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PURPOSE: To perform a systematic review and meta-analysis exploring the effectiveness of porcine small intestinal submucosa (pSIS) compared with autologous grafts for tympanic membrane perforation repair. METHODS: A prospective meta-analysis protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) on June 5th, 2024, under protocol CRD42024551979. PubMed, Embase/Ovid and Cochrane Central databases were searched from inception to 28/05/2024 for studies comparing the use of pSIS versus autologous grafts (perichondrium, cartilage, temporalis fascia or cartilage-perichondrium) for tympanic membrane perforation repair. The outcomes evaluated were persistent perforation after surgery, operative time and hearing outcome. Statistical analyses were performed using the online Review Manager (Cochrane Collaboration). A subgroup analyses were carried out for the paediatric population. RESULTS: We included 1,407 patients (1447 ears) from seven records; six retrospective cohort studies and one randomised controlled trial (RCT). pSIS graft was used in 563 ear surgeries (38.1%). Four studies included children with a mean age ranging from 7.3 to 11.7 years and the other 3 studies included adults with a mean age ranging from 30.8 to 48.4 years. Follow-up ranged from 2 to 132 months. There was no statistically significant difference in the failure rate (persistent perforation) between pSIS graft and autologous graft (RR 0.95; 95% CI 0.67-1.33; p = 0.76). However, reduced operative time was associated with using pSIS grafts (MD -16.12 min; 95% CI -22.94-9.31; p = < 0.00001). CONCLUSION: Tympanic membrane perforation repair with pSIS grafts had a similar failure rate and hearing outcome compared to autologous grafts and demonstrated an association with reduced operative time.
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OBJECTIVE: The purpose of this study was to assess how well ChatGPT, an AI-powered chatbot, performed in helping to manage pediatric sialadenitis and identify when sialendoscopy was necessary. METHODS: 49 clinical cases of pediatric sialadenitis were retrospectively reviewed. ChatGPT was given patient data, and it offered differential diagnoses, proposed further tests, and suggested treatments. The decisions made by the treating otolaryngologists were contrasted with the answers provided by ChatGPT. Analysis was done on ChatGPT response consistency and interrater reliability. RESULTS: ChatGPT showed 78.57% accuracy in primary diagnosis, and 17.35% of cases were considered likely. On the other hand, otolaryngologists recommended fewer further examinations than ChatGPT (111 vs. 60, p < 0.001). For additional exams, poor agreement was found between ChatGPT and otolaryngologists. Only 28.57% of cases received a pertinent and essential treatment plan via ChatGPT, indicating that the platform's treatment recommendations were frequently lacking. For treatment ratings, judges' interrater reliability was greatest (Kendall's tau = 0.824, p < 0.001). For the most part, ChatGPT's response constancy was high. CONCLUSIONS: Although ChatGPT has the potential to correctly diagnose pediatric sialadenitis, there are a number of noteworthy limitations with regard to its ability to suggest further testing and treatment regimens. Before widespread clinical use, more research and confirmation are required. To guarantee that chatbots are utilized properly and effectively to supplement human expertise rather than to replace it, a critical viewpoint is required.
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Endoscopia , Sialadenite , Humanos , Sialadenite/terapia , Sialadenite/diagnóstico , Criança , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Endoscopia/métodos , Reprodutibilidade dos Testes , Diagnóstico Diferencial , AdolescenteRESUMO
Dysfunction of the masseter muscle may cause pathological kinking of the parotid duct leading to parotitis; MR sialography is a non-invasive radiological examination that allows to evaluate dynamically the ductal system of the parotid glands. In the present study we aimed to assess the relationships between Stensen's duct and masseter muscle and their implications in the aetiopathogenesis of recurrent parotitis secondary to masseter muscle dysfunction. Forty-one patients with recurrent unilateral parotitis and nine with bilateral recurrent parotitis, all with a clinical suspicious of masseter muscle hypertrophy due to bruxism were enrolled. They underwent ultrasonography as a first line examination and then MR sialography and sialendoscopy. Different anatomical features were studied. Involved parotid glands had a wider duct compared to contralateral unaffected parotid glands of patients with recurrent parotitis (p = 0.00134); male subjects with parotitis had a longer duct compared to the salivary glands of healthy patients (p = 0.00943 for affected glands and p = 0.00629 for the contralateral). A concordance between the evidence of an acute duct angle during sialendoscopy and a wider duct in patients with parotitis was observed although not statistically significant. These initial findings suggest that the masticatory muscle dysfunction related to bruxism seems to condition alteration of parotid duct course and anatomy thus favouring the occurrence of recurrent parotitis. A specific diagnostic iter based on clinical evaluation, dynamic ultrasonography and MR sialography, is therefore, mandatory to confirm the relationship between masseter muscle anatomy and parotid duct anomalies; this is the premise for an adequate therapeutic approach to underlying masticatory muscle disorder.
