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1.
JAMA ; 331(13): 1135-1144, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563834

RESUMO

Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear. Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy. Design, Setting, and Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy. Exposure: TIL abundance in breast tissue from resected primary tumors. Main Outcomes and Measures: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center. Results: This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6). Conclusions and Relevance: In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.


Assuntos
Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas , Adulto , Humanos , Pessoa de Meia-Idade , Adjuvantes Imunológicos , Colúmbia Britânica , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
2.
Sci Transl Med ; 16(741): eadj5705, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569015

RESUMO

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Sirtuínas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/patologia , Fibroblastos/patologia , Microambiente Tumoral , Proteínas de Ligação a DNA , Ubiquitina-Proteína Ligases , Tetraspaninas/genética , Tetraspaninas/metabolismo
3.
Rinsho Ketsueki ; 65(3): 158-163, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38569859

RESUMO

Although alectinib is effective for relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) and has a favorable safety profile, its role as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the role of allo-HSCT itself in this setting are unknown. A 35-year-old man with ALK-positive ALCL experienced relapse after first-line therapy with CHOP. Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed. However, disease progressed 15 months after transplantation, and alectinib was initiated. Complete response (CR) was achieved after three months of treatment, and alectinib was continued for 5 months. After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate. The post-transplant course was unremarkable except for grade I acute GVHD. The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.


Assuntos
Carbazóis , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma Anaplásico de Células Grandes , Piperidinas , Masculino , Humanos , Adulto , Linfoma Anaplásico de Células Grandes/terapia , Recidiva Local de Neoplasia , Receptores Proteína Tirosina Quinases/uso terapêutico
4.
Ups J Med Sci ; 1292024.
Artigo em Inglês | MEDLINE | ID: mdl-38571887

RESUMO

The complex interplay between genetically diverse tumor cells and their microenvironment significantly influences cancer progression and therapeutic responses. This review highlights recent findings on cellular plasticity and heterogeneity within the breast cancer ecosystem, focusing on the roles of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). We discuss evidence suggesting that breast cancer cells exhibit phenotypic plasticity driven by both intrinsic genetic factors and external microenvironmental cues, impacting treatment responses and disease recurrence. Moreover, single-cell RNA sequencing studies reveal diverse subtypes of CAFs and TAMs, each with distinct functional gene expression programs and spatial organization within the tumor microenvironment. Understanding the hierarchical relationships and niche cues governing cellular phenotypes offers new opportunities for targeted therapeutic interventions. By elucidating the organizational principles of the tumor ecosystem, future therapies may target phenotypic states or entire cellular niches, advancing precision medicine approaches in breast cancer treatment.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Humanos , Feminino , Neoplasias da Mama/genética , Plasticidade Celular , Ecossistema , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Microambiente Tumoral/genética
5.
Int J Colorectal Dis ; 39(1): 47, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578433

RESUMO

BACKGROUND: To evaluate comparative outcomes of outpatient (OP) versus inpatient (IP) treatment and antibiotics (ABX) versus no antibiotics (NABX) approach in the treatment of uncomplicated (Hinchey grade 1a) acute diverticulitis. METHODS: A systematic online search was conducted using electronic databases. Comparative studies of OP versus IP treatment and ABX versus NABX approach in the treatment of Hinchey grade 1a acute diverticulitis were included. Primary outcome was recurrence of diverticulitis. Emergency and elective surgical resections, development of complicated diverticulitis, mortality rate, and length of hospital stay were the other evaluated secondary outcome parameters. RESULTS: The literature search identified twelve studies (n = 3,875) comparing NABX (n = 2,008) versus ABX (n = 1,867). The NABX group showed a lower disease recurrence rate and shorter length of hospital stay compared with the ABX group (P = 0.01) and (P = 0.004). No significant difference was observed in emergency resections (P = 0.33), elective resections (P = 0.73), development of complicated diverticulitis (P = 0.65), hospital re-admissions (P = 0.65) and 30-day mortality rate (P = 0.91). Twelve studies (n = 2,286) compared OP (n = 1,021) versus IP (n = 1,265) management of uncomplicated acute diverticulitis. The two groups were comparable for the following outcomes: treatment failure (P = 0.10), emergency surgical resection (P = 0.40), elective resection (P = 0.30), disease recurrence (P = 0.22), and mortality rate (P = 0.61). CONCLUSION: Observation-only treatment is feasible and safe in selected clinically stable patients with uncomplicated acute diverticulitis (Hinchey 1a classification). It may provide better outcomes including decreased length of hospital stay. Moreover, the OP approach in treating patients with Hinchey 1a acute diverticulitis is comparable to IP management. Future high-quality randomised controlled studies are needed to understand the outcomes of the NABX approach used in an OP setting in managing patients with uncomplicated acute diverticulitis.


