BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis.

BACKGROUND: Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas. METHODS: This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%. RESULTS: Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24-73.89), favoring radical treatment. CONCLUSION: BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.

Surgical margins and prognosis of borderline and malignant phyllodes tumors.

PURPOSE: To investigate the optimal surgical margin and prognostic risk factors for borderline and malignant phyllodes tumors (PTs). METHODS: A retrospective analysis was conducted on patients with borderline and malignant PTs at our hospital from 2011 to 2022. Univariate and multivariate Cox proportional hazard models were employed to analyze the effects of various variables on local recurrence-free survival (LRFS) and disease-free survival (DFS). RESULTS: This study comprised 150 patients, 85 classified as borderline and 65 as malignant. During a median follow-up of 66 months (range: 3-146 months), 34 cases (22.7%) experienced local recurrence, 9 cases (6.0%) exhibited distant metastasis, and 7 cases (4.7%) resulted in death. Irrespective of the histological subtypes, patients with surgical margins ≥ 1 cm exhibit significantly higher 5-year LRFS and 5-year DFS rates compared to those with margins < 1 cm. Among patients with initial margins < 1 cm, LRFS (P = 0.004) and DFS (P = 0.003) were improved in patients reoperated to achieve margins ≥ 1 cm. Surgical margin < 1 cm (HR = 2.567, 95%CI 1.137-5.793, P = 0.023) and age < 45 years (HR = 2.079, 95%CI 1.033-4.184, P = 0.040) were identified as independent risk factors for LRFS. Additionally, surgical margin < 1 cm (HR = 3.074, 95%CI 1.622-5.826, P = 0.001) and tumor size > 5 cm (HR = 2.719, 95%CI 1.307-5.656, P = 0.007) were determined to be independent risk factors for DFS. CONCLUSIONS: A negative surgical margin of at least 1 cm (with secondary resection if necessary) should be achieved for borderline and malignant PTs. Tumor size > 5 cm and age < 45 years were predictive of recurrence, suggesting multiple therapy modalities may be considered for these high-risk patients.

Neoadjuvant chemoimmunotherapy shows major pathological response and low recurrence in head and neck squamous cell carcinoma.

BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.

Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators.

PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.

Predictors of recurrence in breast cancer patients with pathological partial response

SUMMARY OBJECTIVE: Patients with residual disease after neoadjuvant chemotherapy have a relative risk of developing recurrence. This study investigates the risk factors for recurrence in locally advanced breast cancer patients with residual disease and evaluates survival analysis. METHODS: This is a retrospective, single-center study. Breast cancer patients who failed to achieve a pathological complete response after neoadjuvant chemotherapy were included. Demographic, clinicopathological, and treatment characteristics were evaluated to identify predictive factors of recurrence and survival analysis. RESULTS: We included 205 patients in this study. After a median of 31 months of follow-up, 10 patients died, and 20 developed distant metastasis. Disease-free survival and disease-specific survival were 73.8% and 83.1%, respectively. Lymphovascular invasion and non-luminal subtype were independent predictors of locoregional recurrence. In situ carcinoma, lymphovascular invasion, ypTIII stage, and non-luminal molecular subtypes were independent predictors of disease-free survival. The only independent factor affecting disease-specific survival was cNII-III. The number of involved lymph nodes was an independent predictor of disease-free survival in patients without complete axillary response. CONCLUSION: Factors affecting disease-specific survival and disease-free survival were cNII-III and the number of involved lymph nodes, respectively. Patients with non-luminal, large residual tumors with in situ carcinoma, lymphovascular invasion, clinically positive axilla, and residual nodal involvement have a high relative risk for recurrence and may benefit from additional treatments.

Early nutritional intervention does not prevent long-term adverse events in women with breast cancer: A pilot study.