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Imageamento por Ressonância Magnética , Músculo Masseter , Parotidite , Recidiva , Sialografia , Humanos , Masculino , Parotidite/diagnóstico por imagem , Feminino , Músculo Masseter/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Sialografia/métodos , Ductos Salivares/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Bruxismo/diagnóstico por imagem , Bruxismo/complicações , Endoscopia/métodosRESUMO
BACKGROUND: Image-guided vacuum-assisted breast biopsy (VABB) of the tumour bed, performed after neoadjuvant therapy, is increasingly being used to assess residual cancer and to potentially identify to identify pathological complete response (pCR). In this study, the accuracy of preoperative VABB specimens was assessed and compared with surgical specimens in patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-positive invasive ductal breast cancer after neoadjuvant therapy. As a secondary endpoint, the performance of contrast-enhanced MRI of the breast and PET-CT for response prediction was assessed. METHODS: This single-institution prospective pilot study enrolled patients from April 2018 to April 2021 with a complete response on imaging (iCR) who subsequently underwent VABB before surgery. Those with a pCR at VABB were included in the primary analysis of the accuracy of VABB. The performance of imaging (MRI and PET-CT) was analysed for prediction of a pCR considering both patients with an iCR and those with residual disease at postneoadjuvant therapy imaging. RESULTS: Twenty patients were included in the primary analysis. The median age was 44 (range 35-51) years. At surgery, 18 of 20 patients showed a complete response (accuracy 90 (95 per cent exact c.i. 68 to 99) per cent). Only two patients showed residual ductal intraepithelial neoplasia of grade 2 and 3 respectively. In the secondary analysis, accuracy was similar for MRI and PET-CT (77 versus 78 per cent; P = 0.76). CONCLUSION: VABB in patients with an iCR might be a promising method to select patients for de-escalation of surgical treatment in triple-negative or HER2-positive breast cancer. The present results support such an approach and should inform the design of future trials on de-escalation of surgery.
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Neoplasias da Mama , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Projetos Piloto , Estudos Prospectivos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Mama/diagnóstico por imagem , Mama/patologia , Biópsia Guiada por Imagem/métodosRESUMO
Breast cancer risk models represent the likelihood of developing breast cancer based on risk factors. They enable personalized interventions to improve screening programs. Radiologists identify mammographic density as a significant risk factor and test new imaging techniques. Pathologists provide data for risk assessment. Clinicians conduct individual risk assessments and adopt prevention strategies for high-risk subjects. Tumor genetic testing guides personalized screening and treatment decisions. Artificial intelligence in mammography integrates imaging, clinical, genetic and pathological data to develop risk models. Emerging imaging technologies, genetic testing and molecular profiling improve risk model accuracy. The complexity of the disease, limited data availability and model inputs are discussed. A multidisciplinary approach is essential for earlier detection and improved outcomes.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Inteligência Artificial , Mama/diagnóstico por imagem , Mamografia/métodos , Medição de Risco , Fatores de Risco , Detecção Precoce de Câncer/métodosRESUMO
INTRODUCTION: Transsphenoidal surgeries imply the risk of intraoperative lesions to the neurovascular structures surrounding the sphenoid sinus (SS). Aim of the present study is to assess the metrical and morphologic relationships existing between SS and sella turcica (ST). MATERIALS AND METHODS: Two hundred computed tomography-scans of patients were selected. For each patient volumes of SS were calculated from their 3-dimensional models segmented through ITK-SNAP program. Variants of SS in pneumatisation and sellar diameters [antero-posterior (AP) diameter, depth, and length] were evaluated on each computed tomography-scan. Correlations among different measurements were assessed through Spearman test ( P <0.01), whereas associations between sellar parameters and presence of pneumatisation variants were assessed through Mann-Whitney test ( P <0.01). RESULTS: In males, pneumatization of the greater wings was related to smaller AP diameter ( P <0.01) and depth of ST ( P <0.01), whereas in females lower values of depth were found in patients with pneumatization of the pterygoid processes ( P <0.01). In both sexes, a positive correlation was found between AP diameter and, respectively, length and depth of ST ( P <0.01), together with a negative correlation between volume of SS and depth of ST ( P <0.01). Lastly, in females a positive correlation was found between age and, respectively, length and depth of ST ( P <0.01). CONCLUSIONS: The present study highlighted new metrical and morphologic relationships between volume and pneumatisation of SS and diameters of ST. Knowledge of these correlations allows to understand more clearly, in the preoperative setting, the surgical working space. Further studies are needed, especially for what concerns the relationship between sellar measurements and age in females.
