Chilean Patients Research Articles

Physical activity levels and preferences of patients with breast cancer receiving chemotherapy in Chile.

In Chilean patients with breast cancer (BC) receiving chemotherapy we aimed to (a) report the levels of physical activity (PA), (b) compare clinical/socio-demographic parameters among patients with different levels of PA, and (c) explore exercise preferences. Patients (n = 112) completed a questionnaire regarding their PA habits, and another questionnaire regarding their preferences for an exercise program. Patients were then divided into three groups based on the exercise guidelines for patients with BC (150min/week of moderate exercise, or 75min/week of vigorous exercise). The groups were (i) not engaging in any moderate-to-vigorous PA (MVPA), (ii) engaging in some MVPA, but not meeting the guidelines, and (iii) meeting the guidelines. Clinical/socio-demographic parameters and preferences for exercise were compared between groups. Only 13% of patients with BC met the exercise guidelines. These patients were younger, had been diagnosed more recently, and had fewer children than patients not engaging in MVPA. There were no differences in the preferences for exercise between groups. Overall, patients preferred to exercise with other patients (76%), at moderate intensity (67%), performing different activities (94%), supervised (94%), with a fixed schedule (69%), and to do group activities (90%). Most patients with BC receiving chemotherapy did not meet the exercise guidelines. Patients > 50years old and with > 2 children were the most inactive. Efforts to increase PA levels should focus especially on these patients. The preferences for exercise reported here will help to increase adherence to exercise programs and improve outcomes for these patients in Chile.

Assessment of Gastritis and Gastric Cancer Risk in the Chilean Population Using the OLGA System

Gastric cancer (GC) is the first cancer-related cause of death in Chile; however, no plan for GC early detection has been implemented in this country. The OLGA system characterizes gastritis from stages 0 to IV according to the risk of developing GC based on H. pylori infection, atrophy, metaplasia and GC. In this study, the performance of the OLGA system was evaluated in 485 Chilean patients receiving routine endoscopy to improve the detection of early GC or preneoplastic lesions. The results showed that OLGA scores, atrophy, metaplasia and GC increased significantly with age (p < 0.001). Conversely, H. pylori infection was higher in younger groups (p < 0.05). All gastric lesions were more frequent in men than women. The majority of patients with atrophy also had metaplasia (99%, p < 0.0001). Patients with H. pylori infection had more gastric atrophy and metaplasia than those without infection (p < 0.05). Of the 485 patients, 21 (4.3%) had GC, being 2.3 times more frequent among men than women and about 2/3 (14) were in OLGA stage ≥2. In addition, 19 (90%) GC patients had atrophy and 18 (85%) had metaplasia (p < 0.001). In conclusion, the OLGA system facilitated the evaluation of GC precursor lesions particularly in patients with an OLGA score > 2 between 45 and 56years old, because this group showed atrophy and intestinal metaplasia more frequently. Therefore, biennial endoscopic surveillance of patients with an OLGA >2 can be an important health policy in Chile for diagnosing GC in its early stages and reducing mortality over the next two decades.

The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer.

A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor-node-metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman's test. Plasmatic levels of chemokines and inflammatory mediators' vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163+ cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC.

Regorafenib adjusted dose for Chilean patients with chemoresistant metastatic colorectal cancer: a case series.

BackgroundRegorafenib is a therapeutic alternative for patients with metastatic colorectal cancer (MCRC) resistant to conventional therapies. The reported toxicity is relevant and there is no data on Latin American patients. The objective was to evaluate the overall survival (OS), progression-free survival (PFS) and quality of life (QoL) in a prospective cohort of Latin American patients treated with an adjusted dose of regorafenib.MethodsWe prospectively recruited patients with MCRC that progressed to standard therapy. A dose escalation algorithm was used. OS, PFS, response rate and QoL were evaluated.ResultsWe recruited 13 patients between June and November 2015. The median age was 60 years. Median OS was 8.6 months and median PFS was 2.2 months. The response rate was 8%. Grade 3–4 toxicities included grade 3 palmoplantar erythrodysesthesia in 23% and grade 3 fatigue in 12% of patients.ConclusionRegorafenib treatment is effective in Latin American patients with conventional therapy resistant MCRC.