AIM: This study aims to evaluate the effect of early nutritional intervention on adverse clinical events in women with breast cancer undergoing neoadjuvant chemotherapy. DESIGN AND SETTINGS: This is a randomized clinical trial performed at the beginning of neoadjuvant chemotherapy for women with breast cancer treated at an oncology referral center (Brazil) and followed until the end of radiotherapy period, at least. Registered under ClinicalTrials.gov Identifier no. RBR-3SHHXS. METHODS: Participants were allocated to a control group - CG (nutritional guidance on healthy eating practices) or an intervention group - IC (nutritional guidance and individualized food plan). Chemotherapy toxicity (primary endpoint) was considered a precocious adverse clinical event and it was evaluated by self-reported gastrointestinal symptoms observed at any time during the first three cycles of treatment. Post-surgical complications, radiotherapy toxicity, and weight change were considered long-term adverse events. RESULTS: 34 women (19 in the IG and 15 in the CG) were evaluated. The early nutritional intervention was associated with low gastrointestinal chemotoxicity (nausea, vomiting, and constipation, p < 0.001, p < 0.048, and p < 0.024, respectively). However, there were no statically significant differences between both groups in the presence of long-term adverse events (radiotherapy toxicity-88.2% vs 76.9%, weight loss-21.1% vs 26.7% for IC and CG respectively, p > 0.05 for both). CONCLUSION: The early nutritional intervention was associated with a low frequency of precocious events, but not with long-term adverse events in women with breast cancer during treatment.

Clinical outcomes and prognostic factors of head and neck squamous cell carcinoma: a ten-year follow-up study

Abstract Traditional guidelines for determining the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) are used to make therapeutic decisions. However, only 50% of the patients had lived for more than five years. The present study aimed to analyze the correlation of traditional prognostic factors such as tumor size, histological grading, regional metastases, and treatment with the survival of patients with HNSCC. A total of 78 patients diagnosed with HNSCC were followed up for 10 years after diagnosis and treatment. The health status of the patients was tracked at four time points, and according to the evolution of the patients and their final clinical status, we performed a prognostic analysis based on the clinical outcomes observed during the follow-up period. The final study cohort comprised 50 patients. Most patients had tumors < 4 cm in size (64%) and no regional metastases (64%); no patients had distant metastases at the time of diagnosis. Most individuals had tumors with good (48%) and moderate (46%) degrees of malignancy. At the end of the follow-up period, only 14% of the patients were discharged, 42% died of the tumor, and 44% remained under observation owing to the presence of a potentially malignant disorder, relapse, or metastases. This analysis showed that traditional prognostic factors were not accurate in detecting subclinical changes or predicting the clinical evolution of patients.

The clinical significance of lymphovascular space invasion in patients with low-risk endometrial cancer

SUMMARY OBJECTIVE: The aim of this study was to assess the effect of lymphovascular space invasion on recurrence and disease-free survival in patients with low-risk endometrial cancer. METHODS: The study included patients with stage 1A, grade 1-2 endometrioid endometrial cancer who underwent a total hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Independent prognostic predictors of endometrial cancer recurrence were assessed using the Cox regression model. Binary logistic regression analysis was used to identify the predictors of distant recurrence. Kaplan-Meier analysis was used to describe survival curves, and the log-rank test was used to compare the differences in survival curves. RESULTS: A total of 189 patients met the inclusion criteria, of whom 24 (12.7%) had lymphovascular space invasion. The median follow-up time was 60 (3-137) months. Distant recurrence was present in 11 of 22 patients who developed recurrence. Kaplan-Meier survival analysis showed that the 5-year disease-free survival rates of patients with lymphovascular space invasion(+) and lymphovascular space invasion(-) were 62.5 and 91.9%, respectively, which were significantly lower (p<0.001). In multivariate Cox regression analysis, the presence of lymphovascular space invasion (p<0.001) and age ≥60 years (p=0.017) remained as prognostic factors for reduced disease-free survival. In binary logistic regression analysis, only lymphovascular space invasion (adjusted OR=13, 95%CI=1.456-116.092, p=0.022) was a prognostic factor for distant recurrence. CONCLUSION: lymphovascular space invasion is a prognostic risk factor for recurrence and distant metastasis and also a predictor of poorer disease-free survival outcomes in low-risk endometrial cancer.

Hepatic artery lymph node relevance in periampullary tumors: A retrospective analysis of survival outcomes.

