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The dawn of the Internet of Things (IoT) paradigm has brought about a series of novel services never imagined until recently. However, certain deployments such as those employing Low-Power Wide-Area Network (LPWAN)-based technologies may present severe network restrictions in terms of throughput and supported packet length. This situation prompts the isolation of LPWAN systems on islands with limited interoperability with the Internet. For that reason, the IETF's LPWAN working group has proposed a Static Context Header Compression (SCHC) scheme that permits compression and fragmentation of and IPv6/UDP/CoAP packets with the aim of making them suitable for transmission over the restricted links of LPWANs. Given the impact that such a solution can have in many IoT scenarios, this paper addresses its real evaluation in terms not only of latency and delivery ratio improvements, as a consequence of different compression and fragmentation levels, but also of the overhead in end node resources and useful payload sent per fragment. This has been carried out with the implementation of middleware and using a real testbed implementation of a LoRaWAN-to-IPv6 architecture together with a publish/subscribe broker for CoAP. The attained results show the advantages of SCHC, and sustain discussion regarding the impact of different SCHC and LoRaWAN configurations on the performance. It is highlighted that necessary end node resources are low as compared to the benefit of delivering long IPv6 packets over the LPWAN links. In turn, fragmentation can impose a lack of efficiency in terms of data and energy and, hence, a cross-layer solution is needed in order to obtain the best throughput of the network.
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The distribution of Internet of Things (IoT) devices in remote areas and the need for network resilience in such deployments is increasingly important in smart spaces covering scenarios, such as agriculture, forest, coast preservation, and connectivity survival against disasters. Although Low-Power Wide Area Network (LPWAN) technologies, like LoRa, support high connectivity ranges, communication paths can suffer from obstruction due to orography or buildings, and large areas are still difficult to cover with wired gateways, due to the lack of network or power infrastructure. The proposal presented herein proposes to mount LPWAN gateways in drones in order to generate airborne network segments providing enhanced connectivity to sensor nodes wherever needed. Our LoRa-drone gateways can be used either to collect data and then report them to the back-office directly, or store-carry-and-forward data until a proper communication link with the infrastructure network is available. The proposed architecture relies on Multi-Access Edge Computing (MEC) capabilities to host a virtualization platform on-board the drone, aiming at providing an intermediate processing layer that runs Virtualized Networking Functions (VNF). This way, both preprocessing or intelligent analytics can be locally performed, saving communications and memory resources. The contribution includes a system architecture that has been successfully validated through experimentation with a real test-bed and comprehensively evaluated through computer simulation. The results show significant communication improvements employing LoRa-drone gateways when compared to traditional fixed LoRa deployments in terms of link availability and covered areas, especially in vast monitored extensions, or at points with difficult access, such as rugged zones.
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Internet of Vehicles (IoV) is a hot research niche exploiting the synergy between Cooperative Intelligent Transportation Systems (C-ITS) and the Internet of Things (IoT), which can greatly benefit of the upcoming development of 5G technologies. The variety of end-devices, applications, and Radio Access Technologies (RATs) in IoV calls for new networking schemes that assure the Quality of Service (QoS) demanded by the users. To this end, network slicing techniques enable traffic differentiation with the aim of ensuring flow isolation, resource assignment, and network scalability. This work fills the gap of 5G network slicing for IoV and validates it in a realistic vehicular scenario. It offers an accurate bandwidth control with a full flow-isolation, which is essential for vehicular critical systems. The development is based on a distributed Multi-Access Edge Computing (MEC) architecture, which provides flexibility for the dynamic placement of the Virtualized Network Functions (VNFs) in charge of managing network traffic. The solution is able to integrate heterogeneous radio technologies such as cellular networks and specific IoT communications with potential in the vehicular sector, creating isolated network slices without risking the Core Network (CN) scalability. The validation results demonstrate the framework capabilities of short and predictable slice-creation time, performance/QoS assurance and service scalability of up to one million connected devices.
