[How is our practice of mastectomy? Analysis based on population data in a French department]. / Quelles évolutions dans notre pratique de la mastectomie ? Analyse à partir de données de population dans un département français.

OBJECTIVE: The objective of this research was to study the evolution of the mastectomy rate in patients with breast cancer between 1998 and 2015, based on population data from the Côte d'Or breast cancer registry of the FRANCIM network ("France cancer incidence and mortality"). METHODS: In this study on population register we included patients who had presented a primary breast cancer (invasive cancer and/or carcinoma in situ [CIS]) between 1998 and 2015 in the Côte d'Or department. We estimated the annual proportions of mastectomies, then calculated their evolution trends over this period. RESULTS: Between 1998 and 2015, 7093 patients were included. The overall proportion of mastectomies was stable at 28% and did not respond to a time trend (Sen's slope of 0.2% per year; P=0.289). There was an increase in the proportion of lobular carcinomas (slope at 0.3% per year; P <0.05), with a rising proportion of mastectomy for lobular carcinomas (slope at 0.6% per year; P<0.05) but decreasing for ductal (slope at -0.8% per year; P<0.05). The proportion of mastectomy was stable for plurifocal cancers but the proportion of plurifocal cancers increased over time (slope at 0.8% per year; P<0.05). CONCLUSION: Therefore, mastectomy remained a stable practice over the 18 years of analysis in the Côte d'Or region. However, this overall stability is the result of variations in the profiles of diagnosed cancers and surgical practices.

Comparison of postoperative complications following conventional latissimus dorsi flap versus muscle-sparing latissimus dorsi flap breast reconstruction.

INTRODUCTION: Breast reconstruction is becoming increasingly important in the management of breast cancer. Among breast reconstruction with flap, latissimus dorsi flap is the most frequent technique used in France. Lipofilling's emergence led to changes for using latissimus dorsi flap in breast reconstruction. The aim of this study was to compare postoperative complications following conventional latissimus dorsi (CLD) flap versus muscle-sparing latissimus dorsi (MSLD) flap breast reconstruction. MATERIALS AND METHODS: Data from 96 patients, who underwent CLD flap or MSLD flap breast reconstruction, were retrospectively collected from January 2018 to December 2019 in Georges-Francois Leclerc Cancer Center in France. Uni- and multivariate analyses, using a logistic regression, were performed to define operative factors and postoperative morbidity associated with surgical technique and evaluate whether MSLD flap could be associated with less postoperative outcome. RESULTS: After univariate analysis, factors significantly associated with MSLD flap were reduced surgical time (p<0.001), reducing seroma and punctures (p<0.001), postoperative complications of donor site (p=0.09), and a shorter length hospital stay (p<0.001). After multivariate analysis, a shorter length hospital stay was significantly associated with the muscle-sparing group (OR=0.47, 95% CI (0.30-0.73), p<0.001). DISCUSSION: This is the first French study comparing postoperative complications following the two techniques of latissimus dorsi flap breast reconstruction. In this study, the hospital stay was significantly decreased with MSLD flap compared with the CLD flap breast reconstruction. Both seem to be reliable methods with few complications.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

[Comparing prediction performances of 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after neoadjuvant chemotherapy for HER2-positive breast cancers]. / Comparaison des performances prédictives du TEP-TDM et du nomogramme CGFL/Curie pour prédire la réponse histologique complète après chimiothérapie néo-adjuvante des cancers du sein HER2-positifs.

OBJECTIVES: The aim of this study was to compare the value of 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. METHODS: Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC were retrospectively included from January 2005 to December 2015. For 18F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET2.SUVmax). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET2.SUVmax was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Combined prediction was evaluated testing predictor's associations. RESULTS: For CGFL/Curie nomogram's performances, Se, Sp, PPV and NPV were respectively: 76% (95%CI: 58-90%), 57% (95%CI: 43-66%), 55% (95%CI: 42-65), 77% (95%CI: 59-90%). For PET2.SUVmax's performances, Se, Sp, PPV and NPV were respectively: 67% (95%CI: 48-81%), 77% (95%CI: 64-97%), 67% (95%CI: 48-82%), 77% (95%CI: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (95%CI: 0.56-0.64) for PET2.SUVmax and 0.55 (95%CI: 0.50-0.59) for CGFL/Curie nomogram. Combined prediction was efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81%. CONCLUSIONS: CGFL/Curie nomogram and PET2.SUVmax were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy.

