Role of magnetic resonance imaging in the prediction of histological grade in soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas are rare malignant tumors with significant heterogeneity. The importance of classifying histological grades is fundamental to defining the treatment approach. OBJECTIVE: To evaluate magnetic resonance imaging (MRI) in predicting the histological grade of soft tissue sarcomas. METHODS: A retrospective observational study included patients over 18 years undergoing MRI and primary tumor surgery at AC Camargo Cancer Center from January 2015 to June 2022. Two radiologists evaluated MRI criteria (size, margin definition, heterogeneity of the T2 signal, high-intensity peritumoral signal on T2, and postperitumoral contrast), and a grading prediction score was calculated. χ2 and logistic regression analyses were conducted. RESULTS: Sixty-eight patients were included (38 men; median: 48 years). Moreover, 52 high-grade and 16 low-grade tumors were observed. The MRI criteria associated with histological grade were peritumoral high-intensity T2-weighted signals (p < 0.001) and peritumoral postcontrast enhancement (p = 0.006). Logistic regression confirmed their significance (odds ratio [OR]: 11.8 and 8.8, respectively). Each score point increment doubled the chance of high-grade tumors (OR: 2.0; p = 0.014). CONCLUSION: MRI effectively predicts histological grades of soft tissue sarcomas. Peritumoral high-intensity T2-weighted signals and peritumoral postcontrast enhancement are valuable indicators of high-grade tumors. This highlights MRI's importance in treatment decision-making for sarcoma patients.

A Case Study of a Rare Undifferentiated Spindle Cell Sarcoma of the Penis: Establishment and Characterization of Patient-Derived Models.

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models-including patient-derived xenograft (PDX), 3D, and monolayer primary cultures-we successfully replicated crucial molecular traits observed in the patient's tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like TSC2 and FGFR4. These models are helpful in assessing the potential for an in-depth exploration of this tumor's biology. This comprehensive approach holds promise in identifying potential therapeutic avenues for managing this exceedingly rare soft tissue sarcoma.

COLORECTAL CANCER: ASSOCIATION BETWEEN SOCIODEMOGRAPHIC VARIABLES AND THE ADHERENCE TO CANCER SCREENING.

BACKGROUND: Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

Amplicon-based NGS test for assessing MLH1 promoter methylation and its correlation with BRAF mutation in colorectal cancer patients.

Detecting MLH1 promoter methylation is highly relevant to differentiate between possible Lynch syndrome patients or patients with sporadic causes of MLH1/PMS2 deficiency in colorectal (CRC) and endometrial cancers. Here, we aimed to develop a test for assessing MLH1 promoter methylation based in next generation sequencing (NGS), and to evaluate the concordance of MLH1 methylation and BRAF-V600 mutation status in CRC. For that, we performed a series of experiments with DNA from tumor, saliva and commercial control samples and our in house developed amplicon-based NGS test. In patients' samples, MLH1 methylation above 10% was only observed in tumors with MLH1/PMS2 loss. We confirmed the reproducibility and accuracy of MLH1 promoter analysis performing a serial dilution experiment with completely methylated and unmethylated control DNAs and a comparison between two NGS platforms (Ion Proton and Illumina). In MLH1/PMS2 deficient tumors, the MLH1 methylation status was concordant with the BRAF mutation status in 90% (18/20) of the cases. Our amplicon-based NGS test showed a great sensitivity and specificity for detecting MLH1 methylation in CRC samples, with a high agreement with the evaluation of BRAF mutation. This simple and affordable test could be used as a reflex test to identify patients with sporadic causes of MLH1/PMS2 deficiency in CRC, aiding to genetic test referral and identification of Lynch syndrome patients.

Associação entre características demográficas, condição socioeconômica e variáveis clínicas e a taxa de adesão a exames de sangue oculto nas fezes em uma amostra populacional de campanha hospitalar de rastreamento de câncer colorretal / Association between demographic characteristics, socioeconomic status, and clinical variables and the rate of adherence to fecal occult blood tests in a population of a colorectal cancer screening campaign conducted in a hospital