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OBJECTIVE: Cardiac involvement in SSc is characterized by myocardial fibrosis, arrhythmias and pericarditis. Prevalence studies have shown variable results. The objective of this study was to determine the prevalence of cardiac involvement in SSc patients using the non-invasive, highly sensitive diagnostic methods of cardiac MRI and coronary angiotomography. METHODS: We included 62 SSc patients and excluded those with heart disease prior to the onset of SSc, renal failure, diabetes mellitus, hyperlipidaemia, arterial hypertension, untreated thyroid disease, cor pulmonale, pregnancy or contraindications to performing cardiac MRI. All underwent clinical and laboratory evaluation, ECG, coronary angiotomography and cardiac MRI. RESULTS: The prevalence of myocardial fibrosis was 45% and was higher in dcSSc (59%) than in lcSSc patients (33%; P = 0.04). The mean left ventricular ejection fraction (LVEF) was lower in patients with myocardial fibrosis (56%) than in those without fibrosis (63%; P = 0.0009); myocardial fibrosis on MRI was more frequent in the basal-septal segments of the LV. Seventy-nine per cent of patients had subendocardial perfusion defects and these were associated with higher ultrasensitive serum CRP values. There was no association of myocardial fibrosis or microvascular damage with atherosclerosis. CONCLUSION: The prevalence of myocardial fibrosis on MRI attributable to SSc is 45%, is more frequent and severe in dcSSc patients, is associated with lower LVEF and affects mainly basal LV walls. Microvascular damage in SSc is common and is associated with elevated ultrasensitive CRP levels. Cardiac damage due to SSc is not associated with coronary artery disease.
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Enfermedad de la Arteria Coronaria/diagnóstico , Microvasos/patología , Miocardio/patología , Esclerodermia Difusa/diagnóstico , Esclerodermia Limitada/diagnóstico , Adulto , Técnicas de Imagen Cardíaca , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/fisiopatología , Estudios Transversales , Electrocardiografía , Femenino , Fibrosis , Cardiopatías/diagnóstico , Cardiopatías/etiología , Cardiopatías/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Imagen de Perfusión Miocárdica , Esclerodermia Difusa/complicaciones , Esclerodermia Limitada/complicaciones , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Volumen Sistólico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Approximately 5% of all breast cancers can be attributed to a mutation in the BRCA1 or BRCA2 gene. The genetic component of breast cancer in Colombia has been, for the most part, studied on cases from the Bogota region. Five different founder mutations were in two studies of breast cancer patients in the Bogota region. It is important that the frequency of mutations be established among unselected cases of breast cancer of other regions of Colombia in order to estimate the genetic burden of this cancer in Colombia and to plan genetic services. The aim of this study was to establish the mutation frequencies of the BRCA genes in breast cancer patients unselected for family history or age, from Medellin, Colombia. METHODS: We enrolled 280 unselected women with breast cancer from a large public hospital in Medellin, Colombia. A detailed family history from each patient and a blood sample was obtained and processed for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques including a panel of recurrent Hispanic BRCA mutations which consists of fifty BRCA1 mutations and forty-six BRCA2 mutations, including the five recurrent Colombian BRCA mutations. All mutations were confirmed by direct sequencing. RESULTS: Genetic testing was successfully completed for 244 of the 280 cases (87%). Among the 244 cases, three deleterious mutations were identified (two in BRCA1 and one in BRCA2) representing 1.2% of the total. The average age of breast cancer in the mutation-positive cases was 34 years. The two BRCA1 mutations were known founder mutations (3450del4 in exon 11 and A1708E in exon 18). The BRCA2 mutation was in exon 11 (5844del5) and has not been previously reported in individuals of Colombian descent. Among the three mutation-positive families was a breast cancer family and two families with no history of breast or ovarian cancer. CONCLUSION: The frequency of BRCA mutations in unselected breast cancer cases from the Medellin region of Colombia is low and is approximately 1.2%.
