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.

[Lipofilling in the management of breast cancer: An update based on a literature review and national and international guidelines]. / Le lipomodelage du sein dans un contexte cancérologique : mise au point à partir d'une revue de littérature actualisée et des référentiels nationaux et internationaux.

BACKGROUND: Lipomodelling (LM) is an increasingly used technique to reconstruct or correct an aesthetic defect linked to a loss of substance. In France, the Haute Autorité de santé (HAS) published recommendations in 2015 and 2020 concerning the conditions of use of LM on the treated and contralateral breast. These appear to be inconsistently followed. METHODS: Twelve members of the Senology Commission of the Collège national des gynécologues-obstétriciens français (French College of Gynecologists and Obstetricians) reviewed the carcinological safety of LM and the clinical and radiological follow-up of patients after breast cancer surgery, based on French and international recommendations and a review of the literature. The bibliographic search was conducted via Medline from 2015 to 2022, selecting articles in French and English and applying PRISMA guidelines. RESULTS: A total of 14 studies on the oncological safety of LM, 5 studies on follow-up and 7 guidelines were retained. The 14 studies (6 retrospective, 2 prospective and 6 meta-analyses) had heterogeneous inclusion criteria and variable follow-up, ranging from 38 to 120 months. Most have shown no increased risk of locoregional or distant recurrence after LM. A retrospective case-control study (464 LMs and 3100 controls) showed, in patients who had no recurrence at 80 months, a subsequent reduction in recurrence-free survival after LM in cases of luminal A cancer, highlighting the number of lost to follow-up (more than 2/3 of luminal A cancers). About follow-up after LM, the 5 series showed the high frequency after LM of clinical mass and radiological images (in » of cases), most often corresponding to cytosteatonecrosis. Most of the guidelines highlighted the uncertainties concerning oncological safety of LM, due to the lack of prospective data and long-term follow-up. DISCUSSION AND PERSPECTIVES: The members of the Senology Commission agree with the conclusions of the HAS working group, in particular by advising against LM "without cautionary periods", excessively, or in cases of high risk of relapse, and recommend clear, detailed information to patients before undergoing LM, and the need for postoperative follow-up. The creation of a national registry could address most questions regarding both the oncological safety of this procedure and the modalities of patient follow-up.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Modalités et morbidité des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation. DESIGN: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities. RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

Radiosensitivity increase in FCV-F9 virus using combined treatments with natural antimicrobials and γ-irradiation.

AIMS: The objective was to evaluate the possible synergistic effect of cranberry juice (CJ) and commercial citrus extract (BS) against FCV-F9 viral titre in vitro in combination with γ-irradiation and to determinate the D10 values and radiosensitivity increase. METHODS AND RESULTS: Virus samples were treated with a formulation containing a mixture of BS or CJ. Results showed a D10 of 0·05, 0·42% and 1·34 kGy for the virus treated with the BS, the CJ and the irradiation alone respectively. Concentrations needed to reduce 6 log TCID50  ml-1 of viral titre were BS-0·3%, CJ-2·52% and 8·04 kGy. Irradiation combined with BS-0·01% and CJ-0·1% against FCV-F9 virus showed D10 values of 0·74 and 0·72 kGy, respectively, resulting in a viral radiosensitization of 1·28 and 1·50 for respective treatments. CONCLUSION: The higher viral radiosensitization observed after combining γ-irradiation with BS-0·01% and CJ-0·1% indicates that CJ and BS could be used as antiviral agents alone or in combination with γ-irradiation to prevent NoV outbreaks. SIGNIFICANCE AND IMPACT OF THE STUDY: Cranberry juice and BS could be used in hurdle approaches in combined treatment with γ-irradiation to assure food safety without a detrimental effect on nutritional value and maintain low processing cost.

[Clinical practice guidelines: Benign breast tumor--Aims, methods and organization]. / Recommandations pour la pratique clinique: tumeurs bénignes du sein--Objectifs, méthodes et organisation.

