Can TILs be associated with prognostic factors and survival rates in breast cancer? A retrospective analysis

Introduction: The relationship between the tumor inflammatory infiltrate, also known as tumor-infiltrating lymphocytes (TILs), and invasive breast carcinomas has been extensively studied in recent years to verify its association with prognosis and response to treatment. The goal of this study was to associate the presence of TILs with patient's survival time. Methods: We studied prognostic clinicopathological characteristics already established in the literature and their impact on overall five-year survival time of patients with invasive breast cancer treated at Hospital Santa Casa in Belo Horizonte, Minas Gerais, Brazil, in 2011 (n=290). This was an observational and retrospective study. Results: The presence of TILs was associated with tumors of no special type (p=0.018) and with younger age of the patients (p=0.042). Smaller tumor size (HR: 19.24; 95%CI 4.30­86.15; p<0.001), absence of metastasis to the axillary lymph nodes (HR: 2.80; 95%CI 1.02­7.70; p=0.002), positivity for progesterone receptor (HR: 0.39; 95%CI 0.17­0.87; p=0.022), and presence of TILs (HR: 0.23; 95%CI 0.08­0.65; p=0.005) were associated with longer survival times. Conclusions: This study suggests that the presence of TILs, along with other clinicopathological characteristics, is a prognostic factor in breast cancer

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

Preoperative differentiation of benign and malignant non-epithelial ovarian tumors: clinical features and tumor markers / Diferenciação pré-operatória de tumores ovarianos não epiteliais benignos e malignos: características clínicas e marcadores tumorais

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Resumo Objetivo Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. Métodos Cento e dezenovemulheres consecutivas comtumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. Resultados Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estromamalignos foram tratadas comcirurgia preservadora de fertilidade. Cinco (71,4%)mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. Conclusão Os tumores de ovário não epiteliais foram benignos namaioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico préoperatório desses tumores.

Is serum bilirubin level a predictor factor in parotid gland carcinoma? / O nível sérico de bilirrubina é um fator preditivo no carcinoma da glândula parótida?

Abstract Introduction: Bilirubin levels have been associated with risk of several malignancies. The association between pretreatment serum bilirubin levels and overall survival of patients with parotid gland carcinoma is unclear. Objectives: In this study, we assessed the effect of serum bilirubin levels to overall survival in malignant parotid tumors. Methods: This study included a total of 35 patients, 15 female and 20 male. The mean age of these patients was 60.7 ± 14.5 years. All patients who were diagnosed with parotid gland carcinoma and underwent total parotidectomy between 2008 and 2018, were retrospectively assessed. The relationship between the overall survival of patients and total bilirubin, direct bilirubin, and indirect bilirubin levels was estimated. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off points. Results: Patients with low direct bilirubin, total bilirubin and indirect bilirubin had significantly longer overall survival than those with high levels. Cut-off values for total bilirubin, direct bilirubin and indirect bilirubin were detected as 0.545 mg/dL, 0.175 mg/dL and 0.435 mg/dL, respectively. Conclusion: In our study, we observed that increased preoperative bilirubin levels are associated with reduced survival time in the postoperative period of patients with parotid gland carcinoma.

Resumo Introdução: Os níveis de bilirrubina têm sido associados ao risco de várias lesões malignas. A associação entre os níveis séricos de bilirrubina pré-tratamento e a sobrevida global dos pacientes com carcinoma da glândula parótida ainda não é clara. Objetivos: Neste estudo, avaliamos o efeito dos níveis séricos de bilirrubina na sobrevida global em tumores malignos de parótida. Método: Este estudo avaliou 35 pacientes, 15 do sexo feminino e 20 do masculino. A média de idade foi de 60,7 ± 14,5 anos. Pacientes diagnosticados com carcinoma da glândula parótida e submetidos a parotidectomia total entre 2008 e 2018 foram avaliados retrospectivamente. A relação entre a sobrevida global dos pacientes e os níveis de bilirrubina total, bilirrubina direta e bilirrubina indireta foi estimada. A análise da curva Receiver Operating Characteristic foi realizada para determinar os pontos de corte ideais. Resultados: Pacientes com níveis mais baixos de bilirrubina direta, bilirrubina indireta e bilirrubina total tiveram sobrevida global significantemente maior do que aqueles com valores mais altos. Valores de corte para bilirrubina total, bilirrubina direta e bilirrubina indireta foram estabelecidos como 0,545 mg/dL, 0,175 mg/dL e 0,435 mg/dL, respectivamente. Conclusão: Em nosso estudo, verificamos que níveis de bilirrubina aumentados no pré-operatório estão associados à redução do tempo de sobrevida no período pós-operatório em pacientes com carcinoma da glândula parótida.

