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BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published. METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®). RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found. CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics. CLINICAL TRIAL REGISTRATION: This study is registered under NCT02408536 on ClinicalTrials.gov .
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Estudios Prospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Estudios RetrospectivosRESUMEN
Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host's metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host's immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.
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Microbioma Gastrointestinal , Neoplasias Gastrointestinales , Microbiota , Tumores Neuroendocrinos , Disbiosis , HumanosRESUMEN
PURPOSE: Pituitary adenomas (PAs) rarely occur in childhood and adolescence. Management of PAs in this critical age can be particularly challenging considering the auxological sequelae and potential long-term cardiometabolic consequences. We aimed to describe the clinical characteristics of patients with PA aged < 18years at diagnosis and during long-term follow-up, focusing on the prevalence of cardio-metabolic comorbidities and the impact of different therapeutic strategies. METHODS: Clinical data at diagnosis and at last follow-up visit (mean 10.3 ± 9.2 years) of 101 patients aged < 18 years with PA, referred to our University Hospital from 1990 to 2017, were retrospectively evaluated. RESULTS: At diagnosis, 11.9% of patients presented with pituitary hormone deficiencies, whose number was positively correlated with pituitary tumor diameter (p < 0.001). At diagnosis, 26.7% of patients were overweight and 15.8% were obese. In patients with hypercortisolism or GH excess the prevalence of obesity was more than 2-fold greater than in general population. No correlation was found between pituitary tumor size and BMI. At baseline, the greater the number of pituitary hormone deficits, the higher BMI (p = 0.039). In prolactinoma patients still on medical therapy at last visit, BMI was higher than at baseline. CONCLUSION: We found an increased prevalence of overweight/obesity only in pediatric and adolescent patients with GH- or ACTH-secreting PA. Regarding cardio-metabolic comorbidities other than obesity/overweight, we have not found anything worth of mention. The remission of hypercortisolism positively impacted on BMI, while medical therapy in patients with prolactinoma seemed unable to avoid weight gain, suggesting a careful metabolic management of these patients.
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Adenoma , Enfermedades Cardiovasculares , Neoplasias Hipofisarias , Adenoma/epidemiología , Adolescente , Niño , Síndrome de Cushing , Humanos , Sobrepeso , Neoplasias Hipofisarias/epidemiología , Estudios RetrospectivosRESUMEN
AIM: To evaluate activity of metronomic cyclophosphamide (mCTX) in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS & METHODS: We retrospectively evaluated a consecutive series of 74 mCRPC patients treated with at least one new agent after docetaxel failure, who received once-daily oral mCTX treatment at a fixed dose of 50 mg. RESULTS: The treatment was well tolerated. Sixteen percent of the patients experienced a major biochemical response. Median progression-free survival was 4.0 months, and median overall survival was 8.1 months. CONCLUSIONS: In the modern context of mCRPC, mCTX may represent a valuable and inexpensive alternative to new agents, which have shown similar activity in heavily pretreated patients.
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Antineoplásicos Alquilantes/uso terapéutico , Ciclofosfamida/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/secundario , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The optimal duration and intensity of first-line therapy in metastatic colorectal cancer patients once they have achieved an objective response is controversial. In a molecularly selected RAS and BRAF wild-type (wt) population, this concern is amplified. Once disease control has been achieved with a combination therapy including an anti-EGFR antibody, further exposure both to cytotoxic drugs and targeted therapy might result only in increased toxicity. In unresectable metastatic RAS and BRAF wt colorectal cancer patients, a deintensified therapy could represent a valuable option that might preserve quality of life. We designed a study to compare FOLFIRI/cetuximab to FOLFIRI/cetuximab for eight cycles followed by cetuximab alone in first-line treatment of RAS and BRAF (wt) metastatic colorectal cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Camptotecina/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. METHODS: Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. DISCUSSION: DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. TRIAL REGISTRATION: May 11, 2016; NCT02786875 . EUDRACT NUMBER: 2015-005147-14.
