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1.
J Surg Oncol ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522364

RESUMO

OBJECTIVE: To investigate risk factors for nodal upstaging in patients with lung carcinoids and to understand which type of lymphadenectomy is most appropriate. METHODS: Data regarding patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from January 1, 2005 to December 31, 2019, were collected and retrospectively analyzed. Clinical and pathological tumor characteristics were correlated to analyze lymph node upstaging. RESULTS: The analysis was conducted on 283 patients. Pathology showed 230 typical and 53 atypical carcinoids. Nodal and mediastinal upstaging occurred in 33 (11.6%) and 16 (5.6%) patients, respectively. At the univariable analysis, nodal upstaging was significantly correlated with central location (p = 0.003), atypical histology (p < 0.001), pT dimension (p = 0.004), and advanced age (p = 0.043). The multivariable analysis confirmed atypical histology (odds ratio [OR]: 11.030; 95% confidence interval [CI]: 4.837-25.153, p < 0.001) and central location (OR: 3.295; 95% CI: 1.440-7.540, p = 0.005) as independent prognostic factors for nodal upstaging. Atypical histology (p < 0.001), pT dimension (p = 0.036), number of harvested lymph node stations (p = 0.047), and type of lymphadenectomy (p < 0.001) correlated significantly with mediastinal upstaging. The multivariable analysis confirmed atypical histology (OR: 5.408; 95% CI: 1.391-21.020, p = 0.015) and pT (OR: 1.052; 95% CI: 1.021-1.084, p = 0.001) as independent prognostic factors. CONCLUSION: Atypical histology, dimension, and central location are associated with a high-risk for occult hilo-mediastinal metastases, and mediastinal radical dissection may predict nodal upstaging. Thus, we suggest radical mediastinal lymph node dissection in high-risk tumors, reserving sampling, or lobe-specific dissection in peripheral, small typical carcinoids.

2.
J Exp Clin Cancer Res ; 41(1): 148, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440004

RESUMO

BACKGROUND: Despite the promise of dual BRAF/MEK inhibition as a therapy for BRAF-mutant (BRAF-mut) melanoma, heterogeneous responses have been observed in patients, thus predictors of benefit from therapy are needed. We have previously identified semaphorin 6A (SEMA6A) as a BRAF-mut-associated protein involved in actin cytoskeleton remodeling. The purpose of the present study is to dissect the role of SEMA6A in the biology of BRAF-mut melanoma, and to explore its predictive potential towards dual BRAF/MEK inhibition. METHODS: SEMA6A expression was assessed by immunohistochemistry in melanoma cohort RECI1 (N = 112) and its prognostic potential was investigated in BRAF-mut melanoma patients from DFCI and TCGA datasets (N = 258). The molecular mechanisms regulated by SEMA6A to sustain tumor aggressiveness and targeted therapy resistance were investigated in vitro by using BRAF-mut and BRAF-wt melanoma cell lines, an inducible SEMA6A silencing cell model and a microenvironment-mimicking fibroblasts-coculturing model. Finally, SEMA6A prediction of benefit from dual BRAF/MEK inhibition was investigated in melanoma cohort RECI2 (N = 14). RESULTS: Our results indicate higher protein expression of SEMA6A in BRAF-mut compared with BRAF-wt melanoma patients and show that SEMA6A is a prognostic indicator in BRAF-mut melanoma from TCGA and DFCI patients cohorts. In BRAF-mut melanoma cells, SEMA6A coordinates actin cytoskeleton remodeling by the RhoA-dependent activation of YAP and dual BRAF/MEK inhibition by dabrafenib+trametinib induces SEMA6A/RhoA/YAP axis. In microenvironment-mimicking co-culture condition, fibroblasts confer to melanoma cells a proliferative stimulus and protect them from targeted therapies, whereas SEMA6A depletion rescues the efficacy of dual BRAF/MEK inhibition. Finally, in BRAF-mut melanoma patients treated with dabrafenib+trametinib, high SEMA6A predicts shorter recurrence-free interval. CONCLUSIONS: Overall, our results indicate that SEMA6A contributes to microenvironment-coordinated evasion of melanoma cells from dual BRAF/MEK inhibition and it might be a good candidate predictor of short-term benefit from dual BRAF/MEK inhibition.


