Hepatic spheroid-on-a-chip: Fabrication and characterization of a spheroid-based in vitro model of the human liver for drug screening applications.

The integration of microfabrication and microfluidics techniques into cell culture technology has significantly transformed cell culture conditions, scaffold architecture, and tissue biofabrication. These tools offer precise control over cell positioning and enable high-resolution analysis and testing. Culturing cells in 3D systems, such as spheroids and organoids, enables recapitulating the interaction between cells and the extracellular matrix, thereby allowing the creation of human-based biomimetic tissue models that are well-suited for pre-clinical drug screening. Here, we demonstrate an innovative microfluidic device for the formation, culture, and testing of hepatocyte spheroids, which comprises a large array of patterned microwells for hosting hepatic spheroid culture in a reproducible and organized format in a dynamic fluidic environment. The device allows maintaining and characterizing different spheroid sizes as well as exposing to various drugs in parallel enabling high-throughput experimentation. These liver spheroids exhibit physiologically relevant hepatic functionality, as evidenced by their ability to produce albumin and urea at levels comparable to in vivo conditions and the capability to distinguish the toxic effects of selected drugs. This highlights the effectiveness of the microenvironment provided by the chip in maintaining the functionality of hepatocyte spheroids. These data support the notion that the liver-spheroid chip provides a favorable microenvironment for the maintenance of hepatocyte spheroid functionality.

Custom-made holey graphene via scanning probe block co-polymer lithography.

Oxidative chemical etching of metal nanoparticles (NPs) to produce holey graphene (hG) suffers from the presence of aggregated NPs on the graphene surface triggering heterogeneous etching rates and thereby producing irregular sized holes. To encounter such a challenge, we investigated the use of scanning probe block co-polymer lithography (SPBCL) to fabricate precisely positioned silver nanoparticles (AgNPs) on graphene surfaces with exquisite control over the NP size to prevent their aggregation and consequently produce uniformly distributed holes after oxidative chemical etching. SPBCL experiments were carried out via printing an ink suspension consisting of poly(ethylene oxide-b-2-vinylpyridine) and silver nitrate on a graphene surface in a selected pattern under controlled environmental and instrumental parameters followed by thermal annealing in a gaseous environment to fabricate AgNPs. Scanning electron microscopy revealed the uniform size distribution of AgNPs on the graphene surface with minimal to no aggregation. Four main sizes of AgNPs were obtained (37 ± 3, 45 ± 3, 54 ± 2, and 64 ± 3 nm) via controlling the printing force, z-piezo extension, and dwell time. Energy dispersive X-ray spectroscopy analysis validated the existence of elemental Ag on the graphene surface. Subsequent chemical etching of AgNPs using nitric acid (HNO3) with the aid of sonication and mechanical agitation produced holes of uniform size distribution generating hG. The obtained I D/I G ratios ≤ 0.96 measured by Raman spectroscopy were lower than those commonly reported for GO (I D/I G > 1), indicating the removal of more defective C atoms during the etching process to produce hG while preserving the remaining C atoms in ordered or crystalline structures. Indeed, SPBCL could be utilized to fabricate uniformly distributed AgNPs of controlled sizes on graphene surfaces to ultimately produce hG of uniform hole size distribution.

