PROSPERO registration CRD42018115720).

[Sentinel lymph node biopsy in early-stage cervical cancer: current state of art]. / Place du ganglion sentinelle dans les cancers du col utérin débutants.

Lymph node status is the most important prognostic factor of survival in women with early stage cervical cancer. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement in early-stages cervical cancer and has been increasingly used instead of systematic pelvic lymph node dissection (PLND). Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-leg lymphoedema, which affects severely patient quality of life. SLN biopsy allows nodes ultrastaging and provides supplementary histological information by increasing the detection of tumor low-volume (isolated tumors cells and micrometastases). Moreover, SLN biopsy provides accurate anatomical information on pelvic lymphatic drainage pathway by identifying nodes outside of routine lymphadenectomy areas. Selection of a population at low-risk of nodal metastasis, a minimal training, and simple rules may ensure a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Combined detection with technetium-99 and blue dye has been widely used but recently, there has been increasing interest in the use of fluorescent dies such as indocyanine green (ICG) which would improve SLN detection. Although recent international guidelines recommend performing SLN biopsy in addition to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence, especially on long-term oncological safety. Some points remain controversial such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognostic. The prospective randomized clinical trial SENTICOL III will answer to these problematics.

The clinical implication of lymph nodes micrometastases and isolated tumor cells in patients with cervical cancer: A systematic review.

Lymph node macroscopic involvement in cervical cancer is a well-known prognostic factor, allows the gynecologic-oncologist to identify women at increased risk for recurrence. Since the development of sentinel node biopsy, micrometastases (MMs) and Isolated Tumor Cells (ICTs) have been increasingly identified in cervical cancer, however their prognostic value and treatment are still controversial. We reviewed the literature (MEDLINE and EMBASE database analysis) from inception up to January 2019, concerning the incidence of lymph nodes MMs and ITCs in cervical cancer, their controversial histologic and molecular biology definition, their anatomic distribution, the role of frozen section and the prognostic value and treatment options for women diagnosed with lymph nodes MMs/ITCs.

Associations between persistent organic pollutants and risk of breast cancer metastasis.

BACKGROUND: Breast cancer (BC) is a major public health concern with over 2 million new cases diagnosed and over 600,000 deaths in 2018 in women worldwide. When distant metastases are present at diagnosis, the 5-year survival rate is only 26%. Recent studies have suggested that persistent organic pollutants (POPs) that accumulate in adipose tissue (AT) can influence tumor phenotype and stimulate cellular processes important for metastasis such as invasion. We, therefore, tested the hypothesis that POP exposure is associated with BC metastasis. METHODS: We conducted an exploratory case-control study in which the concentrations of 49 POPs were measured in both AT and serum samples from BC patients, with or without lymph node metastasis, who underwent partial or total mastectomies, lymph node biopsies and sampling of the adipocytic tumor microenvironment. Adjusted, unconditional logistic models were used to study the associations between the POP concentrations and the risk of metastasis and other hallmarks of cancer aggressiveness. RESULTS: 2.3.7.8-TCDD concentrations in AT are positively associated with the risk of metastasis in 43 patients who have BMIs equal or higher than 25 kg/m2 (odds ratio: 4.48 (1.32-20.71)). Furthermore, the concentrations of 2.3.7.8-TCDD and two coplanar PCBs (77&169) in AT also were positively associated with the risk of lymph node metastasis and the tumor size. CONCLUSION: Our study suggests that 2.3.7.8-TCDD and some PCBs contribute to the development of tumor metastasis and other hallmarks of cancer aggressiveness. While these results should be considered with caution, this is the first study to identify such potential risk factors. Larger longitudinal studies are necessary to confirm our results. Clinical Trial Protocol Record: 2013-A00663-42.

Innovative DIEP flap perfusion evaluation tool: Qualitative and quantitative analysis of indocyanine green-based fluorescence angiography with the SPY-Q proprietary software.