Assuntos
Melanoma , Semaforinas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mutação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Microambiente Tumoral , Proteína rhoA de Ligação ao GTP/metabolismo
3.
Microbiol Spectr ; 10(2): e0035122, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35416701

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) has become the leading cause of skin and soft tissue infections (SSTIs). Biofilm production further complicates patient treatment, contributing to increased bacterial persistence and antibiotic tolerance. The study aimed to explore the efficacy of different antibiotics on biofilm-producing MRSA isolated from patients with SSTI. A total of 32 MRSA strains were collected from patients with SSTI. The MIC and minimal biofilm eradication concentration (MBEC) were measured in planktonic and biofilm growth. The study showed that dalbavancin, linezolid, and vancomycin all inhibited MRSA growth at their EUCAST susceptible breakpoint. Of the MRSA strains, 87.5% (n = 28) were strong biofilm producers (SBPs), while only 12.5% (n = 4) were weak biofilm producers (WBPs). The MBEC90 values for dalbavancin were significantly lower than those of linezolid and vancomycin in all tested strains. We also found that extracellular DNA (eDNA) contributes to the initial microbial attachment and biofilm formation. The amount of eDNA differed among MRSA strains and was significantly higher in those isolates with high dalbavancin and vancomycin tolerance. Exogenously added DNA increased the MBEC90 and protection of biofilm cells from dalbavancin activity. Of note, the relative abundance of eDNA was higher in MRSA biofilms exposed to MBEC90 dalbavancin than in untreated MRSA biofilms and those exposed to sub-MIC90. Overall, dalbavancin was the most active antibiotic against MRSA biofilms at concentrations achievable in the human serum. Moreover, the evidence of a drug-related increase of eDNA and its contribution to antimicrobial drug tolerance reveals novel potential targets for antibiofilm strategies against MRSA. IMPORTANCE Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) worldwide. In addition, methicillin-resistant S. aureus (MRSA) is increasingly frequent in postoperative infections and responsible for a large number of hospital readmissions and deaths. Biofilm formation by S. aureus is a primary risk factor in SSTIs, due to a higher antibiotic tolerance. Our study showed that the biofilm-forming capacity varied among MRSA strains, although strong biofilm producers were significantly more abundant than weak biofilm producer strains. Notably, dalbavancin demonstrated a potent antibiofilm activity at concentrations achievable in human serum. Nevertheless, dalbavancin activity was affected by an increased concentration of extracellular DNA in the biofilm matrix. This study provides novel insight for designing more targeted therapeutic strategies against MRSA and to prevent or eradicate harmful biofilms.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções dos Tecidos Moles , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , DNA , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Teicoplanina/análogos & derivados , Vancomicina/farmacologia , Vancomicina/uso terapêutico
4.
J Clin Med ; 11(8)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35456265

RESUMO

BACKGROUND: While the thoracotomy approach was considered the gold standard until two decades ago, robotic surgery has increasingly strengthened its role in lung cancer treatment, improving patients' peri-operative outcomes. In this study, we report our experience in robotic lobectomy for early-stage non-small cell lung cancer, with particular attention to oncological outcomes and nodal upstaging rate. METHODS: We retrospectively reviewed patients who underwent lobectomy and radical lymphadenectomy at our Institute between 2016 and 2020. We selected 299 patients who met the inclusion criteria of the study. We analyzed the demographic features of the groups as well as their nodal upstaging rate after pathological examination. Then, we analyzed disease-free and overall survival of the entire enrolled patient population and we compared the same oncological outcomes in the upstaging and the non-upstaging group. RESULTS: A total of 299 patients who underwent robotic lobectomy were enrolled. After surgery, 55 patients reported nodal hilar or mediastinal upstaging. The 3-year overall survival of the entire population was 82.8%. The upstaging group and the non-upstaging group were homogeneous for age, gender, smoking habits, clinical stage, tumor site, tumor histology. The non-upstaging group had better OS (p = 0.004) and DFS (p < 0.0001). CONCLUSION: Our results show that robotic surgery is a safe and feasible approach for the treatment of early-stage NSCLC, especially for its accuracy in mediastinal lymphadenectomy. The oncological outcomes were encouraging and consistent with previous findings.

