Application of Comprehensive Genomic Profiling-Based Next-Generation Sequencing Assay to Improve Cancer Care in a Developing Country.

PURPOSE: Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. METHODS: In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians' request in the clinical care for therapy decisions. Kaplan-Meier survival curves were estimated to characterize the time-to-event variables. RESULTS: Patients median age was 61 years (range: 14-87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment (P = .7). CONCLUSION: CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.

Successful long-term management of metastatic clear cell renal cell carcinoma with nivolumab: a case report and literature review.

In Colombia, renal cancer is a rare condition, with clear cell renal cell carcinoma (ccRCC) being the most prevalent neoplasm. In recent years, immune checkpoint inhibitors (ICI) have been proposed for the management of metastatic disease, as they have shown improved rates of response and long-term survival. Furthermore, they exhibit a favourable tolerance profile, and adverse events causing significant morbidity are infrequent. We report the case of a 61-year-old male patient initially diagnosed with early-stage ccRCC who underwent right nephrectomy in 2009. Six years later, disease recurrence with metastatic compromise was documented, which led to the resection of the L1 vertebral body followed by radiotherapy and maintenance treatment with sunitinib. Due to disease progression, treatment with sunitinib was discontinued. Subsequently, everolimus was initiated as second-line immunotherapy, which was later discontinued due to the appearance of new metastatic lesions. In 2017, the patient was referred to our institution, where a third-line pharmacological treatment with nivolumab was initiated. In 2022, complete remission by positron emission tomography-computed tomography (PET-CT) was evidenced, which has been sustained to date. This case demonstrates the efficacy and safety of ICI in patients with metastatic ccRCC. The case presented is relevant in that it describes the achievement of complete remission in a patient who did not respond to the first two lines of immunotherapy. Given the limited literature regarding the discontinuation of therapy after achieving sustained remission, further research is warranted to explore this topic.

Impact of COVID-19 Infection on Patients with Cancer: Experience in a Latin American Country: The ACHOCC-19 Study.

INTRODUCTION: The ACHOCC-19 study was performed to characterize COVID-19 infection in a Colombian oncological population. METHODOLOGY: Analytical cohort study of patients with cancer and COVID-19 infection in Colombia. From April 1 to October 31, 2020. Demographic and clinical variables related to cancer and COVID-19 infection were collected. The primary outcome was 30-day mortality from all causes. The association between the outcome and the prognostic variables was analyzed using logistic regression models and survival analysis with Cox regression. RESULTS: The study included 742 patients; 72% were >51 years. The most prevalent neoplasms were breast (132, 17.77%), colorectal (92, 12.34%), and prostate (81, 10.9%). Two hundred twenty (29.6%) patients were asymptomatic and 96 (26.3%) died. In the bivariate descriptive analysis, higher mortality occurred in patients who were >70 years, patients with lung cancer, ≥2 comorbidities, former smokers, receiving antibiotics, corticosteroids, and anticoagulants, residents of rural areas, low socioeconomic status, and increased acute-phase reactants. In the logistic regression analysis, higher mortality was associated with Eastern Cooperative Oncology Group performance status (ECOG PS) 3 (odds ratio [OR] 28.67; 95% confidence interval [CI], 8.2-99.6); ECOG PS 4 (OR 20.89; 95% CI, 3.36-129.7); two complications from COVID-19 (OR 5.3; 95% CI, 1.50-18.1); and cancer in progression (OR 2.08; 95% CI, 1.01-4.27). In the Cox regression analysis, the statistically significant hazard ratios (HR) were metastatic disease (HR 1.58; 95% CI, 1.16-2.16), cancer in progression (HR 1.08; 95% CI, 1.24-2.61) cancer in partial response (HR 0.31; 95% CI, 0.11-0.88), use of steroids (HR 1.44; 95% CI, 1.01-2.06), and use of antibiotics (HR 2.11; 95% CI, 1.47-2.95). CONCLUSION: In our study, patients with cancer have higher mortality due to COVID-19 infection if they have active cancer, metastatic or progressive cancer, ECOG PS >2, and low socioeconomic status. IMPLICATIONS FOR PRACTICE: This study's findings raise the need to carefully evaluate patients with metastatic cancer, in progression, and with impaired Eastern Cooperative Oncology Group status to define the relevance of cancer treatment during the pandemic, consider the risk/benefit of the interventions, and establish clear and complete communication with the patients and their families about the risk of complications. There is also the importance of offering additional support to patients with low income and residence in rural areas so that they can have more support during cancer treatment.