Assuntos
Doença Diverticular do Colo , Diverticulite , Humanos , Recidiva Local de Neoplasia , Diverticulite/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Falha de Tratamento , Readmissão do Paciente , Doença Diverticular do Colo/terapia , Doença Aguda , Resultado do Tratamento
6.
JAMA Netw Open ; 7(4): e245217, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578640

RESUMO

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.


Assuntos
Neoplasias da Mama , Mamoplastia , Humanos , Pessoa de Meia-Idade , Feminino , Mastectomia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Mamoplastia/métodos , Mama/patologia
7.
PLoS One ; 19(4): e0301753, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578782

RESUMO

BACKGROUND: Atrial arrhythmias (AA) commonly affect patients with cardiac amyloidosis (CA) and are a contributing risk factor for the development of heart failure (HF). This study sought to investigate the long-term efficacy and impact of catheter ablation on HF progression in patients with CA and AA. METHODS: Thirty-one patients with CA and AA undergoing catheter ablation were retrospectively included (transthyretin-ATTR CA 61% and light chain-AL CA 39%). AA subtypes included atrial fibrillation (AFib) in 22 (paroxysmal in 10 and persistent in 12), atrial flutter (AFl) in 17 and atrial tachycardia (AT) in 11 patients. Long-term AA recurrence rates were evaluated along with the impact of sinus rhythm (SR) maintenance on HF and mortality. RESULTS: AA recurrence was observed in 14 patients (45%) at a median of 3.5 months (AFib n = 8, AT n = 6, AFl = 0). Post-cardioversion, medical therapy or catheter ablation, 10 patients (32%) remained in permanent AA. Over a median follow-up of 19 months, all-cause mortality was 39% (n = 12): 3 with end-stage HF, 5 due to late complications of CA, 1 sudden cardiac death, 1 stroke, 1 COVID 19 (and one unknown). With maintenance of SR following catheter ablation, significant reductions in serum creatinine and natriuretic peptide levels were observed with improvements in NYHA class. Two patients required hospitalization for HF in the SR maintenance cohort compared to 5 patients in the AA recurrence cohort (p = 0.1). All 3 patients with deaths secondary to HF had AA recurrence compared to 11 out of the 28 patients whom were long-term survivors or deaths not related to HF (p = 0.04). All-cause mortality was not associated with AA recurrence. CONCLUSION: This study demonstrates moderate long-term efficacy of SR maintenance with catheter ablation for AA in patients with CA. Improvements in clinical and biological status with positive trends in HF mortality are observed if SR can be maintained.