5.
Mol Cancer Res ; 20(5): 686-698, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35082165

RESUMO

Homeodomain-interacting protein kinase 2 (HIPK2) is an evolutionary conserved kinase that has gained attention as a fine tuner of multiple signaling pathways, among which those commonly altered in colorectal cancer. The aim of this study was to evaluate the relationship of HIPK2 expression with progression markers and mutational pattern and gain insights into the contribution of HIPK2 activity in colorectal cancer. We evaluated a retrospective cohort of colorectal cancer samples by IHC for HIPK2 expression and by next-generation sequencing (NGS) for the detection of mutations of cancer associated genes. We show that the percentage of HIPK2-positive cells increases with tumor progression, significantly correlates with tumor-node-metastasis (TNM) staging and associates with a worse outcome. In addition, we observed that high HIPK2 expression significantly associates with KRAS mutations but not with other cancer-related genes. Functional characterization of the link between HIPK2 and KRAS show that activation of the RAS pathway either due to KRAS mutation or via upstream receptor stimulation, increases HIPK2 expression at the protein level. Of note, HIPK2 physically participates in the active RAS complex while HIPK2 depletion impairs ERK phosphorylation and the growth of tumors derived from KRAS mutated colorectal cancer cells. Overall, this study identifies HIPK2 as a prognostic biomarker candidate in patients with colorectal cancer and underscores a previously unknown functional link between HIPK2 and the KRAS signaling pathway. IMPLICATIONS: Our data indicate HIPK2 as a new player in the complex picture of the KRAS signaling network, providing rationales for future clinical studies and new treatment strategies for KRAS mutated colorectal cancer.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/patologia , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Estudos Retrospectivos , Transdução de Sinais/genética
6.
Anticancer Res ; 42(1): 211-216, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969727

RESUMO

AIM: Anastomotic leakage represents the most fearful complication in colorectal surgery. Important risk factors for leakage are low anastomoses and preoperative radiotherapy. Many surgeons often unnecessarily perform a protective ileostomy, increasing costs and necessitating a second operation for recanalization. The aim of this study was to evaluate the role of indocyanine green in assessing bowel perfusion, even in cases of a low anastomosis on tissue treated with radiotherapy. PATIENTS AND METHODS: Two groups of patients were selected: Group A (risky group) with only low extraperitoneal rectal tumors (<8 cm) previously treated with neoadjuvant chemo-radiotherapy; group B (no risk group) with only intraperitoneal rectal tumors (>8 cm), not previously treated with neoadjuvant therapy. Clinical postoperative outcome, morbidity, mortality and anastomotic leakage were compared between these two groups. RESULTS: In group A, comprised of 35 patients, the overall complication rate was 8.6%, with two patients developing anastomotic leakage (5.7%). In group B, comprised of 53 patients, the overall complication rate was 17% with four cases with anastomotic leakage (7.5%). No statistical difference was observed for conversion rate, general complications, or anastomotic leakage. No statistical differences were observed in clinical variables except for American Society of Anesthesiologist score (p=0.04). Patients who developed complications during radiotherapy had no significant differences in postoperative outcomes compared with other patients. CONCLUSION: Indocyanine green appears to be safe and effective in assessing the perfusion of colorectal anastomoses, even in the highest-risk cases, potentially reducing the rate of ileostomy. The main limitation remains the lack of a universally replicable standard assessment.