[Non-metastatic triple-negative breast cancer in 2016: Definitions and management]. / Tumeurs localisées du sein triple négatives en 2016 : définitions et prise en charge.

Triple-negative breast cancer (TN), as defined by the triple negativity in immunohistochemistry: the absence of estrogen receptor, progesterone receptor and the absence of overexpression or amplification of HER2, corresponds to 15 % of invasive breast cancers. This is a very heterogeneous group of tumors both at the genomic and transcriptomic level and at morphological, clinical and prognostic level. Although there are some good prognosis forms, the majority of TN tumors is characterized by a poor prognosis with a greater frequency of visceral metastases and a maximum risk of relapse in the first two years after diagnosis. Systemic adjuvant treatment with chemotherapy is almost always indicated. The surgical treatment and radiotherapy treatment should be comparable to the other subtypes and obey the same rules of oncologic surgery. TN tumors are not associated with a higher risk of locoregional relapse after conservative treatment and adjuvant radiotherapy. Optimization of systemic therapies is currently and for the last decade a challenge. A number of targeted therapies and efficiency biomarkers identification of these targeted therapies is essential to allow significant progress in optimizing systemic therapy for these tumors.

[Assessment of sentinel lymph node biopsy in patients receiving neoadjuvant chemotherapy in breast cancer: before or after?]. / Peut-on proposer un prélèvement du ganglion sentinelle en cas de chimiothérapie néoadjuvante dans les cancers du sein et à quel moment ?

The main goal of preoperative chemotherapy is to reduce the size of the tumor and allow conservative treatment. Neoadjuvant treatment can affect axillary status with a downstaging in one third of the cases. For these patients, the benefit of axillary node dissection is questioned and the sentinel node biopsy (SLNB) seems to be a relevant option. However, the timing of performing SLNB is still debated especially for clinical negative patients with negative axillary ultrasound before preoperative chemotherapy. For axillary positive nodes proved by biopsy/cytology before preoperative chemotherapy, SLNB can be an option if there is a good clinical and radiological response.

Evaluation of axillary involvement by ultrasound-guided lymph node biopsy: A prospective study.

OBJECTIVES: The primary aim of this prospective study was to evaluate the accuracy of pre-operative ultrasound (US) alone and associated with a fine needle aspiration cytology (FNAC) or a core needle biopsy (CNB) in the diagnosis of axillary node involvement in patient with breast cancer. The secondary study objective was to determine if this US±FNAC or CNB can lead to the adequate axillary surgery in cN0 and cN1 patient. METHODS: A total of 121 consecutive women with stage cT1 to cT2, cN0/cN1, invasive breast cancer were prospectively identified at our institution between February 2, 2013 and August 30, 2013. The sensitivity, specificity, VPP, NPV were calculated, with confidence intervals, using the definitive histological result of the sentinel node biopsy (SLNB) or axillary lymph node dissection (ALND) as the baseline. RESULTS: Twenty-seven CNB and 2 FNAC were performed. For the whole series, the sensitivity and the specificity of US alone were 48.7% [36-59%] and 89% [83-94%]. For US±FNAC or CNB, the sensitivity and the specificity were 35.9% [26-38%] and 98.8% [94-100%]. Seven women with cN1 clinical examination had SLNB, which permit to decrease the number of ALND of 16.3%. It would have avoided unnecessary SLNB, prompting immediate ALND in 9 patients with cN0 axillae, which means a reduction of SLNB of 8.6%. US±FNAC or CNB lead to the adequate surgery in 72.7% of cases. CONCLUSION: US±CNB or FNAC is also a relatively efficient and safe test and should be considered routinely. It allowed triaging patients to the well axillary surgery (SLNB or ALND).

Surgical Duration Estimation via Data Mining and Predictive Modeling: A Case Study.

Operating rooms (ORs) are one of the most expensive and profitable resources within a hospital system. OR managers strive to utilize these resources in the best possible manner. Traditionally, surgery durations are estimated using a moving average adjusted by the scheduler (adjusted system prediction or ASP). Other methods based on distributions, regression and data mining have also been proposed. To overcome difficulties with numerous procedure types and lack of sufficient sample size, and avoid distributional assumptions, the main objective is to develop a hybrid method of duration prediction and demonstrate using a case study.

