Abdominal adiposity as a prognosis biomarker of clinical outcome in metastatic colorectal cancer.

OBJECTIVES: Adipose tissue distribution and radiodensity are associated with prognosis in many types of cancer. However, the roles of adipose tissue distribution and radiodensity in patients with metastatic colorectal cancer (mCRC) remain unclear. The aim of this study was to assess the prognostic effect of adiposity and adipose tissue radiodensities in patients with mCRC. METHODS: Patients with mCRC who received first-line palliative chemotherapy and had a computed tomography (CT) scan at the third lumbar vertebra (L3) level, admitted between January 2010 and December 2018, were sequentially enrolled. Body composition was assessed using CT-derived measurements. Univariate and multivariate logistic regression analyses and Kaplan-Meier curves were used to determine prognostic values. RESULTS: The study included 237 patients. Cox analyses demonstrated that high subcutaneous adipose tissue (SAT) index was associated with a lower risk for death (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.88; Ptrend < 0.025). There was no significant association between visceral adipose tissue (VAT) index tertiles and overall survival. However, high VAT and SAT radiodensities were significantly associated with increased mortality (HR, 1.80; 95% CI, 1.12-2.89; Ptrend < 0.030 and HR, 1.85; 95% CI, 1.19-2.86; Ptrend < 0.021, respectively). CONCLUSIONS: A higher SAT index in patients with mCRC was associated with a favorable overall survival outcome, whereas higher SAT and VAT radiodensities were associated with an increased risk for death, supporting that early nutritional intervention may improve mCRC prognosis.

STUDY OF ANORECTAL PHYSIOLOGY PRE AND POS NEOADJUVANT THERAPY FOR RECTAL CANCER BY ANORECTAL MANOMETRY AND JORGE-WEXNER SCORE.

BACKGROUND: The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated. OBJECTIVE: The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer. METHODS: Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used. RESULTS: Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05). CONCLUSION: NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.

Estudo da fisiologia anorretal pré e pós terapia neoadjuvante para câncer de reto por manometria anorretal e escore de Jorge-Wexner / Study of anorectal physiology pre and pos neoadjuvant therapy for rectal cancer by anorectal manometry and jorge-wexner score

ABSTRACT Background: The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated. Objective: The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer. Methods: Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used. Results: Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05). Conclusion: NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.

RESUMO Contexto: O tratamento do câncer retal distal pode ser acompanhado por distúrbios evacuatórios de etiologia multifatorial. A quimiorradioterapia neoadjuvante faz parte do tratamento padrão para pacientes com câncer retal extraperitoneal localmente avançado. A avaliação da função anorretal após neoadjuvância de longa duração em pacientes com câncer de reto extraperitoneal tem sido pouco estudada. Objetivo: O objetivo do presente estudo foi avaliar os efeitos da neoadjuvância na função anorretal e na incontinência em pacientes com câncer retal extraperitoneal. Métodos: Pacientes com adenocarcinoma de reto candidatos à terapia neoadjuvante foram submetidos a avaliação funcional por manometria anorretal e avaliação do grau de incontinência fecal pelo escore de Jorge-Wexner, pré e oito semanas após a neoadjuvância. Os parâmetros manométricos avaliados foram pressão anal média de repouso, pressão anal de contração voluntária máxima e pressão anal média de contração voluntária. Todos os pacientes foram submetidos ao mesmo protocolo de neoadjuvância baseado na aplicação de fluoropirimidina (5-FU) na dosagem de 350 mg/m2 associada ao ácido fólico na dosagem de 20 mg/m2, por via intravenosa, na primeira e última semana de tratamento, concomitantemente à radioterapia conformacional com dose total de 50,4Gy, dividida em 28 frações diárias de 1,8Gy. Para análise estatística das variáveis quantitativas com distribuição normal, foram calculados a média, desvio padrão, mediana e intervalo interquartil. Para comparação de duas amostras relacionadas (antes e oito semanas após a neoadjuvância, foi utilizado o teste não paramétrico de Wilcoxon. Resultados: Quarenta e oito pacientes com câncer retal foram incluídos no estudo, com média de idade de 62,8 (39-81) anos, sendo 36 (75%) do sexo masculino. O uso de neoadjuvância foi associado à diminuição dos valores de média de pressão de repouso (55,0 mmHg vs 39,1 mmHg, P<0,05) e média de pressão de contração voluntária (161,9 mmHg vs 141,9 mmHg, P<0,05) sem alterar os valores de pressão de contração voluntária máxima ((185,5 mmHg vs 173 mmHg, P=0.05)). Não houve piora do escore de incontinência oito semanas após o uso da quimiorradioterapia neoadjuvante (3,0 vs 3,3; P>0,05). Conclusão: A neoadjuvância associou-se à redução dos valores de média de pressão de repouso e média dos valores contração voluntária. Não houve alteração nos valores de contração voluntária máxima, bem como no grau de continência fecal pelo escore de Jorge-Wexner.

Association of Albumin-Corrected Serum Calcium Levels with Colorectal Cancer Survival Outcomes.

