Mexican Cohort Research Articles

A Multi-Center Study of BRCA1 and BRCA2 Germline Mutations in Mexican-Mestizo Breast Cancer Families Reveals Mutations Unreported in Latin American Population.

The presence of germline and somatic deleterious mutations in the BRCA1 and BRCA2 genes has important clinical consequences for breast cancer (BC) patients. Analysis of the mutational status in BRCA genes is not yet common in public Latin American institutions; thus, our objective was to implement high-performance technology with highly reliable results with the possibility of analyzing several patients simultaneously, therefore reducing cost and work time. A prospective cohort of 252 unrelated sporadic breast cancer patients from the Mexican-mestizo population were analyzed using next generation sequencing (NGS) based on ion semiconductor sequencing. We found 28 pathogenic mutations (25 in BRCA1 and 13 in BRCA2), 11 of which had not been reported previously in Hispanic or Latin American populations. A total of 38 patients were positive for a pathogenic mutation representing 15% of our Mexican women cohort with breast cancer; 25 for BRCA1; and 13 for BRCA2. Our results revealed that there are mutations not analyzed by mutations panels, and our findings support the suitability of massive sequencing approaches in the public institutions of developing countries. Hence, BRCA screening should be offered to patients with breast cancer regardless of their family history of cancer in order to identify unaffected family carriers.

Expansion of disability across successive Mexican birth cohorts: a longitudinal modelling analysis of birth cohorts born 10 years apart

BackgroundLife expectancy (LE) in Mexico has risen rapidly since the 1950s. In high-income contexts, these increases have coincided with a compression of disability to later ages. However, little evidence on...

2422-PUB: Short-Chain Acylcarnitines as Early Predictors of Gestational Diabetes in Mexican Population

Gestational diabetes (GD) represents the main metabolic alteration during pregnancy affecting 17% of pregnancies in Mexico. The clinical relevance of this pathology is the short and long-term complications such as obesity, diabetes, and hypertension; that affect mother and child. GD is often diagnosed between weeks 24 to 28 of gestation through an oral glucose tolerance test. The aim of the present study was to identify early pregnancy metabolites (under 18 weeks of gestation) present on women who were diagnosed with GD; in order, to generate an early prediction model to identify those women who will later be diagnosed with GD. We used targeted metabolomics (11 amino acids and 39 acylcarnitines) to select early serum biomarkers with the most predictive power to identify women who will later be diagnosed with GD on a Mexican cohort of pregnant women. We assessed 79 pregnant women, which 66 underwent a normal pregnancy and 13 were diagnosed with GD under the IADPSG criteria. Random forest analyses were performed to assess the contribution and association of the metabolites identified to the development of GD. We developed a model that included two short-chain acylcarnitines (namely AC4 and AC5:1) that allowed an AUC of 0.904 (0.843-0.965, 95 CI) for classification of gestational diabetes. This model allows the identification of women on early stages of pregnancy that will be diagnosed with gestational diabetes between weeks 24 to 28 of gestation. However, additional studies in a large sample of pregnant women are required. Disclosure M. Razo-Azamar: None. R. Nambo-Venegas: None. J. Delgadillo-Velazquez: None. B. Palacios-Gonzalez: None.

AB0316 ESTABLISHED SERONEGATIVE RHEUMATOID ARTHRITIS IS CONSIDERED A MILD FORM OF THE DISEASE, ALSO WILL IT BE THE SAME REGARD FOR VERY EARLY SERONEGATIVE RHEUMATOID ARTHRITIS?