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Sela Túrcica , Seio Esfenoidal , Masculino , Feminino , Humanos , Sela Túrcica/diagnóstico por imagem , Sela Túrcica/cirurgia , Sela Túrcica/anatomia & histologia , Seio Esfenoidal/diagnóstico por imagem , Seio Esfenoidal/cirurgia , Seio Esfenoidal/anatomia & histologia , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/cirurgia , Osso Esfenoide/anatomia & histologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The aim of this study was to compare robotic mastectomy with open classical technique outcomes in breast cancer patients. SUMMARY BACKGROUND DATA: As the use of robotic nipple sparing mastectomy continues to rise, improved understanding of the surgical, oncologic, and quality of life outcomes is imperative for appropriate patient selection as well as to better understand indications, limits, advantages, and dangers. METHODS: In a phase III, open label, single-center, randomized controlled trial involving 80 women with breast cancer (69) or with BRCA mutation (11), we compared the outcome of robotic and open nipple sparing mastectomy. Primary outcomes were surgical complications and quality of life using specific validated questionnaires. Secondary objective included oncologic outcomes. RESULTS: Robotic procedure was 1 hour and 18 minutes longer than open (P < 0.001). No differences in the number or type of complications (P = 0.11) were observed. Breast-Q scores in satisfaction with breasts, psychosocial, physical and sexual well-being were significantly higher after robotic mastectomy versus open procedure. Respect to baseline, physical and sexual well-being domains remained stable after robotic mastectomy, whereas they significantly decreased after open procedure (P < 0.02). The overall Body Image Scale questionnaire score was 20.7â±â13.8 versus 9.9â±â5.1 in the robotic versus open groups respectively, P < 0.0001. At median follow-up 28.6months (range 3.7-43.3), no local events were observed. CONCLUSIONS: Complications were similar among groups upholding the robotic technique to be safe. Quality of life was maintained after robotic mastectomy while significantly decrease after open surgery. Early follow-up confirm no premature local failure.ClinicalTrials.gov NCT03440398.
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Neoplasias da Mama , Mamoplastia , Procedimentos Cirúrgicos Robóticos , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/métodos , Mutação , Mamilos/cirurgia , Qualidade de VidaRESUMO
PURPOSE: To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS). METHODS: We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients. RESULTS: The median age was 62 years (range 21-80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0-13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%. CONCLUSION: Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis.
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Neoplasias da Mama Masculina , Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/terapia , Antígeno Ki-67 , Mastectomia , Mastectomia Segmentar , Recidiva Local de Neoplasia/patologia , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
BACKGROUND: We recently conducted a de-escalation trial of low-dose tamoxifen 5 mg/day ("babytam", BT) or placebo given for 3 years in 500 women with noninvasive breast cancer. Women on babytam had a 52% reduction of recurrence (invasive breast cancer or DCIS) after 5 years. Since menopausal symptoms are major reasons for treatment withdrawal during tamoxifen preventive therapy, we compared and analyzed the patient-reported outcomes (PROs) with the physician-reported adverse events and studied their association with recurrence. METHODS: Menopausal symptoms recorded by physicians using the Common Terminology Criteria (CTCAEs) were compared with a patient self-reported validated questionnaire reviewed by a research nurse at baseline and every 6 months up to 36 months. Hot flashes (HF), the main outcome measure, were detected through a self-report 7-day diary for frequency and intensity. Treatment adherence and efficacy were assessed by the Kaplan-Meier curves and the Cox model. RESULTS: The number of HF events at 12, 24, and 36 months for PROs versus CTCAEs was 246 versus 12, 238 versus 8, and 210 versus 4, respectively. The majority of events were grade 1. There was no difference in PROs between babytam and placebo except for HF daily frequency, which increased by 1.5 events (95% CI, 1.1-1.8) on placebo to 2.1 on babytam (95% CI, 1.7-2.5, p = 0.05). The presence of HF at baseline was a favorable prognostic factor for recurrence and a predictive factor for response to babytam. Adherence was similar between babytam and placebo. CONCLUSIONS: The use of PROs is effective for identifying frequent mild grade menopausal symptoms which are underestimated by physicians but important prognostic and predictive factors. Research nurse can use these results as a tool to reassure patients about symptoms, improve adherence to treatment, and limit dropouts.