Introdução: O câncer colorretal (CCR) é um problema de saúde pública mundial cujo controle depende do estabelecimento de políticas públicas e programas de prevenção e rastreamento eficazes. No Brasil estudos relacionados à adesão e preferências a diferentes métodos de rastreamento são pouco conhecidos. Objetivo: Avaliar a associação de características demográficas, condição socioeconômica e variáveis clínicas na adesão para realização de testes de sangue oculto nas fezes (PSOF) dos tipos Imunoquimico Mecanizado (FIT) e Guaiaco (G-FOBT) em população de médio risco para o desenvolvimento de câncer colorretal. Método: Estudo observacional transversal, com coleta prospectiva de dados. Entre março de 2015 e abril de 2016 1.254 indivíduos assintomáticos, com idade entre 50 e 75 anos, foram consecutivamente selecionados a partir de campanhas hospitalares de rastreamento para neoplasias conduzidas pelo AC Camargo Cancer Center. Todos os participantes foram convidados ao rastreamento do CCR mediante realização dos testes (G-FOBT) e (FIT) e responderam a um questionário com características demográficas, condição socioeconômica e variáveis clínicas. Análise estatística: Para avaliar a independência entre variáveis qualitativas foi aplicado o teste de Qui-quadrado. As médias das variáveis quantitativas foram comparadas através do Teste t. Os resultados das análises univariadas foram utilizados para selecionar variáveis para os modelos de regressão logística múltipla, considerando-se valores de p≤0.20. As associações estão descritas por Odds Ratio (OR) e o intervalo de confiança adotado foi de 95% (95% CI). A significância considerada foi de 0.05. A partir dos resultados encontrados foi proposto um nomograma para a predição da probabilidade de adesão com base nas características dos indivíduos. Resultados: As taxas de adesão foram 55,6% e 48,8%, respectivamente para os testes FIT e G-FOBT (p<0.001). As médias de anos de estudos foram diferentes entre os grupos aderentes e não aderentes nos métodos FIT e G-FOBT (8.4vs 9.0; p = 0.001). Nas análises univariadas, as variáveis idade, tipo de atividade ocupacional, crença religiosa e realização prévia de PSOF influenciaram as taxas de adesão aos dois tipos de testes. Nos modelos multivariados, respectivamente para os exames FIT e G-FOBT as variáveis idade 60-75 anos (OR = 1.39; 95%IC 1.06­1.81) e (OR = 1.49; 95%IC 1.16­1.49), presença de crença religiosa (OR = 1.99; 95%IC 1.27­3.11) e (OR = 1.70; 95% IC 1.11­2.60), PSOF (OR = 2.22; 95% IC 1.61­ 3.05) e (OR = 1.26; 95% IC 1.26­2.20) e trabalho em tempo integral ou parcial (OR = 0.69; 95% IC 0.05­0.96) e (OR= 0.68; 95%IC 0.50­0.91) estiveram associadas de forma independente à adesão aos métodos de rastreamento do CCR. As variáveis, sexo, raça, estado civil, renda, presença de seguro saúde e distância da residência até o hospital não influenciaram na adesão aos exames FIT e G-FOBT. Conclusão: Maior idade, presença de crença religiosa, ausência de atividade de trabalho formal e realização prévia de PSOF estão relacionados à maior adesão aos testes (FIT) e o (G-FOBT), na população estudada.

INTRODUCTION: Colorectal surgeries are complex procedures, associated with higher rates of complications and readmissions than procedures at other surgical sites. Currently, standardized procedures aim the early recovery of patients treated for colorectal surgeries in order to reduce the length of hospital stay. The reduction in hospitalization time, however, despite being considered a positive result, may lead to a risk , since complications generally occur outside the hospital environment, making it difficult to assess and monitor these patients. OBJECTIVE: The aim of the present study was to develop a mobile health app , accessible on smartphones, to remotely monitor the signs and symptoms of patients in the postoperative period of colorectal surgeries, evaluating the outcomes of admission rate in the emergency department and rate of severe complications. (Clavien-Dindo 3 to 5) within a fifteen-day postoperative period. METHODS: The project was developed in two steps, the first being the structuring of the Digital Journey, with the creation of a platform with a decision algorithm for identifying symptoms and directing conducts, and the second the validation of the program in a pilot study. Patients aged between 18 and 80 years old, who were to undergo oncological colorectal surgeries, were included in the study. The study was conducted on the premises of the A.C.Camargo Cancer Center. Monitoring of patients and reporting of signs and symptoms by patients were performed via a remote monitoring platform, using a smartphone or computer. RESULTS: In the pilot study, in each of the three evaluation phases of the data obtained, the decision algorithm and the instrument for data collection were restructured, aiming to achieve greater sensitivity and specificity in the detection of complications by the platform, as well as greater patient satisfaction. The ability to detect complications increased at each analysis and adjustment phase, and after the third and final phase of adjustments, 45 (71.4%) adverse events were reported, of which 12 (19%) were symptoms classified as high grade. In this sample, the digital solution was able to identify 3 (4.8%) real complications with a sensitivity of 75%, specificity of 84%, accuracy of 83%, positive predictive value of 25% and negative predictive value of 98%. We also had, 5(7.9%) errors in filling out detected and 1(1.6%) complications not detected by the platform, due to error in filling out the daily assessment questionnaire. Our rehospitalization rate by indication of the platform, in this sample was 2 (3.2%) and admission to the emergency room, considering referral or not from the platform, was 8 (12.7%). Complete adherence to the monitoring program was 83%, with an NPS score ranging from 69 to 95, the highest score obtained in the last evaluation phase. CONCLUSION: The a mobile health app created was proved to be safe, with high adherence rates and good acceptance by patients, but it still needs to be adjusted with the intention of reducing costs of referral and admission to the emergency department.