BACKGROUND: Perfusion-related complications remain the most common concern in DIEP flap breast reconstruction. Indocyanine green-based fluorescence angiography can be used for the real-time intra operative assessment of flap perfusion. The SPY Elite system is the most widely used device in this setting. The main objective was to describe the use of SPY-Q proprietary software to perform qualitative and quantitative analysis of flap perfusion. METHODS: This retrospective cohort study was performed at the Curie Institute between 2013 and 2017. We included patients undergoing unilateral DIEP flap breast reconstruction for whom indocyanine green-based angiography videos were of sufficient quality for analysis. Videos were recorded with the SPY Elite System and analyzed with SPY-Q proprietary software. RESULTS: We included 40 patients. We used real-time dynamic color analysis to describe three different patterns of flap perfusion. SPY-Q proprietary software provides quantitative flap perfusion parameters. Our quantitative analysis confirmed that zone I is the best perfused part of the flap and zone IV the less perfused one. There was no significant association between flap perfusion pattern and perforator anatomy, patients' clinical characteristics or postoperative outcomes. After exploratory univariate analysis, quantitative perfusion parameters were significantly impaired in young patients with diabetes mellitus or under hormone therapy by tamoxifen. CONCLUSIONS: We here describe a new approach to assess DIEP flap perfusion using the SPY Elite System proprietary software. It provides interesting qualitative and quantitative analysis that can be used in further studies to precisely assess DIEP flap perfusion.

Prognostic impact of initial tumor load and intraperitoneal disease dissemination patterns in patients with advanced ovarian cancer undergoing complete cytoreductive surgery.

INTRODUCTION: Complete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery. METHODS: We conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria. RESULTS: One hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the "IDS" subgroup. In the "PDS" subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS. CONCLUSION: Initial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved.

Three-Dimensional Modelization of the Female Human Inferior Hypogastric Plexus: Implications for Nerve-Sparing Radical Hysterectomy.

BACKGROUND/AIMS: This study aims to describe the autonomic nervous network of the female pelvis with a 3D model and to provide a safe plane of dissection during radical hysterectomy for cervical cancer. METHODS: Pelvises of 3 human female fetuses were studied by using the computer-assisted anatomic dissection. RESULTS: The superior hypogastric plexus (SHP) was located at the level of the aortic bifurcation in front of the sacral promontory and divided inferiorly and laterally into 2 hypogastric nerves (HN). HN ran postero-medially to the ureter and in the lateral part of the uterosacral ligament until the superior angle of the inferior hypogastric plexus (IHP). IHP extended from the anterolateral face of the rectum, laterally to the cervix and attempted to the base of the bladder. Vesical efferences merged from the crossing point of the ureter and the uterine artery and ran through the posterior layer of the vesico-uterine ligament. CONCLUSIONS: The SHP could be injured during paraaortic lymphadenectomy. Following the ureter and resecting the medial fibrous part of the uterosacral ligament may spare the HN. No dissection should be performed under the crossing point of the ureter and the uterine artery.

Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review.

Malignant phyllodes tumors (MPT) are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM) can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

[Lynch syndrome and endometrial cancer]. / Syndrome de Lynch et cancer de l'endomètre.

Lynch syndrome is a hereditary predisposition to many tumors, in the forefront of which endometrial cancer in women. It is related to the mutation of a mismatch repair gene, involved in DNA mismatch repair. This mutation leads to a loss of expression of the corresponding protein, and to genome instability in tumor cells. Cumulative risk at the age of 70 years is over 40 %. Endometrial cancers related to Lynch syndrome are most of the time sentinel (They reveal the predisposition in half of families.) and are characterized by young age at onset (before 60 years) and low body mass index compared with patients presenting sporadic tumors. Pathological tumor characteristics are debated but it seems to be two types of tumors according to age, older patients having standard tumors and younger ones more aggressive pattern. Endometrial cancers related to Lynch syndrome can be synchronous of ovarian cancer. Therapeutic management does not present any particularity. Conservative treatment can be considered more frequently due to young age of patients but has to respect usual guidelines. Prognosis of these tumors is controversial. Gynaecological screening, although its benefit has not been proved, appears crucial in this population, as well as prophylactic surgery, which remains the best prevention.

