Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Light-Sensitive Alkoxyamines as Versatile Spatially- and Temporally- Controlled Precursors of Alkyl Radicals and Nitroxides.

The use of UV/visible light irradiation as a means to initiate organic syntheses is increasingly attractive due to the high spatial and temporal control conferred by photochemical processes. The aim of this work is thus to demonstrate that alkoxyamines bearing a chromophore on the alkyl moiety can provide a photoprotecting group for the sensitive nitroxide functionality, that is known to degrade through redox processes. The dissociation of various photosensitive alkoxyamines was studied from 223 to 298 K under UV/visible irradiation, depending on the nature of the chromophore. In each case a rapid (typically in less than 1 h) and near-quantitative dissociation was observed. As an illustration of the interest of this approach, a pyrene-based alkoxyamine was employed for the spatially controlled coupling of polymer chains onto Si wafers to produce micropatterned surfaces.

The Role of Sentinel Lymph Node Biopsy and Factors Associated with Invasion in Extensive DCIS of the Breast Treated by Mastectomy: The Cinnamome Prospective Multicenter Study.

BACKGROUND: When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion. METHODS: The SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed. RESULTS: From May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56-77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion. CONCLUSIONS: Underestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy.

Vacuum-assisted adipose tissue suction technique (VAST) to optimize fat harvesting.

BACKGROUND: Nowadays, fat grafting is a widespread technique that is commonly used in plastic and reconstructive surgery. The classical fat-harvesting method in which a 10-cc syringe and a 3.0-mm cannula are used, may be time-consuming when a large quantity of adipose tissue is required. We describe a novel technique to optimize fat harvesting, the vacuum-assisted adipose tissue suction technique (VAST), in which disposable sterile components are used. This study compares the adipose tissue harvesting speed and the adipocyte volume between the VAST and the 10-cc-syringe technique. METHODS: From May 2010 to May 2012, a total of 32 patients who had structural fat grafting for breast reconstruction were enrolled in this prospective study. In 16 patients (control group) fat was harvested by the classical 10-cc-syringe technique, and in the other 16 patients (VAST group) fat was harvested by the VAST. Adipose tissue was harvested from the abdomen area in all patients. The volume of harvested adipose tissue was noted every minute during the operative procedure. The operative harvesting speed was calculated for each patient after 5 min. The volume harvested in 5 min was centrifuged, and the remaining adipocyte volume was noted after centrifugation. The operative harvesting speed and the remaining adipocyte rate were compared in both groups. RESULTS: The average volume of harvested adipose tissue was 18.1 ml in the control group and 156.2 ml in the VAST group (p < 0.001). The average harvesting speed was 3.6 ml/min in the control group using a 10-cc syringe and 31.2 ml/min in the VAST group (p < 0.001). The average remaining adipocyte volume, after centrifugation, was 13.5 ml in the control group, and 118.2 ml in the VAST group (p < 0.001). The average remaining adipocyte rate, after centrifugation, was 74.3 % in the control group and 75.4 % in the VAST group (p = 0.27). CONCLUSIONS: Adipose tissue harvesting can be optimized safely by using the VAST before structural fat grafting. Its quickness, low cost, and efficiency make us choose this method in breast reconstruction when a significant volume of adipocytes is required. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Challenges in intensive medicine: Diversity, equity and inclusion. Gender statement of the Spanish Society of Intensive and Critical Medicine and Coronary Units (SEMICYUC).

Gender is a social determinant that impacts health and generates inequalities at all levels. It has impacts patients and critical conditions, health professionals and professional career development, and scientific societies from a perspective of social justice. All the International scientific societies of Intensive Care Medicine committed to contributing a gender perspective agree on the institutional need for achieving a formal positioning standpoint. The Spanish Society of Intensive and Critical Medicine and Coronary Units (SEMICYUC) is committed to ensuring the equality, inclusion and representativeness of its health professionals to fight the existing gender gap in the field of Intensive Medicine.

Solvent-free Michael addition to non-protected 3-(2-nitrovinyl)indole by ultrasound activation.