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Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia Adyuvante , Terapia Neoadyuvante , Neoplasias Pancreáticas/terapia , Adenocarcinoma/diagnóstico , Anciano , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , GemcitabinaRESUMEN
Neoadjuvant chemotherapy is an accepted strategy for patients with locally advanced breast cáncer. This approach increases the possibilities of conservative treatment and improves the resectability rates of initially unresectable tumors. In addition, preoperative systemic therapy allows the evaluation of prognostic and predictive factors, dynamically and in vivo. Since over 80% of these tumors express estrogen receptors (ER), endocrine therapy seems a logical treatment to employ in the neoadjuvant setting. The advent of new drugs that regúlate the ER function, along with the results of several clinical studies with the use of neoadjuvant endocrine therapy, support the feasibility and safety of utilizing this strategy before surgery. We herein analyze the available clinical evidence about the use of neoadjuvant therapy aiming to regúlate the activity of the ER. We also discuss the valué of predictive factors that could help the oncologist to select those patients most likely to benefit from this approach and the role of endocrine therapy as a research instrument.
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Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/química , Ensayos Clínicos como Asunto , Femenino , Humanos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
Introduction: Breast cancer is the most common type of cancer and the leading cause of death by cancer in women in Colombia. Approximately 15 to 20% of breast cancers overexpress HER2. Objective: To analyze the relationship between multiple clinical and histological variables and pathological complete response in patients with HER2-positive breast cancer undergoing neoadjuvant therapy in a specialized cancer center in Colombia. Materials and methods: We performed a retrospective analysis of non-metastatic HER2-positive breast cancer patients who received neoadjuvant therapy between 2007 and 2020 at the Instituto de Cancerología Las Americas Auna (Medellín, Colombia). Assessed parameters were tumor grade, proliferation index, estrogen receptor, progesterone receptor, HER2 status, type of neoadjuvant therapy, pathologic complete response rates, and overall survival. Results: Variables associated with low pathologic complete response rates were tumor grades 1-2 (OR = 0.55; 95% CI = 0.37-0.81; p = 0.03), estrogen receptor positivity (OR =0.65; 95%; CI = 0.43-0.97; p=0.04), and progesterone receptor positivity (OR = 0.44; 95% CI = 0.29-0.65; p = 0.0001). HER2 strong positivity (score 3+) was associated with high pathological complete response rates (OR = 3.3; 95% CI = 1.3-8.35; p=0.013). Five-year overall survival was 91.5% (95% CI = 82.6-95.9) in patients with pathological complete response and 73.6% (95% CI = 66.4-79.6) in patients who did not achieve pathological complete response (p = 0.001). Additionally, the pathological complete response rate was three times higher in patients receiving combined neoadjuvant chemotherapy with anti-HER2 therapy than in those with chemotherapy alone (48% versus 16%). Conclusions: In patients with HER2-positive breast cancer, tumor grade 3, estrogen receptor negativity, progesterone receptor negativity, strong HER2 positivity (score 3+), and the use of the neoadjuvant trastuzumab are associated with higher pathological complete response rates.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante , Receptores de Progesterona/uso terapéutico , Receptor ErbB-2/uso terapéutico , Receptores de Estrógenos/uso terapéutico , Estudios Retrospectivos , Colombia , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados , Trastuzumab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Thymic epithelial tumours are rare and highly heterogeneous. Reports from the United States suggest an overall incidence of 0.15 per 100,000/year. In contrast, the incidence of these tumours in Latin America is largely unknown and reports are scarce, somewhat limited to case reports. METHODS: Herein, we report a series of 38 thymic tumours from a single institution, retrospectively incorporated into this study. Patient characteristics and outcomes including age, sex, stage, paraneoplastic syndromes, treatment regimens and the date of decease were obtained from medical records. RESULTS: Most cases in our series were females and young age (<50 years old) and early stage by Masaoka-Koga or the Moran staging systems. Also, a 34% of patients had myasthenia gravis (MG). Next, we analysed overall survival rates in our series and found that the quality of surgery (R0, R1 or R2), MG status and staging (Masaoka-Koga, Moran or TNM) were prognostic factors. Finally, we compared our data to larger thymic tumour series. CONCLUSIONS: Overall, our study confirms complete surgical resection as the standard, most effective treatment for thymic epithelial tumours. Also, the Masaoka-Koga staging system remains as a reliable prognostic factor but also the Moran staging system should be considered for thymomas.
