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BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated. PATIENTS AND METHODS: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses. RESULTS: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses. CONCLUSIONS: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.
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PURPOSE: Minimally invasive surgery is the gold standard treatment for adrenal masses, but it may be a challenging procedure in the case of pheochromocytoma (PHEO). The aim of the present study is to report the results of transperitoneal laparoscopic adrenalectomy (TLA) in cases of PHEO in comparison to other types of adrenal lesions. METHODS: From 1994 to 2021, 629 patients underwent adrenalectomy. Twenty-two and thirty-five patients, respectively, were excluded because they underwent bilateral and open adrenalectomy, leaving 572 patients for inclusion. Of these, 114 patients had PHEO (Group A), and 458 had other types of lesions (Group B). To adjust for potential baseline confounders, a propensity score matching (PSM) analysis was conducted. RESULTS: After PSM, 114 matched pairs of patients were identified from each group. Statistically significant differences were not observed when comparing the median operative time (85 and 90 min in Groups A and B, respectively, p = 0.627), conversion rate [6 (5.3%) in each group, p = 1.000], transfusion rate [4 (3.5%) and 3 (2.6%) in Groups A and B, respectively, p = 1.000], complication rate [7 (6.1%) and 9 (7.9%) in Groups A and B, respectively, p = 0.796), median postoperative hospital stay (3.9 and 3.6 days in Groups A and B, respectively, p = 0.110), and mortality rate [1 (0.9%) in each group, p = 1.000]. CONCLUSIONS: Based on this analysis, the results of TLA for PHEO are equivalent to those of TLA for other types of adrenal lesions, but the fundamental requirements are multidisciplinary patient management and adequate surgeon experience. Further prospective studies are required to draw definitive conclusions.
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Neoplasias das Glândulas Suprarrenais , Laparoscopia , Feocromocitoma , Humanos , Adrenalectomia/métodos , Feocromocitoma/cirurgia , Feocromocitoma/patologia , Pontuação de Propensão , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologiaRESUMO
BACKGROUND: Cisplatin-based chemotherapy is the most recommended treatment for metastatic urothelial cancer (mUC). However, about 50% of patients are considered to be cisplatin ineligible. Anti-programmed cell death protein 1/programmed death-ligand 1 (PD-L1) therapies have, nevertheless, increased the options available to clinicians and are especially valuable for treating these patients. This study therefore tested the activity and safety of avelumab as first-line therapy for mUC. PATIENTS AND METHODS: Patients with mUC who were ineligible for cisplatin-based chemotherapy were screened centrally for PD-L1 expression and only those with a tumour proportion score ≥ 5% were enrolled in the trial. The primary endpoint was 1-year overall survival (OS), and the secondary endpoints were median OS, median progression-free survival, overall response rate, duration of the response, safety and tolerability. All the survival rates were estimated with the Kaplan-Meier product-limit methodology and compared across groups using the log-rank test. RESULTS: A total of 198 patients were screened, with 71 (35.9%) whose PD-L1 expression was ≥5% enrolled in the study. The median age was 75 years, bladder cancer was the primary tumour in 73.2% of cases and 25.3% had liver metastases. The main reasons for the cisplatin ineligibility were a low rate of creatinine clearance (<60 ml/min), present in 70.4% of patients, and an Eastern Cooperative Oncology Group performance status of 2, which affected 31%. The median OS was 10.0 months (95% confidence interval 5.5-14.5 months) and 43% of patients were alive at 1 year. A complete response was achieved in 8.5% of cases, and 15.5% had a partial response. Adverse any-grade and high-grade events occurred in 49.3% and 8.5% of patients, respectively. A grade 3 infusion reaction was the only high-grade treatment-related adverse event. No treatment-related deaths were reported. CONCLUSIONS: This ARIES trial confirmed the activity and safety of avelumab for treating mUC, adding a new therapy option to the armamentarium of checkpoint inhibitors already approved for platinum-ineligible, locally advanced/mUC.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Humanos , Antígeno B7-H1 , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino , Neoplasias da Bexiga Urinária/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
Giant-cell tumor (GCT) is often more aggressive when located in the distal radius, and wide resection is then the gold-standard. No single reconstruction protocol is recommended, and the technique depends upon the surgeon's preferences. The aim of the present review was to determine the recurrence rate of GTC of the distal radius after intralesional treatment, to assess the results, advantages and complications of the various surgical techniques, and to draw up a decision-tree for surgical indications. The review of literature was performed in the main healthcare databases, searching for studies that reported results of wide resection and reconstruction of distal radius GCT. Local recurrence rates, metastasis rates, reconstruction techniques and respective results and complications were evaluated and analyzed. Sixteen studies were selected, for a total population of 226 patients; 6.0% and 0.9% experienced local recurrence and lung metastasis, respectively. Arthroplasty with non-vascularized or vascularized ipsilateral fibula were the most common techniques and were associated with the highest satisfaction rates: 86.4% and 88.0%, respectively. Arthroplasty with allograft presented a MusculoSkeletal Tumor Society (MSTS) score of 79.2% and arthroplasty with custom-made prosthesis presented an MSTS score of 81.8%. Arthrodesis was performed in 46 cases, with an MSTS score of 82.7%. Arthroplasty techniques are the most common in literature; they are used in patients who wish to conserve joint motion. Reconstruction with non-vascularized fibula seems to provide the best results, with lower morbidity. Arthrodesis is usually reserved for heavy manual workers or in case of arthroplasty failure.