Câncer colorretal: associação entre variáveis sociodemográficas e a adesão a programas de rastreamento / Colorectal cancer: association between sociodemographic variables and the adherence to cancer screening

ABSTRACT BACKGROUND Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

RESUMO RACIONAL: O câncer colorretal (CCR) é um problema de saúde mundial cujo controle depende do estabelecimento de políticas públicas e programas de prevenção e rastreamento eficazes. No Brasil existem poucos estudos relacionados à adesão métodos de rastreamento. OBJETIVO: Avaliar a associação de características sócio-demográficas à realização de testes de sangue oculto nas fezes do tipo imunoquimicomecanizado (FIM) em população de médio risco para o desenvolvimento de câncer colorretal. MÉTODOS: Estudo observacional transversal, com coleta prospectiva de dados. Entre março de 2015 e abril de 2016, 1.254 indivíduos assintomáticos, com idade entre 50 e 75 anos, foram consecutivamente selecionados a partir de uma campanha hospitalar de rastreamento para neoplasias. RESULTADOS: As taxas de adesão ao teste FIM foi 55.6% (697/1254). Na análise de regressão logística múltipla os fatores independentes associados à adesão ao rastreamento do CCR foram: Idade entre 60-75 anos (oddsratio (OR)=1.30; intervalo de confiança de 95% (IC): 1.02-1.66; p=0.03), crença religiosa (OR=2.04; 95%IC: 1.34-3.11; p<0.01), realização prévia de exame de sangue oculto nas fezes (OR=2.07; 95%IC: 1.55-2.76; p<0.01) e vínculo empregatício em período integral ou parcial (OR=0.66; 95%IC: 0.49-0.89; p<0.01). CONCLUSÃO: Este estudo enfatiza a importância de considerar aspectos laborais ao implementar programas de rastreamento do câncer colorretal e sugere que campanhas de rastreamento implantadas no ambiente de trabalho e de maneira repetida ao longo dos anos podem ser mais efetivas.

Avaliação de programa de seguimento pós-alta com inteligência artificial para monitorar sinais e sintomas de pacientes em pós-operatório de cirurgias colorretais oncológicas / Evaluation of a post-discharge follow-up program with artificial intelligence to monitor signs and symptoms of patients in the postoperative period of oncological colorectal surgeries