Evaluation of high-dose vitamin A treatment in postmolar patients with low and plateauing serum human chorionic gonadotropin levels / Avaliação de alta dose de vitamina A em pacientes pósmola hidatiforme, com valores baixos e em platô de gonadotrofina coriônica humana

Abstract Objective To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the first normal serum hCG value (< 5IU/L). Methods The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identification of a P-hCG level to the first normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted. Results In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths. Conclusion The limited use of HD Vit-A seems to have a safe and significant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.

Resumo Objetivo Comparar o efeito de alta dose de vitamina A (VitA) no seguimento pósmolar de pacientes com gonadotrofina coriônica humana (hCG) sérica apresentando valoresbaixoseem platô(L&P). Métodos Estudo retrospectivo de série de casos comparando duas coortes não simultâneas. Grupo controle (CG): 34 pacientes com títulos de hCG sérico L&P submetidos a manejo expectante por 6 meses após o esvaziamento uterino, de 1992 a 2010; Grupo de Estudo (SG): de 2011 a 2017, 32 pacientes em condições semelhantes de hCG receberam Vit-A na dose de 200.000 IU por dia, do momento da identificação dohCG em platôate o primeirohCG normaloudiagnóstico de progressão para neoplasia trofoblástica gestacional (NTG). O presente estudo foi aprovado pelo Comitê de Ética da Instituição na qual foi desenvolvido. Resultados Em ambososgrupos, aprevalência de hCGL&P foi < 5%. No SG, os níveis de hCGemplatô forammaiores (CG = 85.5 versus SG = 195 IU/L; p = 0,028), e foram significantemente menores tanto a prevalência de NTG pós-molar (CG = 29.4% versus SG = 6.3%, p = 0,034) como o tempo de seguimento (CG = 14 versus SG = 10 meses, p < 0.001). Na evolução para NTG não houve diferença no estadiamento da Interna tional Federation of Gynecology and Obstetrics (FIGO, na sigla em inglês) ou na agressividade do tratamento. Com altas doses de Vit-A não houve qualquer efeito tóxico relevante. Não houve casos de recidiva de NTG ou de óbito. Conclusão O uso limitado de altas doses de Vit-A parace ser seguro e apresenta efeitos significativos na evolução de pacientes em controle pós-molar com títulos de hCG sérico L&P, e pode diminuir o desenvolvimento de NTG pós-molar nessa população.

The Difference in Thyroid Stimulating Hormone Levels between Differentiated Carcinoma and Benign Enlargement

Abstract Introduction Papillary and follicular thyroid carcinoma are common head and neck cancers. This cancer expresses a thyroid stimulating hormone (TSH) receptor that plays a role as a cancer stimulant substance. This hormone has a diagnostic value in the management of thyroid carcinoma. Objective The present study aimed to determine the difference in TSH levels between differentiated thyroid carcinoma and benign thyroid enlargement. Methods The present research design was a case-control study. The subjects were patients with thyroid enlargement who underwent thyroidectomies at the Dr. Sardjito General Hospital, Yogyakarta, Indonesia. Thyroid stimulating hormone levels were mea- sured before the thyroidectomies. The inclusion criteria for the case group were: 1) differentiated thyroid carcinoma, and 2) complete data; while the inclusion criteria for the control group were: 1) benign thyroid enlargement, and 2) complete data. The exclusion criteria for both groups were: 1) patients suffering from thyroid hormone disorders requiring therapy before thyroidectomy surgery, 2) patients receiving thyroid suppression therapy before the thyroidectomy was performed, and 3) patients suffering from severe chronic diseases such as renal insufficiency, and severe liver disease. Results There were 40 post-thyroidectomy case group patients and 40 post-thyroidect- omy control group patients. There were statistically significant differences in TSH levels between the groups with differentiated thyroid carcinoma and benign thyroid enlargement (p = 0.001; odds ratio [OR] = 8.42; 95% confidence interval [CI]: 3.19-36.50). Conclusion Based on these results, it can be concluded that there were significant differences in TSH levels between the groups with differentiated thyroid carcinoma and benign thyroid enlargement.

Predictive and prognostic impact of preoperative complete blood count based systemic inflammatory markers in testicular cancer