Assuntos
Verde de Indocianina/administração & dosagem , Laparoscopia/métodos , Neoplasias Retais/cirurgia , Reto/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Quimiorradioterapia/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protectomia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Reto/diagnóstico por imagem , Reto/patologia
7.
Cancers (Basel) ; 13(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34771417

RESUMO

BACKGROUND: The aim of this study was to evaluate the Masaoka-Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. METHODS: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka-Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. RESULTS: Considering the Masaoka-Koga system, 5- and 10-year overall survival (5-10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5-10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2-T3 curves. Including the number of involved structures, in Masaoka-Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5-10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5-10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). CONCLUSION: The two staging systems present limitations due to overlapping curves in early Masaoka-Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

8.
Langenbecks Arch Surg ; 406(8): 2817-2825, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34686891

RESUMO

PURPOSE: The objective of this study was to analyze the role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy that has developed in the treatment of patients with peritoneal metastasis of non-primary origin. METHODS: Patients who underwent treatment for secondary gastrointestinal and ovarian malignancies over a 20-year period were reviewed. Survival curves were estimated by the Kaplan-Meier product limit method and the log-rank test was used to assess differences between subgroups. RESULTS: The study included 293 patients. The most common histology was ovarian cancer (56.3%). Median PCI was 16 and CC0-1 resection was obtained in 88.1% of cases. Grade III and IV complications occurred in 12 patients (4.1%) and 47 patients (16%), respectively. The 30- and 60-day mortality rate was 1.3% (4 patients) and 2.4% (7 patients). Five-year OS was 21.7%, 73.6%, 42.1%, and 0 for colorectal, appendiceal, ovarian, and gastric cancer (p = < 0.0001), respectively, whereas 5-year DFS was 12.4%, 48.4%, 24.3%, and 0 (p = < 0.0001), respectively. Survival outcomes were significantly higher for CC0 in each subgroup of patients. CONCLUSION: Despite being a complex procedure, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should be considered a safe treatment with acceptable postoperative morbidity and mortality rates, if performed in high-volume centers. Good survival outcomes have been increasingly obtained in selected patients with peritoneal metastasis of non-primary origin.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Front Oncol ; 11: 688889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568019

RESUMO

BACKGROUND: The clinical consequences of pancreatic exocrine insufficiency and its treatment in advanced pancreatic ductal adenocarcinoma (PDAC) are poorly investigated. This retrospective study aims at investigating the pancreatic enzyme replacement therapy (PERT) use and its impact on survival and maldigestion-related symptoms in advanced PDAC patients undergoing chemotherapy. METHODS: A retrospective analysis was conducted on advanced PDAC patients, treated with first-line gemcitabine plus nab-paclitaxel at two academic institutions (March 2015-October 2018). Data were correlated with overall survival (OS) using Cox regression model. Kaplan-Meier curves were compared using Log-Rank test. RESULTS: Data from 110 patients were gathered. PERT was administered in 55 patients (50%). No significant differences in baseline characteristics with those who did not receive PERT were found. Median OS for the entire group was 12 months (95% CI 9-15). At multivariate analysis, previous surgical resection of the primary tumor, (HR 2.67, p=0.11), weight gain after 3 months (HR 1.68, p=0.07) and PERT (HR 2.85, p ≤ 0.001) were independent predictors of OS. Patients who received PERT reported an improvement of maldigestion-related symptoms at 3 months more frequently than patients who did not (85.2% vs 14.8%, p ≤ 0.0001). CONCLUSION: PERT is associated with significantly prolonged survival and maldigestion-related symptoms alleviation in advanced PDAC patients.