INTRODUÇÃO: Cirurgias colorretais são procedimentos complexos, associados a maiores taxas de complicações e readmissões que procedimentos realizados em outros sítios cirúrgicos. Atualmente, medidas padronizadas visando à recuperação precoce de pacientes submetidos a cirurgias colorretais são adotadas com o objetivo de reduzir o tempo de internação hospitalar. A redução do tempo de internação, entretanto, apesar de ser considerada um desfecho positivo, pode propiciar risco de atraso de diagnóstico e deterioração clínica já que as complicações, geralmente acontecem fora do ambiente hospitalar, dificultando a avaliação e acompanhamento destes pacientes. OBJETIVO: O objetivo do presente estudo foi desenvolver um plano de seguimento pós-alta eletrônico, acessível em smartphones, para monitorar remotamente os sinais e sintomas de pacientes em pós-operatório de cirurgias colorretais, avaliando os desfechos de taxa de admissão no setor de emergência e taxa de complicações graves (Clavien-Dindo 3 a 5), no período de quinze dias de pós-operatório. MATERIAL E MÉTODOS: O projeto foi desenvolvido em duas etapas, sendo a primeira a estruturação da Jornada Digital, com a criação de plataforma com algoritmo para identificação de sintomas e direcionamento de condutas e a segunda a validação do programa em um estudo piloto. Foram incluídos no estudo pacientes a serem submetidos a cirurgias colorretais oncológicas, com idade entre 18 e 80 anos. O estudo foi conduzido nas dependências do A.C.Camargo Cancer Center. O monitoramento dos pacientes e o reporte de sinais e sintomas pelos pacientes foram realizados via plataforma de monitoramento remoto, utilizando-se de smartphone ou computador. RESULTADOS: No estudo piloto, em cada uma das três fases de avaliação dos dados obtidos, algoritmo e instrumento para coleta de dados foram reestruturados, visando atingir maior sensibilidade e especificidade na detecção de complicações pela plataforma, bem como maior satisfação dos pacientes em acompanhamento. A capacidade de detecção de complicações aumentou a cada fase de análise e ajuste, sendo que após a terceira e última fase de ajustes tivemos 45(71,4%) eventos adversos reportados, sendo que destes, 12(19%) foram sintomas classificados como graves. Nessa amostra , a solução digital foi capaz de identificar 3(4,8%) complicações reais com sensibilidade de 75%, especificidade de 84%, acurácia de 83%, valor preditivo positivo de 25% e valor preditivo negativo de 98%. Tivemos ainda , 5(7,9%) erros de preenchimentos detectados e 1(1,6%) complicações não detectadas pela plataforma, por erro de preenchimento do questionário de avaliação diária. A nossa taxa de reinternação por indicação da plataforma, nessa amostra foi de 2(3,2%) e de admissão na emergência, considerando encaminhamento ou não da plataforma foi de 8(12,7%). A adesão completa ao programa de monitoramento foi de 83%, com nota NPS variando de 69 a 95, sendo a maior nota obtida na última fase de avaliação. CONCLUSÃO: A plataforma digital criada mostrou-se segura, com altas taxas de adesão e boa aceitação pelos pacientes, mas ainda precisa ser ajustada com a intenção de reduzir custos de encaminhamento e admissão no setor de emergência.

INTRODUCTION: Colorectal surgeries are complex procedures, associated with higher rates of complications and readmissions than procedures at other surgical sites. Currently, standardized procedures aim the early recovery of patients treated for colorectal surgeries in order to reduce the length of hospital stay. The reduction in hospitalization time, however, despite being considered a positive result, may lead to a risk , since complications generally occur outside the hospital environment, making it difficult to assess and monitor these patients. OBJECTIVE: The aim of the present study was to develop a mobile health app , accessible on smartphones, to remotely monitor the signs and symptoms of patients in the postoperative period of colorectal surgeries, evaluating the outcomes of admission rate in the emergency department and rate of severe complications. (Clavien-Dindo 3 to 5) within a fifteen-day postoperative period. METHODS: The project was developed in two steps, the first being the structuring of the Digital Journey, with the creation of a platform with a decision algorithm for identifying symptoms and directing conducts, and the second the validation of the program in a pilot study. Patients aged between 18 and 80 years old, who were to undergo oncological colorectal surgeries, were included in the study. The study was conducted on the premises of the A.C.Camargo Cancer Center. Monitoring of patients and reporting of signs and symptoms by patients were performed via a remote monitoring platform, using a smartphone or computer. RESULTS: In the pilot study, in each of the three evaluation phases of the data obtained, the decision algorithm and the instrument for data collection were restructured, aiming to achieve greater sensitivity and specificity in the detection of complications by the platform, as well as greater patient satisfaction. The ability to detect complications increased at each analysis and adjustment phase, and after the third and final phase of adjustments, 45 (71.4%) adverse events were reported, of which 12 (19%) were symptoms classified as high grade. In this sample, the digital solution was able to identify 3 (4.8%) real complications with a sensitivity of 75%, specificity of 84%, accuracy of 83%, positive predictive value of 25% and negative predictive value of 98%. We also had, 5(7.9%) errors in filling out detected and 1(1.6%) complications not detected by the platform, due to error in filling out the daily assessment questionnaire. Our rehospitalization rate by indication of the platform, in this sample was 2 (3.2%) and admission to the emergency room, considering referral or not from the platform, was 8 (12.7%). Complete adherence to the monitoring program was 83%, with an NPS score ranging from 69 to 95, the highest score obtained in the last evaluation phase. CONCLUSION: The a mobile health app created was proved to be safe, with high adherence rates and good acceptance by patients, but it still needs to be adjusted with the intention of reducing costs of referral and admission to the emergency department

A higher platelet-to-lymphocyte ratio is prevalent in the presence of circulating tumor microemboli and is a potential prognostic factor for non-metastatic colon cancer.