ABSTRACT Purpose To determine the utility of preoperative complete blood count (CBC) based systemic inflammatory markers in the prediction of testicular cancer and its prognosis. Material and Methods Between 2008-2017 the data of all testicular tumor patients undergoing radical orchiectomy were retrospectively analyzed. Patient baseseline characteristics (age, tumor stage, tumor markers, etc.) and results of routine preoperative blood tests including mean platelet volume (MPV), red cell distribution width (RDW), lymphocyte ratio (LR) and neutrophil ratio (NR) were retrieved. In addition, neutrophil to lymphocyte ratio (NLR) was calculated. Results Mean age of the tumor and control group was 36.0±15 and 30.50±11 years, respectively. Mean RDW, NR and NLR were significantly higher in the tumor group with p values<0.001; whereas LR and MPV were significantly higher in the control group (p<0.001). Receiver Operating Characteristic (ROC) analyses of LR, NR, RDW, MPV, and NLR are shown in Table-3. The cut off values for RDW and NR were found as 13,7 (Area under the curve (AUC): 0.687, sensitivity = 42.2%, specificity = 84.8%) and 55.3 (AUC:0.693, sensitivity 72.2%, specificity 62%), respectively. Area under the curve for NLR in tumor group was 0.711, with a threshold value of 1.78 and sensitivity=81.8% and specificity=55.4% (AUC:0.711/sig<0.001) that together with RDW exhibited the best differential diagnosis potential which could be used as an adjuvant tool in the prediction of testicular tumor and its prognosis. Conclusion Several systemic inflammatory markers, which are obtained by routinely performed cost-effective blood tests, could demonstrate incremental predictive and prognostic information adjuvant to preoperativly achieved testiscular tumor markers.

Preoperative serum total cholesterol is a predictor of prognosis in patients with renal cell carcinoma: a meta-analysis of observational studies

ABSTRACT Purpose Several studies have demonstrated the strong correlation between the levels of preoperative serum total cholesterol (TC) and the survival of patients with surgically treated renal cell carcinoma (RCC). However, this association remains controversial. We performed a meta-analysis of published reports to evaluate the prognostic significance of the preoperative serum TC levels for patients with surgically treated RCC. Material and Methods The databases from MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library were systematically searched to identify the eligible studies published before August 2019. Multivariate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance by using random-effects models. Results Nine cohort studies comprising 15.609 patients were identified. Low preoperative serum TC levels were associated with poor cancer-specific survival (CSS; HR=0.98, 95% CI: 0.97-0.99; P=0.005; I2=74.2%) and progression-free survival (PFS; HR=0.69, 95% CI: 0.49-0.98; P=0.036; I2=80%) in patients with surgically treated RCC. However, no significant association was observed between low preoperative serum TC levels and shorter overall survival (HR=0.93, 95% CI: 0.87-1.00; P=0.057; I2=86.2%). Sensitivity analyses validated the reliability and rationality of the results. Conclusions Preoperative serum TC level is an independent poor prognostic factor for patients with surgically treated RCC, with lower levels associated with worse CSS and PFS. Hence, this parameter may provide additional guidance in the selection of therapeutic strategies to improve prognosis, considering that cholesterol is a broadly applied routine marker in clinical practice.

The relationship of neutrophil to lymphocyte ratio with testicular cancer

ABSTRACT Purpose: To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker. Material and Methods: Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared. Results: Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10±2.13 to 1.62±0.59 postoperatively (p=0.010). Conclusions: NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.

Dosagem sérica do marcador tumoral CA 15. 3 em cadelas portadoras de neoplasias mamárias pelo método de eletroquimioluminescência / Serum dosage of the tumor marker Ca 15. 3 in bitches presenting mammary neoplasia with the chemiluminescence method

The objective of the present study was to analyze the serum levels of the tumor marker Ca15.3 in healthy bitches and those with mammary neoplasms, correlating results with tumor type, clinical staging, time until presentation, and presence of ulceration and vascularization. For the study, 30 bitches with mammary tumors and 30 healthy bitches (control group) were selected. Histopathology was performed for identification of tumor type, and blood was collected for measurement of serum concentration of the marker via the chemiluminescence method using a commercial kit. A higher frequency of malignant neoplasms was observed (76.7%), with a higher quantity of carcinoma in mixed tumor (26.7%). Regarding serum concentration of the marker Ca15.3, there was no difference in serum values when comparing the means from bitches with neoplasia and healthy bitches, nor when comparing the other characteristics. The majority of results for serum concentration of Ca15.3, whether in bitches with neoplasia or in healthy bitches, was zero. It is concluded that the measurement of the marker Ca15.3 using the chemiluminescence method and commercial kits for humans did not offer significant results that would make this method or this marker a useful tool for patient monitoring and evaluation of the prognosis of bitches with mammary neoplasms.(AU)

Laboratory predictors of survival in ovarian cancer

SUMMARY OBJECTIVE To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.