A variety of nucleophiles provided by activated methylenes have been added on 3-(2-nitrovinyl)-1H-indole in very good to excellent yields, under sonication and solvent-free conditions, using solid potassium carbonate or sodium acetate as a base. Direct synthesis avoiding preliminary NH protection is reported and exemplified to 15 molecules.

[Desmoid tumor of the breast in a 9 years old little girl]. / Fibromatose mammaire chez une fillette de neuf ans.

Aggressive fibromatosis (desmoid tumour) of the breast is a rare tumour that accounts only for 0.2% of primary breast tumours. This is a benign mesenchymal tumour that develops from muscular fasciae and aponeuroses. It is characterized by its local evolution and its tendency to relapse without metastasizing. Wide radical resection should be attempted whenever possible. Positive margins at resection and reoperation are associated with a high risk of local recurrence. The role of radiotherapy and of medical treatments- especially anti-estrogens - remains unclear. We report here the case of desmoid tumour of the breast arising in a 9-year-old little girl.

Sentinel lymph node biopsy and morbidity outcomes in early cervical cancer: Results of a multicentre randomised trial (SENTICOL-2).

INTRODUCTION: Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated. MATERIALS AND METHODS: In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point. RESULTS: A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm). CONCLUSION: SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.

Sentinel node procedure is warranted in ductal carcinoma in situ with high risk of occult invasive carcinoma and microinvasive carcinoma treated by mastectomy.

Axillary lymph node dissection in patients with ductal carcinoma in situ (DCIS) of the breast is not warranted because DCIS has no metastatic potential. However, the risk of microinvasive carcinoma (MIC) exists in large DCIS treated by mastectomy. The aim of this series is to evaluate the incidence of lymph node metastases in DCIS and DCIS-MIC. We analyzed retrospectively patients treated in six French cancer centers for pure DCIS or DCIS-MIC. Surgical procedures were lumpectomy or mastectomy associated with an axillary sentinel node (SN) procedure. We included 161 patients suffering from pure DCIS (116/161, 72%) or DCIS-MIC (45/161, 28%). Mean age was 56 years (32-78). We observed underestimation between core biopsy and histological result in 43/142 cases (30%). These data show an association between lesion size, solid subtype, high-grade DCIS, and underestimation. Forty-eight breast conservative procedures were performed and 113 mastectomies (70%). SN procedure was performed using blue dye, technetium, or both. In our series, we selected patients with a high risk of occult invasive carcinoma: high grade (55%), mean size (27 mm), and mastectomy (112). Six SN were found positive (3.7%). In the five patients treated with complete axillary dissection, the SN was the only positive node. SN in DCIS is an interesting procedure but not necessary for all patients. We need to focus on the subgroup with or a high risk of occult MIC: extensive calcifications or palpable mass, DCIS diagnosed by core biopsy and underestimation, multifocality, high grade, large tumor size, MIC, and mastectomy.

Reliability of Prognostic and Predictive Factors Evaluated by Needle Core Biopsies of Large Breast Invasive Tumors.

OBJECTIVES: Preoperative biopsy of breast cancer allows for prognostic/predictive marker assessment. However, large tumors, which are the main candidates for preoperative chemotherapy, are potentially more heterogeneous than smaller ones, which questions the reliability of histologic analyses of needle core biopsy (NCB) specimens compared with whole surgical specimens (WSS). We studied the histologic concordance between NCB specimens and WSS in tumors larger than 2 cm. METHODS: Early pT2 or higher breast cancers diagnosed between 2008 and 2011 in our center, with no preoperative treatments, were retrospectively screened. We assessed the main prognostic and predictive validated parameters. Comparisons were performed using the κ test. RESULTS: In total, 163 matched NCB specimens and WSS were analyzed. The correlation was excellent for ER and HER2 (κ = 0.94 and 0.91, respectively), moderate for PR (κ = 0.79) and histologic type (κ = 0.74), weak for Ki-67 (κ = 0.55), and minimal for SBR grade (κ = 0.29). Three of the 21 HER2-positive cases (14% of HER2-positive patients or 1.8% of all patients), by WSS analysis, were initially negative on NCB specimens even after chromogenic in situ hybridization. CONCLUSIONS: NCB for large breast tumors allowed reliable determination of ER/PR expression. However, the SBR grade may be deeply underestimated, and false-negative evaluation of the HER2 status would have led to a detrimental lack of trastuzumab administration.