Colorectal cancer is a common and often deadly cancer. Circulating tumor cells (CTCs) have been implicated as a potentially valuable prognosis factor. The detection of circulating tumor microemboli (CTM) and of simple blood component parameters that reflect inflammatory status, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), may provide information about tumor progression. The aim of this study was to explore the importance of CTCs, CTM, PLR, and NLR prospectively in non-metastatic colon cancer progression. CTCs were enriched using ISETⓇ (Isolation by SizE of Tumor cells) and identified by immunocytochemical exclusion of leukocytes. We evaluated CTCs and blood cell parameters in a cohort of 69 stage I-III colon cancer patients (52.2% men; median age, 61 years; age range, 19-87 years) at a baseline timepoint prior to resection surgery. The median of CTC levels at baseline was 20 cells/8 mL (0-94) and higher levels were associated with CTM presence (p = 0.02). CTM were found in 18 (26.1%) patients. Of 18 stage I patients, 33.3% had CTM and of 51 stages II or III patients, 13.7% had CTM (p = 0.08). Patients with a high PLR (>124) were mostly (75.6%) diagnosed with high-risk stages II/III cancer (stages I/low-risk II, 24.4%; p = 0.014). All 8 patients that had disease recurrence during follow-up had a high PLR (p = 0.02 vs. low PLR). NLR was not significantly associated with disease stage or recurrence. The present results indicate that CTCs and PLR analyses may be clinically useful for colon cancer management and risk stratification.

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer.

The treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs. External validation was carried out with The Cancer Genome Atlas-Rectal Adenocarcinoma (TCGA-READ 99 cases). A classifier based on three-CpGs DM (linked to OBSL1, GPR1, and INSIG1 genes) was able to discriminate pCR from incomplete responders with high sensitivity and specificity. The methylation levels of the selected CpGs confirmed the predictive value of our classifier in 77 LARCs evaluated by bisulfite pyrosequencing. Evaluation of external datasets (TCGA-READ, GSE81006, GSE75546, and GSE39958) reproduced our results. As the three CpGs were mapped near to regulatory elements, we performed an integrative analysis in regions associated with predicted cis-regulatory elements. A positive and inverse correlation between DNA methylation and gene expression was found in two CpGs. We propose a novel predictive tool based on three CpGs potentially useful for pretreatment screening of LARC patients and guide the selection of treatment modality.

Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants.

Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir-Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.

Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response.

Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.

Comparison between an immunochemical fecal occult blood test and a Guaiac based fecal occult blood test in detection of adenomas and colorectal cancer

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Brazil does not have an official well established program for screening colorectal cancer. The aim of this study was to compare Guaiac Based Fecal Occult Blood Test (G-FOBT) to a kind of an Immunochemical Fecal Occult Blood Test (I-FOBT), in search of cancer or advanced adenoma. Methods: Prospective and cross-sectional study. Asymptomatic and average-risk individuals (n = 1500) aged from 50 to 75 years old were invited to participate in the study. The primary endpoint was positivity rate and the secondary endpoints were adherence rate and significant endoscopic findings. All participants received both tests with follow-up colonoscopy if either test was positive. Results: Adherence rate of G- FOBT was 756/1500 (50.4%) while for I- FOBT it was 960/1500(64%). The positivity ratio in the I- FOBT was 94/960 (9.8%) and in the G-FOBT was 20/771 (2.6%). The Positive Predict Value (PPV) for the I- FOBT counted 16/77 (21.0%) while for the G- FOBT it was 6/18 (33.0%), considering significant lesions. Regarding the colorectal cancer findings, the detection in the colonoscopy guided from the positivity of fecal occult blood tests was 5/77 (6.5%) in I- FOBT and 2/18 (11.1%) on the G- FOBT. Conclusions: The positivity, the adherence rate and the capacity to detect significant lesions were higher in I-FOBT. Considering the findings of the study we could conclude that I-FOBT was superior to G- FOBT. Trial registration: This study was reviewed and approved by the Institutional Review Board of A.C.Camargo Cancer Center, São Paulo, Brazil, number: 1877/14