Assuntos
Amiloidose , Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Taquicardia Supraventricular , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Amiloidose/complicações , Amiloidose/cirurgia , Ablação por Cateter/efeitos adversos
8.
Medicine (Baltimore) ; 103(14): e37646, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579099

RESUMO

BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse prognosis in several malignancies. For renal cell carcinoma (RCC), the effect of PBT is still debated. OBJECTIVE: To evaluate the impact of PBT on prognosis after nephrectomy in patients with RCC. METHODS: This study is A systematic review and meta-analysis of published article data (PRISMA protocol) for literature related to PBT and RCC through extensive search of EMBASE, Medline via PubMed, Web of Science and Cochrane Library, language limited to English, with no time constraint until May 20, 2022. We pooled the results of multivariable cox regression analyses from each study, with subgroup analyses by dose and timing of transfusion. All analyses were done using Stata14. RESULTS: A total of 12 studies involving 27,683 participants were included. Our meta-analysis pooled the results of multivariable cox regression analysis in each study, showing that PBT is associated with higher overall Mortality (OM; hazard ratio [HR] = 1.34, 1.23-1.44), cancer-specific mortality (CSM; HR = 1.35, 1.20-1.51), and disease recurrence (HR = 1.54, 1.18-1.89). when only patients with nonmetastatic RCC were included, PBT was still associated with higher OM (HR = 1.29, 1.11-1.47) and disease recurrence (HR = 1.58, 1.18-1.98), but the association with CSM (HR = 1.26, 0.99-1.52) was not statistically significant. In subgroup analysis by transfusion dose, small (1-2) units of PBT were not associated with CSM (HR = 1.84, 0.95-2.73), but large (≥3) units were associated with higher CSM (HR = 2.98, 1.74-4.22) and disease recurrence (HR = 1.99, 1.31-2.67). Each additional unit of PBT resulted in a higher CSM (HR = 1.07, 1.04-1.10). In subgroup analysis by transfusion timing, intraoperative transfusion was associated with higher CSM and disease recurrence, but postoperative transfusion was not. CONCLUSIONS: PBT is associated with higher OM, CSM and disease recurrence. This adverse effect seems to be particularly significant in high-dose intraoperative transfusion. It is necessary to limit the overuse of PBT, especially high-dose intraoperative transfusion, in order to improve the prognosis of patients undergoing nephrectomy for RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Transfusão de Sangue/métodos , Nefrectomia/métodos , Neoplasias Renais/patologia
9.
JCO Precis Oncol ; 8: e2300414, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579191

RESUMO

PURPOSE: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. MATERIALS AND METHODS: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non-muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. RESULTS: Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. CONCLUSION: Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.


Assuntos
Ácidos Nucleicos Livres , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Ácidos Nucleicos Livres/genética , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Metilação , Biópsia Líquida , Músculos/patologia , MicroRNAs/genética , MicroRNAs/uso terapêutico
10.
Life Sci Alliance ; 7(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580393

RESUMO

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)-based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1,195 control samples. ctDNA was detected in 51 of 55 (93%) samples at diagnosis, and 18 of 18 (100%) samples at progression. Positive ctDNA in the last on-treatment sample was associated with rapid progression (median 1.02 versus 3.38 yr, HR = 5.63, P < 0.001) and reduced overall survival (median 2.31 versus NR yr, HR = 8.22, P < 0.001) in patients with high-grade serous cancer. In the case of 12 patients, ctDNA assays detected progression earlier than standard surveillance, with a median lead time of 5.9 mo. To approach the physical limits of ctDNA detection, five patients were analyzed using ultra-sensitive assays interrogating 479-1,856 tumor mutations, capable of tracking ctDNA fractions down to 0.0004%. Our results demonstrate that ctDNA assays achieve high sensitivity and specificity in detecting post-operative residual disease in EOC.