Background: The Periampullary area comprehends a heterogeneous and complex structure with different histological tissues. Surgical standards include the peripancreatic regional lymphadenectomy, and during pancreatoduodenectomy (PD) the hepatic artery lymph node HALN(8a) is dissected. We aimed to describe the prognostic significance of the HALN(8a) lymph node metastasis in terms of disease-free survival (DFS) and overall survival (OS) in a specific cohort of patients in limited economic and social conditions. Methods: A retrospective study was conducted based on a prospective database from the HPB department of patients who underwent pancreaticoduodenectomy (PD) due to periampullary tumors during 2014-2021. Overall survival (OS) and disease-free survival (DFS) were estimated to be associated with positive HALN(8a) using Kaplan-Meier analysis. Log Rank test and Cox proportional hazards regression analysis was used. Results: 111 patients were included, 55,4% female. The most frequent pathology was ductal adenocarcinoma (60.3%). The positive rate of the HALN(8a) node was 21.62%. The Median OS time was 25.5 months, and the median DFS time was 13,8 months. Positive HLAN(8a) node, the cutoff of lymph node ratio resection (LNRR), and vascular invasion showed a strong association with OS. (CoxRegression p = 0.03 HR 0.5, p 0.003 HR = 1.8, p = 0.02 HR 0.4 CI 95%). In terms of DFS, lymph node ratio cutoff, tumoral size, and vascular invasion showed a statistically significant association with the outcome (p = 0.008, HR = 1.5; p = 0.04 HR = 2.1; p = 0.02 HR = 0.4 CI 95%). Conclusion: In this series of PD, OS was reduced in patients with HALN(8a) compromise in patients with pancreatic cancer, however without statistical significance in DFS. In multivariate analysis, lymph node status remains an independent predictor of OS and DFS. Further studies are needed.

A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival.

Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. OBJECTIVE: To identify prognostic markers for treatment and survival in HER2+ patients. METHODS: Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). RESULTS: A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). CONCLUSION: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.

Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis / Papel prognóstico da relação neutrófilo-linfócito no carcinoma espinocelular da laringe: uma metanálise

Abstract Introduction New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. Objective The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. Methods According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. Results Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p< 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p< 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p< 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. Conclusion The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.

Resumo Introdução Novas evidências sugerem que a relação neutrófilo-linfócito está associada ao prognóstico de vários carcinomas, mas a relação neutrófilo-linfócito no carcinoma espinocelular da laringe ainda permanece controversa. Objetivo Esclarecer a eficácia prognóstica da relação neutrófilo-linfócito no carcinoma espinocelular de laringe. Método De acordo com as diretrizes de metanálise, conduzimos uma busca nas bases de dados Embase, PubMed, e Cochrane Library. A relação neutrófilo-linfócito de pacientes com carcinoma espinocelular de laringe foi avaliado com a diferença de médias padronizadas e intervalo de confiança. A sobrevida global, sobrevida livre de doença e sobrevida livre de progressão de pacientes com carcinomaespinocelular de laringe foram expressas pelo método da diferença de médias padronizadas e intervalo de confiança. A razão de risco do intervalo de confiança 95% foi usada como um índice de avaliação para pacientes com carcinoma espinocelular de laringe. Resultados Oito estudos, que incluíram 1.780 pacientes, usaram uma variedade de valores finais diferentes para classificar a relação neutrófilo-linfócito (intervalo de 1,78-4,0). Entre os oito estudos que relataram a razão de risco de sobrevida global, o maior valor médio foi de 2,72 e 2 de 4 estudos relataram resultados com sobrevida livre de doença. O valor crítico de relação neutrófilo-linfócito e deterioração da sobrevida global (razão de risco = 1,68, intervalo de confiança 95% 1,43-1,99, p ˂ 0,001), sobrevida livre de doença (razão de risco = 2,09, intervalo de confiança 95% 1,62-2,6, p ˂ 0,001) e sobrevida livre de progressão (razão de risco = 1,92, intervalo de confiança 95% 1,75-2,10, p ˂ 0,001) foi associado com carcinoma espinocelular de laringe. A relação neutrófilo-linfócito tem valor prognóstico para carcinoma espinocelular de laringe. Conclusão Os resultados da metanálise mostraram que o aumento da relação neutrófilo-linfócito estava relacionado ao mau prognóstico do carcinoma espinocelular de laringe. A relação neutrófilo-linfócito pode servir como um biomarcador custo-efetivo de prognóstico do carcinoma espinocelular de laringe. Entretanto, mais estudos prospectivos de alta qualidade são necessários para avaliar a sua praticabilidade.

Bone Marrow Stromal Cell Regeneration Profile in Treated B-Cell Precursor Acute Lymphoblastic Leukemia Patients: Association with MRD Status and Patient Outcome.