Background Established Seronegative Rheumatoid Arthritis (ESNRA) is considered a mild form of the disease with a good prognosis and response to therapy compared with seropositive (SP) form [1]. Lately evidence indicates that seronegative (SN) form of arthritis in early stage is serious and should not be underestimated in terms of disease activity, response to therapy and radiographic damage [2,3,4]. At present, the influence of SN status of clinical course and treatment choice in very early stages, in other words less than 3 months from time at onset of disease, is still controversial [5]. Objectives To evaluate demographical, clinical and treatment differences between Very Early Seronegative Rheumatoid Arthritis (VESNRA) and Very Early Seropositive Rheumatoid Arthritis (VESPRA) in a Mexican cohort. Methods 64 patients with Very Early Rheumatoid Arthritis [(VERA), Results Of 64 patients with VERA 79% were women. The mean age [standard deviation (SD)] was 49.8 (13.5) years. The mean of time at onset of VERA (SD) was 77.8 (15.5) days. A total of 20 (31.2%) patients had VESNRA. In the univariable analyses VESNRA patients were more likely to have minor disease activity and better functional status during their follow-up to 3, 6 and 12 months [Table 1]. Moreover, VESNRA patients were more likely to present lesser work disability, lower comorbidities including fibromyalgia, to use fewer sulfasalazine, leflunomide, biologic agents and corticosteroids. As expected, the modified Charlson’s comorbidity index score was lower in VESNRA patients through all their follow-up. In multivariable analyses less frequently use of corticosteroids (OR 0.68, 95% CI 0.42-0.88, p= Conclusion This study suggests that in very early stage of disease, SN form presents minor disease activity, better functional status, lower comorbidities, also require less aggressive therapy using biologic agents and corticosteroids than SP form in the course of one year. By these clinical and therapeutic differences should be considered VESNRA a mild form of the disease like as ESNRA. These observations must be confirmed in larger studies with further follow-up.

Clinical characterization and identification of five novel FOXL2 pathogenic variants in a cohort of 12 Mexican subjects with the syndrome of blepharophimosis-ptosis-epicanthus inversus

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant entity characterized by eyelid malformations and caused by mutations in the forkhead box L2 (FOXL2) gene. Clinical and genetic analyses of large cohorts of BPES patients from different ethnic origins are important for a better characterization of FOXL2 mutational landscape. The purpose of this study is to describe the phenotypic features and the causal FOXL2 variants in a Mexican cohort of BPES patients. A total of 12 individuals with typical facial findings were included. Clinical evaluation included palpebral measurements and levator function assessment. The complete coding sequence of FOXL2 was amplified by PCR and subsequently analyzed by Sanger sequencing. A total of 11 distinct FOXL2 pathogenic variants were identified in our cohort (molecular diagnostic rate of 92%), including 5 novel mutations. Our results broaden the BPES-related mutational spectrum and supports considerable FOXL2 allelic heterogeneity in our population.

1. Abusive Behavior Silently Increases Low Self-esteem and Depression in Teenage Pregnancy Patients: A Mexican Cohort

1. Abusive Behavior Silently Increases Low Self-esteem and Depression in Teenage Pregnancy Patients: A Mexican Cohort

Abstract P3-11-11: Prediction of treatment response to neoadjuvant chemotherapy in breast cancer by subtype using tumor-infiltrating lymphocytes: Study of a large Mexican cohort

Abstract Background/aim: Tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Studies have provided evidence that the level of TILs has prognostic value in breast cancer. The level of TILs has been associated with treatment outcome and pathologic response in patients undergoing neoadjuvant chemotherapy. In this study, we analyzed TILs before neoadjuvant therapy and if they correlate with pathological response to treatment Patients and methods We retrospectively analyzed the specimen slides of patients with Breast Cancer from the Centro Oncologico Estatal ISSEMyM treated with Neoadjuvant Chemotherapy (NAC) during 2007–2014. We identified 410 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. The proportions of TILs were categorized into high and low groups using a cut-off value of 10% Resultados The mean age was 51.4 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 369 (90%) patients, 34 (8.3%) lobular and 1.7% other. The BC subtypes among the 410 patients who received NAC were TNBC in 82 (20%), HER2BC in 70 (17.1%), and HRBC in 258 (62.9%) patients. Treatment response was pCR in 164 (40%) and non-pCR in 245 (60%) patients. Based on subtype, pCR was achieved in 43 (52 %) patients with TNBC, 35 (50.0%) with HER2BC, and 87 (33%) with HRBC. There were 191 (46.5%) patients in the high-TIL group and 219 (53.5%) patients in the low-TIL group. Patients were divided into high-TIL and low-TIL groups, and the clinicopathological characteristics of each group were examined. High TILs that had a pathologically complete response were found in 56 % of patients, and low TILs were found in 44 %. There was a significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.04). Conclusion TILs may be a biomarker for predicting treatment response to NAC in patients with Breast Cancer. Studies assessing outcomes and therapeutic efficacies should consider. Citation Format: Campos Gomez S, Cabañas Chávez N, Hernández Alvarez J, Campos Gómez K. Prediction of treatment response to neoadjuvant chemotherapy in breast cancer by subtype using tumor-infiltrating lymphocytes: Study of a large Mexican cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-11.