Assuntos
DNA Tumoral Circulante , Neoplasias Ovarianas , Humanos , Feminino , DNA Tumoral Circulante/genética , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética
11.
BMC Cancer ; 24(1): 423, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580902

RESUMO

BACKGROUND: Total thyroidectomy is the main line of treatment for papillary thyroid cancer. Central lymph node dissection (CLND) is still debatable. In this study, we aimed to correlate the central lymph node status with the age of patients. METHODS: This is a retrospective study including patients with papillary thyroid cancer (PTC) who underwent total thyroidectomy and CLND at a tertiary cancer center during the period from January 2012 to September 2022. Patients were subdivided into 3groups: patients younger than 20 years old, patients between 20 and 40 years old, and patients older than 40 years old. Correlation between central lymph node status, lateral lymph node status, and harvest count with each other and between age groups was done. RESULTS: 315 patients were included. The younger the age group the higher the possibility of harboring positive central nodes, however, the positivity of lateral nodes was similar. Neither central nodal harvest nor positive central node count significantly differed between groups. The lateral nodal harvest was significantly higher in the < 20 years group with no affection to the number of positive nodes retrieved. The younger the age group the longer the disease-free survival (DFS). CONCLUSION: We can conclude that patients younger than twenty years had a higher probability of harboring malignancy in central nodes and higher lateral node harvest on dissection. In contrast, they do have a lower incidence of recurrence.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Adulto Jovem , Adulto , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Excisão de Linfonodo , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Esvaziamento Cervical , Tireoidectomia , Recidiva Local de Neoplasia/patologia
12.
BMC Cancer ; 24(1): 421, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580937

RESUMO

BACKGROUND: We designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice. METHODS: A 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers. RESULTS: In ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2-7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI. CONCLUSIONS: There is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Adulto , Humanos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Etoposídeo , Estudos Retrospectivos , Recidiva Local de Neoplasia , Carboplatina
13.
Respir Res ; 25(1): 156, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581044

RESUMO

BACKGROUND: Lung cancers represent the main cause of cancer related-death worldwide. Recently, immunotherapy alone or in combination with chemotherapy has deeply impacted the therapeutic care leading to an improved overall survival. However, relapse will finally occur, with no efficient second line treatment so far. New therapies development based on the comprehension of resistance mechanisms is necessary. However, the difficulties to obtain tumor samples before and after first line treatment hamper to clearly understand the consequence of these molecules on tumor cells and also to identify adapted second line therapies. METHODS: To overcome this difficulty, we developed multicellular tumor spheroids (MCTS) using characterized Non-Small Cell Lung Cancer (NSCLC) cell lines, monocytes from healthy donors and fibroblasts. MCTS were treated with carboplatin-paclitaxel or -gemcitabine combinations according to clinical administration schedules. The treatments impact was studied using cell viability assay, histological analyses, 3'RNA sequencing, real-time PCR, flow cytometry and confocal microscopy. RESULTS: We showed that treatments induced a decrease in cell viability and strong modifications in the transcriptomic profile notably at the level of pathways involved in DNA damage repair and cell cycle. Interestingly, we also observed a modification of genes expression considered as hallmarks of response to immune check point inhibitors and immunogenicity, particularly an increase in CD274 gene expression, coding for PD-L1. This result was validated at the protein level and shown to be restricted to tumor cells on MCTS containing fibroblasts and macrophages. This increase was also observed in an additional cell line, expressing low basal CD274 level. CONCLUSIONS: This study shows that MCTS are interesting models to study the impact of first line therapies using conditions close to clinical practice and also to identify more adapted second line or concomitant therapies for lung cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia , Esferoides Celulares , Paclitaxel/uso terapêutico , Antígeno B7-H1
14.
Cancer Med ; 13(7): e7146, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581118