Diabetes posterior a tratamiento no quirúrgico de un insulinoma maligno: reporte de caso y revisión literatura / Diabetes after non-surgical treatment of a malignant insulinoma: Case report and literature review

Resumen Los tumores neuroendocrinos pancreáticos (TNEsP) son un grupo poco frecuente de neoplasias, pueden ser funcionales y causan síndromes clínicos diversos, o no funcionales, con síntomas secundarios a invasión a estructuras cercanas o enfermedad metastásica (1). Se presenta el caso de una paciente de 55 años con insulinoma maligno con compromiso metastásico extenso, no candidata a intervención quirúrgica, hipoglucemia de difícil manejo sin respuesta a tratamiento con diazóxido y prednisolona, y que requirió manejo con quimioterapia y embolización de metástasis hepáticas, con posterior mejoría clínica, estabilidad de la enfermedad por imágenes diagnósticas y retiro de medicamentos para manejo de hipoglucemia. En seguimiento presenta síntomas de hiperglucemia con HbA1c en 12%, con lo cual se diagnosticó diabetes mellitus de novo y se inició manejo con insulina.

Abstract Pancreatic neuroendocrine tumors (TNEP) are a rare group of neoplasms, which can secrete peptide hormones causing various clinical syndromes, or be non-secretory, with symptoms secondary to invasion of neighboring or distant structures (1). The case of a 55-year-old patient with malignant insulinoma with extensive metastatic involvement, not operable, with persistent hypoglycemia refractory to treatment with diazoxide and prednisolone, who received management with chemotherapy and embolization of liver metastases, achieving the withdrawal of medications for the management of hypoglycemia and a tumor response of stable disease in the comparison of images during the 12-month follow-up. During the 15th cycle of chemotherapy, he presented symptoms of hyperglycemia with HbA1c in 12%, with which diabetes de novo mellitus was diagnosed and insulin management was initiated.

Valorization of papaya (Carica papaya L.) agroindustrial waste through the recovery of phenolic antioxidants by supercritical fluid extraction.

In this work, supercritical fluid extraction (SFE) for the recovery of phenolic antioxidants from papaya agroindustrial waste (seeds) was explored, making use of neat supercritical CO2 and CO2 added with ethanol (CO2-EtOH). A full factorial design played on in order to evaluate the effect of CO2 extraction parameters (temperature between 40 and 60 °C, and pressure between 10 and 30 MPa) on yield and total phenols content (TPC), then ethanol was applied as a co-solvent and its effect on the recovery of phenolics was analyzed. The SFE was compared to the conventional extraction using ethanol. The antioxidant activity of all extracts was evaluated, and the phenolic composition in selected extracts was assessed by HPLC-ESI-MS. The highest extraction yields (21.02-26.46%) and TPC (15.34-34.23 mgGAE/g) were found in extracts obtained with CO2-EtOH and ethanol. Good and selective phenolic recovery was obtained by using CO2-EtOH, (44.81% of TPC recovered). The CO2-EtOH extracts showed high radical scavenging activity and higher antioxidant effect against lipid oxidation. Some phenolic acids and flavonoids were observed in the extracts with better antioxidants properties. The results showed that SFE is a suitable green technology for the phenolic recovery from papaya agroindustrial waste, and also an alternative for its valorization.

Bioactive Phenolic Compounds from the Agroindustrial Waste of Colombian Mango Cultivars 'Sugar Mango' and 'Tommy Atkins'-An Alternative for Their Use and Valorization.