RESUMO OBJETIVO Relacionar a sobrevida livre de doença e sobrevida global com câncer de ovário tipos I e II, assim como com parâmetros laboratoriais pré-operatórios biomarcadores. MÉTODOS Estudo retrospectivo realizado com base na coleta de dados de prontuários de pacientes com tumor ovariano. As curvas de Kaplan-Mayer foram realizadas em relação à análise estatística dos dados, sendo comparadas pelo teste de Log-rank. RESULTADOS A sobrevida livre de doença nas pacientes com câncer de ovário tipo I foi significativamente maior do que nas pacientes com câncer de ovário tipo II (p = 0,0013), bem como maior naquelas com níveis normais de CA-125 (p = 0,0243) e com relação plaquetas-linfócitos (RPL) inferior a 200 (p = 0,0038). A sobrevida global de pacientes com câncer de ovário tipo I foi significativamente maior do que em pacientes com tipo II, maior em pacientes com níveis séricos normais de CA-125 (p = 0,0039) e naquelas com glicemia de jejum pré-operatória menor que 100 mg / dL. CONCLUSÃO Os níveis de CA-125 podem predizer uma sobrevida global e livre de doença. A RPL < 200 pode sugerir uma maior sobrevida livre de doença, enquanto uma glicemia normal de jejum, uma maior sobrevida global.

High D-dimer levels are associated with prostate cancer

RESUMO OBJETIVO O câncer de próstata é uma das neoplasias mais comuns em homens. Os principais fatores de risco para a ativação da coagulação e trombose são malignidade e idade mais avançada. O risco de trombose pode estar associado ao aumento do nível dos marcadores de coagulação, tais como o fibrinogênio e D-dímero. O objetivo deste estudo é avaliar a relação entre os marcadores de coagulação e o câncer de próstata. METODOLOGIA Este estudo prospectivo incluiu os pacientes que foram submetidos à biópsia de próstata transretal guiada por ultrassonografia e que passaram por cirurgia da próstata entre janeiro de 2015 e janeiro de 2016. Os níveis no plasma de antígeno prostático específico (PSA), PSA livre (fPSA), porcentagem de fPSA, D-dímero e fibrinogênio foram medidos antes dos procedimentos. Os pacientes foram divididos em dois grupos de acordo com os resultados de patologia. Os pacientes com hiperplasia benigna da próstata foram colocados no grupo 1 e os pacientes com câncer de próstata no grupo 2. RESULTADOS No total, 76 pacientes foram incluídos neste estudo. Houve um total de 53 pacientes no grupo 1 e 23 pacientes no grupo 2. A idade média dos pacientes e os níveis de PSA, fPSA, fibrinogênio e D-dímero foram, respectivamente, 65.33 ± 7.47 anos, 8.21 ± 4.59, 1.41 ± 0.74 ng/ml, 309.75 ± 80.46 mg/dl e 0.42 ± 0.39 µg/ml no grupo 1. No grupo 2, a idade média dos pacientes e os níveis de PSA, fPSA, fibrinogênio e D-dímero foram, respectivamente, 66.08 ± 6.7 anos, 145.69 ± 509.35, 7.32 ± 15 ng/ml, 312.16 ± 69.48 mg/dl, 1.09 ± 2.11 µg/ml. Biópsia da próstata e cirurgia transuretal foram realizadas em 64 (%84,21) e 12 (%15,79) pacientes, respectivamente. CONCLUSÃO O presente estudo demonstrou que os níveis de D-dímero no plasma foram maiores em pacientes com câncer de próstata. Novos estudos com um maior número de pacientes são necessários para definir a relação entre câncer de próstata e distúrbios de coagulação.

The evaluation of pretreatment neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio in patients with laryngeal neoplasms / Avaliação da relação neutrófilo-linfócito e relação neutrófilo-linfócito derivadano pré-tratamento em pacientes com neoplasias laríngeas

Abstract Introduction: Systemic inflammatory biomarkers are promising predictive and prognostic factors for solid cancers. The neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio are used to predict inflammation and used as biomarker in several malignancies. Objective: The purpose of this study was to demonstrate the diagnostic, predictive and prognostic role of neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio in patients with laryngeal neoplasms. Methods: A retrospective study was conducted on medical records involving 229 patients with benign, premalignant and malignant laryngeal neoplasms between 2002 and 2015. The diagnostic, predictive and prognostic role of neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were evaluated using uni- and multivariate analysis. Results: The neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were not statistically different between patients with benign, premalignant and malignant laryngeal neoplasms. Both neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were predictive factors for stage, lymph node metastasis, and distant metastasis. Patients with high neutrophil-lymphocyte ratio value (≥4) had a poor prognosis when compared with patients with low neutrophil-lymphocyte ratio value (5 year, Overall Survival: 69.0% vs. 31.1%, p < 0.001; 5 year, disease free survival: 70.0% vs. 32.7%, p ˂ 0.001; 5 year, locoregional recurrence free survival: 69.7% vs. 32.0%, p < 0.001). Furthermore, neutrophil-lymphocyte ratio was an independent prognostic factor for 5 year: Overall survival (HR = 2.396; 95% CI 1.408-4.077; p = 0.001), Disease free survival (HR = 2.246; 95% CI 1.322-3.816; p = 0.006) and locoregional recurrence free survival (HR = 2.210; 95% CI 1.301-3.753; p = 0.003). Conclusion: Pretreatment neutrophil-lymphocyte ratio is a useful and reliable predictive and prognostic biomarker for patients with laryngeal carcinoma.