In epidemiological studies, higher calcium intake has been associated with decreased colorectal cancer (CRC) incidence. However, whether circulating calcium concentrations are associated with CRC prognosis is largely unknown. In this retrospective cohort analysis, we identified 498 patients diagnosed with stage I-IV CRC between the years of 2000 and 2018 in whom calcium and albumin level measurements within 3 months of diagnosis had been taken. We used the Kaplan-Meier method for survival analysis. We used multivariate Cox proportional hazards regression to identify associations between corrected calcium levels and CRC survival outcomes. Corrected calcium levels in the highest tertile were associated with significantly lower progression-free survival rates (hazard ratio (HR) 1.85; 95% confidence interval (CI) 1.28-2.69; p = 0.001) and overall survival (HR 1.86; 95% CI 1.26-2.74, p = 0.002) in patients with stage IV or recurrent CRC, and significantly lower disease-free survival rates (HR 1.44; 95% confidence interval (CI) 1.02-2.03; p = 0.040) and overall survival rates (HR 1.72; 95% CI 1.18-2.50; p = 0.004) in patients with stage I-III disease. In conclusion, higher corrected calcium levels after the diagnosis of CRC were significantly associated with decreased survival rates. Prospective trials are necessary to confirm this association.

Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study.

Body composition performed by computed tomography (CT) impacts on cancer patients' prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07-6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31-25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52-2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33-1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Repurposing metformin for the treatment of gastrointestinal cancer.

Diabetes mellitus type 2 and cancer share many risk factors. The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue. Particularly, modulation of inflammation, metabolism, and cell cycle arrest are potential therapeutic cancer targets utilized by metformin to boost the anti-cancer effects of chemotherapy. Studies in vitro and in vivo models have demonstrated the potential of metformin as a chemo- and radiosensitizer, besides its chemopreventive and direct therapeutic activity in digestive system (DS) tumors. Hence, these aspects have been considered in many cancer clinical trials. Case-control and cohort studies and associated meta-analyses have evaluated DS cancer risk and metformin usage, especially in colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Most clinical studies have demonstrated the protective role of metformin in the risk for DS cancers and survival rates. On the other hand, the ability of metformin to enhance the actions of chemotherapy for gastric and biliary cancers is yet to be investigated. This article reviews the current findings on the anti-cancer mechanisms of metformin and its apparatus from pre-clinical and ongoing studies in DS malignancies.

Sarcopenia as an independent prognostic factor in patients with metastatic colorectal cancer: A retrospective evaluation.

BACKGROUND & AIMS: Sarcopenia has been associated with poor prognosis in a number of malignancies. However, whether sarcopenia is associated with colorectal cancer (CRC) prognosis in a metastatic setting remains unclear. The aim of the study presented was to evaluate the impact of sarcopenia on progression-free survival (PFS) and overall survival (OS) in patients with metastatic CRC. METHODS: We retrospectively studied 72 patients with stage IV CRC treated at the University of Campinas between 2009 and 2015. Computed tomography images were analyzed to assess body composition. The Kaplan-Meier and multivariate Cox proportional hazards regression were used for survival analysis and to evaluate the influence of sarcopenia on PFS and OS. RESULTS: Median PFS for sarcopenic patients (n = 32) was 7.2 months, which was significantly different from non-sarcopenic patients (n = 40), which was 15.2 months (hazard ratio [HR]: 1.78; 95% confidence interval [CI], 1.00-3.14; P = 0.048). Sarcopenia was also a significant predictor of OS. Median OS for sarcopenic patients was 12.5 months versus 36.7 months for non-sarcopenic patients (HR: 1.86; 95% CI, 1.02-3.38; P = 0.043), after adjustment for number of metastatic lesions, metastasectomy, and performance status. CONCLUSIONS: Sarcopenia was associated with worse CRC PFS and OS. These findings require prospective trials to validate this association.

"Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in Brazilian Institutions".

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.

The impact of simulated medical consultations on the empathy levels of students at one medical school.

PURPOSE: To examine the impact of simulated medical consultations using standardized patients (SPs) on the empathy levels of fourth- and sixth-year students at the Unicamp medical school in Brazil. METHOD: Throughout 2011 and 2012, the authors conducted this study with two classes of fourth-year (n = 124) and two classes of sixth-year (n = 123) medical students. Students completed the medical student version of the Jefferson Scale of Physician Empathy before and after simulated medical consultations with SPs, followed by an in-depth debriefing dealing with the feelings of the patient about the disease, such as fear, guilt, anger, and abandonment; the feelings of the doctor towards the patient; and other topics as they arose. RESULTS: The simulation activity increased the empathy scores of the fourth-year students (from 115.8 to 121.1, P < .001, effect size = 0.61) and of the sixth-year students (from 117.1 to 123.5, P < .001, effect size = 0.64). CONCLUSIONS: Although the study results were obtained via self-report-a limitation-they suggest that the effective simulation of medical consultations with SPs may improve medical students' empathy levels. One unexpected result was that this activity, during the debriefing, became a forum for debating topics such as the doctor-patient relationship, the hidden curriculum, negative role models, and emotionally significant experiences of students in medical school. This kind of activity in itself may influence young doctors to become more empathetic and compassionate with their patients and foster a more meaningful way of practicing medicine.