P2.03-01 Prevalence of EGFR Alterations in Chilean Lung Cancer Patients: A Retrospective Study

P2.03-01 Prevalence of EGFR Alterations in Chilean Lung Cancer Patients: A Retrospective Study

DUCHENNE MUSCULAR DYSTROPHY - GENETICS: P.214Genetic profile of Chilean patients with Duchenne muscle dystrophy

Duchenne muscle dystrophy (DMD), is a progressive muscular disease, inherited as a X link. Is caused by the mutations of the dystrophin gene. Deletions of one or more exons account for approximately 50-65%, duplications 5-10% and point mutations 20-25%. Analyze the genetic profile of patients with DMD through regular checkups at the pediatric neurology department of the San Borja Arriarán Hospital. Retrospective descriptive study. Analysis of clinical records of 41 patients in evaluation by DMD, excluding patients diagnosed prior to the year 2010, with only biopsy and/ or PCR (polymerase chain reaction) without alterations. 41 patients with clinical manifestations and/or muscle biopsy with markedly reduced or no detectable dystrophin immunostaining, were studied by PCR, MLPA (multiplex ligation probe amplification) and/or Sanger sequencing techniques. 27/41 (66%) of patients had large deletions, 20/27 had compromised exons 44-55, and 3/26 had compromised exons 3-7. The most frequent deletion was exon 50, followed by exon 49. 3/41 (7,3%) presented duplications, which all affected exon 2. 10/41(24,4%) of patients had a negative MLPA, but a compatible muscle biopsy. In 1/41, sequencing was performed, showing nonsense mutation, in exon 41. Our study of the genetic profile of chileans patients is similar to previously reported, deletions are the most frequent alterations. It should be noted that biopsy continues to be an important tool for confirming diagnostics, due to our countries limited access to sequencing techniques. Because of this, we can extrapolate and conclude that the large percentage of patients with compatible muscle biopsy and negative MLPA, could correspond to point mutations, which would then coincide with the published. Therefore, it is important to make genetic diagnosis advances thus giving us the possibility of integrating new therapies and the ability to offer genetic counseling.

PD.1.05 Molecular Characterization of EGFR Somatic Mutations in Lung Adenocarcinoma Tumors from Chilean Patients

PD.1.05 Molecular Characterization of EGFR Somatic Mutations in Lung Adenocarcinoma Tumors from Chilean Patients

P25 Preliminary Experience With the Use of Osimertinib in Chilean Patients

P25 Preliminary Experience With the Use of Osimertinib in Chilean Patients

P07 Preliminary Orthogonal Analysis of EML4-ALK Gene Fusion Detection Methods in Chilean Patients with Lung Adenocarcinoma

P07 Preliminary Orthogonal Analysis of EML4-ALK Gene Fusion Detection Methods in Chilean Patients with Lung Adenocarcinoma

PD.1.04 A Comprehensive Description of the Molecular Epidemiology of Somatic Mutations in Actionable Genes in NSCLC Chilean Patients

PD.1.04 A Comprehensive Description of the Molecular Epidemiology of Somatic Mutations in Actionable Genes in NSCLC Chilean Patients

Prognostic value of HPV status and tumoral markers (p16/Ki67) in chilean patients with anal cancer

Prognostic value of HPV status and tumoral markers (p16/Ki67) in chilean patients with anal cancer

Cross-cultural adaptation and validation of the VISA-A questionnaire for Chilean Spanish-speaking patients

BackgroundThe purpose of this study is to translate, culturally adapt, and validate the VISA-A questionnaire for Chilean Spanish speakers with Achilles tendinopathy (AT), which has been originally developed for English-speaking population.MethodsAccording to the guidelines published by Beaton et al., the questionnaire was translated and culturally adapted to Chilean patients in six steps: initial translation, synthesis of the translation, back translation, expert committee review, test of the pre-final version (cohort n = 35), and development of VISA-A-CH. The resulting Chilean version was tested for validity on 60 patients: 20 healthy individuals (group 1), 20 patients with a recently diagnosed AT (group 2), and 20 with a severe AT that already initiated conservative treatment with no clinical improvement (group 3). The questionnaire was completed three times by each participant: at the time of study enrollment, after an hour, and after a week of the initial test.ResultsAll six steps were successfully completed for the translation and cultural adaptation of the VISA-A-CH. VISA-A-CH final mean scores in the healthy group was significantly higher than those in the other groups. Group 3 had the lowest scores. Validity showed excellent test-retest reliability (rho c = 0.999; Pearson’s r = 1.000) within an hour and within a week (rho c = 0.837; Pearson’s r = 0.840).ConclusionsVISA-A was translated and validated to Chilean Spanish speakers successfully, being comparable to the original version. We believe that VISA-A-CH can be recommended as an important tool for clinical and research settings in Chilean and probably Latin-American Spanish speakers.