The aim of this study was to explore the potential of the agroindustrial waste from two Colombian mango cultivars as sources of bioactive phenolic compounds. Phenolic extracts from mango waste (peels, seed coats, and seed kernels) of 'sugar mango' and 'Tommy Atkins' cultivars were obtained. The bioactive properties of the phenolic extracts were accessed by measuring their free radical scavenging activity and antioxidant effects against lipid oxidation in food products; moreover, their antiproliferative effects against some cell lines of human cancer were explored. It is observed that the agroindustrial waste studied provides promising sources of bioactive phenolics. 'Sugar mango' waste provided extracts with the highest antioxidant effect in food products and antiproliferative activity; these extracts reduced lipid oxidation and cell growth by more than 57% and 75%, respectively. The seed kernel from 'sugar mango' supplied the extract with the best bioactive qualities; in addition, some recognized bioactive phenolics (such as mangiferin and several galloyl glucosides) were observed in this extract and related with its properties. The results obtained suggest that 'sugar mango' waste may be considered a source of bioactive phenolics, with promising uses in food and pharmaceutical products. Thus, a suitable alternative for the use and valorization of agroindustrial waste from Colombian mango cultivars is presented.

Evaluación del efecto protector contra la oxidación lipídica de fracciones obtenidas a partir del epicarpio de tomate de árbol (Solanum betaceum Sendtn) / Evaluation of protective effect against lipid oxidation of fractions obtained from tree tomato (Solanum betaceum Sendtn) epicarp / Avaliação do efeito protetor contra oxidação lipídica de frações obtidas a partir da casca de tomate da árvore (Solanum betaceum Sendtn)

Resumen Se obtuvieron fracciones a partir del epicarpio de tomate de árbol (Solanum betaceum Sendtn) y se evaluó su efecto protector contra la oxidación lipídica en carne de res cocida (CRC). Un extracto obtenido a través de extracción supercrítica fue fraccionado empleando, a su vez, extracción en fase sólida; dichas fracciones fueron adicionadas a CRC (concentración 200 mg/kg). El efecto protector fue determinado a través de la comparación de algunos productos de oxidación y el antioxidante sintético terbutilhidroxiquinona (TBHQ, concentración 200 mg/kg). Cuatro fracciones fueron obtenidas, la fracción de mayor polaridad mostró una alta eficiencia para inhibir la oxidación lipídica en CRC, reduciendo la formación de hidroperóxidosHPL y TBARS en 100 y 98,5%, respectivamente; esta mostró una eficiencia superior a la observada para el TBHQ. Esta fracción más activa fue sometida a análisis HPLC-DAD y se identificaron algunos compuestos fenólicos: tres catequinas (epigalocatequina, epicatequina y galato de epigalocatequina) y un ácido fenólico (rosmarínico). Los resultados obtenidos permitieron evidenciar que el epicarpio de tomate de árbol es fuente de antioxidantes con efecto protector sobre CRC, alternativa de aprovechamiento y valorización para dicho residuo agroindustrial.

Abstract Fractions from tree tomato (Solanum betaceum Sendtn) epicarp were obtained and their effect against lipid oxidation in cooked beef meat (CBM) was evaluated. An extract obtained by supercritical fluids extraction was fractionated using solid phase extraction and these fractions were added to CBM (at 300 mg/kg). The protector effect against lipid oxidation was determined by measuring some lipid oxidation products and comparison against the synthetic antioxidant tert-butylhydroquinone (TBHQ at 300 mg/ kg). Four fractions were obtained, the most polar fraction showed high efficiency to reduce the lipid oxidation on CBM, this fraction reduced the LHP and TBARS formation at 100.0 and 98.5%, respectively. This fraction showed an ability to retard lipid oxidation in CRC higher than TBHQ. The fraction with the highest protector effect was analyzed for its phenolic composition by High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD). Three catechin (epigallocatechin, epicatechin and epigallocatechin gallate) and a phenolic acid (rosmarinic acid) were identified. The results revealed that the tree tomato epicarp is a source of antioxidants with protective effect on CBM, an alternative for the use and valorization of this agroindustrial waste.