Neoadjuvant treatment in a Mexican cohort of patients with locally advanced rectal cancer: Oncologic outcomes and prognostic factors.

704 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy (CT) is the standard of care for locally advanced rectal cancer (LARC). Total neoadjuvant therapy (TNT) consists of induction CT followed by CRT prior to surgery. This is an alternative strategy recommended in guidelines. Objective: To describe neoadjuvant strategies, oncologic outcomes and prognostic factors in a cohort of patients (pts) with LARC treated at a referral center in Mexico City. Methods: We retrospectively reviewed medical records from pts with LARC (T3-T4 or N+) treated with any neoadjuvant strategy at Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” from January 2010 to December 2015. Clinical and pathological information was registered. Survival was estimated by Kaplan-Meier method. Univariate analysis for prognostic factors was performed and survival was compared by the log rank test. Results: 43 pts were included. Median age was 62 y/o (19-83), 51% were female. Clinical stage (CS) II 9% and CS III 91%. 36 pts were T3-4 and N+(86%). Localization was lower third 30%, middle third 56% and upper third 12%. 63% were moderately differentiated adenocarcinoma. 84% had TNT: induction CT with FOLFOX-4 regimen for 3 months followed by CRT (50.4 Gy in 28 fractions concurrently with fluoropyrimidines) and TME. Surgery: ultra-low anterior resection (AR) 48%, low AR 28% and abdominoperineal resection 24%. One patient did not accept surgery. Of the 32 pts with ultra-low and low AR, 94% had protective ileostomy. The pathologic complete response (pCR) ypT0ypN0 rate was 45% (19/42). Median follow-up was 48 months. There were 8/42 recurrences (19%): local-only 2.3%, systemic only 12% and both 5%. None of the pts with pCR recurred. All pts with residual nodal disease recurred (5/5). The 5-year relapse-free survival rate was 73%. There were 6 deaths, one patient died without disease. The 5-year overall survival rate was 83%. Conclusions: In pts with LARC the TNT is associated with high rates of pCR and favorable oncological outcomes. pCR and residual nodal disease after neoadjuvant therapy were strongly associated with recurrence and survival.

Heart Failure with preserved Ejection Fraction (HFpEF); A Mexican cohort from Mexican Institute of Social Security (IMSS)

Heart Failure with preserved Ejection Fraction (HFpEF); A Mexican cohort from Mexican Institute of Social Security (IMSS)

Predictive factors and prognostic effect of telomere shortening in pulmonary fibrosis.

The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications. Consecutive Spanish patients were included at diagnosis and followed up for 3 years. DNA blood samples from a Mexican cohort were used to validate the results found in Spanish sporadic IPF. Prior to treatment, telomere length was measured through quantitative polymerase chain reaction (qPCR) and Southern blot. Outcome was assessed according to mortality or need for lung transplantation. A multivariate regression logistic model was used for statistical analysis. Family aggregation, age of <60 years and the presence of non-specific immunological or haematological abnormalities were associated with a higher probability of telomere shortening. Overall, 66.6% of patients younger than 60 years with telomere shortening died or required lung transplantation, independent of functional impairment at diagnosis. By contrast, in patients older than 60 years with telomere shortening, the negative impact of telomere shortening in outcome was not significant. Our data indicate that young sporadic IPF patients (<60 years) with some non-specific immunological or haematological abnormalities had higher risk of telomere shortening, and furthermore, they presented a poorer prognosis.

