Endocrine Disruptors in Food, Estrobolome and Breast Cancer.

The microbiota is now recognized as one of the major players in human health and diseases, including cancer. Regarding breast cancer (BC), a clear link between microbiota and oncogenesis still needs to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called "estrobolome", influences sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, may impact on the onset, progression, and treatment of hormonal dependent cancers (which account for more than 70% of all BCs). The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on the one side disruptors can alter the composition and functions of the estrobolome, ad on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new "oncobiotic" perspective.

Screening for Physical Activity Levels in Non-Metastatic Breast Cancer Patients Undergoing Surgery: An Observational Study.

BACKGROUND: Physical activity (PA) can play a role in lowering the risk of breast cancer (BC), but also in reducing perioperative complications and treatments related side effects, improving the quality of life and decreasing mortality in BC survivors. PA and nutritional screening are not offered to patients after cancer diagnosis as standard of care, even in high quality breast units. METHODS: From February 2019 to March 2020, we performed a preoperative physical and nutritional screening in 504 consecutive BC patients waiting for surgery. The screening included an IPAQ questionnaire to evaluate the level of physical activity; nutritional screening with measurement of anthropometric parameters (weight, height, waist and hips circumference, BMI, and waist hip ratio) and evaluation of body composition using Bioelectrical Impedance Analysis (BIA). RESULTS: The majority of patients in our series resulted physically inactive: clustering the IPAQ scores, 47% of patients proved to be physically inactive (MET score <700), 34% moderately active (MET score 700-2520), and only 19% physically active (MET score > 2520). In addition, approximately half of the patients (49.01%) resulted overweight or obese, and more than half (55.2%) had a percentage of fatty tissue over the recommended cut off for adult women. CONCLUSIONS: Our data confirm that assessment of PA levels should become part of the standard preoperative evaluation of BC patients and behavioral interventions should be offered to them, in order to pre-habilitate for surgery and improve outcomes. IPAQ Questionnaire and body composition analysis could be quick and easy screening tools in order to identify which patients may need more support in being active during and after anticancer treatments.

Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles.

BACKGROUND: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. METHODS: Lehman's TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. RESULTS: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug-target interactions were found among the upregulated genes in the M, IM and MSL subsets. CONCLUSIONS: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amount of information from several data sets has allowed us to identify a well-determined minimal number of genes that may help in the recognition of TNBC subtypes. These genes, most of which have been previously found to be associated with breast cancer, have the potential to become novel diagnostic markers and/or therapeutic targets for specific TNBC subsets.

A Model of an Integrative Approach to Breast Cancer Patients.

BACKGROUND: Breast cancer (BC) survivors have physical and psychological needs that require convincing responses by health care providers. The quality of life issue and clinical unmet needs are among the main reasons pushing a number of patients toward "natural" therapies that are often misleading and alternative to mainstream cancer care. Integrative Oncology (IO) tries to respond to many of those needs, by combining lifestyle counseling, body-mind activities, and complementary evidence-informed therapies with anticancer standard treatments. METHODS: In our model at Fondazione Policlinico Gemelli (FPG), every woman diagnosed with a BC waiting for surgery or candidate to neoadjuvant chemotherapy undergoes a preliminary psycho-oncological distress evaluation and a brief lifestyle interview. Anthropometric measurements, body composition analysis, and individual levels of physical activity are recorded. Patients are given evidence based recommendations about the advisable diet and physical activity in a prehabilitation setting. A physician provides patients with information about integrative care plans to treat symptoms related to the disease or its treatments. Therapeutic approaches include acupuncture, mindfulness-based protocols, qigong, massage therapy, and classes of music/art therapy. RESULTS: Between September 2018 and February 2020, the Center for Integrative Oncology at FPG has carried out 1249 lifestyle counseling sessions, 1780 acupuncture treatments, 1340 physiotherapy sessions, 3261 psycho-oncological consultations, 218 herbal medicine counseling sessions. Moreover, 90 BC patients completed the mindfulness based stress reduction (MBSR) protocol and 970 patients participated in qigong, art therapy, and music therapy classes. CONCLUSIONS: Our integrative approach aims to achieve a person-centered medicine by improving symptoms management, adherence to oncological protocols, and eventually overall quality of life.

Neoadjuvant Chemotherapy in Breast Cancer: An Advanced Personalized Multidisciplinary Prehabilitation Model (APMP-M) to Optimize Outcomes.