Resumo Introdução: Biomarcadores inflamatórios sistêmicos são fatores preditivos e prognósticos promissores para cânceres sólidos. A relação neutrófilo-linfócito e a relação neutrófilo-linfócito derivada são utilizadas para predizer a inflamação e como biomarcadores em várias malignidades. Objetivo: O objetivo deste estudo foi demonstrar o papel diagnóstico, preditivo e prognóstico da relação neutrófilo-linfócito e relação neutrófilo-linfócito derivada em pacientes com neoplasias laríngeas. Método: Foi realizado um estudo retrospectivo em prontuários médicos de 229 pacientes com neoplasias laríngeas benignas, pré-malignas e malignas entre 2002 e 2015. O papel diagnóstico, preditivo e prognóstico da relação neutrófilo-linfócito e relação neutrófilo-linfócito derivada foi avaliado por meio de análise uni- e multivariada. Resultados: A relação neutrófilo-linfócito e a relação neutrófilo-linfócito derivada não foram estatisticamente diferentes entre pacientes com neoplasias laríngeas benignas, pré-malignas e malignas. Ambas as relação neutrófilo-linfócito e relação neutrófilo-linfócito derivada foram fatores preditivos para o estágio, metástase linfonodal e metástase a distância. Pacientes com valor alto da relação neutrófilo-linfócito (≥ 4) apresentaram pior prognóstico quando comparados com pacientes com valor mais baixo da relação neutrófilo-linfócito (5 anos, Sobrevida Global: 69,0% vs. 31,1%, p < 0,001; 5 anos, sobrevida livre de doença: 70,0% vs. 32,7%, p < 0,001; 5 anos, sobrevida livre de recorrência loco-regional: 69,7% vs. 32,0%, p < 0,001). Além disso, a relação neutrófilo-linfócito foi um fator prognóstico independente para 5 anos: Sobrevida global (HR = 2,396; IC95% 1,408-4,077; p = 0,001), sobrevida livre de doença (HR = 2,246; IC95%: 1,322-3,816; p = 0,006) e sobrevida livre de recorrência loco-regional (HR = 2,210; IC95%: 1,301-3,753; p = 0,003). Conclusão: A relação neutrófilo-linfócito no pré-tratamento é um biomarcador preditivo e de prognóstico útil e confiável para pacientes com carcinoma de laringe.

Estudo de biomarcadores lipídicos em pacientes portadores com pólipos e câncer colorretal / Study of lipid biomarkers of patients with polyps and colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer worldwide. Early diagnostic methods using serum biomarkers are required. The study of omics, most recently lipidomics, has the purpose of analyzing lipids for a better understanding of human lipidoma. The evolution of mass spectrometry methods, such as MALDI-MS technology, has enabled the detection and identification of a wide variety of lipids with great potential to open new avenues for predictive and preventive medicine. OBJECTIVE: To determine the lipid profile of patients with colorectal cancer and polyps. METHODS: Patients with stage I-III CRC, adenomatous polyps and individuals with normal colonoscopy were selected. All patients underwent peripheral blood collection for lipid extraction. The samples were analyzed by MALDI-MS technique for lipid identification. STATISTICAL ANALYSIS: Univariate and multivariate (principal component analysis [PCA] and discriminant analysis by partial least squares [PLS-DA]) analyses workflows were applied to the dataset, using MetaboAnalyst 3.0 software. The ions were identified according to the class of lipids using the online database Lipid Maps (http://www.lipidmaps.org). RESULTS: We included 88 individuals, 40 with CRC, 12 with polyps and 32 controls. Boxplot analysis showed eight VIP ions in the three groups. Differences were observed between the cancer and control groups, as well as between cancer and polyp, but not between polyps and control. The polyketide (810.1) was the lipid represented in cancer and overrepresented in polyp and control. Among the patients with CRC we observed differences between lipids with lymph node invasion (N1-2) compared to those without lymph node invasion (N). CONCLUSION: Possible lipid biomarkers were identified among cancer patients compared to control and polyp groups. The polyketide lipid (810.1) was the best biomarker to differentiate the cancer group from control and polyp. We found no difference between the biomarkers in the polyp group in relation to the control.

