Deciphering oxygen distribution and hypoxia profiles in the tumor microenvironment: a data-driven mechanistic modeling approach.

Objective. The distribution of hypoxia within tissues plays a critical role in tumor diagnosis and prognosis. Recognizing the significance of tumor oxygenation and hypoxia gradients, we introduce mathematical frameworks grounded in mechanistic modeling approaches for their quantitative assessment within a tumor microenvironment. By utilizing known blood vasculature, we aim to predict hypoxia levels across different tumor types.Approach. Our approach offers a computational method to measure and predict hypoxia using known blood vasculature. By formulating a reaction-diffusion model for oxygen distribution, we derive the corresponding hypoxia profile.Main results. The framework successfully replicates observed inter- and intra-tumor heterogeneity in experimentally obtained hypoxia profiles across various tumor types (breast, ovarian, pancreatic). Additionally, we propose a data-driven method to deduce partial differential equation models with spatially dependent parameters, which allows us to comprehend the variability of hypoxia profiles within tissues. The versatility of our framework lies in capturing diverse and dynamic behaviors of tumor oxygenation, as well as categorizing states of vascularization based on the dynamics of oxygen molecules, as identified by the model parameters.Significance. The proposed data-informed mechanistic method quantitatively assesses hypoxia in the tumor microenvironment by integrating diverse histopathological data and making predictions across different types of data. The framework provides valuable insights from both modeling and biological perspectives, advancing our comprehension of spatio-temporal dynamics of tumor oxygenation.

How to promote physical activity during pregnancy : A systematic review.

INTRODUCTION: Sedentary lifestyles and physical inactivity have been shown to increase during pregnancy and are a cause of obstetric comorbidity. The objective of this study was to conduct a systematic review of interventions aiming to promote physical activity during pregnancy. MATERIAL AND METHODS: Databases were searched from January 2008 to September 2019. Selection criteria included randomized controlled trials evaluating the efficacy of interventions promoting physical activity during pregnancy. RESULTS: In total, 256 articles were extracted from databases. 202 articles were excluded. Finally, 15 articles were included in the study. 5633 patients were included from various populations. Six studies rated physical activity (PA) as the primary outcome. Five studies suggested promoting physical activity through individual interviews which in two studies showed an increase in PA. Three studies evaluated an intervention based on group interviews and one of these reported a significant increase in PA. Two studies evaluated the use of a Smartphone application to promote physical activity but they did not conclude that they were effective because they were designed with low statistical power. CONCLUSION: The practice of regular PA during pregnancy reduces obstetrical comorbidity. However, interventions seem to have a low impact on the promotion of PA during pregnancy. New intervention strategies need to assessed, such as the use of mobile health interventions.

Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study.

PURPOSE: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone. RESULTS: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed. CONCLUSION: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

Sub-Doppler Frequency Metrology in HD for Tests of Fundamental Physics.

Weak transitions in the (2,0) overtone band of the hydrogen deuteride molecule at λ=1.38 µm were measured in saturated absorption using the technique of noise-immune cavity-enhanced optical heterodyne molecular spectroscopy. Narrow Doppler-free lines were interrogated with a spectroscopy laser locked to a frequency comb laser referenced to an atomic clock to yield transition frequencies [R(1)=217105181895(20) kHz; R(2)=219042856621(28) kHz; R(3)=220704304951(28) kHz] at three orders of magnitude improved accuracy. These benchmark values provide a test of QED in the smallest neutral molecule, and they open up an avenue to resolve the proton radius puzzle, as well as constrain putative fifth forces and extra dimensions.

The ASACUSA antihydrogen and hydrogen program: results and prospects.

The goal of the ASACUSA-CUSP collaboration at the Antiproton Decelerator of CERN is to measure the ground-state hyperfine splitting of antihydrogen using an atomic spectroscopy beamline. A milestone was achieved in 2012 through the detection of 80 antihydrogen atoms 2.7 m away from their production region. This was the first observation of 'cold' antihydrogen in a magnetic field free region. In parallel to the progress on the antihydrogen production, the spectroscopy beamline was tested with a source of hydrogen. This led to a measurement at a relative precision of 2.7×10-9 which constitutes the most precise measurement of the hydrogen hyperfine splitting in a beam. Further measurements with an upgraded hydrogen apparatus are motivated by CPT and Lorentz violation tests in the framework of the Standard Model Extension. Unlike for hydrogen, the antihydrogen experiment is complicated by the difficulty of synthesizing enough cold antiatoms in the ground state. The first antihydrogen quantum states scan at the entrance of the spectroscopy apparatus was realized in 2016 and is presented here. The prospects for a ppm measurement are also discussed.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

Evaluation of sentinel lymph node biopsy after previous breast surgery for breast cancer: GATA study.

AIM: Sentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context. PATIENTS AND METHODS: From 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy. RESULTS: The detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%. CONCLUSION: Previous conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement. CLINICAL TRIAL REGISTRATION NUMBER: NCT00293865.