Resumo Frações da casca de tomate de árvore (Solanum betaceum Sendtn) foram obtidas e seu efeito para retardar a oxidação dos lipídios em carne bovina cozida (CBC) foi avaliado. Um extrato obtido através da extração supercrítica foi fracionado utilizando extração em fase sólida e as frações obtidas foram adicionadas á CBC (concentração 300 mg/kg). O efeito protetor contra a oxidação dos lipídios foi determinado medindo alguns produtos de oxidação e comparando com a terbutil-hidroquinona (TBHQ, concentração 300 mg/kg). Quatro frações foram obtidas, destas, a fração de maior polaridade mostrou a maior eficiência para inibir a oxidação dos lipídios da CBC, reduzindo a formação de HPL e TBARS em 100 e 98,5%, respectivamente; mostrou uma eficiência maior da observada para TBHQ. Esta foi submetida a análise por a cromatografia líquida de alta eficiência com detector de díodos (HPLC-DAD) e foram identificados alguns compostos fenólicos: três catequinas (epigalocatequina, galato de epicatequina e galato de epigalocatequina) e um ácido fenólico (rosmarínico). Os resultados permitiram evidênciar que a casca do tomate de árvore é uma fonte de compostos antioxidantes comefeito protetor sobre a CBC, esta é uma alternativa de utilização e aproveitamento deesse resíduo agroindustrial.

Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study.

INTRODUCTION: There is no clear relationship between type 2 diabetes mellitus and lung function decline; it is also unclear whether the type of treatment can modify spirometric variables and levels of inflammatory biomarkers.  OBJECTIVES: To compare pulmonary function in patients with type 2 diabetes treated with an insulin-sensitizing agent (metformin) and in those treated with secretagogues, as well as combined with insulin, and to evaluate differences in inflammatory biomarkers between treatment groups.  MATERIAL AND METHODS: We conducted a cross-sectional analytic study in 196 diabetic patients with type 2 diabetic mellitus. Spirometric variables and levels of inflammatory biomarkers (ferritin, fibrinogen, C-reactive protein, interleukin 6, tumor necrosis factor-alpha), were obtained. Residual values (observed minus expected) for forced vital capacity and for forced expiratory volume were calculated and compared between treatment types. Differences in median levels of biomarkers were also compared.  RESULTS: After adjustment by known determinants of lung function, and by the control and duration of type 2 diabetes, patients treated with the insulin-sensitizing agent had statistically significant lower differences against expected values for forced vital capacity compared with secretagogues (-212.1 ml vs 270.2 ml, p=0.039), as well as for forced expiratory volume, but without statistical significance (-133.2 mL vs -174.8 mL, p>0.05). In the group of patients treated with the insulin-sensitizing agent, ferritin and tumor necrosis factor-alpha levels were lower (p<0.01).  CONCLUSION: This study supports the hypothesis that insulin-sensitizing agents appear to be associated with less deterioration of lung function and less systemic inflammation in type 2 diabetes. The present study serves to formulate new hypothesis and research projects.

Tratamiento farmacológico y deterioro de la función pulmonar en pacientes con diabetes de tipo 2: un estudio de corte transversal / Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study