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BACKGROUND: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain. MATERIALS AND METHODS: We retrieved and analysed medical records from a total of 156 Chilean stage I-III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres. RESULTS: Median age was 51 years (range: 24-81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216). CONCLUSIONS: To the best of authors' knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors' results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.
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Objective: Clinical guidelines recommend the use of endocrine therapy (ET) in advanced hormone receptor positive (HR+) human epidermal growth factor receptor type 2 negative (HER2-) breast cancer (BC) patients in the absence of visceral disease or ET resistance. Furthermore, studies indicate similar response and survival rates using ET or cytotoxic chemotherapy (CT).Methods: Herein, we assessed clinical characteristics, type of systemic therapy and survival rates of advanced HR + HER2-BC patients in our database.Results: A total of 172 advanced HR + HER2-BC patients were treated at our institution between 1997 and 2019. Sixty percent received first-line ET (4% received combined ET). Median age of this subset was 55 years (range: 30-86). Similarly, the median age of patients that received CT was 54 years (range: 21-83). Over time, 30% of patients received ET in the 2000-2005 period; this increased to 70% in the 2016-2019 period (p = .045). Overall survival (OS) was 97 months and 51 months for patients treated with ET or CT, respectively (p = .002).Conclusions: To the best of our knowledge this is the first study assessing the use of ET in Chilean advanced HR + HER2-BC patients. Several patients in our institution receive CT without indication. The increase in ET usage over time can be attributed to better and faster immunohistochemical detection methods for Estrogen Receptor (ER), changes in educational and government policies, and a wider variety of ET options. Finally, clinical trials have failed to demonstrate a substantial benefit of CT over ET in this setting.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/química , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Receptor ErbB-2/análisis , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Adulto JovenRESUMEN
Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein-Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53-). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic.
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PURPOSE: Like other malignancies, GI stromal tumors (GIST) are highly heterogeneous. This not only applies to histologic features and malignant potential, but also to geographic incidence rates. Several studies have reported GIST incidence and prevalence in Europe and North America. In contrast, GIST incidence rates in South America are largely unknown, and only a few studies have reported GIST prevalence in Latin America. PATIENTS AND METHODS: Our study was part of a collaborative effort between Chile and Mexico, called Salud con Datos. We sought to determine GIST prevalence and patients' clinical characteristics, including survival rates, through retrospective analysis. RESULTS: Overall, 624 patients were included in our study. Our results found significant differences between Mexican and Chilean registries, such as stage at diagnosis, primary tumor location, CD117-positive immunohistochemistry status, mitotic index, and tumor size. Overall survival (OS) times for Chilean and Mexican patients with GIST were 134 and 156 months, respectively. No statistically significant differences in OS were detected by sex, age, stage at diagnosis, or recurrence status in both cohorts. As expected, patients categorized as being at high risk of recurrence displayed a trend toward poorer progression-free survival in both registries. CONCLUSION: To the best of our knowledge, this is the largest report from Latin America assessing the prevalence, clinical characteristics, postsurgery risk of recurrence, and outcomes of patients with GIST. Our data confirm surgery as the standard treatment of localized disease and confirm a poorer prognosis in patients with regional or distant disease. Finally, observed differences between registries could be a result of registration bias.