For the last two decades, measurable residual disease (MRD) has become one of the most powerful independent prognostic factors in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the effect of therapy on the bone marrow (BM) microenvironment and its potential relationship with the MRD status and disease free survival (DFS) still remain to be investigated. Here we analyzed the distribution of mesenchymal stem cells (MSC) and endothelial cells (EC) in the BM of treated BCP-ALL patients, and its relationship with the BM MRD status and patient outcome. For this purpose, the BM MRD status and EC/MSC regeneration profile were analyzed by multiparameter flow cytometry (MFC) in 16 control BM (10 children; 6 adults) and 1204 BM samples from 347 children and 100 adult BCP-ALL patients studied at diagnosis (129 children; 100 adults) and follow-up (824 childhood samples; 151 adult samples). Patients were grouped into a discovery cohort (116 pediatric BCP-ALL patients; 338 samples) and two validation cohorts (74 pediatric BCP-ALL, 211 samples; and 74 adult BCP-ALL patients; 134 samples). Stromal cells (i.e., EC and MSC) were detected at relatively low frequencies in all control BM (16/16; 100%) and in most BCP-ALL follow-up samples (874/975; 90%), while they were undetected in BCP-ALL BM at diagnosis. In control BM samples, the overall percentage of EC plus MSC was higher in children than adults (p = 0.011), but with a similar EC/MSC ratio in both groups. According to the MRD status similar frequencies of both types of BM stromal cells were detected in BCP-ALL BM studied at different time points during the follow-up. Univariate analysis (including all relevant prognostic factors together with the percentage of stromal cells) performed in the discovery cohort was used to select covariates for a multivariate Cox regression model for predicting patient DFS. Of note, an increased percentage of EC (>32%) within the BCP-ALL BM stromal cell compartment at day +78 of therapy emerged as an independent unfavorable prognostic factor for DFS in childhood BCP-ALL in the discovery cohort­hazard ratio (95% confidence interval) of 2.50 (1−9.66); p = 0.05­together with the BM MRD status (p = 0.031). Further investigation of the predictive value of the combination of these two variables (%EC within stromal cells and MRD status at day +78) allowed classification of BCP-ALL into three risk groups with median DFS of: 3.9, 3.1 and 1.1 years, respectively (p = 0.001). These results were confirmed in two validation cohorts of childhood BCP-ALL (n = 74) (p = 0.001) and adult BCP-ALL (n = 40) (p = 0.004) treated at different centers. In summary, our findings suggest that an imbalanced EC/MSC ratio in BM at day +78 of therapy is associated with a shorter DFS of BCP-ALL patients, independently of their MRD status. Further prospective studies are needed to better understand the pathogenic mechanisms involved.

Environmental factors associated with the time to tuberculosis diagnosis in prisoners in São Paulo, Brazil.

BACKGROUND: Environmental conditions play an important role in the high incidence of tuberculosis in prisons. We estimated the effect of environmental factors, including measurements based on cell dimensions, on the time to tuberculosis diagnosis in prison population of Brazil. METHODS: This is a retrospective cohort of 2,257 prisoners diagnosed with tuberculosis in 2014 and 2015. We collected environmental data from 105 prisons and linked with routine tuberculosis surveillance and prison data. We estimated tuberculosis-free survival time with Cox risk models, guided by a validated directed acyclic graph. RESULTS: The median disease-free time was 1.71 years (95% confidence interval [95% CI] 1.64-1.78). Each 50% increase in occupancy-rate, increased the tuberculosis speed incidence by 16% (95% CI 8%-25%) in the first 2 years, and 9% (95% CI 3%-16%) up to 5 years. An increase in the cell area per person (ln[m2/person]) reduced the hazard of tuberculosis by 13% (95% CI 3%-23%) for up to 2, and 12% (95% CI 3%-21%) for up to 5 years. DISCUSSION: Most tuberculosis cases were diagnosed within 2 years of incarceration. Prison overcrowding and physical space per person in the cell were associated with the tuberculosis-free disease time. CONCLUSIONS: Interventions to reduce overcrowding or increase physical space are crucial to prevent tuberculosis in prisons.

Prognostic Value of Galectin Expression in Patients with Breast Cancer: Systematic Review and Meta-Analysis.