Conversely to breast cancer, few data and guidelines are available to explore and manage benign breast disorders. Therefore, the Collège national des gynécologues et obstétriciens français (CNGOF - French College of Gynaecologists and Obstetricians) decided to establish clinical practice guidelines for benign breast tumour (BBT). CNGOF appointed a committee with responsibility for selecting experts, compiling questions and summarizing the recommendations. The summary of valid scientific data for each question analyzed by the experts included a level of evidence, based on the quality of the data available and defined accordingly rating scheme developed by the Haute Autorité de santé (French National Authority for Health).

[Benign breast tumors: Recommendations of Collège National des Gynécologues Obstétriciens Français (CNGOF)--Short text]. / Tumeurs bénignes du sein: recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF)--Texte court.

Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C).

Nipple discharge: The role of imaging.

Nipple discharge is a common symptom in breast medicine. It is usually benign in origin (papillomas and galactophore duct ectasia) although it is essential not to miss the risk of an underlying malignant lesion (5%) mostly due to in situ carcinomas. Clinical examination is essential in the management, distinguishing benign "physiological" discharge from discharge suspected of being "pathological" in which further investigations with mammography and ultrasound are required. When the conventional imaging assessment for pathological nipple discharge is normal, breast MRI is gradually replacing galactography although this is still an emerging and invalidated indication. In this context and if the whole imaging assessment is normal, surgery is no longer the only solution for patients, who can now be offered regular monitoring.

Establishment of a consultation to announce the results of a breast biopsy.

PURPOSE: Establishment of post-breast biopsy consultations to announce the results. Evaluation of this system in order to help improve the practice. PATIENTS AND METHODS: The radio-senologists benefited from continuing medical education for the in-house announcement. Fifty patients (with malignant results) received questionnaires comprising 13 items and the possibility of free and anonymous comments. RESULTS: The authors present tools to help in the interview. Thirty-one questionnaires were returned by the patients and were analysed. Thirty patients (96.8%) considered the information provided as rather or fully sufficient, and only one considered that she did not have enough time to ask all of the questions she wanted to ask. Two patients (6.6%) found the scheduling of the subsequent appointments insufficient. The patients had a rather positive overall judgement about this consultation. CONCLUSION: The radiologist may provide one of the consultations to announce the results, depending on their involvement in senology, their personal expertise and their integration in the care network.

Correlation between imaging and prognostic factors: molecular classification of breast cancers.

The new molecular classification of breast cancers defines cancer sub-groups with a distinct prognosis and response to treatment. Studies on the literature deal with the imaging of each tumour sub-type. The radiologist should be familiar with them in order to adapt the care of an aggressive sub-type. In view of the current knowledge, the following have been significantly more often observed: mammographical spiculated mass with echogenic halo in luminal A sub-type; architectural distortion in luminal B sub-type; an irregular mass with indistinct margin comprising microcalcifications, with an abrupt interface in the sonography, or non-sonographic mass in the HER2 sub-type; a very hypoechogenic, lobulated mass with indistinct or microlobulated margin, with an abrupt interface, sometimes pseudo-benign, in the triple-negative sub-type.

Correlation between imaging and molecular classification of breast cancers.

The histological type of tumour according to the WHO: ductal, lobular, rare forms, is correlated with specific aspects of the imaging based on each type. This morphological classification was improved by knowledge of the molecular anomalies of breast cancers, resulting in the definition of cancer sub-groups with distinct prognoses and different responses to treatment: luminal A, luminal B, HER2 positive, basal-like, triple-negative. Studies are beginning to deal with the appearance of each sub-type in the imaging. It is now important for the radiologist to be familiar with them.

Radiological features of triple-negative breast cancers (73 cases).