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Tumores del Estroma Gastrointestinal , Sistema de Registros , Chile/epidemiología , Europa (Continente) , Tumores del Estroma Gastrointestinal/epidemiología , Humanos , América Latina/epidemiología , México/epidemiología , Recurrencia Local de Neoplasia , América del Norte , Estudios RetrospectivosRESUMEN
Background: Lung cancer (LC) is the second leading cause of cancer death in Chile, causing >3,000 deaths every year. Epidemiological LC data in Chile is scarce and scattered. Here, we aimed to quantify the prevalence of Epidermal Growth Factor Receptor (EGFR) gene mutations in a Chilean cancer center. These data may identify individuals that could benefit from targeted therapies such as Tyrosine Kinase Inhibitors (TKIs). Methods: A total of 1,405 Biopsies from 1,381 LC patients were retrospectively analyzed retrieving clinical data from EGFR mutants including age, gender, histological type, smoking habits and type of EGFR mutation. We also analyzed overall survival (OS) rates. Results: From all patients 21.7% had clinically relevant EGFR mutations, and a median age at diagnosis of 65 years. Most were female (64%), classified as adenocarcinomas (94.5%), and non-smokers/light smokers (93.1%). The most prevalent mutation was exon-19 deletions (50.6%) followed by Leucine-to Arginine 858; OS was 15 months. Clinical follow-up information was available for 83 patients. The use of TKIs in these patients significantly improved OS. Conclusion: The prevalence of EGFR mutations in the studied population was 21.7%, comparable to other countries in Latin America. The most frequent EGFR mutation was exon-19 deletion, OS in this group was 15 months, and TKIs significantly improved OS.
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Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Mutación , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/genética , Chile/epidemiología , Estudios Transversales , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.
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Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/epidemiología , Sistema de Registros , Adulto , Anciano , Anciano de 80 o más Años , Chile/epidemiología , Cromogranina A/sangre , Femenino , Humanos , Ácido Hidroxiindolacético/sangre , Incidencia , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/mortalidad , Estimación de Kaplan-Meier , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/mortalidad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/mortalidad , Serotonina/sangre , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/mortalidad , Resultado del Tratamiento , Adulto JovenRESUMEN
Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.
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With the aim of determining the formation of alpha-dicarbonyl intermediates during beer aging on the shelf, alpha-dicarbonyls were identified and quantified after derivatization with 1,2-diaminobenze to generate quinoxalines. The sensory effects of alpha-dicarbonyls were evaluated by the quantification of key Strecker aldehydes and by GC-olfactometry (GCO)analysis of beer headspace using solid phase microextraction. Four alpha-dicarbonyls, reported here for the first time, were detected in fresh and aged beers, three were derived from the 2,3-enolization pathway of mono- and disaccharides, and the fourth was derived from the epimerization of 3-deoxy-2-hexosulose. Ten alpha-dicarbonyls were quantified during beer processing and during different periods of beer aging at 28 degrees C. The aging periods were from 15 to 105 days. During beer aging, 1-deoxydiuloses were produced and degraded, while 1,4-dideoxydiuloses were produced at the highest rates. The GCO analysis indicated that forced beer aging increased the amounts of furaneol, trans-2-nonenal, and phenylacetaldehyde. The blockage of alpha-dicarbonyls inhibited the accumulation of sensory-active aldehydes in the beer headspace.