10.
Breast ; 60: 6-14, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34454324

RESUMO

PURPOSE: The impact of the adherence to dietary guidelines of early-stage breast cancer (EBC) patients on body composition changes during treatment is not entirely defined. This study aimed to evaluate the role of an evidence-based nutrition educational intervention, according to adherence to dietary guidelines, in EBC patients. METHODS: This prospective study included EBC patients, candidates for neoadjuvant/adjuvant therapy. Patients received an evidence-based tailored nutrition educational intervention. The adherence to dietary guidelines, anthropometric and dietary assessments, and blood glucose and lipid profile tests were evaluated at baseline and after a 12-months nutritional intervention. RESULTS: Two hundred and forty-three patients were enrolled. At baseline, 38.3% and 23.9% of patients were overweight and obese, weight gain ≥5% (compared to 6-months before enrollment) and central obesity were observed in 47.3% and 52.7% of patients, respectively. Adherence to dietary guidelines was low (median Med-Diet score: 6 [IQR 4-8]). After the nutritional intervention (median follow-up: 22 months [range 12-45]), adherence to dietary guidelines significantly increased (median Med-Diet score: 12 [IQR 8-13]), p < 0.0001). High adherence to dietary guidelines (defines as Med-Diet score ≥10) significantly correlated with: 1) overall weight loss ≥5% (21.8% vs. 2.5%, p = 0.003); 2) median BMI drop (from 25.6 kg/m2 to 24.4 kg/m2, p = 0.003); 3) lower prevalence of central obesity (38.2% vs. 7.2%, p = 0.01); 4) improvement in blood glucose levels and lipid profile. CONCLUSION: This study suggests that an evidence-based tailored nutrition educational intervention during treatment for EBC significantly increases overall adherence to dietary guidelines, and it improves both anthropometric measures and serum metabolic biomarkers in patients with high adherence.


Assuntos
Neoplasias da Mama , Biomarcadores , Índice de Massa Corporal , Feminino , Humanos , Política Nutricional , Estudos Prospectivos
11.
Minerva Surg ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338459

RESUMO

BACKGROUND: The prognostic role of the extension of lymphadenectomy in Non-small-cell lung cancer is still a debated and intriguing issue. The aim of this study is to validate a prognostic score including the number of resected lymph-nodes previously reported using a large multicentre dataset. METHODS: From 01/2002 to 12/2012, data on 4858 NSCLC patients undergoing curative-intent surgery in six Institutions were retrospectively reviewed. To test the discriminative ability of the model, composed of a panel of high-risk,pathologic stage, nodal status, age, number of Resected Nodes and intermediate risk factors (gender, grading, histology), was determined. The Kaplan-Meier method was used to estimate Overall(OS), Cancer-Specific(CSS) and Disease-free Survival(DFS) curves, and the log rank test was adopted to evaluate the differences between groups. RESULTS: Pathological stages were: I in 46,5%, II in 24,1%, III in 27,8% and IV in 1,6% of cases. Overall, 5-years OS, CSS and DFS were 54,6%, 76,7% and 44,8%, respectively. Stratifying the sample of 3948 patients with complete data into Low-risk (LR, #107), Intermediate-risk (IR, #1268) and High-Risk (HR, #2573) groups, the optimal prognostic discrimination power of this score was confirmed (C-statistics: 0.71, 95%CI 69-73). Specifically in LR, IR and HR, 5-years OS was 83,5%, 66,4% and 46,2% (p<0.0001), 5y-CSS was 95,8%, 89% and 69% (p<0.0001), and 5y-DFS was 74,7%, 59.1% and 35,5% (p<0.0001), respectively CONCLUSIONS: Our study confirms the optimal prognostic discrimination power of the previous prognostic model including the number of harvested nodes.

12.
Front Surg ; 8: 666158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277693

RESUMO

Introduction: The standard surgical procedures for patients with early-stage NSCLC is lobectomy-associated radical lymphadenectomy performed by using the thoracotomy approach. In the last few years, minimally invasive techniques have increasingly strengthened their role in lung cancer treatment, especially in the early stage of the disease. Although the lobectomy technique has been accepted, controversy still surrounds lymph node dissection. In our study, we analyze the rate of upstaging early non-small cell lung cancer patients who underwent radical surgical treatment using the robotic and the VATS techniques compared to the standard thoracotomy approach. Methods and Materials: We retrospectively reviewed patients who underwent a lobectomy and radical lymphadenectomy at our Institute between 2010 and 2019. We selected 505 patients who met the inclusion criteria of the study: 237 patients underwent robotic surgery, 158 patients had thoracotomy, and 110 patients were treated with VATS. We analyzed the demographic features between the groups as well as the nodal upstaging rate after pathological examination, the number of dissected lymph nodes and the ratio of dissected lymph nodes to metastatic lymph nodes of the three groups. Results: The patients of the three groups were homogenous with respect to age, sex, and histology. The postoperative major morbidity rate was significantly higher in the thoracotomy group, and hospital stay was significantly longer. The percentage of the mediastinal nodal upstaging rate and the number of dissected lymph nodes was significantly higher in the robotic group compared with the VATS group. The ratio of dissected lymph nodes to metastatic lymph nodes was significantly lower compared with the VATS group and the thoracotomy group. Discussion: The prognostic impact of the R(un) status is still highly debated. A surgical approach that allows better results in terms of resection has still not been defined. Our results show that robotic surgery is a safe and feasible approach especially regarding the accuracy of mediastinal lymphadenectomy. These findings can lead to defining a more precise pathological stage of the disease and, if necessary, to more accurate postoperative treatment.