Neoadjuvant chemotherapy is increasingly being employed in the management of breast cancer patients. Efforts and resources have been devoted over the years to the search for an optimal strategy that can improve outcomes in the neoadjuvant setting. Today, a multidisciplinary approach with the application of evidence-based medicine is considered the gold standard for the improvement of oncological results and patient satisfaction. However, several clinical complications and psychological issues due to various factors can arise during neoadjuvant therapy and undermine outcomes. To ensure that health care needs are adequately addressed, clinicians must consider that women with breast cancer have a high risk of developing "unmet needs" during treatment, and often require a clinical intervention or additional care resources to limit possible complications and psychological issues that can occur during neoadjuvant treatment. This work describes a multidisciplinary model developed at "Fondazione Policlinico Universitario Agostino Gemelli" (FPG) in Rome in an effort to optimize treatment, ease the application of evidence-based medicine, and improve patient quality of life in the neoadjuvant setting. In developing our model, our main goal was to adequately meet patient needs while preventing high levels of distress.

The low level laser therapy in the management of neurological burning mouth syndrome. A pilot study.

BACKGROUND AND OBJECTIVE: Burning Mouth Syndrome (BMS) is a common disease but still a diagnostic and therapeutic challenge for clinicians. Despite many studies its nature remains obscure and controversial; nowadays there is no consensus about definition, diagnosis and classification. BMS is characterized clinically by burning sensations in the tongue or other oral sites, often without clinical and laboratory findings. According to the etiology, BMS cases should be subdivided into three subtypes: BMS by local factors (lfBMS), BMS by systemic factors (sfBMS) and neurological BMS (nBMS), the most frequent, in which the symptom is caused by central or peripheral neurological malfunctions affecting in particular the taste pathway. To establish the type of BMS, both anamnesis and clinical examination, including laboratory tests, are necessary; nBMS cases will be recognized by exclusion of any other type. In case of lfBMS or sfBMS, the treatment of the main pathology will be resolutive; in nBMS cases many Authors proposed different pharmacological trials without satisfactory results and the current opinion is that a multidisciplinary approach is required to keep the condition under control. This pilot study aimed to investigate whether the biostimulative effect of Low Level Laser Therapy (LLLT) could enhance the symptoms of nBMS cases, improving patients' quality of life. STUDY DESIGN/MATERIALS AND METHODS: Among 160 patients affected by oral burning sensation attending to the Oral Pathology Complex Operative Unit of the Department of Stomatological Sciences of Sapienza University of Rome, 77 resulted affected by nBMS. Twenty-five of these patients, 16 females and 9 males, were randomly selected for low level laser applications. All the patients were irradiated with a double diode laser (Lumix 2 Prodent, Italy) emitting contemporarily at 650 nm and 910 nm, with a fluence of 0.53 J/cm(2) for 15 minutes twice a week for 4 weeks. The areas of irradiation were the sides of the tongue on the path of taste fibers. A NRS (numerical rating scale) evaluation of maximum and minimum pain was registered before and after the treatment. In each case to the total value of NRS rates registered before the treatment was deducted the total NRS rate registered after the treatment. The difference was estimated effective if over two points. The Kruskall-Wallis test revealed the significance of the study (p<0.0001) and the Dunn's Multiple Comparison test, applied to compare NRS rates before and after the treatment, showed that there is not a statistically relevant difference between min NRS ratings before and after treatment, while there are statistically significant differences between max NRS ratings (p<0.05). RESULTS: All the patients agreed the treatment confirming the general good compliance related to laser treatments. No side effects were registered and all the patients completed the therapy without interruption. Seventeen patients (68%) had relevant benefits from the treatment with valid reduction of NRS ratings. In 8 cases the differences of NRS rates were not relevant being under the limit of reliability established in study design. In no case there was a worsening of the symptoms. CONCLUSIONS: According to the results of this pilot study it is reasonable to suppose that LLLT may play an important role in the management of nBMS cases, more investigations are needed to clarify, by a greater number of cases and a placebo control group, the real effectiveness of this innovative LLLT application.

Bone damage induced by different cutting instruments--an in vitro study.

The aim of this study was to compare the peripheral bone damage induced by different cutting systems. Four devices were tested: Er:YAG laser (2.94 mm), Piezosurgery, high-speed drill and low-speed drill. Forty-five bone sections, divided into 9 groups according to different parameters, were taken from pig mandibles within 1 h post mortem. Specimens were fixed in 10% buffered formalin, decalcified and cut in thin sections. Four different parameters were analyzed: cut precision, depth of incision, peripheral carbonization and presence of bone fragments. For statistical analysis, the Kruskal-Wallis test was applied to assess equality of sample medians among groups. All sections obtained with the Er:YAG laser showed poor peripheral carbonization. The edges of the incisions were always well-shaped and regular, no melting was observed. Piezosurgery specimens revealed superficial incisions without thermal damage but with irregular edges. The sections obtained by traditional drilling showed poor peripheral carbonization, especially if obtained at lower speed. There was statistically significant differences (p<0.01) among the cutting systems for all analyzed parameters. Er:YAG laser, gave poor peripheral carbonization, and may be considered an effective method in oral bone biopsies and permits to obtain clear and readable tissue specimens.