Follow-up status, patient retention and data collection of the “Joven & Fuerte” cohort for young women with breast cancer in Mexico

Background: Understanding the characteristics of young women with breast cancer (YWBC) in limited-resource settings and the issues they face is of great relevance to the medical community, in order to tailor clinical interventions and supportive care. Thus, the Mexican cohort “Joven & Fuerte” was established in November 2014, with the aim of comprehensively characterizing YWBC in Mexico using patient- and physician-based questionnaires. Patients are evaluated at diagnosis, and follow-up evaluations are scheduled after 6 months (m), and annually for 5 years (y). For the completion of patients’ surveys, our team reaches out to patients on the date of their medical appointments. We aim to describe the current progress of our cohort, assess patient retention and data collection, and plan adjustments to minimize losses during follow-up.

Clinicopathological Characteristics and Outcomes of the Ongoing “Joven &amp; Fuerte” Cohort of Young Women With Breast Cancer in Mexico

Background: Despite high rates of breast cancer (BC) in young women from low and middle income countries, their needs and concerns are not systematically studied or addressed. Understanding the characteristics of young women with BC in limited-resource settings and the issues they face is of great relevance to the medical community, to tailor clinical interventions and supportive care for this unique and understudied patient population. The Mexican cohort Joven &amp; Fuerte has the goal of comprehensively characterizing and assessing the needs of YWBC in Mexico using patient- and physician-based surveys. Aim: The Mexican cohort Joven &amp; Fuerte has the goal of comprehensively characterizing and assessing the needs of YWBC in Mexico using patient- and physician-based surveys. Methods: A prospective cohort of newly diagnosed YWBC was established at the three Joven &amp; Fuerte sites. Eligible women answer electronic surveys on relevant topics, such as sociodemographic characteristics, fertility, genetics, and psychosocial needs, among others, while clinicians complete prespecified surveys registering clinicopathologic features and outcomes. Patients are evaluated at diagnosis, after 6 months, and annually for 5 years. Substudies assessing changes in cognition, sexual function and satisfaction, quality of life, and depression/anxiety are being carried out, and biologic samples are obtained and stored frozen for future research. Here, we report the baseline clinicopathological characteristics of patients included up to March 2018, as well as data on recurrence and mortality. Results: To date, 276 young women with BC with median age at diagnosis of 36 years (2140 y) have been accrued. 22% were single and 23%, childless. 42% had higher education and 31% were used. 80% presented with a self-detected mass. Clinical stage at diagnosis was distributed as follows: stage 0: 3%, I: 11%, IIA: 26%, IIB: 18%, III: 36%, and stage IV: 8%. The most frequent subtype was hormone-receptor (HR) pos/HER2 neg (52%), followed by triple neg (23%), HER2 pos/HR pos (17%) and HER2 pos/HR neg (8%). Histologic grade distribution among the patients was as follows: low grade (16%), intermediate grade (18%), and high grade (66%). Up to June 2017, 15 patients out of 120 (12.5%) have developed distant recurrences, and 12 patients (10%) have died as a consequence of breast cancer. With a median follow-up of 19 months, breast cancer free survival and overall survival was 87.7% and 89.9%, respectively. Conclusion: To our knowledge, this represents the first prospective cohort of young women with BC in Latin America. We are expanding this project to other centers in the region. Our findings will help develop culturally tailored interventions aimed at improving the medical and psychosocial outcomes of this vulnerable patient population.