RESUMO CONTEXTO: O câncer colorretal (CCR) é, mundialmente, uma das principais causas de câncer. Métodos de diagnóstico precoce através de biomarcadores séricos são necessários. O estudo das ômicas, mais recentemente a lipidômica, tem a finalidade de analisar os lipídeos para melhor compreensão do lipidoma humano. A evolução dos métodos de espectrometria de massa, como a tecnologia por MALDI-MS, possibilitou a detecção e a identificação de uma ampla variedade de lipídeos com grande potencial para abrir novos caminhos para a medicina preditiva e preventiva. OBJETIVO: Determinar o perfil lipidômico de pacientes com câncer colorretal e pólipos. MÉTODOS: Foram selecionados pacientes com CCR estádio I-III, com pólipos adenomatosos e indivíduos com colonoscopia normal. Todos os pacientes foram submetidos a coleta do sangue periférico para extração do lipídeo. As amostras foram analisadas por técnica de MALDI-MS para a identificação dos lipídeos. ANÁLISE ESTATÍSTICA: Para análise univariada e multivariada foram utilizados a análise de componentes principais (PCA) e a análise discriminante pelos quadrados mínimos (PLS-DA). Os íons foram identificados de acordo com a classe de lipídeos usando-se o Lipid Maps (http://www.lipidmaps.org). RESULTADOS: Foram incluídos 88 indivíduos, 40 com CCR, 12 com pólipos e 32 controles. A análise de boxbolt evidenciou oito íons VIP nos três grupos. Observou-se diferenças entre os grupos câncer e controle, assim como entre câncer e pólipo, mas não entre pólipos e controle. O policetídeo (810,1) foi o lipídeo hipo-representado no câncer e hiperrepresentado no pólipo e controle. Entre os pacientes com CCR observamos diferenças entre os lipídeos com invasão linfonodal (N1-2) comparados aos sem invasão linfonodal (N0). CONCLUSÃO: Foram identificados possíveis biomarcadores lipídicos entre os pacientes com câncer comparados aos grupos controle e pólipo. O lipídeo policetídeo (810,1) foi o melhor biomarcador para diferenciar o grupo câncer do controle e pólipo. Não encontramos diferença entre os biomarcadores no grupo pólipo em relação ao controle.

Gynecological cancer and metabolic screening of 1001 elderly Brazilian women

SUMMARY OBJECTIVE The aim of this study was to evaluate gynecological cancer and metabolic screening of Brazilian women aged 65 years or older. METHODS This retrospective descriptive study was conducted by including 1,001 Brazilian patients of the gynecological geriatric outpatient office of our institution to evaluate the influence of age on gynecological cancer and metabolic screening parameters at the first clinical visit. All patients were divided into three groups: a) 65 to 69 years; b) 70 to 74 years; c) ≥ 75 years. We considered clinical, laboratorial, and image data as variables of this study. The Chi-square test was used to assess the proportion of differences among the age groups, and Kruskal-Wallis was used for quantitative variables. RESULTS The values of BMI and height in the group over 75 years was lower than that of the 65 to 69 years (p = 0.001). Regardless of the age group, high arterial blood pressure levels were found in 85.45% of participants. Also, many patients had glucose intolerance in the blood. The pelvic ultrasonography showed abnormal endometrial echo thickness (> 5 mm) in 6.14% of patients, but with no significant statistical difference between the age groups. A total of 4.04% of patients had ovaries with high volume values ( > 6.1 mL). Abnormal mammography (BI-RADS 3 or 4) was observed in 12.21%. CONCLUSIONS our data suggest that a great reduction in BMI and stature is more frequent in the group over 75 years. Also, systemic arterial hypertension and carbohydrate disturbance are frequent morbidities in women over 65 years.

RESUMO OBJETIVO O objetivo deste trabalho foi estudar retrospectivamente alguns dados clínicos, laboratoriais e imagens de um grupo de idosas brasileiras. MÉTODOS Estudo observacional retrospectivo realizado com inclusão de 1.001 mulheres brasileiras atendidas no ambulatório de geriatria ginecológica de nossa instituição. Foram analisados: a idade dos pacientes na primeira consulta clínica e a idade na menopausa natural; alguns achados clínicos durante um exame ginecológico; resultados de análises laboratoriais. Considerou-se a relação dessas variáveis com o grupo da idade das mulheres. O teste do qui-quadrado foi utilizado para avaliar os dados e para algumas variáveis, Kruskal-Wallis ou Anova. RESULTADOS A avaliação do IMC e da estatura nas diferentes faixas etárias das mulheres mostrou que, com o aumento da idade, há diminuição do IMC e da estatura (p=0,001). Nível anormal de pressão arterial estava presente em 85,45%. De acordo com o grupo de idade, as medidas laboratoriais foram avaliadas pelo método estatístico Kruskal-Wallis, e a Anova mostrou diferença estatisticamente significante apenas no valor da creatinina, com pequeno aumento com a idade. A ultrassonografia pélvica foi alterada com espessura endometrial normal (>5 mm) em 29 (6,14%), mas sem diferença estatística significativa com os grupos de idade, e os ovários mostraram sete (4,04%) com volume anormal (>6,1). Mamografia anormal (BI-Rads 3 ou 4) foi observada em 104 pacientes (12,21%). CONCLUSÕES O estudo conclui que, com o aumento da idade, há redução do IMC e da estatura. A hipertensão é morbidade frequente. Os dados laboratoriais e a avaliação de imagens deste estudo são importantes para aumentar o conjunto de informações sobre mulheres idosas e talvez para melhorar a assistência à saúde.