Laparoscopic hysterectomy after concurrent radiochemotherapy in locally advanced cervical cancer compared to laparotomy: A multi institutional prospective pilot study of cost, surgical outcome and quality of life.

OBJECTIVE: Laparoscopy allows hysterectomies after chemoradiation to be performed without opening the abdominal wall. We measured the costs and quality of life for locally advanced cervical cancer patients operated on via laparoscopy compared to laparotomy. STUDY DESIGN: We conducted an observational prospective multicenter study on locally advanced cervical cancer patients undergoing an extrafascial hysterectomy after concurrent chemoradiotherapy (CRT). We assessed the costs from the medical visit before surgery up to the first month after surgery from the providers' perspective and measured the quality of life using the EORTC QLQ-C30 and QLQ-CX24 up to six months. RESULTS: Sixty two patients (39 laparoscopy and 23 laparotomy) from December 2008 to November 2011 were included. There was no difference in operative time, or intraoperative and post-operative complication rates between the two groups. Intraoperative transfusion and abdominal drain were significantly lower in the laparoscopy group (respectively, p = 0.04 and p < 0.01), as well as the duration of hospital stay (7.3 d vs. 5.7 d, p < 0.001). All patients who underwent laparoscopic hysterectomy were discharged to home, whereas 4 laparotomy patients used convalescence homes (p = 0.01). Mean costs at one month were €10,991 for laparotomy and €11,267 for laparoscopy (p = 0.76). Sexual activity is better for the laparoscopy group at six months (p = 0.01). CONCLUSION: Laparoscopy for an extrafascial hysterectomy after CRT in locally advanced cervical cancer patients brought better quality of life with similar costs compared to laparotomy, and should therefore be the first choice for surgeons.

The cytotoxic effect of combined hyperthermia and taxane chemotherapy on ovarian cancer cells: results of an in vitro study.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is under continuous evaluation as a potential treatment for ovarian cancer. The purpose of this study was to evaluate the effect of chemotherapy, drug concentration and temperature. MATERIALS AND METHODS: We examined the combined effects of hyperthermia and taxane chemotherapy on the clonogenic survival of the human ovarian carcinoma SHIN-3 cell line in vitro. RESULTS: When hyperthermia was combined with chemotherapy, the median lethal dose (LD50) was equivalent regardless of the duration of exposure, and was independent of the exposure temperature. Taxanes showed a similar LD50 over the temperature range tested. CONCLUSIONS: In our study, hyperthermia does not increase the cytotoxic effects of taxanes, at least for the concentrations and durations tested.

[Quantitative assessment of medical students' clinical practical learning in department of obstetrics and gynecology of Brest Hospital University]. / Évaluation quantitative de l'enseignement pratique des étudiants hospitaliers en gynécologie-obstétrique au CHU de Brest.

OBJECTIVE: The main objective of this study was to describe how medical students got progressively trained to perform the most frequent medical procedures in obstetrics and gynecology. The secondary objective was to rationalize and plan the training. METHODS: The medical students in our University Hospital were contacted either directly or by e-mail. They were given an anonymous simple choice questionnaire relating to eight most important acts in the specialty. RESULTS: Three hundred and eighty-two medical students have been consulted. We got 173 answers which means a participation rate of 45.3%. The survey showed up that the considered procedures were progressively put into practice with the exception of two: the insertion of an intrauterine contraceptive device (coil) and of an implant. CONCLUSION: The study showed off some insufficiency in the training in two of the considered procedures. An amendment was proposed with simulated performances of the acts and the setting up of a training course booklet.

[MRI evaluation of residual breast carcinoma after neoadjuvant chemotherapy]. / Cancer du sein traité par chimiothérapie néoadjuvante: évaluation du reliquat tumoral par l'IRM mammaire.

PURPOSE: This study aims to evaluate the sensibility and specificity of MRI in the detection and size measuring of residual breast cancer in patients treated with neoadjuvant chemotherapy before surgery. PATIENTS AND METHODS: This is a retrospective study of 32 women, who underwent breast MRI before and after neoadjuvant treatment. MRI has been confronted to surgical pathology results. RESULTS: The sensibility of MRI to assess pathologic Complete Response (no invasive residual tumor) was excellent (100%) but the specificity was low (55,5%). There was no false negative case and four false positive cases (Two ductal carcinomas in situ and two scars-like fibrosis). When MRI outcomes were compared with the presence or absence of invasive or in situ residual carcinoma, only one false negative case was noticed (one "in situ" residual tumor). The correlation between tumor size measured by MRI and histopathology was low (r=0,32). Underestimations of tumor size were due to non-continuous tumor regression or invasive lobular carcinoma or association of invasive carcinoma and intra ductal breast cancer. Over estimations of tumor size were due to chemotherapy-induced changes. CONCLUSION: MRI is a sensitive but poorly specific method to assess the pathological complete response after neoadjuvant chemotherapy. Estimation of tumor size and detection of isolated residual in situ carcinoma are fare. Therefore, surgical intervention remains necessary whatever the MRI outcomes.