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Neoplasias de la Mama/dietoterapia , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Neoplasias de la Mama/patología , Dieta Mediterránea , Supervivencia sin Enfermedad , Terapia por Ejercicio , Femenino , Índice Glucémico , Humanos , Persona de Mediana Edad , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Factores de Riesgo , Resultado del TratamientoRESUMEN
Vemurafenib is a potent and selective BRAF inhibitor, which is effective on patients with BRAF V600E mutated late-stage melanoma. Common and less common adverse skin reactions include photosensitivity, maculo-papular exanthema, hand-foot skin reactions, hyperkeratotic follicular rash, pruritus, benign verrucous papillomas, plantar hyperkeratosis, keratoacanthomas, squamous cell carcinomas, infections, and melanoma. To our knowledge, vitiligo has been reported in 2 cases only. This paper reports the case of a 63-year-old man with metastatic melanoma, who developed sudden facial depigmentation after 4 weeks of treatment with vemurafenib 960 mg twice daily. Features consistent with vitiligo were evident at clinical and ultraviolet light examination, as well as at in vivo reflectance confocal microscopy. The latter examination showed lack of normal brightly refractile papillary rings at the dermo-epidermal junction in lesional skin, as well as decreased brightness and half-rings with "scalloped border-like" features in adjacent non-lesional skin. Vitiligo is an adverse reaction to be expected in patients treated with vemurafenib and whether its occurrence may be associated with a positive outcome, as suggested by previous investigations, is still a matter of debate.
J Drugs Dermatol. 2016;15(6):766-768.
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Antineoplásicos/efectos adversos , Cara , Indoles/efectos adversos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/inducido químicamente , Sulfonamidas/efectos adversos , Vitíligo/inducido químicamente , Antineoplásicos/administración & dosificación , Cara/diagnóstico por imagen , Humanos , Indoles/administración & dosificación , Masculino , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico por imagen , Sulfonamidas/administración & dosificación , Vemurafenib , Vitíligo/diagnóstico por imagenRESUMEN
Ampullary carcinoma is an uncommon gastrointestinal disease. Its natural history is often characterized by the occurrence of liver metastases. Among patients who undergo pancreatoduodenectomy, those presenting with lymph nodes involvement are more prone to early distant disease relapse. In this report, a patient previously diagnosed with ampullary carcinoma had been treated with curative surgery. After subsequent adjuvant gemcitabine, the patient developed significant myelotoxicity and suffered from a single liver metastasis a few months later. A hepatic intra-arterial mitomycin plus fluorouracil-based chemotherapy was administered in order to avoid any serious systemic toxicity. The treatment was well tolerated and no serious side effects occurred. Extra-hepatic cancer relapse, involving intra-thoracic and abdominal lymph nodes, was observed not long after the initial intra-hepatic almost complete response. In conclusion, the locoregional chemotherapy administration was effective in overcoming any systemic toxicities and showed activity against the liver metastasis but it did not prevent extra-hepatic cancer dissemination.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Conducto Colédoco/patología , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Ampolla Hepatopancreática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Conducto Colédoco/terapia , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Mitomicina/administración & dosificaciónRESUMEN
AIM: The Italian Retrospective Analysis of Sorafenib as First or Second Target Therapy study assessed the efficacy and safety of sorafenib in metastatic renal cell carcinoma patients treated in the community. PATIENTS & METHODS: Patients receiving first- or second-line single-agent sorafenib between January 2008 and December 2010 were eligible. Retrospective data collection started in 2012 and covers at least 1-year follow-up. The primary end point was overall survival (OS). RESULTS: Median OS was 17.2 months (95% CI: 15.5-19.6): 19.9 months (95% CI: 15.9-25.3) in patients treated with first-line sorafenib and 16.3 months (95% CI: 13.1-18.2) with second-line sorafenib. Overall median (95% CI) progression-free survival was 5.9 months (95% CI: 4.9-6.7): 6.6 (95% CI: 4.9-9.3) and 5.3 months (95% CI: 4.3-6.0) in first- and second-line patients, respectively. CONCLUSION: The efficacy and safety of sorafenib in routine community practice was generally good, especially in relation to OS in patients treated in the second line, where results were similar to those seen in recent prospective clinical trials.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Sorafenib , Resultado del TratamientoRESUMEN
INTRODUCTION: Several data demonstrated that chemical pollutants can be endocrine disruptors and they have an important role in tumorigenic processes. It has been shown that pollution exposure can affect pituitary cells' function and biology, indeed an increased prevalence of acromegaly has been reported in highly polluted areas. EVIDENCE ACQUISITION: One transcription factor that has a role in both carcinogenesis and in xenobiotics' detoxification is the aryl hydrocarbon receptor (AHR). Its deregulation could have a pivotal role in pituitary tumors, especially in GH-secreting pituitary tumors. Environmental chemicals affect the expression and function of ncRNAs (miRNA, lncRNA and circRNA) through different mechanisms. EVIDENCE SYNTHESIS: However, to date, few data on the role of the environmental pollutants in the clinical expression and pathogenesis of GH-secreting pituitary tumors are available. CONCLUSIONS: This article presents a summary of the AHR signaling pathways that are triggered by various ligands and emphasizes the significant distinctions between the potential biological and toxicological effects of AHR gene activation. We also deepen the functions of ncRNAs and acromegaly and provide current data on their regulation by the AHR. Overall, more studies are still needed to fully understand the dynamic interplay between the AHR signaling pathway and ncRNAs in GH-secreting pituitary adenomas.