Estrogen or raloxifene during postmenopausal weight loss: adiposity and cardiometabolic outcomes.

OBJECTIVE: Estrogen-based hormone therapy (HT) attenuates abdominal fat gain after menopause, but whether HT improves abdominal fat loss during weight loss is unknown. It was hypothesized that HT or a selective estrogen receptor modulator (raloxifene) would augment reductions in abdominal visceral fat during weight loss when compared to placebo, potentially increasing improvements in glucose tolerance and lipid profile. METHODS: Healthy postmenopausal women (n = 119; age 50-70 yr) underwent a 6-month weight-loss (primarily exercise) intervention with randomization to raloxifene (60 mg/d), HT (conjugated estrogens, 0.625 mg/d), or placebo. Outcomes were change in total and abdominal (visceral and subcutaneous) fat mass, lipid profile, and fasting and post-challenge glucose and insulin. RESULTS: Neither HT nor raloxifene augmented loss of total or abdominal fat mass during exercise-induced weight loss when compared with placebo. Weight loss-induced improvements in risk factors were similar among the three groups, except for a greater reduction in fasted glucose in the HT group (difference in change [95%CI] from placebo; -0.40 [-0.76, -0.05]) and greater reductions in LDL (-0.36 [-0.63, -0.09]) and increases in HDL (0.15 [0.07, 0.24]) in both treatment groups. CONCLUSIONS: Postmenopausal HT and raloxifene did not increase abdominal fat loss during weight loss, but did improve some cardiometabolic outcomes.

Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.

Protection of bone mass by estrogens and raloxifene during exercise-induced weight Loss.

The aim of this study was to determine whether estrogen and/or raloxifene help to conserve bone mineral density (BMD) during moderate weight loss. Postmenopausal women (n = 68) participated in a 6-month weight loss program that consisted primarily of supervised exercise training. Another 26 women were studied over 6 months of weight stability. All participants were randomized to three treatment arms: placebo, raloxifene (60 mg/d), or hormone therapy (HT; conjugated estrogens, 0.625 mg/d; trimonthly medroxyprogesterone acetate, 5 mg/d for 13 d, for women with a uterus). Changes in body weight (mean +/- se) averaged 0.8 +/- 0.5 kg in the weight-stable group and -4.1 +/- 0.4 kg in the weight loss group. Across all measured skeletal sites, average changes in BMD in weight stable women were -0.6 +/- 1.1% (n = 7), 0.9 +/- 0.6% (n = 9), and 3.0 +/- 0.7% (n = 10) in the placebo, raloxifene, and HT groups, respectively; comparable BMD changes in the weight loss groups were -1.5 +/- 0.5% (n = 22), -0.5 +/- 0.5% (n = 23), and 1.1 +/- 0.4% (n = 23). There were no significant interactions between weight loss and drug treatment on changes in BMD, but there were significant main effects of weight loss on lumbar spine (P = 0.022), total hip (P = 0.010), and trochanter BMD (P < 0.001). These findings suggest that weight loss, even when modest in magnitude and induced by exercise training, causes a reduction in BMD, particularly in women not taking raloxifene or HT. It is not known whether reductions in BMD of this magnitude increase the risk for osteoporotic fracture.

Application of gas chromatography-tandem mass spectrometry to the analysis of inhibition of dimerisation of tributylphosphate under radiolysis. Identification of isomeric tributylphosphate-alkylbenzene inhibitor coupling products.

Tributylphosphate (TBP), solvent used as extractant for reprocessing spent nuclear fuel, can dimerise under radiolysis. This occurs by radical radical recombination, leading to 10 isomeric dimers (TBP-TBP). These species are complexation agents and are responsible of fission product retention in the organic phase that increases the solvent degradation. In order to limit their formation two free radical inhibitors (In), isopropyl and 1,4-diisopropylbenzenes, were used. These additives reduce by about 50% the concentration of TBP-TBP dimers but this reduction is not strictly followed by TBP regeneration as mixed coupling products from TBP and inhibitor are detected. By using GC-MS-MS and selectively deuterated compounds, the identification of these different isomers (TBP-In) has been realised. From these identifications and from the analysis of the proportion of the different isomers, the major primary TBP radical generated under radiolysis was determined.