[Uterine sarcoma associated with tamoxifen use after breast cancer: Review of the pathogenesis]. / Sarcomes utérins après exposition au tamoxifène dans les suites d'un cancer du sein : mise au point sur l'étiopathogénie.

Tamoxifen is widely used in the breast cancer treatment. Its side effects on the endometrium are well-known, but more and more worse prognosis uterine sarcoma are described. Based on recent literature review, the cause and effect chain between tamoxifen and uterine sarcoma is argued, which confirms that a risk exists as from 2 years of treatment, a cumulative dose of 15 g, and that malignant mixed mesodermal tumours appear to be the most frequent.

[Retrospective study conducted in northern Finistère about the role of breast MRI in normal breast screening, experience in 51 patients]. / Etude rétrospective dans le Nord-Finistère sur la place de l'IRM mammaire devant un bilan sénologique normal, à propos de 51 cas.

OBJECTIVES: To study the role and indications of breast MRI in normal breast screening. PATIENTS AND METHODS: Retrospective study of 51 patients (mean age of 51 years) conducted in northern Finistère. Each patient had a normal (BI-RADS 1 or 2) breast screening (mammography and echography). Four indications for MRI were chosen: screening of high-risk patients, high-density breasts, radio-clinical discordance, and breasts prostheses. Breast MRI were reviewed according to BI-RADS classification. Abnormalities categorized in BI-RADS 4 or 5 were confirmed histologically. RESULTS: Thirteen patients underwent histological analysis. Nine invasive carcinomas were identified (six invasive lobular carcinomas (ILC), two mixed carcinomas, one invasive ductal carcinoma). For these patients, the reason for performing MRI was a radio-clinical discordance. DISCUSSION AND CONCLUSION: The study demonstrates the breast MRI value for radio-clinical discordance and the key role of MRI in diagnostic challenge of ILC. In literature review, MRI has a role even if breast screening is normal: radio-clinical discordance, screening of patients with high-risk, breasts prostheses in certain cases. Breast density comes as an additional criteria to perform this exam.

[Carcinosarcoma of the ovary]. / Le carcinosarcome ovarien.

Ovarian carcinosarcoma, also called malignant mixed mesodermal tumour, is a rare ovarian tumour representing less than two per cent of ovarian cancers. Carcinosarcoma is an aggressive tumour, which associates some epithelial elements (carcinoma) with a stromal component (sarcoma). This tumour can be found in the female genital tractus, mostly in the uterus. It can be found even more rarely on the ovaries. The initial stage of the disease at the diagnostic is considered as the only prognostic factor. There is no existing consensus concerning treatment. Nevertheless, surgical treatment is paramount for the survival of patients. Response rates to chemotherapy are about 20%.

[Role of outpatient surgery in breast surgery. Prospective feasibility study]. / Place de la chirurgie ambulatoire en chirurgie sénologique. Etude prospective de faisabilité.

STUDY AIM: The objective of this prospective study was to assess the feasibility of outpatient breast surgery, the reasons for inpatient procedures (IPP), the reasons for conversion and the conversion rate, and the postoperative morbidity after outpatient procedures (OPP). PATIENTS AND METHODS: In 1999, among 625 patients eligible for OPP (diagnostic surgery or conservative curative surgery), OPP was performed in 418 patients (67%) and IPP was performed in 207 patients (33%). The reasons for IPP rather than OPP were environmental (64%) rather than medical (16%). RESULTS: The conversion rate to conventional surgery was 12.4% and the definitive OPP rate was 58.6%. The reasons for conversion were more often medical (50%) and environmental (21%) than surgical (23%). The morbidity, except for axillary seroma, was similar for OPP and IPP. The axillary seroma rate after axillary lymph node dissection was higher with OPP (27.4 vs 16.1%). CONCLUSION: OPP is a good alternative to IPP in breast surgery, especially for diagnostic purposes. OPP is also feasible for partial mastectomy with axillary lymph node dissection, but patients must be clearly informed about the risks of axillary morbidity. The patients' quality of life and satisfaction index should also be evaluated.

Quasiunimodal tunable pulsed dye laser at 440 nm: theoretical development for using a quad prism beam expander and one or two gratings in a pulsed dye laser oscillator cavity.

In the first section of this paper a theoretical discussion is presented for the performance of a pulsed dye laser oscillator cavity, without an intracavity etalon, using the Gaussian beam approximation. Optimal conditions for achievement of narrow spectral linewidth are discussed (location of the grating or of the beam expander). Various configurations of oscillator cavities are investigated, including a dispersive device composed of one grating and one virtual grating. The use of a beam expander is treated. We find that the same spectral linewidth is obtained theoretically for the optical cavity with two gratings as with one grating and a virtual grating. In the second part we describe the performance (in terms of spectral linewidth 1.3-GHz FWHM quasiunimodal structure, divergence of the beam, etc.) of the dye laser in light of the theoretical arguments. The complete laser contains an oscillator stage, a preamplifier stage, and an amplifier stage, each pumped by an UV beam (355 nm) from a pulsed Nd:YG laser.