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PURPOSE: X-linked hypophosphatemia (XLH) is a rare multi-systemic disease characterized by low plasma phosphate levels. The aim of this study was to investigate the annual XLH prevalence and internally evaluate predictive algorithms' application performance for the early diagnosis of XLH. METHODS: The PediaNet database, containing data on more than 400,000 children aged up to 14 years, was used to identify a cohort of XLH patients, which were matched with up to 10 controls by date of birth and gender. The annual prevalence of XLH cases per 100,000 patients registered in PediaNet database was estimated. To identify possible predictors associated with XLH diagnosis, a logistic regression model and two machine learning algorithms were applied. Predictive analyses were separately carried out including patients with at least 1 or 2 years of database history in PediaNet. RESULTS: Among 431,021 patients registered in the PediaNet database between 2007-2020, a total of 12 cases were identified with a mean annual prevalence of 1.78 cases per 100,000 patients registered in PediaNet database. Overall, 8 cases and 60 matched controls were included in the analysis. The random forest algorithm achieved the highest area under the receiver operating characteristic curve (AUC) value both in the one-year prior ID (AUC = 0.99, 95% CI = 0.99-1.00) and the two-year prior ID (AUC = 1.00, 95% CI = 1.00-1.00) analysis. Overall, the XLH predictors selected by the three predictive methods were: the number of vitamin D prescriptions, the number of recorded diagnoses of acute respiratory infections, the number of prescriptions of antihistamine for systemic use, the number of prescriptions of X-ray of the lower limbs and pelvis and the number of allergology visits. CONCLUSION: Findings showed that data-driven machine learning models may play a prominent role for the prediction of the diagnosis of rare diseases such as XLH.
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Raquitismo Hipofosfatémico Familiar , Humanos , Masculino , Niño , Raquitismo Hipofosfatémico Familiar/epidemiología , Raquitismo Hipofosfatémico Familiar/diagnóstico , Preescolar , Femenino , Italia/epidemiología , Adolescente , Lactante , Prevalencia , Bases de Datos Factuales , Recién Nacido , Algoritmos , Diagnóstico Precoz , Aprendizaje AutomáticoRESUMEN
INTRODUCTION: Adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) is very rare condition in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of CS, which in most cases occurs in the context of Carney complex (CNC). CNC is a rare autosomal-dominantly inherited genetic syndrome, usually due to pathogenic variants of the PRKAR1A (regulatory subunit R1A of the protein kinase A) gene located at 17q22-24. The clinical picture is characterized by spotty skin pigmentation, cardiac, cutaneous, and mammary myxomas, melanocytic schwannomas, endocrinopathies, and tumours of the endocrine glands (mostly adrenal, pituitary, and thyroid). CASE PRESENTATION: A 10-year-old boy first came to our outpatient clinic due to severe obesity. During the first 3 months of follow-up, the height growth rate was normal, but the response to dietary-behavioural indications was poor in terms of weight loss. Later, 10 months after the last evaluation, there was evidence of significant worsening of obesity, growth failure (growth velocity 0.7 cm/year), arterial hypertension, and the occurrence of violaceous striae at the trunk and root of the limbs. Endocrinological causes of obesity associated with growth failure were investigated. The circadian rhythm of cortisol, ACTH, and cortisoluria were suggestive of ACTH-independent hypercortisolaemia. Iatrogenic causes were ruled out. Adrenal ultrasound and computer tomography scan were performed, which initially indicated the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, magnetic resonance imaging showed a significant increase in the global dimensions of the adrenals with a bilateral micronodular appearance. In light of the association between ACTH-independent hypercortisolism and bilateral micronodular adrenal hyperplasia, a genetic investigation was performed, which found a pathogenic variant of the PRKAR1A gene. The patient was begun on treatment with metyrapone which was well tolerated over a 2-year period. The clinical picture has slightly improved, cortisoluria returned and remains within normal limits, but ACTH suppression persists. CONCLUSION: This is the first report on the clinical and biochemical effects of 2-year medical treatment with metyrapone of PPNAD-related hypercortisolaemia in a paediatric patient with CNC. Currently, there are no established protocols for the management of hypercortisolism in PPNAD and data are scarce, especially in the paediatric field. Medical therapies may play a role in reducing the need, at least initially, for patients to undergo bilateral adrenalectomy. However, further studies on larger case series are needed to clarify this aspect. In cases of CS due to PPNAD in which medical therapy was the initial approach, in the absence of clear clinical, auxological, and biochemical improvements, metyrapone may have to be discontinued in favour of another approach, including surgery.