HIF-1α Levels in patients receiving chemoradiotherapy for locally advanced non-small cell lung carcinoma

SUMMARY AIM To examine the relationship between treatment response and hypoxia-inducible factor-1 alpha (HIF-1α) levels in patients with locally advanced non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT). METHODS Eighty patients with NSCLC were included in the study and treated at Acibadem Mehmet Ali Aydınlar University Medical Faculty. HIF-1 α levels were measured before and after CRT by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS Patients' stages were as follows; stage IIIA (65%) and stage IIIB (35%). Squamous histology was 45%, adenocarcinoma was 44%, and others were 11%. Chemotherapy and radiotherapy were given concurrently to 80 patients. Forty-five (56%) patients received cisplatin-based chemotherapy, and 35 (44%) received carboplatin-based chemotherapy. Serum HIF-1α levels (42.90 ± 10.55 pg/mL) after CRT were significantly lower than the pretreatment levels (63.10 ± 10.22 pg/mL, p<0.001) in patients with locally advanced NSCLC. CONCLUSION The results of this study revealed that serum HIF-1α levels decreased after CRT. Decrease of HIF-1α levels after the initiation of CRT may be useful for predicting the efficacy of CRT.

RESUMO OBJETIVO Examinar a relação entre a resposta ao tratamento e os níveis de fator 1 induzida por hipóxia (HIF-1α) em pacientes com câncer de pulmão de células não pequenas localmente avançado (NSCLC) que receberam quimiorradioterapia (CRT). MÉTODO Oitenta pacientes com NSCLC foram incluídos no estudo e foram tratados na Faculdade de Medicina da Acibadem Mehmet Ali Aydınlar University. O nível de HIF-1α foi medido antes e depois da TRC pelo método de ensaio imunoenzimático (ELISA). RESULTADOS Os estágios dos pacientes foram os seguintes; estágio IIIA (65%) e estágio IIIB (35%). A histologia escamosa foi de 45%, o adenocarcinoma de 44% e o outro de 11%. Quimioterapia e radioterapia foram dadas simultaneamente a 80 pacientes. Quarenta e cinco (56%) pacientes receberam quimioterapia à base de cisplatina e 35 (44%) receberam quimioterapia à base de carboplatina. Os níveis séricos de HIF-1α (42,90 ± 10,55 pg / mL) após a TRC foram significativamente menores do que os níveis pré-tratamento (63,10 ± 10,22 pg / mL, p <0,001) em pacientes com NSCLC localmente avançado. CONCLUSÃO Os resultados deste estudo revelaram que os níveis séricos de HIF-1α diminuíram após a TRC. A diminuição dos níveis de HIF-1α após o início da TRC pode ser útil para prever a eficácia da TRC.

Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma

ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.

Role of native thiol, total thiol and dynamic Disulphide in diagnosis of patient with prostate cancer and prostatitis

ABSTRACT Background: Our study investigates whether Native Thiol, Total Thiol and disulphide levels measured in serum of patients with prostate cancer and prostatitis and of healthy subjects, have any role in differential diagnosis. Materials and Methods: Patients followed up for histopathologically verified diagnosis of prostate cancer and prostatitis in 2016-2017 at the Medicalpark Gaziantep Hospital Urology Clinic were included in the study. Native Thiol (NT), Total Thiol (TT), Dynamic Disulphide (DD) levels in serum were measured by a novel automated method. Results: NT, TT, DD, NT / TT ratios, DD / TT ratio and DD / NT ratio were measured as 118.4 ± 36.8μmoL / L, 150.3 ± 45.3μmoL / L, 15.9 ± 7μmoL / L, 78.8 ± 7μmoL / L, 10.5 ± 3.5μmoL / L, 13.8 ± 5.8μmoL / L respectively in patients with prostate cancer; as 116.4 ± 40.5μmoL / L, 147.5 ± 50.1μmoL / L, 15.5 ± 8.7μmoL / L, 79.7 ± 9μmoL / L, 10.1 ± 4.5μmoL / L, 13.5 ± 7.2μmoL / L in patients with prostatitis and as 144.1 ± 21.2μmoL / L, 191 ± 32.3μmoL / L, 23.4 ± 10.1μmoL / L, 76.1 ± 98.3μmoL / L, 11.9 ± 4.1μmoL / L, 16.4 ± 6.9μmoL / L in healthy subjects. Significant difference was detected between groups of NT, TT and DD levels (p = 0.008, p = 0.001, p = 0.002). No significant difference was detected in terms of the NT / TT, DD / TT and DD / NT rates (p = 0.222, p = 0.222, p = 0.222). Conclusions: Serum NT, TT, DD levels in patients with prostatitis and prostate cancer were found significantly lower compared to the control group. This indicates that just as inflammation, prostate cancer also increases oxidative stress on tissues.