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Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Rádio (Anatomia)/patologia , Rádio (Anatomia)/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Lichen sclerosus is a chronic relapsing inflammatory dermatosis with a predilection for anogenital skin in 85%-98% of cases and is more prevalent in women (3%) than in men (> 0.07%). OBJECTIVES: The purpose of this study was to investigate gender differences in clinical presentation and therapeutic response to treatment with platelet-rich plasma (PRP), an emerging innovative strategy for LS. METHODS: Forty-three male and 51 female patients affected by LS were evaluated. Each patient was subjected to PRP treatment (1 infiltration every 15 days, for 3 times). RESULTS: The PRP procedure was well tolerated by all patients and an overall significant decrease in symptoms was reported 6 months after PRP infiltration. Reduction in pain and burning sensation was significant in both gender but more accentuated in women than in men, whereas reduction of itching was similar. On the contrary, dyspareunia evidenced sex-related difference since a significant diminution was observed only in male. CONCLUSIONS: This study demonstrates that PRP based therapy may exert a relevant role in LS patient management due to its effect on Quality of Life (QoL) and sexual function in both gender. In addition, the study underlined gender-related differences in severity of symptoms and disease age onset.
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Líquen Escleroso e Atrófico , Plasma Rico em Plaquetas , Líquen Escleroso Vulvar , Doença Crônica , Feminino , Genitália , Humanos , Líquen Escleroso e Atrófico/diagnóstico , Líquen Escleroso e Atrófico/terapia , Masculino , Qualidade de Vida , Fatores Sexuais , Líquen Escleroso Vulvar/tratamento farmacológicoRESUMO
In recent years, the number of trials incorporating health-related quality of life (HRQoL) data has increased. The impact of HRQoL on regulatory decision making in the European context and on clinical practice is not well established. We conducted an analysis of the role of QoL data extracted from the clinical trials of the drugs approved for hormone receptor positive/HER2-negative advanced/metastatic breast cancer (mBC). The results from the HRQoL were collected and a meta-analysis was performed to evaluate the impact of experimental drugs compared to standard treatments. The results showed a non-detrimental effect in HRQoL from the new treatments. As regards the approval process, from an examination of the European Medicine Agency (EMA) documents, HRQoL was reported nonextensively and contained and discussed in the European assessment reports (EPARs) for eleven trials in the approval process and cited in three cases in the EPARs and summary of medicinal product characteristics (SmPC). An effort should be made by all the stakeholders to increase the visibility of the HRQoL results in order to allow increased consideration in the approval process to make QoL data more easily and visibly available for the clinician and the patients. The evaluation should be reflected in the SmPC in order to increase the amount of information provided to the physician.
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Neoplasias da Mama , Qualidade de Vida , Neoplasias da Mama/tratamento farmacológico , Europa (Continente) , Feminino , Hormônios , HumanosRESUMO
PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.