[Solitary fibrous tumour of the kidney and other sites in the urogenital tract: morphological and immunohistochemical characteristics]. / Tumeur fibreuse solitaire du rein et autres localisations à l'appareil urogénital: caractéristiques morphologiques et immunohistochimiques.

Solitary fibrous tumours are spindle cell tumours initially described in the pleura, but which can also occur in a large number of other sites. The authors report a case of solitary fibrous tumour involving the kidney and present a brief review of the main sites currently described in the urogenital tract and the most characteristic elements of the diagnosis based on histological and immunohistochemical examination designed to improve their subsequent recognition within the wide range of spindle cell tumours.

Delineation of small mobile tumours with FDG-PET/CT in comparison to pathology in breast cancer patients.

PURPOSE: Various segmentation methods for 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images were correlated with pathological volume in breast cancer patients as a model of small mobile tumours. METHODS: Thirty women with T2-T3/M0 breast invasive ductal carcinoma (IDC) were included prospectively. A FDG-PET/CT was acquired 4 ± 3d before surgery in prone and supine positions, with/without respiratory gating. The segmentation methods were as follows: manual (Vm), relative (Vt%) and adaptive (Va) standard uptake value (SUV) threshold and semi-automatic on CT (Vct). Pathological volumes (Vpath) were measured for 26 lesions. RESULTS: The mean (±SD) Vpath was 4.1 ± 2.9 mL, and the lesion displacements were 3.9 ± 2.8 mm (median value: 3 mm). The delineated VOIs did not vary with the acquisition position nor with respiration, regardless of the segmentation method. The Vm, Va, Vct and Vt% methods, except Vt30%, were correlated with Vpath (0.5

[Primary squamous cell carcinoma of the breast: clinical study and review of the literature]. / Carcinomes épidermoïdes primitifs du sein : étude clinique et revue de la littérature.

From the analysis of our series and a review of the literature, we have done a summary of the clinicopathologic patterns and treatment of squamous cell carcinoma of the breast. It usually presents as a large palpable mass in a woman over 50 years old. There are no specific iconographic features, but a relative frequency of presentation as abscess or cyst. The overall and disease-free survivals are worse than other histological types of breast cancer. These neoplasms have a basal-like and triple negative profile and they respond poorly to standard treatment of breast carcinomas. They are usually treated by radical surgery. Optimal chemotherapy regimens is not yet determined and platin based chemotherapy could offer an effective alternative as the developpement of specific targeted therapies (anti Her1) could do.

Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of the xylose scaffold for the design of potential glycogen phosphorylase inhibitors.

Various acetylenic derivatives and acetylated ß-D-xylopyranosyl azide or the 5-thio-ß-d-xylopyranosyl analogue were coupled by Cu(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition (CuAAC) to afford a series of 1-xylosyl-4-substituted 1,2,3-triazoles. Controlled oxidation of the endocyclic sulfur atom of the 5-thioxylose moiety led to the corresponding sulfoxides and sulfones. Deacetylation afforded 19 hydroxylated xylose and 5-thioxylose derivatives, found to be only sparingly water-soluble. Compared to glucose-based analogues, they appeared to be much weaker inhibitors of glycogen phosphorylase, as the absence of a hydroxymethyl group weakens their binding at the enzyme active site. However, such new xylose derivatives might be useful glycomimetics.

Elevated HER2 extracellular domain level in primary breast cancer with HER2 overexpression predicts early failure of adjuvant trastuzumab.