OBJECTIVES: Triple-negative breast cancers generally occur in young women and they have the potential to be aggressive. It is important for this subtype of tumour to be detected early. We studied the appearance of 73 tumours on mammography, sonography and MRI in order to determine what specific features they showed on imaging. PATIENTS AND METHODS: From July 2009 to December 2010, we retrospectively reviewed mammogram and sonogram images of 73 triple-negative cancers. Colour Doppler had been used to depict vascularisation in 34 cases and elastography score calculated in 17 cases. Sixteen patients had undergone MRI. The radiological description of these different modalities draws on the BI-RADS lexicon and categorisation. RESULTS: On mammography, triple-negative cancers often presented as a round mass (59.3%) or an oval or lobulated mass (65%), with circumscribed (15%), microlobulated (12.5%), indistinct (55%) or occasionally spiculated margins (15%). On sonography, the vast majority of these cancers appeared as masses (92.8%) with occasional posterior acoustic attenuation (22.6%). MRI showed more suspicious images than the standard examinations, notably rim-enhancement (eight out of 12 masses). CONCLUSION: . Radiological images appear as lobulated masses more readily, while on sonography posterior enhancement is shown more often than attenuation, and MRI finds rim-enhancement.

Imaging benign inflammatory syndromes.

Benign mastitis is a rare disease and its management is difficult. The diagnostic challenge is to distinguish it from carcinomatous mastitis. We make a distinction between acute mastitis secondary to an infection, to inflammation around a benign structure or to superficial thrombophlebitis, and chronic, principally plasma cell and idiopathic granulomatous mastitis. Imaging is often non-specific but we need to know and look for certain ultrasound, mammogram or magnetic resonance imaging (MRI) signs to give a pointer as early as possible towards a benign aetiology. A biopsy should be undertaken systematically where there is the slightest diagnostic doubt, to avoid failing to recognise a carcinomatous mastitis.

The inflammatory breast: management, decision-making algorithms, therapeutic principles.

Inflammatory syndrome is one of the rare emergency breast situations. Its etiology is benign, infectious in most cases. The clinical examination is often self-evident and suggests the diagnosis. But alone it is insufficient, and diagnostic tests are necessary to guide therapy. As essential as it is, mammography's limitations reinforce the benefit of ultrasonography, which in all cases reveals an abscess and has greater sensitivity for detecting a malignant tumor. If the etiology is benign, clinical signs will disappear with medical treatment, with no need for further investigation. While it is legitimate to initiate a trial treatment, it must not delay oncologic management, because of the severity of inflammatory cancer.

Effect of antimicrobial coatings on the radiosensitization of Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes in fresh broccoli.

Radiosensitization of Listeria monocytogenes, Escherichia coli, Salmonella Typhimurium, and aerobic microflora was evaluated in broccoli florets coated by antimicrobial coatings and treated with different doses of γ-radiation. Broccoli florets were inoculated with aerobic microflora isolated from broccoli and with pathogenic bacteria (L. monocytogenes, E. coli, and Salmonella Typhimurium) at 10(6) CFU/ml. Inoculated florets were then coated with methylcellulose-based coating containing various mixtures of antimicrobial agents: organic acids plus lactic acid bacteria (LAB metabolites), organic acids plus citrus extract, organic acids plus citrus extract plus spice mixture, and organic acids plus rosemary extract. Coated florets were irradiated with various doses (0 to 3.3 kGy), and microbial analyses were conducted to calculate the D(10)-value and relative sensitivity. All antimicrobial coatings had almost the same effect of increasing the radiosensitivity of L. monocytogenes (from 1.31 to 1.45 times) to γ-irradiation. The coating containing organic acid plus citrus extract was the most efficient formulation for increasing the radiosensitization of E. coli and aerobic microflora, by 2.40 and 1.76 times, respectively, compared with the control without the antimicrobial coating. The coating containing organic acids plus LAB metabolites was the most effective formulation for increasing the radiosensitization (by 2.4 times) of Salmonella Typhimurium. Results suggest that the spice extract, when mixed with organic acids and citrus extract, might protect E. coli and aerobic microflora from the effects of γ-irradiation.

[Evaluation of suspicious nipple discharge with MRI: review of 50 cases]. / Apport de l'IRM dans les écoulements mamelonnaires pathologiques: analyse de 50 cas.

