Androgen Receptor Expression in Locally Advanced Breast Cancer Predicts Lack of Pathological Complete Response After Neoadjuvant Treatment

Background: Data regarding the prognostic value of androgen receptor (AR) expression in locally advanced breast cancer (LABC) is limited. We aimed to determine the pathological complete response, defined as ypT0/is and ypN0, in a group of patients with AR-positive breast cancer after preoperative treatment. Methods: We evaluated immunohistochemical AR expression in 40 patients treated in our referral center. Univariate and multivariate models were used to assess the association between AR expression and pathological complete response (pCR). Results: AR expression varied from 75% in estrogen receptor-positive tumors to 11.7% in triple-negative tumors (P < 0.001). Three patients with AR-positive tumors achieved pCR. In the univariate model, AR expression was significantly associated with the absence of pCR (OR = 0.18; 95% CI, 0.04–0.75; P = 0.023). After adjusting for intrinsic breast cancer subtypes, AR-positive tumors had less probability of achieving a pCR compared with AR-negative ones (OR = 12.33; P = 0.046). Conclusions: AR expression was negatively correlated with pCR in our subset of patients with LABC who underwent neoadjuvant chemotherapy.UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

Liver Metastasectomy and Systemic Therapy Improve Overall Survival Compared With Surgery Alone After Curative Liver Resection of Colorectal Metastases in a Developing Country (Costa Rica)

Background Resection of liver-isolated metastases of colorectal cancer (CRC) offers the greatest likelihood of cure. Nevertheless, recurrence rates after this procedure are high, and chemotherapy is a reasonable choice with inconclusive evidence. We aimed to determine if there is a survival difference between patients receiving systemic therapy with surgery versus surgery alone for resection of liver metastases. Methods From a source population of 170 patients treated in our National Centre (Centro Nacional de Cirugía Hepatobiliar, San José, Costa Rica), with liver metastases from various primary sites, we selected 51 patients with CRC who underwent hepatic resection with curative intent. We categorized patients according to the treatment received (fluoropyrimidine-based chemotherapy plus or minus monoclonal antibody and surgery v surgery alone) and then calculated the overall survival (OS) rate according to the Kaplan-Meier method. A Cox proportional hazard model was used to assess the influence of potential confounding variables on OS. Results After a median follow-up of 41.6 months, OS was significantly better for patients treated with systemic therapy (before and/or after hepatic resection) versus surgery alone (3-year OS: 66.7% v 41.7%; hazard ratio, 0.37; 95% CI, 0.15 to 0.91; log-rank test: P = .025). There were no differences among patients who underwent neoadjuvant (48.7%), perioperative (46.2%), and adjuvant therapy (5.1%). The use of systemic therapy was significantly associated with better OS after adjustment for confounding variables (hazard ratio, 0.23; 95% CI, 0.07 to 0.92; P = .03). Conclusion Our findings support the use of systemic therapy (either perioperative, neoadjuvant, or adjuvant) as part of isolated hepatic metastasectomy from CRC.UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

Sunitinib effectiveness and safety as first line treatment in metastatic renal cell carcinoma, in the Costa Rican population

Aim: Tyrosine kinase inhibitors are part of the armamentarium to treat metastatic renal cell carcinomas (mRCC). Costa Rica has approved sunitinib in the first line setting. The authors conducted a retrospective study to address the effectiveness and safety profile of sunitinib in our population in terms of overall survival (OS) and progression free survival (PFS). Methods: The authors analyzed all patients who were treated with sunitinib diagnosed with mRCC in the three National Hospitals (Hospital Mexico, Hospital San Juan de Dios, and Hospital Calderon Guardia) from February 2007 to June 2015. Demographics, safety profile, and efficacy (OS and PFS) were obtained from medical records. OS and PFS were calculated using the Kaplan Meier method and a Cox Proportional Model Analysis was used when OS and PFS were compared in subset of patients. Results: Seventy-seven patients were included; mean age was 58.9 years. Fifty-four patients were male (70.1%). The most common histologic type was clear cell carcinoma (87%), followed by papillary (9.1%) and chromophobe (2.0%) types. Median OS was 21.0 months [95% confidence interval (CI): 13.42-28.58]. Median PFS was 13.7 months (95% CI: 11.24-16.16). Patients aged 65 years or older experienced worse PFS and OS than younger patients (median PFS: 8.2 vs. 17.6 months; P = 0.011) (median OS: 19.0 vs. 29.0 months; P = 0.022). Sunitinib was well tolerated and no serious side effects were reported. Conclusion: This is the first study in Central America showing that sunitinib, first line, in mRCC is as effective as reported in pivotal clinical trials and expanded use studies in terms of PFS and OS.UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