Las alteraciones de la microbiota intestinal en la patogenia del hígado graso no alcohólico

Non-alcoholic fatty liver disease (NAFLD) is currently considered in Chile and worldwide, as the main cause of cirrhosis and liver transplantation. It is therefore one of the main public health objectives for reducing its prevalence. In last years, it was suggested that the intestinal microbiota (IM) might contribute to the pathophysiology of NAFLD, as well as in the progression toward nonalcoholic steatohepatitis (NASH) and cirrhosis. It is known that changes in the composition of IM are associated with alterations in intestinal permeability and the production of inflammatory metabolites. These alterations are part of the pathophysiological mechanisms leading to the development of NASH. However studies on MI in patients with NAFLD and NASH in Chile are scarce. Through a research grant, recently awarded at the Hospital Clínico Universidad de Chile, we aim to confirm and characterize the intestinal dysbiosis associated with NAFLD in Chilean patients and to establish the relationship between the changes in microbial composition with the progression of liver damage. The description of these alterations represents an opportunity to explore new therapeutic approaches for future interventions. In effect, through the restoration of an intestinal microbial environment towards homeostasis in these patients, we expect to reverse or improve the progression of damage provoked by this disease.

Survival of 1,103 Chilean patients with multiple myeloma receiving different therapeutic protocols from 2000 to 2016

Multiple myeloma (MM) is one of the most common malignancies found in hematology. To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016. Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2. The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p < 0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p < 0.01). Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

Explorations in the development of novel early diagnosis and disease monitoring tools in digestive tract cancers

Exploring the possibility that genomic DNA (exoDNA) may represent a highly promising next-generation biomarker for early detection. The research team hope to validate the use of circulating exoDNA as a new generation biomarker using KRAS mutation status as a surrogate source of primary tumour information. This may be useful for early diagnosis in cases of pancreatic biliary cancer (PBC) and a valid tool for clinical decision making, disease monitoring and therapeutic stratification. Point mutations in KRAS are found in 50% of gallbladder cancers, thus the team will use an ultra-sensitive droplet digital PCR (ddPCR) platform to identify mutant KRAS in samples of circulating exoDNA isolated from 75 early stage pancreatic biliary cancer patients at the time of diagnosis. These samples will be matched with exoDNA from 'benign disease' controls that have been match on the basis of age and gender. Roa hopes to use exoDNA to query the 'actionable' exome in PBC using a head-to-head comparison using next generation sequencing. Bizama's main objective in investigating patient-derived organoids is to establish and characterise organoid cultures from GBC patients in order to evaluate the drug responses of these organoids both to standard treatments and to specific pathway inhibitors. Current human GBC research lacks in vitro models that can capture the pathophysiological traits of the original tumour and normal epithelia. The research team hope to demonstrate that organoid cultures can be successfully established from normal and tumour gallbladder tissues from Chilean patients and that these organoids will be representative of the primary specimens. The team plan to develop an organoid culture platform as a prototype for the prediction of prognosis and efficiency of standard and targeted therapy. This ex vivo organoids model project may help clinicians predict the response of particular patients to specific treatments, thus avoiding unnecessary therapies.

Determination and hierarchy of clinical signs for early detection of cerebrotendinous xanthomatosis