AIM: To investigate in a prospective study the prognostic value of serum HER2 extracellular domain (ECD) level in patients with primary breast cancer overexpressing HER2 treated with adjuvant chemotherapy and trastuzumab. PATIENTS AND METHODS: All the patients treated for primary breast cancer with chemotherapy and adjuvant trastuzumab from April 1, 2005 to December 31, 2006 at the Centre de Lutte Contre le Cancer de Haute Normandie were enrolled in this prospective study. HER2 ECD was measured in frozen serum by a commercial kit with a cut-off value of 15 ng/ml. RESULTS: Sixty-five patients were enrolled. Seven patients (11%) had an elevated serum HER2 ECD level (mean=25.1 ng/ml, range 15.1-38.9 ng/ml). During follow-up, 13 patients (20%) developed metastases and seven patients (11%) died. Death was related to breast cancer metastases in six patients (9%). Out of the seven patient with elevated serum HER2 ECD level, five (71%) developed metastases and three (43%) died of metastases during follow-up. Multivariate analysis showed that elevated serum HER2 ECD level was the unique factor for both disease-free survival (p<0.0006) and overall survival (p=0.008) in this series. CONCLUSION: Elevated serum HER2 ECD level is a strong prognostic factor in primary breast cancer overexpressing HER2 treated with adjuvant therapy of trastuzumab. In addition, our results suggest that it could predict failure of adjuvant therapy of trastuzumab.

Breast cancer occurred after Hodgkin's disease: clinico-pathological features, treatments and outcome: analysis of 214 cases.

BACKGROUND: Secondary tumours (ST) represent a major concern in survivors of Hodgkin's disease (HD). Breast cancer (BC) is the most frequent ST among young treated women. MATERIAL AND METHODS: One hundred and eighty-nine women treated for HD by radiotherapy (RT) and/or chemotherapy (CT) subsequently developed 214 BCs. RESULTS: Median age at HD diagnosis was 25 years (34% were less than 20). Median interval between HD and BC was 18.6 years, with a 42-year median age at first BC. According to the TNM classification, there were 30 (14%) T0 (non palbable lesions), 86 (40%) T1, 56 (26%) T2, 13 (6%) T3T4 and 29 (14%) Tx. There were 25 (13.2%) contralateral BC. 160 (75%) and 15 (7%) tumours were infiltrating ductal and lobular carcinomas, 7 (3.3%) were other subtypes and 27 (22%) DCIS. The rate of axillary nodal involvement was 32%. Among 203 operated tumours, 79 (39%) were treated by breast conserving surgery (BCS), with RT in 56 (71%) cases. CT and hormonal treatment were delivered in 51% and 45% of the patients. With a 50-month median follow-up, local recurrence occurred in 12% of the tumours (9% after mastectomy, 21% after lumpectomy alone and 13.7% after lumpectomy with RT). Metastasis occurred in 47 (26%) patients. The risk factors were pN+, pT, high SBR grade and young age (< 50 years). The ten-year overall and specific survival rates were 53% and 63.5%, respectively. The ten-year specific survival rates were 79% for pT0T1T2, 48% for pT3T4 (p = 0.0002) and 79% for pN0 versus 38.5% for pN+ (p = 0.00026). Among 67 deaths, 43 (73%) were due to BC. CONCLUSION: Patients and physicians should be aware that BC is the most frequent secondary tumour in young women treated for HD. The new RT modalities (lower doses and involved fields) may decrease the risk in the future. However, these women require a careful monitoring as from 8 to 10 years after HD treatment, combining mammography, ultrasound and MRI according to several ongoing studies. BC with whole breast irradiation is feasible in some selected cases.

Exploring cell tropism as a possible contributor to influenza infection severity.

Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity. Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types. The two cell types differ only in their susceptibility to infection and rate of virus production. We show the existence of a parameter regime which is characterized by high viral loads sustained long after the onset of infection. This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus. The two target cell mathematical model offers good agreement with experimental data from severe influenza infections, as does the usual, single target cell model albeit with biologically unrealistic parameters. Both models predict that while neuraminidase inhibitors and adamantanes are only effective when administered early to treat an uncomplicated seasonal infection, they can be effective against more severe influenza infections even when administered late.

Ovarian tissue thawing: a comparison of two conditions.

Two different protocols to thaw cryopreserved human ovarian cortex have been evaluated using a histological analysis. The slower one, based on a progressive dilution of cryoprotectants, seems to maintain an optimal follicle morphology.