Autoimmune associations in a Mexican cohort with primary biliary cholangitis

Several groups have reported associations of primary biliary cholangitis with other autoimmune entities, particularly Sjögren's syndrome and hypothyroidism. Its prevalence and characteristics in Mexican patients is unknown. To determine the frequency and characteristics of autoimmune diseases in a Mexican cohort of patients with primary biliary cholangitis. The medical records of patients that presented with primary biliary cholangitis within the time frame of 2005 and 2012 were reviewed and assessed for other autoimmune diseases. Seventy-eight patients, 75 women and 3 men, were included. Their mean age was 55.8 years. Seventy-three cases had positive antimitochondrial antibodies (94.8%) and disease was confirmed in 5 through liver biopsy. Five patients (8%) had anti-smooth muscle antibodies and 55/78 (70.5%) had antinuclear antibodies by indirect immunofluorescence. Forty-nine patients (62.8%) were positive for an autoimmune disease other than primary biliary cholangitis. Among those, 20 patients had one associated disease, 14 had 2, and 15 patients had 3 concomitant diseases. They included: Sjögren's syndrome in 23/78 patients (29.5%), dysthyroidism in 21/78 cases (26.9%), Raynaud syndrome in 11/78 (14.1%), CREST syndrome in 9/78 patients (11.4%), rheumatoid arthritis in 6/78 patients (7.7%), vitiligo in 5/78 (6.4%), scleroderma in 4/78 patients (5.1%), and other diseases in 8 patients. In 12/78 patients (15.4%), there was a documented family background of autoimmune disease. The presence of autoimmune associations in our cohort was frequent, and similar in characteristics to the information reported by other groups. The clinical implications of those findings remain to be determined. La colangitis biliar primaria es una enfermedad hepática colestásica crónica de origen autoinmune. Diferentes grupos han reportado asociaciones de esta enfermedad con otros padecimientos autoinmunes, particularmente el síndrome de Sjögren y el hipotiroidismo. Se desconoce la prevalencia y las características en pacientes mexicanos. El objetivo del presente trabajo fue determinar la frecuencia y las características de padecimientos autoinmunes en una cohorte mexicana de pacientes con colangitis biliar primaria. Se realizó una revisión de los expedientes de pacientes con colangitis biliar primaria entre 2005 y 2012 evaluando por otras enfermedades autoinmunes. Se incluyeron 78 pacientes, 75 mujeres y 3 hombres, con una edad promedio de 55.8 años. Setenta y tres de ellos presentaron anticuerpos antimitocondriales positivos (94.8%) y 5 fueron confirmados mediante biopsia hepática. Cinco (8%) de los pacientes presentaron anticuerpos antimúsculo liso positivos y 55/78 (70.5%) presentaron anticuerpos antinucleares positivos por inmunofluorescencia indirecta. Cuarenta y nueve de los 78 (62.8%) pacientes presentaron otra enfermedad autoinmune además de la colangitis biliar primaria. De estos, 20 tuvieron solo una enfermedad asociada, 14 mostraron 2 enfermedades asociadas y 15, 3 enfermedades asociadas. Por orden de frecuencia descendente se encontraron: síndrome de Sjögren en 23/78 (29.5%) pacientes, distiroidismo en 21/78 (26.9%), fenómeno de Raynaud en 11/78 (14.1%), CREST en 9/78 (11.4%), artritis reumatoide en 6/78 (7.7%), vitiligo en 5/78 (6.4%), esclerodermia en 4/78 (5.1%) y otras en 8 pacientes. En 12/78 (15.4%) existió antecedente documentado de enfermedades autoinmunes en la familia. La presencia de asociaciones autoinmunes en nuestra cohorte fue frecuente y con características similares a lo reportado por otros grupos. Desconocemos las implicaciones clínicas de estos hallazgos.