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Background: A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up. Methods: We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months. Results: The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p<0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p=0.035; 33.8% at baseline versus 54.0% at LFUV, p<0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p=0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p=0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p=0.02) than males. At LFUV, a similar sex-related pattern was observed. Conclusion: Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol.
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Neoplasias de las Glándulas Suprarrenales , Comorbilidad , Hipertensión , Humanos , Femenino , Masculino , Neoplasias de las Glándulas Suprarrenales/epidemiología , Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Hipertensión/epidemiología , Factores Sexuales , Hiperglucemia/epidemiología , Hiperglucemia/sangre , Dislipidemias/epidemiología , Estudios de Seguimiento , Italia/epidemiología , Estudios TransversalesRESUMEN
Health-related quality of life (HRQoL) represents one of the most concerning aspects for cancer patients. The Healthy Eating Index (HEI) is an a priori diet quality index directly associated with health outcomes and HRQoL in cancer survivors in North American populations. We evaluated, in a Mediterranean population, the baseline associations between HEI-2015 and HRQoL in 492 women with breast cancer recruited in a DEDiCa lifestyle trial. Dietary data were obtained from 7-day food records; HRQoL was assessed through the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) and the C30 Summary Score (SumSc). Analysis of variance and multivariable linear and log-gamma regression models were performed. Mean and standard deviation for HEI-2015 score was 68.8 ± 11.2; SumSc was 81.5 ± 12.9. Women with lower HEI-2015 score had higher BMI, were more frequently exposed to tobacco smoke and had fewer years of education. Patients with a HEI-2015 score greater than 68.7 (median value) showed a significant increase in SumSc of 4% (p = 0.02). HEI-2015 components also associated with SumSc were beans and greens (ß = 1.04; p = 0.02). Weak associations were found for total vegetables and saturated fats. Higher diet quality in breast cancer survivors was associated with higher overall HRQoL in this cross-sectional analysis.
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Introduction: To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients. Methods: F1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients' characteristics. Results: Overall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3-6) and 2 (IQR 1-3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS, so as TP53 with RB1. Median tumor mutational burden was 6 (IQR 3-10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5-19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months. Conclusion: This study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights.
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INTRODUCTION: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials. This national initiative, here presented, aims to address the following knowledge gap: a) how much does histological diversity translate into clinical manifestation variety? b) are those chemotherapy regimens, recommended for conventional biliary tract cancers, potentially active in rare variants?Therefore, epidemiological, pathological, and clinical characterization of series of rare biliary histotypes/variants, for which therapeutic and follow-up data are available, will be collected. METHODS: An Italian task force on rare tumors of the biliary tract (IRaBiCa) has been created, whose initiative is a multicenter retrospective study involving 34 Italian cancer centers.Clinical data from approximately 100 patients will be collected and analyzed. Continuous variables will be presented as median ± standard deviation, while categorical variables will be expressed in terms of frequency. Kaplan-Maier analyses will be used to compare disease free, progression free and overall survival, according to the different histotypes. CONCLUSIONS: We expect to gather novel data on rare histotypes of biliary tract cancer that will be useful to support their molecular and immunological characterization.