Cerebrotendinous Xanthomatosis (CTX) is an autosomal recessive disease caused by mutations in the CYP27A1 gene resulting in a decreased synthesis of bile acids. An early diagnosis and treatment would reduce the longterm complications observed in this disease. To identify and hierarchize initial clinical signs of CTX to establish an early diagnostic suspicion index. Clinical information was collected from 387 patients diagnosed with CTX, published in MEDLINE between 1968 and 2016. Clinical manifestations were identified, determining their prevalence and age of onset. Sensitivity, specificity and the positive Likelihood ratio (LR+) was calculated for each clinical sign evaluated. The average ages for early symptoms' onset and CTX diagnosis were 13.3 ± 10.6 years and 34.6 ± 12.6 years respectively. The early clinical signs and their respective LR+ were: juvenile cataracts (143), epilepsy (81), chronic diarrhea (15.6) and psychomotor development delay (3.4). The presence of consanguinity among parents resulted in a LR+ of 31. The combination of two early signs increased the post-test probability to 30%. If the early diagnostic criteria would have been applied in three Chilean patients with diagnosis of CTX, their disease would have been diagnosed from 12 to 25 years earlier. The use of a hierarchical system of predictive clinical signs allows an early screening of CTX, which may avoid the natural progression of the disease using an appropriate treatment.

Study of Ras/MAPK pathway gene variants in Chilean patients with Cryptorchidism.

Cryptorchidism is one of the most common congenital disorders in boys, and several genetic, hormonal, and environmental factors have been proposed as possible causes for this genitourinary defect. Genetic factors have been intensively searched, but relatively few pathogenic variants have been described. Cryptorchidism is a frequent finding in patients with RASopathies, a group of syndrome caused by mutations in genes of the Ras/MAPK pathway. Our aim was to determine whether patients with isolated cryptorchidism (IC) exhibit Ras/MAPK pathway gene variants associated with RASopathies. Two hundred thirty-nine patients with IC were recruited after orchidopexy. Determination of Ras/MAPK pathway gene variants was performed by high-resolution melting (HRM) analysis followed by sequencing. Restriction or allele-specific amplification assay was applied to (i) variant confirmation; (ii) search in healthy controls; and (iii) segregation analysis. Controls correspond to 100 healthy Chilean adults without a history of cryptorchidism. Molecular analysis showed one synonymous substitution (BRAF_p.Q456Q) in two patients and four missense substitutions (SOS1_ p.R497Q, BRAF_ p.F595L, NRAS_ p.T50I, and MAP2K2_ p.Y134C) in five patients. Our results suggest that some patients with isolated cryptorchidism, but with no evidence of dysmorphic features suggestive of RASopathies, may harbor Ras/MAPK pathway gene alterations.

Discrete typing units of Trypanosoma cruzi detected by real-time PCR in Chilean patients with chronic Chagas cardiomyopathy

Chagas disease is a major public health problem in Latin America and has spread to other countries due to immigration of infected persons. 10–30% of patients with chronic Chagas disease will develop cardiomyopathy. Chagas cardiomyopathy is the worst form of the disease, due to its high morbidity and mortality. Because of its prognostic value and adequate medical monitoring, it is very important to identify infected people who could develop Chagas cardiomyopathy. The aim of this study was to determine if discrete typing units (DTUs) of Trypanosoma cruzi are related to the presence of heart disease in patients with chronic Chagas disease. A total of 86 untreated patients, 41 with cardiomyopathy and 45 without heart involvement were submitted to clinical study. Electrocardiograms and echocardiograms were performed on the group of cardiopaths, in which all important known causes of cardiomyopathy were discarded. Sinus bradycardia and prolonged QTc interval were the most frequent electrocardiographic alterations and patients were classified in group I (46%) and group II (54%) of New York Hearth Association. In all cases real-time PCR genotyping assays were performed. In the group with cardiomyopathy, the most frequent DTU was TcI (56.1%), followed by TcII (19.5%). Mixed infections TcI + TcII were observed in 7.3% of the patients. In the group without cardiac pathologies, TcI and TcII were found at similar rates (28.9 and 31.1%, respectively) and mixed infections TcI + TcII in 17.8% of the cases. TcIII and TcIV were not detected in any sample. Taken together, our data indicate that chronic Chagas cardiomyopathy in Chile can be caused by strains belonging to TcI and TcII.

Early disease stage of Multiple Sclerosis in Chilean patients: cognitive impairment is a key domain and does not relate to MRI measures (P1.412)

Early disease stage of Multiple Sclerosis in Chilean patients: cognitive impairment is a key domain and does not relate to MRI measures (P1.412)

29P Preliminary assessment of a targeted breakpoint NGS assay for ALK gene fusion detection in lung adenocarcinoma samples from Chilean patients

29P Preliminary assessment of a targeted breakpoint NGS assay for ALK gene fusion detection in lung adenocarcinoma samples from Chilean patients