Efectividad y seguridad de la quimioterapia de inducción en el tratamiento del cáncer de colon en el Hospital San Juan de Dios durante los años 2010 y 2011

La neoplasia colorrectal es un proceso maligno que implica varias alteraciones genéticas y fenotípicas que favorecen la proliferación de células malignas que terminan generando una lesión rígida que puede ser detectada por técnicas como la proctoscopia. El presente estudio analiza los posibles beneficios de la quimioterapia de inducción en pacientes diagnosticados con este tumor. Se realizó un análisis retrospectivo de 20 pacientes tratados del año 2010 al 2011, en donde la mediana de seguimiento fue de 69.5 meses. La quimioterapia de inducción se le aplicó al 30% de la población del estudio. Aunque no hay diferencias estadísticamente significativas en la sobrevida entre los dos grupos, se demostró un “downstaging” positivo en un 30% de la población estudiada y la ausencia de la recurrencias locales y sistémicas en el 80% de los pacientes.Colorectal neoplasia is a malignant process involving several genetic and phenotypic alterations favoring the proliferation of malignant cells that end up generating a rigid lesion can be detected by techniques such as proctoscopy. This study analyzes the potential benefits of induction chemotherapy in patients diagnosed with this tumor. A retrospective analysis of 20 patients treated from 2010 to 2011, where the median follow-up was 69.5 months was performed. Induction chemotherapy was applied to 30% of the study population. Although no statistically significant differences in survival for patients receiving induction chemotherapy and that a "downstaging" positive no, it was shown by 30% of the study population and the absence of local and systemic recurrences in 80% from the patients.UCR::Vicerrectoría de Docencia::Salud::Facultad de Farmaci

Femenina de 48 años con edema pulmonar neurogénico

El edema pulmonar neurogénico (EPN) es definidocomo un edema pulmonar agudo posterior aun insulto neurológico central, sin patologíacardiovascular o pulmonar que predisponga almismo(1). Fue descrito inicialmente por Shanahanen 1908 y desde entonces, se ha catalogado comouna entidad clínica frecuente y subdiagnosticada(2). Constituye una complicación potencialmentefatal que ocurre después de un daño específicoal sistema nervioso central (SNC) y supresencia debe sospecharse en pacientes queevidencian súbitamente disnea y un cocientePaO2/FiO2 bajo, luego de una lesión del SNC(3,4).Muchos mecanismos fisiopatológicos se hanvisto implicados en el desarrollo del EPN, sinembargo, la interacción específica de dichosmecanismos aún no está completamente dilucidada(5). En el presente trabajo, se reporta el casode una paciente quien presentó EPN de formareincidente, asociado a un cambio en su patrónconvulsivo usual. El caso es instructivo ya que esel primer reporte de reincidencia en un pacienteadulto con una evolución clínica y radiológicatípica, en donde se cuenta con la clínica y losestudios de laboratorio y gabinete que respaldanel diagnóstico de EPN

Epidemiology and Outcomes of Bloodstream Infections in Patients With Solid Tumors in a Central American Population at Mexico Hospital, San Jose, Costa Rica