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Neoplasias da Mama , Médicos , Neoplasias da Mama/tratamento farmacológico , Feminino , Fogachos/induzido quimicamente , Humanos , Medidas de Resultados Relatados pelo Paciente , Tamoxifeno/efeitos adversosRESUMO
Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of ß-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.
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Pólipos Adenomatosos/prevenção & controle , Antocianinas/farmacologia , Neoplasias Colorretais/prevenção & controle , Curcumina/farmacologia , Suplementos Nutricionais , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
The natural history of ductal carcinoma in situ (DCIS) is highly variable and difficult to predict. Biomarkers are needed to stratify patients with DCIS for adjuvant therapy. We investigated the prognostic and predictive relevance of cell cycle progression (CCP) score in women with DCIS. We measured the expression of 23 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumor samples, and assessed the correlation of a predefined score with histopathologic features and recurrence. The signature was analyzed in a cohort of 909 consecutive DCIS with full histopathological features treated in a single institution. The main outcome measure was ipsilateral breast event (IBE) as first event observed, be it in situ or invasive. Median follow-up time was 8.7 years (IQR 6.5-10.5 years). There were 150 ipsilateral IBEs, 84 (56%) of which were invasive. In the first 5 years of follow-up, the score provided statistically different findings (p = 0.009), with IBE rates of 14.7% (95% CI, 10.4-19.7) for the highest quartile of CCP score (Q4) and 8.7% (95% CI, 6.7-11.0) for the lowest quartiles (Q1-3). The prognostic value for IBEs approached significance also in women treated with mastectomy (adjusted hazard ratio [HR] Q4 vs. Q1-3 = 2.60; 95% CI: 0.96-7.08; P = 0.06). Radiotherapy provided a greater benefit in women with higher CCP score. In addition, Q4 predicted a different risk after tamoxifen depending on menopausal status, with a beneficial trend on IBEs in postmenopausal women (HR 0.30; 95% CI, 0.07-1.39), and an opposite trend in premenopausal women (HR 1.68; 95% CI, 0.38-7.44) (P-interaction = 0.03). The results of this study provide for the first time the evidence that CCP score is a prognostic marker, which, after additional validation, could have an important role in personalizing the management of DCIS.
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Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Ciclo Celular/fisiologia , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Mastectomia Segmentar/métodos , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
Polymorphisms of genes involved in estrogen synthesis have been linked to breast cancer risk, prognosis, and treatment response. We investigated the prognostic impact of a deletion spanning the entire UGT2B17 gene (UGT2B17*2) and genetic variants of the aromatase CYP19A1 and estrogen receptor α (ESR1) in 125 postmenopausal women with ER-positive breast cancer enrolled in a randomized pre-surgical trial. The UGT2B17*2 was estimated by copy number variation assays and the CYP19A1 rs10046/rs4646 and ESR1 rs2077647/rs2234693/rs9340799 by TaqMan allelic discrimination assays. Serum exemestane/17-hydroxy exemestane were determined by MS and estrone (E1)/estradiol (E2)/ by GC-MS/MS. The association of genetic polymorphisms with "any event" was assessed by the Cox proportional hazards models adjusted for confounders. The UGT2B17*2 was associated with higher levels of 17-hydroxy exemestane (P = 0.04) and better prognosis (HR = 0.45; 95% CI: 0.20-1.01; P = 0.05) compared with homozygote UGT2B17 wt. The CYP19A1 rs10046 A and rs4646 C alleles were associated with higher estrogen levels: rs10046 AA vs. AG/GG genotypes had median E1 of 35.9 vs. 27.4 pg/mL (P = 0.05) and E2 of 7.57 vs. 3.9 pg/mL (P < 0.004). After a median follow-up of 7 years, women carrying the "low estrogen" alleles rs10046 G and rs4646 A had a better prognosis compared with homozygote wt for both polymorphisms (HR = 0.40; 95% CI: 0.17-0.93; P = 0.03). Our analysis points to an impact of UGT2B17 and CYP19A1 in postmenopausal endocrine responsive breast cancer. Carriers of UGT2B17*2 and CYP19A1 low estrogen variants may have better prognosis, supporting studies addressing the role of these polymorphisms in optimizing endocrine therapy. Trial registration: http://www.isrctn.com/ISRCTN86894592.
