No abstract

Thymidylate synthase (TYMS) is an important enzyme for 5-fluorouracil (5-FU) metabolism in metastatic colorectal cancer (mCRC) patients. The search for this enzyme in circulating tumor cells (CTCs) can be a powerful tool to follow-up cancer patients. mCRC patients were enrolled before the beginning of 5-FU-based chemotherapy. The blood was filtered on Isolation by Size of Epithelial Tumor Cells (ISET), and the analysis of TYMS expression in CTCs was made by immunocytochemistry. Additionally, we verified TYMS staining in primary tumors and metastases from the same patients. There were included 54 mCRC patients and 47 of them received 5-FU-based chemotherapy. The median CTCs number was 2 per mL. We were not able to analyze immunocytochemistry in 13 samples (9 patients with absence of CTCs and 4 samples due to technical reasons). Therefore, TYMS expression on CTCs was analyzed in 34 samples and was found positive in 9 (26.5%). Six of these patients had tumor progression after treatment with 5-FU. We found an association between CTC TYMS staining and disease progression (DP), although without statistical significance (P 5 0.07). TYMS staining in primary tumors and metastases tissues did not have any correlation with disease progression (P 5 0.67 and P 5 0.42 respectively). Patients who had CTC count above the median (2 CTCs/mL) showed more TYMS expression (P 5 0.02) correlating with worse prognosis. Our results searching for TYMS staining in CTCs, primary tumors and metastases suggest that the analysis of TYMS can be useful tool as a 5-FU resistance predictor biomarker if analyzed in CTCs from mCRC patients.Colorectal cancer (CRC) was the third most commonly diagnosed cancer in both men and women in the last 3 years in the United States. 1-3 For metastatic patients, the strategy for treatment is mostly 5-Fluorouracil-based chemotherapy, which shows high efficacy in a subset of patients. However, even those patients can experience disease progression due to 5-FU resistance. 4 TYMS is a constitutive enzyme that catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) by CH 2 H 4 folate to produce deoxythymidine monophosphate (dTMP) and H 2 folate leading to DNA replication and repair. 5 An upgrade of resistance to the treatment has been often correlated to increased levels of TYMS in cancer cells. 6 Others have demonstrated that intratumoral TYMS mRNA expression levels (in paraffin-embedded tissues) are independent predictive markers of survival for 5-FU and oxaliplatin combination therapy. 7 Although the presence of high levels of TYMS presents poor outcome, it becomes hard to evaluate since there are heterogeneity among the population, methods and techniques as well. Furthermore, the best way to detect the presence of TYMS and its real value remains unclear 8 as there is not a consensus about the role of TYMS expression in mCRC published in the last 20 years. Thence, analyzing

Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p < 0.01) during the first year of residency, and the prevalence of burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.

Circulating tumor cells are important markers of tumor progression and can reflect tumor behavior in metastatic colorectal cancer (mCRC). Identification of proteins that confer resistance to treatment is an important step to predict response and better selection of treatment for patients. Multidrug resistance-associated protein 1 (MRP1) and Multidrug resistance-associated protein 4 (MRP4) play a role in irinotecan-resistance, and Excision Repair Cross-Complementation group 1 (ERCC1) expression can confer resistance to platinum compounds. Here, we included 34 patients with mCRC and most of them received FOLFIRI or FOLFOX chemotherapy (91.1%). CTCs were isolated by ISET V R Technology and identified in 30 patients (88.2%), with a median of 2.0 CTCs/mL (0-31.0). We analyzed the immunocytochemical expression of MRP1, MRP4 and ERCC1 only in patients who had previously detectable CTCs, accordingly to treatment received (n 5 19, 15 and 13 patients, respectively). Among patients treated with irinotecan-based chemotherapy, 4 out of 19 cases with MRP1 positive CTCs showed a worse progression free survival (PFS) in comparison to those with MRP1 negative CTCs (2.1 months vs. 9.1 months; p 5 0.003). None of the other proteins studied in CTCs had significant association with PFS. We analyzed also histological sections of primary tumors and metastases by immunohistochemistry, and found no association with clinicopathological characteristics or with PFS. Our results show MRP1 as a potential biomarker of resistance to treatment with irinotecan when found in CTCs from mCRC patients. This is a small proof-of-principle study and these early findings need to be validated in a larger cohort of patients.Colorectal cancer (CRC) is the third most common tumor in men and the second in women worldwide.

BackgroundColorectal cancer (CRC) is the third most prevalent cancer worldwide. New prognostic markers are needed to identify patients with poorer prognosis, and circulating tumor cells (CTCs) seem to be promising to accomplish this.Patients and methodsA prospective study was conducted by blood collection from patients with metastatic CRC (mCRC), three times, every 2 months in conjunction with image examinations for evaluation of therapeutic response. CTC isolation and counting were performed by Isolation by Size of Epithelial Tumor Cells (ISET).ResultsA total of 54 patients with mCRC with a mean age of 57.3 years (31–82 years) were included. Among all patients, 60% (n=32) were carriers of wild-type KRAS (WT KRAS) tumors and 90% of them (n=29) were exposed to monoclonal antibodies along with systemic treatment. Evaluating CTC kinetics, when we compared the baseline (pretreatment) CTC level (CTC1) with the level at first follow-up (CTC2), we observed that CTC1-positive patients (CTCs above the median), who became negative (CTCs below the median) had a favorable evolution (n=14), with a median progression-free survival (PFS) of 14.7 months. This was higher than that for patients with an unfavorable evolution (CTC1− that became CTC2+; n=13, 6.9 months; P=0.06). Patients with WT KRAS with favorable kinetics had higher PFS (14.7 months) in comparison to those with WT KRAS with unfavorable kinetics (9.4 months; P=0.02). Moreover, patients whose imaging studies showed radiological progression had an increased quantification of CTCs at CTC2 compared to those without progression (P=0.04).ConclusionThis study made possible the presentation of ISET as a feasible tool for evaluating CTC kinetics in patients with mCRC, which can be promising in their clinical evaluation.

Patients with gastric cancer presenting with signet-ring histology, vascular invasion, or visceral metastasis appear to be at higher risk for the development of peritoneal carcinomatosis.

At the 2018 Gastrointestinal Cancer Symposium, sponsored by the American Society of Clinical Oncology, significant advances in the management of hepatocellular carcinoma (HCC) were announced. In intermediate-stage disease (Barcelona Clinic Liver Cancer stage B), interest in combining transarterial chemoembolization and sorafenib has been reignited as a consequence of the TACTICS trial. In advanced-stage disease (BCLC C), external-beam radiotherapy combined with transarterial chemoembolization proved to be superior to sorafenib in patients with portal vein thrombosis according to the START trial. Also, in patients with advanced-stage HCC, the CELESTIAL trial demonstrated survival benefits for patients undergoing treatment with cabozantinib in the second-line setting. Lastly, recent data on the activity of pembrolizumab in patients with HCC highlight the role of immunotherapy in the management of this disease in the years to come.

Oncologists and intensivists share different views regarding life support measures in critically ill patients with cancer. Oncologists tend to focus on the cancer characteristics, whereas intensivists focus on multiple organ failure when weighing in on the same decisions. Regular meetings between oncologists and intensivists may reduce possible conflicts regarding the critical care of patients with cancer.