Purpose Bloodstream infections (BSIs) are an important cause of mortality in patients with solid tumors. We conducted a retrospective study to evaluate the epidemiologic profile and mortality of patients with solid tumors who have BSIs and were admitted to Mexico Hospital. This is the first study in Costa Rica and Central America describing the current epidemiologic situation. Methods We analyzed the infectious disease database for BSIs in patients with solid tumors admitted to Mexico Hospital from January 2012 to December 2014. Epidemiology and mortality were obtained according to microorganism, antibiotic sensitivity, tumor type, and presence of central venous catheter (CVC). Descriptive statistics were used. Results A total of 164 BSIs were recorded, the median age was 58 years, 103 patients (63%) were males, and 128 cases of infection (78%) were the result of gram-negative bacilli (GNB). Klebsiella pneumoniae (21%), Escherichia coli (21%), and Pseudomonas aeruginosa (15%) were the most common microorganisms isolated. Gram-positive cocci (GPC) were found in 36 patients, with the most frequent microorganisms being Staphylococcus aureus (10%) and Staphyloccocus epidermidis (6%). With respect to tumor type, BSIs were more frequent in the GI tract (57%) followed by head and neck (9%) and genitourinary tract (8%). Regarding antibiotic susceptibility, only 17% (GNB) expressed extended-spectrum beta-lactamase and 12% (GPC) had methicillin resistance. Patients with CVCs (n = 59) were colonized mainly by GNB (78%). Overall the mortality rate at 30 days was about 30%. Conclusion GNB are the most frequent cause of BSIs in solid tumors and in patients with CVCs. GI cancers had more BSIs than other sites. Mortality and antibiotic sensitivity remained stable and acceptable during this observational period in this Latin American population.UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Asociación de los polimorfismos C677T y A1298C del gen de la metilentetrahidrofolato reductasa con la efectividad del tratamiento con quimioterapia en una cohorte de pacientes costarricenses con cáncer colorrectal metastásico