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Cerveza/análisis , Conservación de Alimentos , Acetaldehído/análogos & derivados , Acetaldehído/análisis , Aldehídos/análisis , Cromatografía de Gases , Desoxiglucosa/análogos & derivados , Desoxiglucosa/análisis , Manipulación de Alimentos , Furanos/análisis , Humanos , Olfato , Factores de TiempoRESUMEN
Introduction. Breast cancer is the most common type of cancer and the leading cause of death by cancer in women in Colombia. Approximately 15 to 20% of breast cancers overexpress HER2. Objective. To analyze the relationship between multiple clinical and histological variables and pathological complete response in patients with HER2-positive breast cancer undergoing neoadjuvant therapy in a specialized cancer center in Colombia. Materials and methods. We performed a retrospective analysis of non-metastatic HER2- positive breast cancer patients who received neoadjuvant therapy between 2007 and 2020 at the Instituto de Cancerología Las Americas Auna (Medellín, Colombia). Assessed parameters were tumor grade, proliferation index, estrogen receptor, progesterone receptor, HER2 status, type of neoadjuvant therapy, pathologic complete response rates, and overall survival. Results. Variables associated with low pathologic complete response rates were tumor grades 1-2 (OR = 0.55; 95% CI = 0.37-0.81; p = 0.03), estrogen receptor positivity (OR = 0.65; 95%; CI = 0.43-0.97; p=0.04), and progesterone receptor positivity (OR = 0.44; 95% CI = 0.29-0.65; p = 0.0001). HER2 strong positivity (score 3+) was associated with high pathological complete response rates (OR = 3.3; 95% CI = 1.3-8.35; p=0.013). Five-year overall survival was 91.5% (95% CI = 82.6-95.9) in patients with pathological complete response and 73.6% (95% CI = 66.4-79.6) in patients who did not achieve pathological complete response (p = 0.001). Additionally, the pathological complete response rate was three times higher in patients receiving combined neoadjuvant chemotherapy with anti- HER2 therapy than in those with chemotherapy alone (48% versus 16%). Conclusion. In patients with HER2-positive breast cancer, tumor grade 3, estrogen receptor negativity, progesterone receptor negativity, strong HER2 positivity (score 3+), and the use of the neoadjuvant trastuzumab are associated with higher pathological complete response rates.
Introducción. El adenocarcinoma de seno es el tipo de cáncer más frecuente y con mayor tasa de mortalidad asociada en mujeres en Colombia. Aproximadamente entre el 15 al 20 % de estos cánceres sobreexpresan el gen HER2. Objetivo. Analizar las asociaciones existentes entre múltiples variables clínicas e histológicas con respecto a la respuesta patológica completa en pacientes con cáncer de mama HER2 positivo que fueron tratadas con quimioterapia neoadyuvante en un centro especializado en el tratamiento del cáncer en Colombia. Materiales y métodos. Se realizó un análisis retrospectivo de las pacientes con cáncer de mama HER2 positivo, no metastásicas, que recibieron quimioterapia neoadyuvante entre el 2007 y el 2020 en el Instituto de Cancerología Las Américas Auna (Medellín, Colombia). Se evaluaron los parámetros de grado tumoral, índice de proliferación, estatus de receptores de estrógeno y de progesterona, tipo de quimioterapia neoadyuvante recibida, tasas de respuesta patológica completa y supervivencia global. Resultados. Las variables asociadas con tasas de respuesta patológica completa más bajas fueron grados tumorales 1-2 (OR = 0,55; IC 95% = 0,37-0,81; p= 0,03), positividad de receptores de estrógeno (OR = 0,65; IC 95 % = 0,43-0,97; p = 0,04) y positividad de receptores de progesterona (OR = 0,44; IC 95 % = 0,29-0,65; p = 0,0001). La positividad fuerte para HER2 (puntaje 3+) se asoció a tasas de respuesta patológica completa más altas (OR = 3.3; IC 95 % = 1,3-8,35; p = 0,013). La supervivencia global a cinco años fue del 91,5 % (IC 95 % = 82,6-95,9) en pacientes con respuesta patológica completa y del 73,6 % (IC 95 % = 66.4-79.6) en pacientes sin respuesta patológica completa (p = 0.001). La tasa de respuesta patológica completa fue tres veces mayor en los pacientes que recibieron quimioterapia neoadyuvante con terapia anti-HER2 comparado con aquellos que recibieron quimioterapia sola sin agentes anti-HER2 (48 % versus 16 %). Conclusión. En pacientes con cáncer de mama con sobreexpresión de HER2, grado tumoral tres, receptores de estrógeno y progesterona negativos, positividad fuerte para HER2 (puntaje 3+) y uso de quimioterapia neoadyuvante con trastuzumab se asociaron con mayores tasas de respuesta patológica completa.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , ColombiaRESUMEN