Repercussions of melatonin on the risk of breast cancer: a systematic review and meta-analysis

SUMMARY Breast Cancer is common in women, but its etiology is not yet fully understood. Several factors may contribute to its genesis, such as genetics, lifestyle, and the environment. Melatonin may be involved in the process of breast cancer. Therefore, the aim of this study is to evaluate the influence of the levels of melatonin on breast cancer through a systematic review and meta-analysis. We performed a systematic review according to PRISMA recommendations. The primary databases MEDLINE, Embase, and Cochrane were consulted. There was no restriction on the year of publication and language. Data of systematic reviews from April 2017 to September to 2017 were analyzed. The meta-analysis was conducted using RevMan 5.3 software provided by the Cochrane Collaboration. From a total of 570 articles, 9 manuscripts were included in this review. They analy onzed women with breast cancer and control patients, of which 10% and 90% were in the reproductive period and after menopause, respectively. The lowest level of melatonin was found in approximately 55% of studies with breast cancer in post-menopause. The metanalyses of the studies demonstrated low levels of melatonin in breast cancer patients (n=963) compared with control patients (n= 1332), with a mean difference between the studies of 8722;3.54 (CI8722;6.01,8722;1.06). Another difference found was in the comparison between smoking patients, with an average difference between 1.80 [0.97-2.63]. Our data suggest that low levels of melatonin might be a risk factor for breast cancer.

RESUMO O câncer de mama é comum em mulheres, mas sua etiologia ainda não é totalmente compreendida. Vários fatores podem contribuir para sua gênese, genética, estilo de vida e meio ambiente. A melatonina pode estar envolvida no processo de câncer de mama. Portanto, o objetivo deste estudo é avaliar a influência dos níveis de melatonina no câncer de mama por meio de uma revisão sistemática e meta-análise. Realizamos uma revisão sistemática de acordo com as recomendações do Prisma. Os principais bancos de dados, Medline, Embase e Cochrane, foram consultados. Não houve restrição quanto ao ano de publicação e idioma. Os dados de revisão sistemática obtidos de abril de 2017 a setembro a 2017 foram analisados. A meta-análise foi conduzida pelo programa RevMan 5.3 fornecido pela Cochrane Collaboration. De um total de 570 artigos, nove foram incluídos nesta revisão. As análises foram conduzidas em mulheres com câncer de mama e pacientes controle, dos quais 10% e 90% estavam no período reprodutivo e após a menopausa, respectivamente. O nível mais baixo de melatonina foi encontrado em aproximadamente 55% dos estudos com câncer de mama na pós-menopausa. As meta-análises de estudos demonstraram os baixos níveis de melatonina em doentes com câncer da mama (n=963), em comparação com os pacientes de controle (n=1.332), sendo a diferença de médias entre os estudos da 8722;3,54 (CI 8722;6,01, 8722;1,06). Outra diferença é demonstrada nas comparações entre pacientes fumantes, sendo a diferença da média entre 1,80 [0,97-2,63]. Nossos dados sugerem que baixos níveis de melatonina podem ser um fator de risco para câncer de mama.

Serum calcitonin nadirs to undetectable levels within 1 month of curative surgery in medullary thyroid cancer

ABSTRACT Objective: Because serum calcitonin (CT) is a reliable marker of the presence, volume, and extent of disease in medullary thyroid cancer (MTC), both the ATA and NCCN guidelines use the 2-3 month post-operative CT value as the primary response to therapy variable that determines the type and intensity of follow up evaluations. We hypothesized that the calcitonin would nadir to undetectable levels within 1 month of a curative surgical procedure. Subjects and methods: This retrospective review identified 105 patients with hereditary and sporadic MTC who had at least two serial basal CT measurements done in the first three months after primary surgery. Results: When evaluated one year after initial surgery, 42 patients (42/105, 40%) achieved an undetectable basal calcitonin level without additional therapies and 56 patients (56/84, 67%) demonstrated a CEA within the normal reference range. In patients destined to have an undetectable CT as the best response to initial therapy, the calcitonin was undetectable by 1 month after surgery in 97% (41/42 patients). Similarly, in patients destined to have a normalize their CEA, the CEA was within the reference range by 1 month post-operatively in 63% and by 6 months in 98%. By 6 months after curative initial surgery, 100% of patients had achieved a nadir undetectable calcitonin, 98% had reached the CEA nadir, and 97% had achieved normalization of both the calcitonin and CEA. Conclusion: The 1 month CT value is a reliable marker of response to therapy that allows earlier risk stratification than the currently recommended 2-3 month CT measurement.