Introducción. La relación de la diabetes mellitus de tipo 2 con el deterioro de la función pulmonar no es clara, como tampoco si el tipo de tratamiento modifica los parámetros espirométricos e inflamatorios. Objetivo. Comparar la función pulmonar de pacientes con diabetes mellitus de tipo 2 tratados con un agente de sensibilización a la insulina (metformina) y de los tratados con secretagogos, así como de estos combinados con insulinas, y evaluar las diferencias en los biomarcadores de inflamación de los grupos. Materiales y métodos. Se hizo un estudio analítico de corte transversal en 196 pacientes con diabetes mellitus de tipo 2. Se midieron las variables espirométricas y la concentración sanguínea de biomarcadores de inflamación (ferritina, fibrinógeno, proteína C reactiva, interleucina 6 y factor de necrosis tumoral alfa). Se analizaron los valores residuales (valores observados menos valores predichos) para la capacidad vital forzada y el volumen espiratorio forzado en los diferentes tipos de tratamiento. También, se compararon las diferencias en las medianas de las concentraciones de los biomarcadores, según los tipos de tratamiento. Resultados. Después de ajustar según los factores determinantes de la función pulmonar y el control y la duración de la diabetes mellitus de tipo 2, los valores esperados de la capacidad vital forzada de los pacientes tratados con agentes de sensibilización a la insulina fue menor que los de aquellos tratados con secretagogos (-212,1 ml Vs. -270,2 ml; p=0,039), y lo mismo se registró en el volumen espiratorio forzado durante el primer segundo (-133,2 ml Vs. -174,8 ml; p>0,05), aunque dichas diferencias no fueron estadísticamente significativas. En el grupo de pacientes tratados con agentes de sensibilización a la insulina, las concentraciones de ferritina y del factor de necrosis tumoral alfa fueron menores (p<0,01). Conclusión. Los resultados de este estudio respaldan la hipótesis de que los agentes de sensibilización a la insulina estarían asociados con un menor deterioro de la función pulmonar y una menor inflamación sistémica en los pacientes diabéticos. Asimismo, sirve como base para la formulación de nuevas hipótesis y trabajos de investigación.

Introduction: There is no clear relationship between type 2 diabetes mellitus and lung function decline; it is also unclear whether the type of treatment can modify spirometric variables and levels of inflammatory biomarkers. Objectives: To compare pulmonary function in patients with type 2 diabetes treated with an insulin-sensitizing agent (metformin) and in those treated with secretagogues, as well as combined with insulin, and to evaluate differences in inflammatory biomarkers between treatment groups. Materials and methods: We conducted a cross-sectional analytic study in 196 diabetic patients with type 2 diabetic mellitus. Spirometric variables and levels of inflammatory biomarkers (ferritin, fibrinogen, C-reactive protein, interleukin 6, tumor necrosis factor-alpha), were obtained. Residual values (observed minus expected) for forced vital capacity and for forced expiratory volume were calculated and compared between treatment types. Differences in median levels of biomarkers were also compared. Results: After adjustment by known determinants of lung function, and by the control and duration of type 2 diabetes, patients treated with the insulin-sensitizing agent had statistically significant lower differences against expected values for forced vital capacity compared with secretagogues (-212.1 ml vs 270.2 ml, p=0.039), as well as for forced expiratory volume , but without statistical significance (-133.2 mL vs -174.8 mL, p>0.05). In the group of patients treated with the insulin-sensitizing agent, ferritin and tumor necrosis factor-alpha levels were lower (p<0.01). Conclusion: This study supports the hypothesis that insulin-sensitizing agents appear to be associated with less deterioration of lung function and less systemic inflammation in type 2 diabetes. The present study serves to formulate new hypothesis and research projects.

Valorization of agroindustrial wastes: Identification by LC-MS and NMR of benzylglucosinolate from papaya (Carica papaya L.) seeds, a protective agent against lipid oxidation in edible oils.

In the present study we report the characterization of benzylglucosinolate (BG) isolated from papaya (Carica papaya L.) seeds. A methanolic extract was fractionated and further purified by solid phase extraction (SPE). It was analyzed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and nuclear magnetic resonance spectroscopy ((1) H and (13) C-NMR) as well, and the target compound BG was identified by these two techniques. The effect of BG on lipid oxidation in edible vegetable oil (EO) was shown by observing some lipid oxidation products (linoleic acid hydroperoxides, LHP; hexanal, HEX; nonanal, NON; thiobarbituric acid reactives species, TBARS). BG reduced lipid oxidation production in EO by over 80%, as compared to a control sample and in this way has proved to be a useful antioxidant, even more effective than some antioxidants used by food industry.