13.
J Neurooncol ; 154(1): 101-112, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34255272

RESUMO

PURPOSE: Intradural extramedullary spinal metastases (IESM) represent an extremely rare manifestation of systemic cancer. We evaluated the surgical indications, complications and outcome in a series of 43 patients with solitary intradural extramedullary metastases originating from solid cancer of non-neurogenic origin. METHODS: Patients' age, histopathological diagnoses of primary cancer, tumor size, spinal location, and extramedullary tumor dissemination were collected. Preoperative functional status, pre- and post-operative neurological status, extent of the tumor resection were also analyzed. RESULTS: The majority of IEMS occurred in the thoracic area, with the most common presenting symptoms ranging from motor (76.7%) to sensory (72%) deficits. Gross total resection was achieved in 55.8% of cases, while In 44.2% of patients a subtotal resection was performed due to strong adherence between the tumor and neural tissue. After surgery, 72.1% of patients exhibited improvement of symptoms in terms of pain relief and partial recovery of motor and/or sensory deficits, while neurologic functional status was severely affected postoperatively in 3 patients. CONCLUSION: Although there was no statistical significance between the different parameters and overall survival, KPS and the presence of other metastases were the strongest prognostic factors for overall survival and postoperative neurologic outcome.


Assuntos
Segunda Neoplasia Primária , Neoplasias da Medula Espinal , Humanos , Segunda Neoplasia Primária/cirurgia , Neoplasias da Medula Espinal/cirurgia , Resultado do Tratamento
14.
J Thorac Oncol ; 16(11): 1936-1945, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34256111

RESUMO

INTRODUCTION: The International Thymic Malignancy Interest Group (ITMIG) classifies thymoma recurrences on the basis of the topographic location, but its effectiveness in prognosis prediction has not been well investigated yet. Aims of this study are to analyze survival outcome of patients surgically treated for thymoma recurrence according to the ITMIG recurrence classification and to investigate possible alternatives. METHODS: From January 1, 1990, to January 7, 2017, data on 135 surgically treated patients for thymoma recurrence from three high-volume centers were collected and retrospectively analyzed. Patients were classified according to the ITMIG classification as local, regional, and distant. The ITMIG classification and alternative classifications were correlated to overall survival (OS). RESULTS: According to the ITMIG classification, recurrence was local in 17 (12.5%), regional in 97 (71.8%), and distant in 21 (15.7%) patients, with single localization in 38 (28.2%) and multiple localizations in 97 (71.8%). The 5- and 10-year OS were 79.9% and 49.7% in local, 68.3% and 52.6% in regional, and 66.3% and 35.4% in distant recurrences, respectively, but differences were not statistically significant (p = 0.625). A significant difference in survival was present considering single versus multiple localizations: 5- and 10-year OS of 86.2% and 81.2% versus 61.3% and 31.5% (p = 0.005, hazard ratio = 7.22, 95% confidence interval: 0.147-0.740), respectively. Combining the localization number with the recurrence site, ITMIG locoregional single recurrence had a statistically significant better survival compared with patients with ITMIG locoregional multiple recurrence or ITMIG distant recurrence (p = 0.028). Similarly, a significant difference was present considering intrathoracic single versus intrathoracic multiple versus distant recurrence (p = 0.024). CONCLUSIONS: The ITMIG classification for thymoma recurrence did not have significant survival differences comparing local, regional, and distant recurrences. Integrating this classification with the number of the localizations may improve its effectiveness in prognosis prediction.