Doppler ultrasonography and exercise testing in diagnosing a popliteal artery adventitial cyst.

We describe popliteal arterial adventitial cystic disease which causes intermittent claudication in a young athletic man, with atypical manifestation, without loss of foot pulses on knee flexion nor murmur in the popliteal fossa. The findings obtained from Magnetic Resonance Imaging were non-diagnostic. The diagnosis resulted from Echo-Doppler ultrasonography along with peak exercise testing. Ultrasonography also provided useful physiopathological informations suggesting that a popliteal artery adventitial cyst can become symptomatic if muscle exertion increases fluid pressure within the cyst, enough to cause hemodynamically significant endoluminal stenosis. Rapid diagnosis is essential to prevent progressive claudication threatening limb viability. To guarantee this professional sportsman a reliable and durable outcome, instead of less aggressive management, we resected the involved arterial segment and interposed an autologous saphenous-vein graft.

Bone damage induced by different cutting instruments: an in vitro study

The aim of this study was to compare the peripheral bone damage induced by different cutting systems. Four devices were tested: Er:YAG laser (2.94 mm), Piezosurgery, high-speed drill and low-speed drill. Forty-five bone sections, divided into 9 groups according to different parameters, were taken from pig mandibles within 1 h post mortem. Specimens were fixed in 10 percent buffered formalin, decalcified and cut in thin sections. Four different parameters were analyzed: cut precision, depth of incision, peripheral carbonization and presence of bone fragments. For statistical analysis, the Kruskal-Wallis test was applied to assess equality of sample medians among groups. All sections obtained with the Er:YAG laser showed poor peripheral carbonization. The edges of the incisions were always well-shaped and regular, no melting was observed. Piezosurgery specimens revealed superficial incisions without thermal damage but with irregular edges. The sections obtained by traditional drilling showed poor peripheral carbonization, especially if obtained at lower speed. There was statistically significant differences (p<0.01) among the cutting systems for all analyzed parameters. Er:YAG laser, gave poor peripheral carbonization, and may be considered an effective method in oral bone biopsies and permits to obtain clear and readable tissue specimens.

O objetivo deste estudo foi comparar o dano ósseo periférico produzido por diversos sistemas de corte. Foram avaliados 4 dispositivos: laser Er:YAG (2,94 mm), Piezo-cirurgia, broca em alta rotação e broca em baixa rotação. Para isto, foram utilizadas 45 seções ósseas retiradas de mandíbulas de suínos, até 1 h post-mortem, divididas em 9 grupos de acordo com diversos parâmetros. As amostras foram fixadas em formalina a 10 por cento tamponada, descalcificadas e cortadas em lâminas finas. Foram analisados 4 parâmetros diferentes: a precisão do corte, a profundidade da incisão, a carbonização periférica e presença de fragmentos ósseos. A análise estatística empregou o teste de Kruskal-Wallis para avaliar a similaridade das medianas entre os grupos. Todas as seções feitas com o laser Er:YAG exibiram pouca carbonização. As margens das incisões foram todas bem acabadas e regulares, sem apresentar pontos de fusão. As amostras obtidas por piezo-cirurgia apresentaram incisões superficiais sem danos térmicos, mas com margens irregulares. As seções obtidas pelas brocas convencionais apresentaram pouca carbonização marginal, particularmente as feitas em baixa rotação. Foram observadas diferenças estatisticamente significantes (p<0,01) entre todos os sistemas de corte para cada um dos parâmetros analisados. O laser Er:YAG apresentou pouca carbonização e pode ser considerado como um método eficaz para biópsias de ossos bucais, produzindo amostras de tecido limpas e fáceis de analisar.

Posterior mediastinal melanoma causing severe dysphagia: a case report.