Gastric cancer (GC) is the world's second-leading cause of neoplastic mortality. Genetic alterations, response to treatments, and mortality rates are highly heterogeneous across different regions. Within Latin America, GC is the leading cause of cancer death in Chile, affecting 17.6 per 100,000 people and causing >3000âdeaths/y. Clinical outcomes and response to "one size fits all" therapies are highly heterogeneous and thus a better stratification of patients may aid cancer treatment and response.The Gastric Cancer Task Force is a Chilean collaborative, noninterventional study that seeks to stratify gastric adenocarcinomas using clinical outcomes and genomic, epigenomic, and protein alterations in a cohort of 200 patients. Tumor samples from the Pathology Department and the Cancer Center at UC-Christus healthcare network, Pontificia Universidad Católica de Chile will be analyzed using a panel of 143 known cancer genes (Oncomine Comprehensive Assay) at the Center of Excellence in Precision Medicine in Santiago, Chile. In addition, promoter methylation for selected genes will be performed along with tissue microarray for clinically relevant proteins (e.g., PD-L1, Erb-2, VEGFR2, among others) and Helicobacter pylori and Epstein-Barr virus status. Obtained data will be correlated to 120 clinical parameters retrieve from medical records, including general patient information, cancer history, laboratory studies, comorbidity index, chemotherapy, targeted therapies, efficacy, and follow-up.The development of a clinically meaningful classification that encompasses comprehensive clinical and molecular parameters may improve patient treatment, predict clinical outcomes, aid patient selection/stratification for clinical trials and may offer insights into future preventive and/or therapeutic strategies in patients from Latin America region. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03158571, Registered on May 18, 2017.
Asunto(s)
Adenocarcinoma/clasificación , Neoplasias Gástricas/clasificación , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Chile , Metilación de ADN , Femenino , Herpesvirus Humano 4/genética , Humanos , Masculino , Mutación , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Análisis de Matrices TisularesRESUMEN
RESUMEN La infección por el coronavirus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-COV2, por sus siglas en inglés), ha sido asociada con múltiples manifestaciones cardiovasculares. El mecanismo por el cual el virus afecta el corazón es objeto de discusión; sin embargo, se ha planteado que el receptor de la enzima convertidora de angiotensina (ACE2) sirve como entrada directa del virus. Así mismo, un estado de inflamación mediado por una tormenta de citoquinas puede generar falla multiorgánica y explicar algunas manifestaciones cardíacas. Las principales asociaciones al sistema cardiovascular reportadas en la infección por COVID-19 son el síndrome coronario agudo, la falla cardiaca aguda, el choque cardiogénico y las arritmias. La pericarditis aguda es un síndrome inflamatorio de etiología principalmente viral, pero su relación con la infección por SARS-COV2 parece ser infrecuente, con pocos reportes en la literatura. Se presenta el caso de una paciente que desarrolló pericarditis concomitante a la infección por SARS-COV2.
SUMMARY Infection by coronavirus type 2 that causes severe acute respiratory syndrome (SARS-CoV-2) has been associated with multiple cardiovascular manifestations. The mechanism by which the virus affects the heart is under discussion; however, it has been proposed that the angiotensinconverting enzyme 2 (ACE2) serves as a direct entry point for the virus; likewise, the state of inflammation mediated by cytokine storm can generate multiorgan failure, explaining some cardiac manifestations. The main associations to the cardiovascular system reported in COVID-19 infection are acute coronary syndrome, acute heart failure, cardiogenic shock and arrhythmias. Acute pericarditis is an inflammatory syndrome of mainly viral etiology, and its relationship to SARS-CoV-2 infection seems infrequent, with few reports in the literature. We present the case of a patient who developed pericarditis, concomitant with SARS-CoV-2 infection.