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Aromatase/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Variação Genética/genética , Glucuronosiltransferase/genética , Antígenos de Histocompatibilidade Menor/genética , Pós-Menopausa/genética , Idoso , Androstadienos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Antineoplásicos/administração & dosagem , Aromatase/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Celecoxib/administração & dosagem , Feminino , Variação Genética/efeitos dos fármacos , Glucuronosiltransferase/sangue , Humanos , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/sangue , Polimorfismo de Nucleotídeo Único/genética , Pós-Menopausa/sangue , Pós-Menopausa/efeitos dos fármacos , PrognósticoRESUMO
Silybin is a flavonolignan extracted from Silybum marianum with chemopreventive activity against various cancers, including breast. This study was designed to develop an HPLC-MS/MS method for the determination of silybin in human plasma, urine and breast tissue in early breast cancer patients undergoing Siliphos® supplementation, an oral silybin-phosphatidylcholine complex. The determination of silybin was carried out by liquid-liquid extraction with methyl-tert-butyl ether (MTBE); total silybin concentration was determined by treating the samples with ß-glucuronidase, while for the determination of free silybin, the hydrolytic step was omitted. Naringenin and naproxen were selected as internal standards. The detection of the analyte was carried out by mass spectrometry and by chromatography. The HPLC-MS/MS method was evaluated in terms of selectivity, linearity, limit of quantification, precision and accuracy, and carryover. The method proved to be selective, linear, precise and accurate for the determination of silybin. To the best of our knowledge, this presents the first analytical method with the capacity to quantify the major bioactive components of milk thistle in three different biological matrices with a lower limit of quantification of 0.5 ng/mL for plasma. Silybin phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue.
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Cromatografia Líquida de Alta Pressão/métodos , Silibina/análise , Espectrometria de Massas em Tandem/métodos , Neoplasias da Mama/química , Calibragem , Feminino , Humanos , Limite de Detecção , Extração Líquido-Líquido , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/farmacocinética , Reprodutibilidade dos Testes , Silibina/sangue , Silibina/urina , Silimarina/administração & dosagem , Silimarina/farmacocinética , Solventes/químicaRESUMO
Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46-62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54-0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49-0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42-0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33-0.77 versus HR = 0.84, 95% CI: 0.60-1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.
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Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Tamoxifeno/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Terapia Combinada , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Resultado do TratamentoRESUMO
Treatment of diabetics with metformin is associated with decreased breast cancer risk in observational studies, but it remains unclear if this drug has clinical antineoplastic activity. In a recent presurgical trial, we found a heterogeneous effect of metformin on breast cancer proliferation (ki-67) depending upon insulin resistance (HOMA index). Here, we determined the associations of additional serum biomarkers of insulin resistance, tumor subtype, and drug concentration with ki-67 response to metformin. Two-hundred non-diabetic women were randomly allocated to metformin (850 mg/bid) or placebo for 4 weeks prior to breast cancer surgery. The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery. For patients with a blood sample taken within 24 h from last drug intake, metformin level was measured. Compared with placebo, metformin significantly decreased ki-67 in women with HOMA > 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors. In women with HOMA index > 2.8, drug levels were positively correlated with the ki-67 decrease, whereas no trend was noted in women with HOMA < 2.8 (p-interaction = 0.07). At conventional antidiabetic doses, the effect of metformin on tumor ki-67 of non-diabetic breast cancer patients varies with host and tumor characteristics. These findings are relevant to design breast cancer prevention and treatment trials with metformin.
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Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Metformina/uso terapêutico , Adulto , Neoplasias da Mama/sangue , Proliferação de Células/efeitos dos fármacos , Método Duplo-Cego , Feminino , HumanosRESUMO
Leishmaniasis represents an emerging public health issue in Mediterranean countries. The incidence of this condition has progressively risen in Northern Italy due to the growing number of immunocompromised people and probably due to climate changes. We hereby describe a case of relapsing laryngeal leishmaniasis in a female immunocompetent patient, presenting as aspecific chronic laryngitis. She was affected by severe asthma treated by inhaled steroid therapy, likely responsible for the parasite's diffusion through a locus minori resistentiae. The aspecific clinical presentation led to a delayed diagnosis and the lack of guidelines for the treatment caused multiple relapses. Biopsies of laryngeal lesions in the follow-up were performed by operative flexible videolaryngoscopy, thus avoiding general anesthesia and reducing associated healthcare costs. The aim of this report is to underline the diagnostic and therapeutic challenges that patients with this condition face and to present what is, to the best of our knowledge, the first application of prophylactic aerosolized pentamidine for relapsing laryngeal leishmaniasis.