Assuntos
Neoplasias Pulmonares , Timoma , Neoplasias do Timo , Humanos , Recidiva Local de Neoplasia/cirurgia , Opinião Pública , Estudos Retrospectivos , Análise de Sobrevida , Timoma/cirurgia , Neoplasias do Timo/cirurgia
15.
Cell Death Dis ; 12(7): 636, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155195

RESUMO

Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-ß5, Survivin, TGF-ß, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.


Assuntos
Biomarcadores Tumorais/sangue , Vesículas Extracelulares/metabolismo , Proteínas de Neoplasias/sangue , Neoplasias da Próstata/sangue , Proteoma , Proteômica , Adulto , Idoso , Linhagem Celular Tumoral , Vesículas Extracelulares/ultraestrutura , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias da Próstata/ultraestrutura , Análise Serial de Proteínas , Reprodutibilidade dos Testes , Estudos Retrospectivos
16.
J Geriatr Oncol ; 12(8): 1253-1255, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34175246

RESUMO

Central studies carried out on vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) excluded patients receiving immunosuppressive therapy and those diagnosed with an immunosuppressive condition. Moreover, there are no data on vaccine efficacy regarding older patients with cancer. OBJECTIVES: The primary objective was to evaluate the seroprevalence of the SARS-CoV2 IgG in older patients (aged ≥80 years) diagnosed with solid or hematological malignancies, one month after administering the second dose of the BNT162b2 vaccine. MATERIALS AND METHODS: We screened 74 older patients with cancer, 45 of them accepted to receive the vaccination and collected serum samples from 36 patients; a group of medical doctors and nurses from our hospital was used as a control in a 1:2 ratio. RESULTS: The median age was 82 years (range 80-89). Median serum IgG were 2396,10 AU/ml (range 0-32,763,00) in patients with cancer and 8737,49 AU/ml (398.90-976,280,00) in the control group, p < 0.0001. Additional subgroup analyses were performed comparing males and females, patients treated with chemotherapy versus other therapies (immunotherapy, targeted therapy), solid tumors versus hematological malignancies, early (I-II) versus advanced (III-IV) stage of disease, continuative corticosteroid use or not. None of them reached statistical significance. CONCLUSION: Our study shows for the first time that patients with cancer aged ≥80 years can have a serological response to the BNT162b2 COVID-19 vaccine one month after vaccination and consequently support the vaccination campaign currently underway in this frail population.


Assuntos
COVID-19 , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Vacinas contra COVID-19 , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , RNA Viral , SARS-CoV-2 , Estudos Soroepidemiológicos , Vacinação
17.
Anticancer Res ; 41(5): 2553-2561, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952483

RESUMO

BACKGROUND/AIM: Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have have been shown to improve overall survival in patients with refractory metastatic colorectal cancer. The aim of our study was to evaluate the efficacy and safety profiles of these agents administered in sequence in real world practice. PATIENTS AND METHODS: Clinical data of patients treated beyond the 2°line with REG or FTD/TPI between January 2016 and August 2020, were retrospectively collected from eight institutes in the Lazio Region. RESULTS: We included 49 patients treated with both drug sequences. A total of 28 G3/G4 toxicity events (53.8%) were recorded in the FTD/TPI-to-REG sequence vs. 24 (46.1%) in the reverse sequence. Median overall survival for the patients included in the FTP/TPI-to-REG group was 20 months (95%CI=16.7-23.3) vs. 27 months in the reverse group (95%CI=17.8-36.2). The disease control rate was 45.0% for patients treated with the REG-to-FTD/TPI sequence vs. 24.1% in those treated with the FTD/TPI-to-REG sequence (p=0.18). CONCLUSION: The sequence REG-to-FTD/TPI and vice versa can extend survival, whereas only REG-to-FTD/TPI stabilizes cancer growth.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Pirrolidinas/administração & dosagem , Timina/administração & dosagem , Trifluridina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Pirrolidinas/efeitos adversos , Timina/efeitos adversos , Trifluridina/efeitos adversos
18.
Cancer Treat Rev ; 97: 102202, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33838596