[Feasibility and accuracy of day surgery: Review of 396 operated breast cancer patients]. / La chirurgie du cancer du sein en ambulatoire est faisable et fiable de nos jours : étude portant sur 396 patientes.

INTRODUCTION: Breast cancer surgery is suitable for outpatient practice. Indeed, this is a planned surgery with short operative time. Objective was to evaluate the recognized success indicators in day surgery: rate of conversion into conventional hospitalization, rate of complications and re-hospitalizations the month following surgery. METHODS: Consecutive cases of breast cancer patients operated in day surgery were prospectively entered into the Day Surgery database between 25 November 2012 and 31 December 2013. Patient characteristics and tumor pathology, preoperative procedures and type of surgery were collected. Statistical analysis was performed. RESULTS: Three hundred and ninety-six consecutive patients were included. The mean age was 54 years [25-84], we performed 382 conservative breast surgery (98.2%), 238 sentinel node (60.1%) and 40 axillary lymphadenectomy (10.1%). Thirty-nine scheduled for outpatient surgery were hospitalized in conventional surgery being a conversion rate of 9.8%, 95% CI [6.9-12.7] with 24 patients because of a drainage (61.5%). We have observed 15 complications in the month after the surgery (3.7%, 95% CI [1.8-5.6]), and 5 rehospitalization in the month following surgery (1.2%, IC 95% [0.1-2.3]). CONCLUSION: Postoperative complication and readmissions are very low (<5%) after breast ambulatory surgery. This confirms its feasibility and safety in a breast cancer center. Adaptating anaesthetic methods to ambulatory care and preparing patient going home with an axillary drain are necessary to reduce rate of conversion to hospitalisation.

Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast Conserving Surgery.

BACKGROUND: The poor prognosis of patients who experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A short time between primary cancer and IBTR is a prognostic factor but no clinically relevant threshold was determined. Classification of IBTR may help tailor treatment strategies. PURPOSE: We determined a specific time frame, which differentiates IBTR into early and late recurrence, and identified prognostic factors for patients with IBTR at time of the recurrence. METHODS: We analyzed 2209 patients with IBTR after BCS. We applied the optimal cut-points method for survival data to determine the cut-off times to IBTR. A subgroup analysis was performed by hormone receptor (HR) status. Survival analyses were performed using a Cox proportional hazard model to determine clinical features associated with distant-disease-free survival (DDFS) after IBTR. We therefor built decision trees. RESULTS: On the 828 metastatic events observed, the majority occurred within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR negative group. We found different prognostic times to IBTR: 49 months in the HR positive group, 33 in the HR negative group. After multivariate analysis, time to IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95% [0.54-0.79] and 0.42 [0.30-0.57] respectively). The other following variables were significantly correlated with the DDFS: the initial number of positive lymph nodes for both groups, the initial tumor size and grade for HR positive tumors. CONCLUSION: A short interval time to IBTR is the strongest factor of poor prognosis and reflects occult distant disease. It would appear that prognosis after IBTR depends more on clinical and histological parameters than on surgical treatment. A prospective trial in a low-risk group of patients to validate the safety of salvage BCS instead of mastectomy in IBTR is needed.

Carbon Monoxide Poisoning during Pregnancy: Presentation of a Rare Severe Case with Fetal Bladder Complications.

Carbon monoxide poisoning during pregnancy is a rare and potentially serious condition. Fetal complications are uncommon, related to anoxic lesions. The severity of these complications does not depend on the level of maternal COHb. We report the case of a 22-year-old pregnant woman who at 30 weeks of gestation had carbon monoxide poisoning secondary to a fire in her home, complicated by cardiac arrest and severe fetal damage. The child had not brain damage, but presented bladder lesions not previously described, with urinary ascites complicating megacystis.