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Posterior glottic lesions resembling granulomas unresponsive to conservative treatment should raise suspicion of a neoplastic condition. Although surgery is rarely recommended for arytenoid granulomas due to their high recurrence rate, histological evaluation is mandatory in cases of uncertain diagnosis. Clinicians should be aware that, although very rare, a laryngeal neuroendocrine tumor occurring in the posterior glottis can mimic the appearance of an idiopathic granuloma, presenting a diagnostic challenge.
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Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer-Cuzick score and the lipid-lowering medications/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36-1.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00-1.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI > 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98-1.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.
Assuntos
Adiponectina , Índice de Massa Corporal , Neoplasias da Mama , Obesidade , Pós-Menopausa , Humanos , Adiponectina/sangue , Feminino , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Pós-Menopausa/sangue , Obesidade/sangue , Pessoa de Meia-Idade , Fatores de Risco , Estudos de Coortes , Idoso , Leptina/sangue , Biomarcadores/sangue , Modelos de Riscos Proporcionais , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análiseRESUMO
Breast cancer remains a significant global health challenge, with projections indicating a troubling increase in incidence. Breast cancer screening programs have long been hailed as life-saving initiatives, yet their true impact on mortality rates is a subject of ongoing debate. Screening poses the risk of false positives and the detection of indolent tumors, potentially leading to overtreatment. Bias factors, including lead time, length time, and selection biases, further complicate the assessment of screening efficacy. Recent studies suggest that AI-driven image analysis may revolutionize breast cancer screening, maintaining diagnostic accuracy while reducing radiologists' workload. However, the generalizability of these findings to diverse populations is a critical consideration. Personalized screening approaches and equitable access to advanced technologies are essential to mitigate disparities. In conclusion, the breast cancer screening landscape is evolving, emphasizing the need for risk stratification, appropriate imaging modalities, and a personalized approach to reduce overdiagnosis and focus on cancers with the potential to impact lives while prioritizing patient-centered care.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/métodos , Radiologistas , Incidência , Mamografia/métodos , Programas de Rastreamento/métodosRESUMO
Background: Surgery is still the standard treatment for breast lesions such as in situ ductal carcinoma (DCIS); however, its survival benefit is minimal, particularly for low-grade DCIS. Surgical complications and related depression status can adversely affect patients' quality of life. Approximately 25% of breast cancer (BC) cases are in situ forms, with DCIS making up 90% of these. Low and intermediate-grade DCIS often grow slowly and do not always progress clinically significant diseases. Identifying non-invasive lesions could help prevent overtreatment. In this context, new diagnostic tools like vacuum-assisted excision (VAE) could enhance the management of these conditions. Methods: The prospective VACIS study explores the role of VAE in ensuring the absence of pathology at subsequent surgery and reducing the diagnostic underestimation of breast biopsies for microcalcifications. Patients with suspicious breast microcalcifications up to 15 mm, who are candidates for stereotactic biopsy, will be enrolled and randomised into two groups. The control group will complete the biopsy with typical sampling, aiming to collect some microcalcifications from the target, while the experimental group will focus on the complete removal of the biopsy target (confirmed by mammography on the biopsy table), followed by a second sequence of cleaning samples. Radiograms will confirm lesion removal. Pathologic outcomes at surgery will be compared between the groups, and the percentage of underestimation will be assessed. The sample size is calculated to be 70 patients per group, using statistical tests and multivariate logistic models to detect a significant difference in the absence of pathology. Data collected will include patient age, lesion characteristics, and details of the biopsy, pathology and surgery. Discussion: Current surgical treatments for low-and sometimes intermediate-grade DCIS offer limited survival benefits and may hurt patients' quality of life due to surgery-related complications and associated depression. These lesions often grow slowly and might not become clinically significant, suggesting a need to avoid overtreatment. Improved diagnostics procedures, such as VAE, could help distinguish non-invasive from potentially invasive lesions, reduce biopsy underestimation, enable personalised management and optimise treatment strategies. This study hypothesises that VAE could be a viable alternative to surgery, capable of removing pathology during the biopsy procedure. Clinical trial registration: Clinicaltrials.gov, identifier NCT05932758.