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COVID-19/complicações , Síndromes do Eutireóideo Doente/complicações , Doenças da Glândula Tireoide/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Síndromes do Eutireóideo Doente/sangue , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/complicações , Estudos Retrospectivos , Doenças da Glândula Tireoide/sangue , Testes de Função Tireóidea , Glândula Tireoide/fisiopatologia , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
OBJECTIVE: To evaluate the feasibility and clinical application of fusion imaging with virtual navigation, combining 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) with real-time ultrasound imaging, in assessing superficial lymph nodes in breast-cancer and gynecological-cancer patients. METHODS: This was a pilot study of breast- and gynecological-cancer patients with abnormal uptake of 18 F-FDG by axillary or groin lymph nodes on PET/CT scan, examined at our institution between January 2017 and May 2019. Fusion imaging was performed, uploading preacquired PET/CT DICOM images onto the ultrasound machine and synchronizing them with real-time ultrasound scanning performed at the lymph-node site. In the first phase, we assessed the feasibility and reliability of fusion imaging in a series of 10 patients with suspicious lymph nodes on both PET/CT and ultrasound, and with full correspondence between both techniques in terms of size, shape and morphology of the lymph nodes (Group A). In the second phase, we included 20 patients with non-corresponding findings between PET/CT and ultrasound: 10 patients with lymph nodes that were suspicious or pathological on PET/CT scan but not suspicious on ultrasound assessment (Group B), and 10 patients with suspicious or pathological lymph nodes on both PET/CT and ultrasound but with no correspondence between the two techniques in terms of number of affected lymph nodes (Group C). RESULTS: In the 30 selected patients, fusion imaging was assessed at 30 lymph-node sites (22 inguinal and eight axillary nodes). In the first phase (Group A), the fusion technique was shown to be feasible in all 10 lymph-node sites evaluated. In the second phase, fusion imaging was completed successfully in nine of 10 cases in Group B and in all 10 cases in Group C. In all groups, fusion imaging was able to identify the target lymph node, guiding the examiner to perform a core-needle aspiration biopsy or to inject radiotracer for selective surgical nodal excision, according to the radio-guided occult lesion localization technique. CONCLUSION: Fusion imaging with virtual navigation, combining PET/CT and real-time ultrasound imaging, is technically feasible and able to detect target lymph nodes even when PET/CT and ultrasound findings are inconsistent. Fusion imaging can also be used to guide the performance of core-needle aspiration biopsy, avoiding further surgical diagnostic procedures, or the injection of radiotracer for selective surgical nodal excision, enabling more sparing, selective surgery. This innovative technique could open up multiple diagnostic and therapeutic opportunities in breast and gynecological oncology. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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Neoplasias da Mama/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Imagem Multimodal/estatística & dados numéricos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Ultrassonografia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Sistemas Computacionais , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18 , Humanos , Metástase Linfática/diagnóstico por imagem , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Ultrassonografia/métodosRESUMO
INTRODUCTION: Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule. METHODS: 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate. RESULTS: Higher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01). CONCLUSION: To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/terapia , Linfonodos/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Braquiterapia , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/terapia , Carcinoma Endometrioide/patologia , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia , Laparoscopia , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Omento , Lavagem Peritoneal , Compostos de Platina/administração & dosagem , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Procedimentos Cirúrgicos Robóticos , Salpingo-Ooforectomia , Taxoides/administração & dosagemRESUMO
Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-ß and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-ß and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials.
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Biofilmes/crescimento & desenvolvimento , Citocinas/metabolismo , Dermatite Atópica/metabolismo , Dermatite Atópica/microbiologia , Mediadores da Inflamação/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Criança , Pré-Escolar , Coagulase/metabolismo , Dermatite Atópica/patologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Oxacilina/farmacologia , Índice de Gravidade de Doença , Pele/microbiologia , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificaçãoRESUMO
PURPOSE: The everolimus and exemestane combination represents a treatment option for the endocrine sensitive metastatic breast cancer (MBC) patients. The toxicity profile reported in the Bolero 2 trial showed the feasibility in the selected patients. Few data are available for the unselected population. METHODS: In order to evaluate the safety in the unselected population of the clinical practice and to evaluate a possible association of toxicities with previous treatments, clinical data from 181 consecutive patients were retrospectively collected. RESULTS: Due to toxic events, everolimus dosage was reduced to 5 mg in 27% of patients. No association was found in the analysis between toxicity and number of prior therapies, neither between toxicity and response. In the multivariate analysis the previous exposure to anthracyclines for advanced disease represents the only predictive factor of developing grade ≥2 toxicity (OR = 2.85 CI 95% 1.07-7.59, p = 0.036). CONCLUSIONS: The association of everolimus and exemestane has confirmed to be a safe and effective treatment for endocrine sensitive MBC patients even in routine clinical practice. The rate of treatment discontinuation due to toxicity is low and none association between previous number of treatments and response or between toxicity and response was found.