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Neoplasias del Sistema Biliar , Colangiocarcinoma , Humanos , Italia/epidemiología , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/terapia , Neoplasias del Sistema Biliar/tratamiento farmacológico , Estudios Retrospectivos , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Femenino , Masculino , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Persona de Mediana Edad , AncianoRESUMEN
Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was 2,558.91 and 3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were 798.13 and 1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of 3,201.15 compared to bromocriptine, based on a willingness-to-pay of 40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of 44,846.64. Considering a willingness-to-pay of 40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.
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OBJECTIVE: Primary empty sella (PES) is a frequent anatomical condition rarely causing pituitary dysfunction. We assessed cardiovascular risk in a cohort of PES patients referred to Endocrine Units. DESIGN: The study was performed in three Italian tertiary referral centres. We evaluated pituitary function and cardiovascular risk, on the basis of lipid and glucose metabolism parameters and of Framingham score (FS), in 94 consecutive patients with PES diagnosis and in 94 gender, age and BMI matched controls. PATIENTS: Pituitary function was normal in 30 patients (group A), whereas a single or multiple pituitary hormone deficiency was demonstrated in 64 (group B). Growth hormone deficiency (GHD) was diagnosed in 56, central hypothyroidism in 35, hypogonadotropic hypogonadism in 32 and central hypoadrenalism in 24 cases. RESULTS: Framingham score was higher and glucose and lipid profile were worse in PES patients than in controls. Cardiovascular risk parameters were not different between group A and B. In group B, increased cardiovascular risk was associated with hypothyroidism and hypogonadism, but not with GHD. In group A, cardiovascular risk was higher and FT3 and FT4 levels were lower than in controls. Moreover, PES patients stratified for BMI showed a worse glucose and lipid profile and (in the overweight subgroup) higher FS than matched controls. CONCLUSIONS: Primary empty sella patients show increased cardiovascular risk, regardless of BMI. A worse lipid and glucose profile and higher FS were associated with secondary hypothyroidism, even subclinical, as well as hypogonadism.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Síndrome de Silla Turca Vacía/complicaciones , Hipopituitarismo/complicaciones , Hipófisis/fisiopatología , Adulto , Femenino , Glucosa/metabolismo , Hormona de Crecimiento Humana/deficiencia , Humanos , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Mitomycin and irinotecan are widely used in the treatment of colorectal cancer, furthermore both of these drugs are active agents against nonsmall cell lung cancer and their combination has shown synergism in preclinical studies. The aim of the study was to evaluate the efficacy and safety of mitomycin- and irinotecan-based chemotherapy combination in patients with advanced nonsmall cell lung cancer progressing after previous antineoplastic therapies. METHODS: Thirty-one consecutive patients suffering from nonsmall cell lung cancer, who underwent mitomycin- plus irinotecan-based chemotherapy as salvage treatment after failure of at least two previous systemic treatments, were retrospectively identified in our database. Between September 2003 and March 2011, 31 patients with histologically proven stage IIIB or IV nonsmall cell lung cancer, received mitomycin 5 mg/m(2) on day 1 followed by irinotecan 150 mg/m(2) on day 2. Cycles were repeated at 2-week interval. RESULTS: A total of 164 cycles of treatment were given with a median of five per patient (range 1-10). The objective responses included partial response in 6 patients (19.3%), stable disease in 4 (13%), and progressive disease in 21 (67.7%). Median time to disease progression was 4 months, and median survival was 9+ months. Twelve patients (38%) reached 1-year survival. Grade 3-4 toxicities occurred in seven patients (22.5%), mainly myelosuppression (neutropenia, anemia, and thrombocytopenia), mucositis, and diarrhea. No treatment-related death was recorded. CONCLUSION: The mitomycin- and irinotecan-based combination chemotherapy seems to be tolerated and active in this subset of heavily pretreated patients with advanced nonsmall cell lung cancer. However, evaluation or recruitment of a larger number of patients would be needed to provide more adequate data on safety and activity of the described combination.