Obstetric outcomes in a Mexican cohort of patients with AQP4-antibody-seropositive neuromyelitis optica

Previous studies have investigated the influence of neuromyelitis optica (NMO) on pregnancy in other ethnic groups. However, there are potential variations among ethnic groups. The obstetric outcome of Mexican patients with NMO and AQP4-IgG positivity (AQP4-IgG[+]) is currently unknown. To describe the obstetric history of Mexican patients with NMO and AQP4-IgG(+). Patients with NMO and AQP4-IgG(+) were identified from the database of the Demyelinating Diseases Clinic. These patients were interviewed by telephone. Out of a total of 40 eligible patients, 29 were contacted and completed the survey. Of these, 19 patients reported at least one previous pregnancy. In total, 50 pregnancies were reported: 44 of them occurred ≥ 3 years before the first clinical manifestation, 1 occurred ≥ 1 years before, and 1 occurred after the first manifestation. Of all pregnancies, 12 were pregnancy losses: 5 were classified as miscarriages and 3 as stillbirths. Of all pregnancy losses, 10 occurred ≥ 3 years before the diagnosis, 1 occurred after the first manifestation. All pregnancy losses occurred in 8 patients. Close to half of the patients with previous pregnancies reported at least one pregnancy loss, most of these occurred ≥ 3 years before the diagnosis. This percentage is higher than expected for their age group in our country.

Diurnal Cortisol Concentrations and Growth Indexes of 12- to 48-Month-Old Children From Mexico City.

Early life cortisol plays an important role in bone, muscle, and fat mobilization processes, which could influence body composition, affecting anthropometric indicators such as weight and height. To explore the association between diurnal cortisol levels and growth indexes in children from 12 to 48 months of age. This study includes data from 404 children from the Programming Research in Obesity, Growth, Environment and Social Stressors Mexican birth cohort. Cortisol was measured in eight saliva samples collected at four time points during the day (from wakeup to bedtime), over 2 days, when the child was either 12, 18, or 24 months old. Total daytime cortisol levels were calculated by averaging the area under the curve (AUC) for the 2 days. Height and weight were measured from 12 to 48 months of age. Growth indexes were constructed according to z scores following World Health Organization standards: weight-for-age z score (Z-WFA), height/length-for-age z score, weight-for-height/length z score (Z-WFH), and body mass index-for-age z score (Z-BMIFA). Mixed models were used to analyze the association between cortisol AUC quartiles and growth indexes. Cortisol showed an inverted U-shaped association with the four growth indexes. Compared with the first quartile, all quartiles had a positive association with indexes that include weight, with the second quartile having the strongest association, resulting in an average change of β (95% CI) 0.38 (0.13-0.64) for Z-WFA, 0.36 (0.10-0.62) for Z-WFH, and 0.43 (0.17-0.69) for Z-BMIFA. Results suggest that early life daytime cortisol levels, as a reflection of hypothalamic-pituitary-adrenal axis development, might influence growth in early infancy.

Long-term survival of kidney grafts in lupus nephritis: a Mexican cohort.

Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23-38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival ( p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.

Improvement in health utility after transcervical radiofrequency ablation of uterine fibroids with the sonata system: Health utility after radiofrequency ablation

To establish the improvement in patient health utilities following treatment of symptomatic uterine fibroids with the Sonata™ System. A prospective, single-arm trial was conducted in which 49 women in the United Kingdom, Netherlands and Mexico with fibroids were treated with transcervical, intrauterine ultrasound- guided radiofrequency ablation. The EQ-5D-3L system was utilized to collect patient health status at baseline, 3, 6, and, 12 months post-procedure. Patient-reported health states at each time point were converted into a health utility value using time-trade off methodology. In the overall cohort, patient health utility increased from a mean of 0.745 at baseline, to means of 0.838, 0.852, and 0.914 at 3 months, 6 months, and 12 months, respectively. The change from baseline at 12 months was significant. When stratified by country, the 12-month improvement in health utility remained significant for both the Mexican and Dutch cohorts. Transcervical radiofrequency ablation of uterine fibroids with the Sonata System resulted in statistically significant 12-month improvements in health utility for the overall patient cohort and for the Mexican and Dutch sub-populations.

Oncological outcomes in a Mexican cohort of patients with gallbladder cancer.