Objectiu: Les fluoropirimidines són el pilar del tractament citotòxic per als pacients amb càncer colorectal. No obstant això, la resposta farmacològica a aquests agents varia segons l'individu. Aquest estudi té com a objectiu determinar si els polimorfismes C677T (rs1801133) i A1298C (rs1801131) del gen de l'enzim metilentetrahidrofolat reductasa (MTHFR) afecten la toxicitat i l'efectivitat dels esquemes basats en fluoropirimidines per al tractament del càncer colorectal metastàtic. Pacients i mètodes: Es van reclutar 68 pacients amb càncer colorectal metastàtic que es van tractar amb capecitabina o 5-fluorouracil en combinació amb oxaliplatí o irinotecan com a teràpia de primera línia. Els pacients es van avaluar prospectivament des del gener del 2019 fins al novembre del 2020 a l'Hospital San Juan de Dios, a San José (Costa Rica). Es va extraure l'ADN de línia somàtica i de línia germinal a partir de teixit parafinat i sang perifèrica, respectivament. Durant el seguiment es van valorar la toxicitat i la resposta objectiva induïda pel tractament citotòxic. Per a cada genotip estudiat es va calcular, mitjançant una anàlisi de regressió logística, la probabilitat de toxicitat i de resposta objectiva, definida com a percentatge d'individus que van assolir una resposta parcial o completa amb l'ús del tractament citotòxic. Es va utilitzar una anàlisi de regressió de Cox per identificar els efectes dels genotips dels polimorfismes C677T i A1298C del gen MTHFR sobre la supervivència lliure de progressió (SLP) i la supervivència global (SG). Es van correlacionar les variants genètiques identificades amb la presència d'inestabilitat microsatel·lital i la presència de mutacions en els gens KRAS, NRAS i BRAF. Es va utilitzar un model de correlació de Spearman per associar els polimorfismes del gen MTHFR trobats a la línia germinal i la somàtica. Resultats: Els individus amb almenys un al·lel mutant del polimorfisme MTHFR C677T van tenir més risc d'anèmia (odds ratio OR=1,69, IC95%=1,13-2,53, p=0,005), neutropènia (OR=2,27, IC95%=1,47-3,42, p<0,001) trombocitopènia (OR=1,91, IC95% =1,30-2,70, p<0,001), neuropatia perifèrica (OR=1,77, IC95% =1,16-2,70, p=0,02), diarrea (OR=1,69, IC95%=1,13-2,53, p=0,005) i síndrome mà-peu (OR=1,56, IC95%=1,08-2,27, p=0,013), en comparació amb els pacients homozigots per a la variant normal. La presència de l'al·lel mutant C del polimorfisme MTHFR A1298C es va associar a un risc més gran d'anèmia (OR=2,75, IC95%=1,01-7,48, p=0,02) i trombocitopènia (OR=3,14, IC95%=1,01-9,78, p=0,03). Cap polimorfisme es va associar amb el risc de mortalitat. Els pacients amb l'al·lel T del polimorfisme MTHFR C677T van tenir millors respostes objectives que els individus amb la variant no mutada (OR= 3,21, IC95%=1,05-9,81, p=0,03), i també una SLP més gran (hazard ratio HR=0,53, IC95%=0,28-0,98, p=0,045), fins i tot després de l'ajust per possibles variables de confusió (HR=0,50, IC95%=0,25-0,98, p=0,04). No hi va haver cap associació entre el polimorfisme MTHFR A1298C i la resposta objectiva ni la SLP. Cap de les variants analitzades es va associar amb canvis en la SG (HR=0,86, IC95%=0,38-1,94, p=0,71 per al polimorfisme MTHFR C677T i HR=1,24, IC95%=0,58-2,67, p=0,58 per al polimorfisme MTHFR A1298C). Conclusions: Els polimorfismes MTHFR C677T i A1298C són biomarcadors farmacogenètics que prediuen la toxicitat en un grup de pacients mestissos tractats amb quimioteràpia basada en fluoropirimidines com a tractament del càncer colorectal metastàtic. A més, la presència de l'al·lel mutat T del polimorfisme MTHFR C677T es va associar a una millor resposta objectiva i una SLP més gran que la variant homozigota no mutada. Cap dels polimorfismes estudiats es va associar amb SG.Objetivo: Las fluoropirimidinas son el pilar del tratamiento citotóxico para los pacientes con cáncer colorrectal. Sin embargo, la respuesta farmacológica a estos agentes es variable entre individuos. El presente estudio tiene como objetivo determinar si los polimorfismos C677T (rs1801133) y A1298C (rs1801131) del gen de la enzima metilentetrahidrofolato reductasa (MTHFR) afectan la toxicidad y la efectividad de los esquemas basados en fluoropirimidinas para el manejo del cáncer colorrectal metastásico. Pacientes y métodos: Se reclutaron 68 pacientes con cáncer colorrectal metastásico que fueron tratados con capecitabina o 5-fluorouracilo en combinación con oxaliplatino o irinotecan como terapia de primera línea. Los pacientes se evaluaron de forma prospectiva desde Enero de 2019 hasta Noviembre de 2020 en el Hospital San Juan de Dios, San José, Costa Rica. Se extrajo el ADN de línea somática y de línea germinal a partir de tejido parafinado y sangre periférica respectivamente. Durante el seguimiento se valoró tanto la toxicidad como la respuesta objetiva inducida por el tratamiento citotóxico. Para cada genotipo estudiado se calculó, mediante un análisis de regresión logística, la probabilidad de toxicidad y de respuesta objetiva, definida como el porcentaje de individuos que alcanzaron una respuesta parcial o completa con el uso del tratamiento citotóxico. Se empleó un análisis de regresión de Cox para identificar los efectos de los genotipos de los polimorfismos C677T y A1298C del gen MTHFR sobre la supervivencia libre de progresión (SLP) y supervivencia global (SG). Se correlacionaron las variantes genéticas identificadas con la presencia de inestabilidad microsatelital y la presencia de