Galectins are a family of proteins with affinity for ß-galactosides and their expression correlates with overall survival (OS) in several cancers. However, in breast cancer their prognostic potential is unclear. In this study we performed a meta-analysis to clarify the prognostic value of galectin expression in breast cancer and to identify sources of heterogeneity. For this purpose, we performed a search of related publications in PubMed, Central-Conchrane, Web of Science database, OVID-EMBASE, Scope and EBSCOhost until November 2021.Thirteen articles were included with a total of 2700 patients. High galectin expression was found not to correlate with OS in breast cancer (HR = 1.11, 95% CI 0.93-1.31). In the case of galectin-3, correlation with OS was observed when performing subgroup analysis by cellular localization (HR = 0.59, 95% CI 0.36-0.94 for cytoplasmic and HR = 1.82, 95% CI 1.00-3.29 for cytoplasmic plus nuclear). Galectin-7 correlates with DFS/PFS/DSS (HR = 2.43; 95% CI 1.36-4.31). Finally, galectin-3 correlates with some clinicopathological features such as lymph node metastasis, estrogen receptor expression and age. In conclusion, galectin-3 correlates with OS in breast cancer when cellular localization is considered while galectin-7 correlates with DFS/PFS/DSS. The cellular localization of galectins should be as fundamental aspect to be determined in future studies.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Oral squamous cell carcinoma outcome in adolescent/young adult: Systematic review and meta-analysis.

To perform a systematic review focusing on the prognosis of oral cavity squamous cell carcinoma (OSCC) in young patients (≤40 years old) compared to older (>40 years old). Four databases were used in our search strategy. First, all titles were systematically organized using the Covidence platform online. In the second phase, 118 full texts of potentially eligible studies were analyzed by reviewers independently and in pairs. Twelve studies were considered eligible for data extraction. The relapse was higher in the young than in controls (pooled relative risk (RR) = 1.31; 95% CI [1.10-1.56]). The 5-year disease-free survival (DFS) was worse in young group (pooled hazard ratio (HR) = 0.73; 95% CI [0.63-0.85]) but the 5-year overall survival (OS) estimate was similar between the groups (pooled HR = 0.84; 95% CI [0.70-1.00]). While the 5-year OS was similar between groups, the number of relapses and 5-year DFS were worse in patients with OSCC ≤40 years old.

Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis.

INTRODUCTION: New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. OBJECTIVE: The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. METHODS: According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. RESULTS: Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p < 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p < 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p < 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. CONCLUSION: The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.

Axillary surgical approach in T1-T2N0M0 clinical breast cancer staging: Survival in a women's hospital cohort in Rio de Janeiro

The concerns regarding the prognosis and quality of life of patients with early breast cancer staging without lymph node involvement have increased, especially with regard to the axillary surgical approach. The aim of the present study was to determine overall survival and disease-free survival according to the axillary surgical approach. Methods: Retrospective cohort study of 827 women with clinical T1-T2N0M0 diagnosis attended at the Cancer Hospital III of the Brazilian National Cancer Institute, from January 2007 to December 2009, with a follow-up period of 60 months. Data were obtained from the Hospital Registry of Cancer through the medical records. Results: 683 women underwent sentinel lymph node biopsy and 144 underwent sentinel lymph node biopsy followed by axillary lymphadenectomy. After 5 years of follow-up, considering adjustment, it was observed overall survival (96.2% vs 93.6%; HR 0.98; 95%CI 0.42­2.29) and disease-free survival (93.7% vs 91.2%; HR 0.78; 95%CI 0.39­1.48) similar among patients undergoing either one or the other approach. In patients with micrometastasis, both overall (93.3%) and diseasefree survival (100%) were higher in women who underwent only sentinel lymph node biopsy compared to those who underwent this procedure followed by axillary lymphadenectomy (OS: 87.5%; DFS: 90,7%), albeit not statistically significant.

Resultados del tratamiento del hepatoblastoma en los Andes Ecuatorianos / Results of the treatment of hepatoblastoma in the Ecuadorian Andes

RESUMEN: El hepatoblastoma (HB), es una neoplasia maligna, que se origina en el hígado. La supervivencia (SV) depende de la extensión de avance de la enfermedad. El objetivo de este estudio fue determinar diferencias en la SV actuarial global (SVAG) y libre de enfermedad (SVLE) en pacientes con HB, según la extensión de su enfermedad. Serie de casos con seguimiento. Se incluyeron pacientes de entre 4 y 160 meses de edad tratados en un centro oncológico de Los Andes ecuatorianos (2000-2019). Las variables resultado fueron: lóbulo afectado, metástasis pulmonar, infiltración vascular, estadio PRETEXT, riesgo, histología, niveles de alfafetoproteína (AFP), remisión completa (RC), SVAG y SVLE. Se utilizó estadística descriptiva y analítica (Chi2, exacto de Fisher y corrección por continuidad). Se realizaron análisis de SV con curvas de Kaplan Meier y log-rank. Fueron estudiados 28 pacientes (53,6 % hombres), con una mediana de edad de 40 meses. Se verificaron metástasis pulmonares e infiltración vascular en el 25,0 % y 35,7 % de los casos respectivamente. La histología, estadio clínico y riesgo alto fueron mayoritariamente tipo epitelial (42,8 %), PRETEXT II (50,0 %) y riesgo alto (67,8 %) respectivamente. La media de AFP al diagnóstico fue 1055712ng/ml y 9 pacientes alcanzaron RC. La SVAG y SVLE general a 19 años fue 33,1 % y 26,0 % respectivamente. Según su extensión, la SVAG y la SVLE para los pacientes de riesgo estándar y alto fueron 50,0 % y 25,4 % (p=0,148); y 50,0 % y 14,7 % (p=0,037) respectivamente. La SVAG y SVLE verificadas son menores a las reportadas en otros estudios. La SVLE según su extensión, presentó diferencia significativa, sin embargo, este resultado debe ser tomado con cautela debido al número pequeño de pacientes.