RESUMO

BACKGROUND: De-escalation strategies for newly-diagnosed p16-positive oropharyngeal squamous cell carcinoma (p16+ OPSCC), aim to reduce treatment-related morbidity without compromising disease control. One strategy is neoadjuvant cisplatin and docetaxel chemotherapy (NAC + S) before transoral robotic surgery, with pathology-based risk-adapted adjuvant treatment. METHODS: We examined the recurrence-free survival (RFS) for patients who received NAC + S. RESULTS: Comparing outcomes in 103 patients between 2008 and 2023, 92% avoided adjuvant treatment and showed significantly higher 2-year recurrence-free survival (RFS) compared to those with adjuvant treatment (95.9% vs. 43.8%, p = 0.0049) CONCLUSION: Our findings suggest that pathology-based risk-adapted omission of adjuvant treatment following NAC + S does not appear to elevate recurrence risk and that NAC may identify patients with favorable tumor biology, yielding a 2-year RFS probability exceeding 95% without adjuvant treatment. Further, the study identifies a patient subset experiencing disease recurrence despite triple modality therapy. Despite limitations, including a retrospective design and modest sample size, the data advocate for controlled NAC + S studies.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Humanos , Terapia Neoadjuvante , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Orofaríngeas/cirurgia , Quimioterapia Adjuvante , Neoplasias de Cabeça e Pescoço/etiologia
15.
Arch Endocrinol Metab ; 68: e220506, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38578436

RESUMO

Objective: Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). Subjects and methods: We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. Results: After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-riskto high-risk patients with postoperative s-Tg > 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. Conclusion: The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based ondynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.


Assuntos
Recidiva Local de Neoplasia , Tireoglobulina , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo , Recidiva Local de Neoplasia/diagnóstico , Estudos Retrospectivos , Medição de Risco , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
17.
J Gastrointest Surg ; 28(4): 394-401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583889

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) has been recommended as the first-line treatment for early gastric cancer (EGC). However, poor visualization of the operative field increases both the procedure time and the risk of complications, especially for large and difficult lesions. We introduced a novel technique, magnetic anchor-guided ESD (MAG-ESD) and compared it with conventional ESD (C-ESD) for the treatment of large EGCs in terms of efficacy, safety, and advantages. METHODS: Patients with large EGCs who underwent MAG-ESD or C-ESD at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to March 2022 were retrospectively enrolled in this study. The patients in the MAG-ESD cohort were matched to those in the C-ESD cohort using propensity score-based matching. The operation time, submucosal dissection time, complete resection status, magnetic anchor, adverse event rate, and tumor recurrence rate were evaluated. RESULTS: Twenty-two patients who underwent MAG-ESD were ultimately matched to those who underwent C-ESD. The median operation time of MAG-ESD and C-ESD was 43 minutes (IQR, 35.2-49.5) and 50.5 minutes (IQR, 42.0-76.0), respectively, among which the submucosal dissection time was 7.6 minutes (IQR, 5.2-10.4) and 14.8 minutes (IQR, 10.8-19.6), respectively. The operation time of MAG-ESD was shorter than that of C-ESD, especially the submucosal dissection time (P < .05). There was a lower incidence of adverse events associated with MAG-ESD (P < .05) when magnetic anchors were successfully placed and retrieved. CONCLUSION: MAG-ESD is feasible, effective, safe, and simple for the treatment of large EGCs at different sites and has a high anchor success rate, which could shorten the operation time and reduce the adverse event rate.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Estudos de Coortes , Resultado do Tratamento , Recidiva Local de Neoplasia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Fenômenos Magnéticos
19.
Zhonghua Gan Zang Bing Za Zhi ; 32(3): 193-200, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38584099

RESUMO

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).


Assuntos
Hepatite B Crônica , Hepatite B , Feminino , Humanos , Hepatite B Crônica/tratamento farmacológico , Antígenos E da Hepatite B , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B , Estudos Retrospectivos , DNA Viral , Recidiva Local de Neoplasia/tratamento farmacológico , Hepatite B/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Vírus da Hepatite B/genética , Resultado do Tratamento
20.
Iran J Med Sci ; 49(3): 156-166, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38584650

RESUMO

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.


Assuntos
Carcinoma , Infecções por Papillomavirus , Neoplasias dos Seios Paranasais , Humanos , Fator A de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2 , Papillomavirus Humano , Prognóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Papillomaviridae , Recidiva Local de Neoplasia/complicações , Carcinoma/diagnóstico , Carcinoma/patologia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/patologia , Receptores ErbB , Recidiva , Biomarcadores
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