RESUMO

BACKGROUND: The real impact of bevacizumab maintenance as single agent in metastatic colorectal cancer (mCRC) remains unclear. SAKK-41/06 and PRODIGE-9 failed to demonstrate the non-inferiority and superiority of bevacizumab versus no maintenance, respectively, while AIO-KRK-0207 showed the non-inferiority of maintenance bevacizumab versus bevacizumab and fluoropyrimidines for time to strategy failure. METHODS: Bibliography electronic databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials) were searched for English published clinical trials prospectively randomizing mCRC patients to receive bevacizumab maintenance or not after first-line chemotherapy plus bevacizumab. Individual patients' data (IPD) were provided by investigators for all included trials. Primary end-points were progression-free survival (PFS) and overall survival (OS), both from the start of induction and maintenance. Univariate and multivariate analyses for PFS and OS were performed. RESULTS: Three phase III studies - PRODIGE-9, AIO-KRK-0207 and SAKK-41/06 - were included. Considering the different timing of randomization, IPD of patients not progressed during induction and starting maintenance phase entered the analysis. 909 patients were included, 457 (50%) received bevacizumab maintenance. Median PFS from induction start was 9.6 and 8.9 months in bevacizumab group versus no maintenance group, respectively (HR 0.78; 95%CI: 0.68-0.89; p < 0.0001). Subgroups analysis for PFS showed a significant interaction according for RAS status (p = 0.048), with a maintenance benefit limited to RAS wild-type patients. No difference in terms of OS was observed. CONCLUSIONS: Despite the statistically significant PFS improvement for bevacizumab maintenance, the absolute benefit appears limited. Subgroup analysis shows a differential effect of bevacizumab maintenance in favor of RAS wild-type patients. Considering these results, maintenance therapy with fluoropyrimidine with or without bevacizumab remains the first option. Single agent bevacizumab maintenance can be considered in selected cases, such as cumulative toxicity or patient's refusal, in particular for RAS wild-type patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Neoplasias Colorretais/secundário , Humanos , Prognóstico
19.
Int J Med Sci ; 18(10): 2245-2250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859534

RESUMO

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
20.
Cancers (Basel) ; 13(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805310

RESUMO

BACKGROUND: Optimal recurrent thymoma management remains arguable because of limited patient numbers, and relatively late and variable recurrence patterns. Given the absence of high-quality evidence and relatively small study cohorts, we performed a quantitative meta-analysis to determine the outcome of surgical and non-surgical approaches assessing the five-year overall survival (5y overall survival (OS)) in patients with recurrent thymoma. METHODS: We performed a comprehensive literature search and analysis according to PRISMA guidelines of studies published from 1 January 1980 until 18 June 2020 from PubMed/MEDLINE, EMBASE, and Scopus. We included studies with the cohorts' superior to 30 patients describing recurrent thymoma treatment, comparing surgical and non-surgical approaches reporting survival data. RESULTS: Literature search revealed 3017 articles. Nine studies met all inclusion criteria and were selected for the meta-analysis. The recurrences were local/regional in 73-98% of cases and multiple in 49-72%. After treatment, 5y OS ranged from 48-77% and 10y OS from 37-51%. The quantitative meta-analysis showed a better outcome comparing surgical vs other treatments. Two studies showed statistically significant risk differences in the 5y OS favoring complete resection. After pooling results of seven studies using the random model, the combined 5y OS risk difference was 0.39, with lower and upper limits of 0.16 and 0.62, respectively (p = 0.001), and a moderate heterogeneity among studies (p = 0.098, I2 = 43.9%). Definitive conclusions could not be drawn regarding the prognostic impact of myasthenia gravis, histology, and patterns of relapse reported in literature. CONCLUSIONS: Surgical treatment after thymoma recurrence is associated with a significant better 5y OS; therefore, surgical resection should be preferred in all technically feasible cases.

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