mutaciones en los genes KRAS, NRAS y BRAF. Se empleó un modelo de correlación de Spearman para asociar los polimorfismos del gen MTHFR encontrados en línea germinal y somática. Resultados: Los individuos con al menos un alelo mutante del polimorfismo MTHFR C677T tuvieron mayor riesgo de anemia (Odds Ratio OR=1,69; IC95%=1,13-2,53; p=0,005), neutropenia (OR=2,27; IC95%=1,47-3,42; p<0,001) trombocitopenia (OR=1,91; IC95%=1,30-2,70; p<0,001), neuropatía periférica (OR=1,77; IC95%=1,16-2,70; p=0,02), diarrea (OR=1,69; IC95%=1,13-2,53; p=0,005) y síndrome mano-pie (OR=1,56; IC95%=1,08-2,27; p=0,013), en comparación con los pacientes homocigotos para la variante normal. La presencia del alelo mutante C del polimorfismo MTHFR A1298C se asoció a mayor riesgo de anemia (OR=2,75; IC95%=1,01-7,48; p=0,02) y trombocitopenia (OR=3,14; IC95%=1,01-9,78; p=0,03). Ningún polimorfismo se asoció con el riesgo de mortalidad. Los pacientes con el alelo T del polimorfismo MTHFR C677T tuvieron mejores respuestas objetivas que los individuos con la variante no mutada (OR= 3,21; IC95%=1,05-9,81; p=0,03), al igual que mayor SLP (Hazard ratio HR=0,53; IC95%=0,28-0,98; p=0,045), aún después del ajuste por posibles variables confusoras (HR=0,50; IC95%=0,25-0,98; p=0,04). No hubo asociación entre el polimorfismo MTHFR A1298C y la respuesta objetiva ni SLP. Ninguno de las variantes analizadas se asoció con cambios en la SG (HR=0,86; IC95%=0,38-1,94; p=0,71 para el polimorfismo MTHFR C677T y HR=1,24; IC95%=0,58-2,67; p=0,58 para el polimorfismo MTHFR A1298C). Conclusiones: Los polimorfismos MTHFR C677T y A1298C son biomarcadores farmacogenéticos que predicen la toxicidad en un grupo de pacientes mestizos tratados con quimioterapia basada en fluoropirimidinas como tratamiento del cáncer colorrectal metastásico. Además, la presencia del alelo mutado T del polimorfismo MTHFR C677T se asoció a mejor respuesta objetiva y mayor SLP que la variante homocigota no mutada. Ninguno de los polimorfismos estudiados se asoció con SG.Aim: Fluoropyrimidines are the core of cytotoxic treatment for patients with colorectal cancer. However, the pharmacological response to these agents is variable among individuals. The aim of this study is to determine if the C677T (rs1801133) and A1298C (rs18011131) polymorphisms of the methylenetetrahydrofolate reductase gene affect the toxicity and efficacy of chemotherapy schemes based on fluoropyrimidines as treatment for patients with metastatic colorectal cancer. Patients and Methods: A total of 68 patients with metastatic colorectal cancer were recruited. These patients were treated with capecitabine or 5-fluorouracyl in association with oxaliplatin or irinotecan as first-line therapy. Patients were evaluated from January 2019 to November 2020 in San Juan de Dios Hospital, San José, Costa Rica. Somatic and germline DNA was extracted from paraffined embedded tissue or peripheral blood, respectively. Toxicity and objective response to cytotoxic treatment were prospectively assessed. A logistic regression model was used to calculate, for each genotype, the probability of toxicity and objective response, defined as the percentage of patients with partial or complete response to treatment. A Cox regression analysis was used to identify the effect of C677T and A1298C MTHFR polymorphisms on progression-free survival (PFS) and overall survival (OS). The identified genetic variants were correlated to microsatellite instability and the presence of KRAS, NRAS, and BRAF mutations. A Spearman correlation model was used to associate germline and somatic MTHFR polymorphisms. Results: Individuals with at least one mutant allele of the C677T MTHFR polymorphism had higher risk of anemia (Odds ratio OR=1.69; 95%CI=1.13-2.53, p=0.005) neutropenia (OR=2.27, 95%CI=1.47-3.42, p<0.001) thrombocytopenia (OR=1.91, 95%CI=1.30-2.70, p<0.001), peripheral neuropathy (OR=1.77, 95%CI=1.16-2.70, p=0.02), diarrhea (OR=1.69, 95%CI=1.13-2.53, p=0.005), and hand-foot syndrome (OR=1.56, 95%CI=1.08-2.27, p=0.013) in comparison with homozygous patients for the normal gene variant. The presence of the mutant allele C of the A1298 MTHFR polymorphism was associated to higher risk of anemia (OR=2.75, 95%CI=1.01-7.48, p=0.02) and thrombocytopenia (OR=3.14, 95%CI=1.01-9.78, p=0.03). None of the studied polymorphisms were associated to mortality. Patients with the T allele of the C677T MTHFR polymorphism had better objective response (OR= 3.21, 95%CI=1.05-9.81, p=0.03) and longer PFS (Hazard ratio HR=0.53, 95%CI=0.28-0.98, p=0.045) than homozygous patients with the normal gene variant, even after the adjustment of possible confounding variables (HR=0.50, 95%CI=0.25-0.98, p=0.04). There was no association between the A1298 MTHFR polymorphism, objective response, and PFS. None of the analyzed variables were associated with OS (HR=0.86, 95%CI=0.38-1.94, p=0.71 for the C677T MTHFR polymorphism and HR=1.24, 95%CI=0.58-2.67, p=0.58 for the A1298C MTHFR polymorphism). Conclusions: The MTHFR C677T y A1298C polymorphisms are pharmacogenetic biomarkers that predict toxicity in a cohort of Mestizo patients treated with fluoropyrimidine-based chemotherapy as treatment for metastatic colorectal cancer. Furthermore, the presence of the mutant T allele of the C677T MTHFR polymorphism was associated to better objective response and longer PFS that the homozygous non-mutated gene variant. None of the studied polymorphisms was related to OS