Self-association of an amphipathic helix peptide inhibitor of HIV-1 integrase assessed by electro spray ionization mass spectrometry in trifluoroethanol/water mixtures.

Establishing the auto-associative properties of a molecule in solution can be important for determination of its structure and function. EAA26 (VESMNEELKKIIAQVRAQAEHLKTAY) has been designed to inhibit HIV-1 integrase via formation of a stable coiled-coil structure with a nearly homologous segment in the enzyme. The latter catalyzes the permanent incorporation of a DNA copy of the retrovirus genome into host cell DNA, and is thus essential to the life of the retrovirus. This makes integrase an obvious drug target in the therapy of AIDS. The present work has demonstrated, using electrospray ionization mass spectrometry (ESI-MS), that EAA26 is monomeric in pure water, and tetrameric and dimeric at respectively low and medium concentrations of 2,2,2-trifluoroethanol (TFE), and again monomeric at higher TFE concentrations. Thus, the apolar solvent TFE may contribute to either stabilization or disruption of the intermolecular hydrophobic contacts depending on its concentration in aqueous solution. Previous NMR and ultracentifugation results are thus confirmed, indicating the reliability of ESI-MS for defining the self-association state of biologically relevant peptides in both water and organic-water solutions.

Long palindromic sequences induce double-strand breaks during meiosis in yeast.

Inverted-repeated or palindromic sequences have been found to occur in both prokaryotic and eukaryotic genomes. Such repeated sequences are usually short and present at several functionally important regions in the genome. However, long palindromic sequences are rare and are a major source of genomic instability. The palindrome-mediated genomic instability is believed to be due to cruciform or hairpin formation and subsequent cleavage of this structure by structure-specific nucleases. Here we present both genetic and physical evidence that long palindromic sequences (>50 bp) generate double-strand breaks (DSBs) at a high frequency during meiosis in the yeast Saccharomyces cerevisiae. The palindrome-mediated DSB formation depends on the primary sequence of the inverted repeat and the location and length of the repeated units. The DSB formation at the palindrome requires all of the gene products that are known to be responsible for DSB formation at the normal meiosis-specific sites. Since DSBs are initiators of nearly all meiotic recombination events, most of the palindrome-induced breaks appear to be repaired by homologous recombination. Our results suggest that short palindromic sequences are highly stable in vivo. In contrast, long palindromic sequences make the genome unstable by inducing DSBs and such sequences are usually removed from the genome by homologous recombination events.

Nursing management of soft tissue sarcomas of the extremities.

Soft tissue sarcomas of the extremities are uncommon malignancies that require combined modality treatment. Treatments include extensive surgical procedures, usually radiation therapy, and, in some cases, chemotherapy. Nursing care requires an understanding of surgical and reconstructive procedures, brachytherapy implants, radiation safety regulations, and chemotherapeutic agents. The combination of extensive surgery and radiation has greatly reduced the need for amputation, but the complexity of the treatments requires skilled and knowledgeable nursing care.

Radiation protection for nurses. Regulations and guidelines.

Rules and regulations of federal agencies and state radiation protection programs provide the bases for hospital policy regarding radiation safety for nurses. Nursing administrators should work with the radiation safety officer at their institutions to ensure that radiation exposures to staff nurses will be as low as reasonably achievable and that special consideration will be given to pregnant nurses. Nurses' fears about their exposure to radiation can be greatly reduced through education.

Radiation exposure of nurses in a coronary care unit.

In response to increasing awareness of radiation as a possible occupational hazard, nursing personnel staffing a hospital CCU were monitored over a 3-year period to determine occupational exposure. Portable x-ray machines, fluoroscopic units, and patients injected with radiopharmaceuticals were all potential radiation sources on such a unit. Whole-body TLD badges, exchanged monthly, indicated no cumulative exposures over 80 mR during the entire study period. The minimal exposures reported do not justify regular use of dosimeters. Adherence to standard protective measures precludes most exposure to machine-produced radiation. Close, prolonged contact with a patient after an RVG study that utilizes 99mTc may account for some exposure. The data indicate that radiation is not a significant occupational hazard for CCU nurses at this hospital; similar minimal exposures would be expected of other nonoccupationally exposed nursing personnel in like environments.