INTRODUCTION: We describe an original case of progressive severe dysphagia caused by a posterior mediastinal metastatic melanoma of unknown origin. To the best of our knowledge, such an event has never been described before in the literature. CASE PRESENTATION: A progressive severe dysphagia case is reported induced by a melanoma of unknown origin (metastatic to a posterior mediastinal lymph node). At the time of diagnosis, the lesion appeared as a large posterior mediastinal mass mimicking a neurogenic tumour with oesophageal involvement. After complete resection, pathological assessment of the tumour by immunohistochemistry was consistent with nodal metastatic melanoma. CONCLUSION: This report of a posterior mediastinal lymph node melanoma is unique. The nodal origin is definitely unusual: a primary melanoma should always be carefully ruled out. In fact no other evidence, a part from the absence of the tumour elsewhere, can support the diagnosis of a primary nodal melanoma.

Rhino sinusal bilateral hamartoma: a case report.

The hamartoma is a benign rare tumor constituted by a mixture of tissue. It is very unusual in the nasal cavity. The objective of the study is to describe an unusual case of bilateral nasal hamartoma. We report a 52-year-old male patient with a bilateral paranasal hamartoma of the ethmoid and maxillary sinus. Functional endoscopic sinus surgery was performed to completely remove the masses. The reported localization is unusual because the most common site in the nose is the posterior septum. Although hamartoma arising from the rhino sinusal region is very rare, head and neck surgeons must know this entity in order to differentiate it from inverted papilloma and adenocarcinoma. Misinterpretation of this lesion may result in aggressive surgery for a benign lesion.

Cytologic diagnosis of pulmonary lesions.

The major types of cytologic preparations used in most laboratories to detect the lesions of the lower respiratory tract (LRT) are examined. These methods include sputum, bronchial washing, bronchial brushing, bronchoalveolar lavage (BAL) and fine-needle aspiration biopsy (FNAB). Sputum represents the simplest and most cost-effective sampling method even though fiberoptic bronchoscopy and radiologic guided FNAB are superseding it as the first diagnostic choice in most cases. There are advantages and disadvantages associated with each technique:bronchial brushing and FNABs tend to preserve both the cellular details and their architectural arrangement whereas sputum and bronchial washing often cause a variable degree of cellular degeneration and fragmentation. As a result, most pulmonary lesions may be detected and correctly diagnosed if multiple techniques are used to acquire diagnostic material. CT-guided FNAB represents the most effective method to achieve a correct diagnosis in pulmonary tumors.

Histological classification of lung cancer.

A histological classification should provide guidelines for tumor diagnosis in order to evaluate patient prognosis and therapy. Pre-invasive lesions identified as precursors of invasive lung carcinoma are: squamous dysplasia/carcinoma in situ, atypical adenomatous hyperplasia and idiopatic pulmonary neuroendocrine cell hyperplasia. Squamous carcinoma and adenocarcinoma are the commonest types of lung carcinoma with the latter increasing in many countries mainly for changed smoking habits. Bronchioloalveolar carcinomas include exclusively noninvasive mucinous or non-mucinous tumors. Neuroendocrine tumors range from well differentiated neuroendocrine carcinoma (typical carcinoid) to intermediate grade (atypical carcinoma) to very aggressive poorly differentiated lesions (large cell neuroendocrine carcinoma and small cell carcinoma).

Possible involvement of hMLH1, p16(INK4a) and PTEN in the malignant transformation of endometriosis.

Endometriosis is a common gynecologic disease, which generally follows a benign course. Notwithstanding, several clinical and histologic studies as well as molecular data show that endometriosis could be a precursor of sporadic endometrioid and clear cell carcinomas at extrauterine loci. Several reports have implicated alterations of the hMLH1 and p16(ink4a) (p16) genes, in particular hypermethylation of the promoter region, and of the PTEN gene, principally genetic mutations, in endometrial and ovarian cancers and have indicated that these alterations are already present in precancer conditions. In this report, we analyzed the methylation status of hMLH1 and p16 and the protein expression of PTEN and hMLH1 in 46 cases of endometriosis stages III and IV to better define the possible involvement of these genes in the malignant transformation of endometriosis. We found abnormal methylation of hMLH1 in 4 of the 46 cases (8.6%). In addition, these cases had no detectable hMLH1 protein expression. Regarding patients with hMLH1 alterations, 2 were classified as stage IV and 2 showed coexistent endometriosis and carcinoma. Only 1 case of endometriosis (2.17%), classified as atypical, showed abnormal methylation of p16. Reduced PTEN protein expression was detected in 7 of 46 cases (15.21%): 5 were clinically classified as stage IV, and the other 2 presented both cancer and hypermethylated hMLH1. Our preliminary study suggests that reduced expression of both hMLH1 and PTEN may be involved in the malignant evolution of endometriosis and should be used as markers of neoplastic transformation in aggressive endometriosis with elevated tumor markers.