518 Background: gallbladder cancer is the most common malignancy of the biliary tract. Treatment modalities and outcomes for this disease in Mexican population have been infrequently reported. Methods: we retrospectively reviewed medical records from 61 patients with histologically confirmed gallbladder cancer treated at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from January 2005 to December 2015.Clinical and pathological information was recorded. Survival was estimated by Kaplan Meir method and compared by Log rank test. Results: we found 68.9% women and 31.1% men, with a median age of 68 years (32-93). Clinical stage was advanced in 65.6% (n=40), regional in 23% (n=14), localized in 4.9% (n=3) and in situ in 6.6% (n=4). For patients with localized disease (n=21), which included in situ, localized and regional disease, a potentially curative surgery was attempted in 100% of patients, achieving a R0 resection in 47.6% (n=10) of cases. The morbidity rate was 33.3% (n=7). There were 5 surgical deaths. For advanced disease (n=40), the initial treatment was: 42.5% (n=17) palliative surgery, 25% (n=10) palliative care and for 30% (n=12) systemic chemotherapy, more frequently gemcitabine plus cisplatin (n=7). At progression seven patients received second-line chemotherapy. Median overall survival (OS) in the global cohort was 5.6 months (IC 95, 2.4-8.77). According to clinical stage survival at 5 years was 100% for in situ and 67% for localized disease. Median survival was 6.3 months (IC 95, 2.3-10-3) for regional disease and 4.2 months (IC 95, 1.1-6.4) for advanced disease. For patients with localized disease not achieving R0 resection (p=0.03) and perineural invasion (p=0.025) were associated with decreased survival. For patients with advanced disease poor performance status (p=0.004) and absence of chemotherapy (p=0.002) were adverse prognostic factors. Conclusions: global poor outcomes may be explained by metastatic disease at presentation. Even for patients with apparent localized disease, a potentially curative resection could be offered to only half of the patients.

First results of universal screening for Lynch syndrome in a Mexican cohort of colorectal cancer patients.

590 Background: universal screening has been proposed as an alternative to clinical criteria for detection of Lynch syndrome (LS). Results of such policy have not been evaluated in mexican population with low incidence of colo-rectal cancer (CCR). Objective: to determine the proportion of patients tested by immunohistochemistry (IHC) for mismatch repair-deficient (dMMR) and characterize subsequent molecular and clinical work up for abnormal results. Methods: we identified all consecutive cases of CCR during 2016 at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico. We recorded clinical variables, IHC for mismatch repair (MMR) proteins and/or clinical genetics evaluation and molecular confirmation of LS if available. Results: universal screening policy was adopted by our institution in 2016. 209 CRC patients had an outpatient consultation. The median age at diagnosis was 59.8 years. 103 IHC for MMR proteins were done (49%) regardless of age at diagnosis and a family history of CRC. 36/103 (35%) IHC showed abnormal result meaning lack of expression of at least one of four MMR proteins: 26 MLH1, 7 MSH2, 10 MSH6 and 23 PMS2. 11/36 patients (30%) had a family history of CRC. 26/36 (72%) were evaluated by clinical genetics service. Of 26 MLH1 deficient patients, only one case was tested for BRAF mutation. 14/36 patients (39%) were tested by sequencing analysis: 7 MLH1, 5 MSH2, 1 MSH6, 1 PMS2. 2/14 patients were tested by MLPA assay given negative sequencing analysis. Germ-line mutations were identified in 7/36 patients (19%). All mutations were identified in patients with a clinical suspicion given strong family history of CRC. No identified mutations could be attributed to universal screening policy. Conclusions: during the first year of implementing universal screening for LS in CRC patients only half of the patients were screened by IHC. Despite MLH1/PMS2 deficiency was the most frequent abnormality, BRAF mutation analysis was not performed as recommended, given the lack of access to the test. A clinical suspicion of LS was a determinant driver for confirmatory molecular testing therefore limiting the usefulness of universal screening.

Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.