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Androstadienos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Everolimo/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstadienos/administração & dosagem , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Everolimo/administração & dosagem , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Receptor ErbB-2/análise , Análise de Regressão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The correlation between ALK gene copy number gain (ALK-CNG) and prognosis in the context of advanced non-small-cell lung cancer (NSCLC) remains a controversial issue. This study aimed to evaluate the association among ALK-CNG according to Fluorescent In Situ Hybridization (FISH), clinical characteristics and survival in resectable and advanced NSCLC. METHODS: Clinical and pathological data of patients with resectable and advanced NSCLC were retrospectively collected. Tumor tissues were analyzed for ALK-CNG by FISH, and patients were divided in 3 groups/patterns on the basis of ALK signals: disomic [Pattern A], 3-7 signals [Pattern B], >7 signals [Pattern C]. The association between clinical and pathological features and ALK-CNG patterns was evaluated. Disease/progression-free and overall survival (DFS/PFS and OS) were estimated using the Kaplan-Meyer method. RESULTS: A number of 128 (76.6 %) out of the 167 eligible patients were evaluable for ALK-CNG, displaying pattern A, B and C in 71 (42.5 %), 42 (25.1 %) and 15 (9 %) patients, respectively. Gains in ALK-CNG appear to be more frequent in smokers/former smokers than in non-smokers (74.2 % versus 20.4 %, respectively, p = 0.03). Pattern A and C seem more frequently associated with higher T-stage (T3-4), while pattern B appears more represented in lower T-stage (T 1-2) (p = 0.06). No significant differences in survival rate were observed among the above groups. CONCLUSIONS: A high ALK-CNG pattern might be associated with smoking status and theoretically it might mirror genomic instability. The implications for prognosis should be prospectively investigated and validated in larger patients' series. TRIAL REGISTRATION: We confirm that all the study was performed in accordance with relevant guidelines and regulations and that all the protocol (part of a larger project MFAG 2013 N.14282) was approved by the local Ethics Committee of the Azienda Ospedaliera Universitaria Integrata of Verona on November 11st, 2014.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Variações do Número de Cópias de DNA , Dosagem de Genes , Neoplasias Pulmonares/genética , Receptores Proteína Tirosina Quinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Instabilidade Genômica , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Fenótipo , Pneumonectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/genética , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Although extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors. METHODS: 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups. RESULTS: Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03). CONCLUSIONS: We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered.
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Neoplasias Renais/cirurgia , Nefrectomia/métodos , Conjuntos de Dados como Assunto , Humanos , Análise de Regressão , Estudos RetrospectivosRESUMO
In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC.
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Mutação/genética , Patologia Molecular , Prognóstico , Neoplasias Gástricas/genética , Quinases Proteína-Quinases Ativadas por AMP , Idoso , Idoso de 80 Anos ou mais , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Smad4/genética , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVES: Many studies show that a large portion of medical prescriptions for diagnostic examinations may be not useful for patient's management or unnecessary. Rapid technological advancement has made it possible for magnetic resonance imaging (MRI) to be increasingly used all over the world, particularly for musculoskeletal disorders. The aim of this study was to assess the appropriateness of the knee MRI prescriptions. MATERIALS AND METHODS: A panel of experts found standard clinical practice guidelines in the management of knee disorders. Secondly, the finalized set of guidelines chosen was compared with the data of 400 patients who underwent previous knee MRIs, which were then reported in a specific questionnaire prepared by the authors. The rate of appropriateness of knee MRI prescriptions was then calculated. RESULTS: Almost 21% of prescriptions were totally inappropriate, 18.8% were uncertain, and 60.2% could be considered totally appropriate. The most frequent prescription indication was for meniscal disorders that account for 26.8% of the total indications. CONCLUSIONS: Our results demonstrate that approximately 40% of the total prescriptions were totally inappropriate or uncertain and that most of these were made by general practitioners. In light of these results, the economic impact of inappropriate prescriptions on the Italian healthcare system has to be seriously considered.
Assuntos
Artropatias/patologia , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Prescrições , Adolescente , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/economia , Masculino , Pessoa de Meia-Idade , Prescrições/economia , Estudos Retrospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Psoriasis is a chronic recurrent inflammatory skin disease that affects 2-3% of the world population. Biologics are relatively new systemic treatments that block molecular steps important in the pathogenesis of psoriasis. In vivo Reflectance confocal microscopy (RCM) is a non-invasive, imaging technique already reported to be useful in the evaluation of the follow-up of PP under treatment with topical actives and phototherapy. No reports on systemic treatments have been proposed in literature so far. OBJECTIVE: The aim of this study was to evaluate the feasibility of RCM in the monitoring of microscopic response to a subcutaneous anti-TNF treatment, Adalimumab. METHODS: One target lesion with typical clinical aspect, from 48 psoriatic patients, was evaluated using RCM at baseline, after 4 and 8 weeks of treatment. RESULTS: Microscopic confocal changes were followed up during treatment. Results disclosed identification of early microscopic evidence of the anti-inflammatory activity of Adalimumab not detected at clinical examination. Confocal feature related to the effect of TNF-α on melanocytes activity has been also identified. CONCLUSION: Early detected RCM parameters related to Adalimumab activity could be used to identify an early response to the treatment. RCM seems to be able to give useful and practical information about follow-up in patients with PP under treatment with Adalimumab.