SUMMARY: Hepatoblastoma (HB), is a malignant neoplasm, which originates in the liver. Survival (SV) depends on the extent of disease progression. The objective of this study was to determine differences in overall SV (OS) and disease-free (DFS) in patients with HB, according to the extent of their disease. Case series with follow-up. Patients between 4 and 160 months of age treated at an oncology center in the Ecuadorian Andes (2000-2019) were included. The result variables were affected lobe, lung metastasis, vascular infiltration, PRETEXT stage, risk, histology, alpha-fetoprotein levels (AFP), complete remission (RC), OS and DFS. Descriptive and analytical statistics (Chi2, Fisher's exact and continuity correction) were used. SV analyzes were performed with Kaplan Meier and log-rank curves. In this analysis 28 patients (53.6 % men), with a median age of 40 months, were studied. Lung metastases and vascular infiltration were verified in 25.0 % and 35.7 % of the cases, respectively. Histology, clinical stage, and high risk were mainly epithelial type (42.8 %), PRETEXT II (50.0 %), and high risk (67.8 %), respectively. The mean AFP at diagnosis was 1055712 ng / ml and 9 patients achieved CR. OS and DFS at 19 years were 33.1 % and 26.0 % respectively. According to their extension, the OS and DFS for standard and high risk patients were 50.0 % and 25.4 % (p = 0.148); and 50.0 % and 14.7 % (p = 0.037) respectively. The verified OS and DFS are lower than those reported in other studies. DFS according to its extension, presented a significant difference, however, this result should be considered with caution due to the small number of patients.

Thioredoxin reductase-1 levels are associated with NRF2 pathway activation and tumor recurrence in non-small cell lung cancer.

Activating mutations in the KEAP1/NRF2 pathway characterize a subset of non-small cell lung cancer (NSCLC) associated with chemoresistance and poor prognosis. We herein evaluated the relationship between 64 oxidative stress-related genes and overall survival data from 35 lung cancer datasets. Thioredoxin reductase-1 (TXNRD1) stood out as the most significant predictor of poor outcome. In a cohort of NSCLC patients, high TXNRD1 protein levels correlated with shorter disease-free survival and distal metastasis-free survival post-surgery, including a subset of individuals treated with platinum-based adjuvant chemotherapy. Bioinformatics analysis revealed that NSCLC tumors harboring genetic alterations in the NRF2 pathway (KEAP1, NFE2L2 and CUL3 mutations, and NFE2L2 amplification) overexpress TXNRD1, while no association with EGFR, KRAS, TP53 and PIK3CA mutations was found. In addition, nuclear accumulation of NRF2 overlapped with upregulated TXNRD1 protein in NSCLC tumors. Functional cell assays and gene dependency analysis revealed that NRF2, but not TXNRD1, has a pivotal role in KEAP1 mutant cells' survival. KEAP1 mutants overexpress TXNRD1 and are less susceptible to the cytotoxic effects of the TXNRD1 inhibitor auranofin when compared to wild-type cell lines. Inhibition of NRF2 with siRNA or ML-385, and glutathione depletion with buthionine-sulfoximine, sensitized KEAP1 mutant A549 cells to auranofin. NRF2 knockdown and GSH depletion also augmented cisplatin cytotoxicity in A549 cells, whereas auranofin had no effect. In summary, these findings suggest that TXNRD1 is not a key determinant of malignant phenotypes in KEAP1 mutant cells, although this protein can be a surrogate marker of NRF2 pathway activation, predicting tumor recurrence and possibly other aggressive phenotypes associated with NRF2 hyperactivation in NSCLC.