PURPOSE: To determine the role of MRI in the evaluation and management of patients with suspicious nipple discharge and normal mammographic and US evaluation. PATIENTS AND METHODS: A total of 50 patients with suspicious nipple discharge and normal mammographic and US evaluation prospectively underwent MRI. The first 16 patients underwent routine breast MRI, while MR-ductography with image fusion at the console was added for the last 34 patients. RESULTS: In 22 of 25 high-risk and malignant lesions, MRI showed enhancement whereas it was normal in three cases. In 25 benign cases (resolution of discharge/benign non-proliferative breast disease), MRI was negative in 22 cases and falsely positive in three cases. CONCLUSION: In this clinical setting, MRI shows excellent sensitivity, PPV and NPV. A negative result on MRI would support clinical follow-up as opposed to surgery.

Insulin but not leptin protects olfactory mucosa from apoptosis.

The mammalian olfactory mucosa (OM) is continually renewed throughout life. Owing to their position in the nasal cavity, OM cells are exposed to multiple insults, including high levels of odourants that can induce their death. OM regeneration is therefore essential to maintain olfactory function, and requires the tight control of both cell death and proliferation. Apoptosis has been implicated in OM cell death. Olfaction is one of the senses involved in food intake and depends on individual nutritional status. We have previously reported the influence of hormones related to nutritional status on odour perception and have shown that the OM is a target of insulin and leptin, two hormones known for their anti-apoptotic properties. In the present study, we investigated the potential anti-apoptotic effect of these metabolic hormones on OM cells. Both Odora cells (an olfactive cell line) and OM cells treated with etoposide, a p53 activity inducer, exhibited mitochondrial-dependent apoptosis that was inhibited by the pan-caspase inhibitor zVAD-fmk. Insulin, but not leptin, impaired this apoptotic effect. Insulin addition to the culture medium reduced p53 phosphorylation, caspase-3 and caspase-9 cleavage, and caspase-3 enzymatic activity induced by etoposide. The apoptotic wave observed in the OM after interruption of the neuronal connections between the OM and the olfactory bulb by bulbectomy was impaired by intranasal insulin treatment. These findings suggest that insulin may be involved in OM cellular dynamics, through endocrine and/or paracrine-autocrine effects of circulating or local insulin, respectively.

Analyzing cranberry bioactive compounds.

There is a growing public interest for the North American cranberry (Vaccinium macrocarpon) as a functional food because of the potential health benefits linked to phytochemical compounds present in the fruit--the anthocyanin pigments, responsible for its brilliant red color, and other secondary plant metabolites (flavonols, flavan-3-ols, proanthocyanidins, and phenolic acid derivatives). Isolation of these phenolic compounds and flavonoids from a sample matrix is a prerequisite to any comprehensive analysis scheme. By far the most widely employed analytical technique for the characterization of these compounds has been high-performance liquid chromatography(HPLC) coupled with ultraviolet-visible(UV/Vis) and mass spectrometer(MS) detection. This review covers the cranberry major bioactive compounds, the extraction and purification methods, and the analytical conditions for HPLC used to characterize them. Extraction, chromatographic separation and detection strategies, analyte determinations, and applications in HPLC are discussed and the information regarding methods of specific cranberry analyte analyses has been summarized in tabular form to provide a means of rapid access to information pertinent to the reader.

Bioactive compounds in cranberries and their biological properties.

Cranberries are healthy fruit that contribute color, flavor, nutritional value, and functionality. They are one of only three fruits native to America. Over the past decade, public interest for the North American cranberry (Vaccinium macrocarpon) has been rising with reports of their potential health benefits linked to the numerous phytochemicals present in the fruit--the anthocyanins, the flavonols, the flavan-3-ols, the proanthocyanidins, and the phenolic acid derivatives. The presence of these phytochemicals appears to be responsible for the cranberry property of preventing many diseases and infections, including cardiovascular diseases, various cancers, and infections involving the urinary tract, dental health, and Helicobacter pylori-induced stomach ulcers and cancers. Recent years have seen important breakthroughs in our understanding of the mechanisms through which these compounds exert their beneficial biological effects, yet these remain to be scientifically substantiated. In this paper these characteristics, as well as the antioxidant, radical scavenging, antibacterial, antimutagen, and anticarcinogen properties of cranberry major bioactive compounds are explained.