Polymeric Reactor for the Synthesis of Superparamagnetic-Thermal Treatment of Breast Cancer.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) have been studied extensively for their localized homogeneous heat generation in breast cancer therapy. However, challenges such as aggregation and inability to produce sub-10 nm SPIONs limit their potential in magnetothermal ablation. We report a facile, efficient, and robust in situ method for the synthesis of SPIONs within a poly(ethylene glycol) (PEG) reactor adsorbed onto reduced graphene oxide nanosheets (rGO) via the microwave hydrothermal route. This promising modality yields crystalline, stable, biocompatible, and superparamagnetic PEGylated SPION-rGO nanocomposites (NCs) with uniform dispersibility. Our findings show that rGO acts as a breeding ground for the spatially distributed nanosites around which the ferrihydrite seeds accumulate to ultimately transform into immobilized SPIONs. PEG, in parallel, acts as a critical confining agent physically trapping the accumulated seeds to prevent their aggregation and create multiple domains on rGO for the synthesis of quantum-sized SPIONs (9 ± 1 nm in diameter). This dual functionality (rGO and PEG) exhibits a pronounced effect on reducing both the aggregation and the sizes of fabricated SPIONs as confirmed by the scanning transmission electron microscopy images, dynamic light scattering analyses, and the specific absorption rates (SARs). Reduced aggregation lowered the toxicity of NCs, where PEGylated SPION-rGO NCs are more biocompatible than PEGylated SPIONs, showing no significant induction of cell apoptosis, mitochondrial membrane injury, or oxidative stress. Significantly less lactate dehydrogenase release and hence less necrosis are observed after 48 h exposure to high doses of PEGylated SPION-rGO NCs compared with PEGylated SPIONs. NCs induce local heat generation with a SAR value of 1760 ± 97 W/g, reaching up to 43 ± 0.3 °C and causing significant MCF-7 breast tumor cell ablation of about 78 ± 10% upon applying an external magnetic field. Collectively, rGO and PEG functionalities have a synergistic effect on improving the synthesis, stability, biocompatibility, and magnetothermal properties of SPIONs.

Evaluación rápida "in situ" de punción con aguja fina guiada por endosonografía mejora rendimiento diagnóstico de lesiones pancreáticas sólidas / Rapid on-site evaluation with endoscopic ultra sound-guided fine needle improves diagnostic yield of solid pancreatic masses

BACKGROUND: The use of endoscopic ultrasound with fine needle aspiration (EUS-FNA) has improved the characterization and staging of pancreatic solid masses. The primary strategy for improving the ability to diagnose malignant masses is the use of rapid on site evaluation (ROSE) by a cytopathologist. OBJECTIVE: To evaluate the diagnostic yield of EUS-FNA after the implementation of ROSE in an academic center. MATERIAL AND METHODS: Prospective enrollment and follow-up of EUS-FNA with ROSE during 2015 and 2016, was compared to EUS-FNA without ROSE in previous years (2011-2014) in Hospital Clínico UCChristus. Clinical and endosonographic features, cytopathological and histological diagnosis and number of passes per procedure were evaluated. All EUS-FNA included cytology and cellular block for definitive diagnosis. RESULTS: 59 pancreatic solid masses were included in the analysis. 44 EUS-FNA were performed with ROSE, compared with 15 EUS-FNA without ROSE. The mean age of patients included was 62.8 years, 54.2% male gender, and most masses studied were in the head of pancreas (77.6%). In EUS 86.5% were hypoechoic and 56.9% had poor defined margins. No differences in baseline characteristics were observed between groups. EUS-FNA led to diagnosis in 86.2% of the overall sample. The diagnostic rate was superior in the group of EUS-FNA with ROSE, compared to EUS-FNA without ROSE (97.7% vs 50%, p < 0.0001). The mean number of passes was inferior in EUS-FNA ROSE (+) (2.71 vs 5.78, p < 0.0001). No differences in rate of complications were observed between groups. CONCLUSION: The use of ROSE associated to EUS-FNA improves the diagnostic yield in the evaluation of pancreatic solid masses. Our findings are consistent with those described in the literature, recommending the use of ROSE in EUS-FNA in centers where the diagnostic yield is less than 90% without the use of ROSE

INTRODUCCIÓN: La adquisición de tejido mediante el uso de endosonografía, con punción con aguja fina, (EUS-FNA) ha mejorado el diagnóstico de lesiones pancreáticas sólidas. La principal medida para aumentar el rendimiento diagnóstico de la EUS-FNA es la evaluación por citopatólogo próximo al lugar de punción (in situ) (técnica conocida en inglés como ROSE "rapid on-site evaluation"). OBJETIVO: Evaluar el rendimiento diagnóstico de EUS-FNA en lesiones pancreáticas sólidas posterior a la implementación de ROSE en un centro universitario. MATERIAL Y MÉTODOS: Registro prospectivo de EUS-FNA realizadas con ROSE durante el período 2015-2016, comparado con EUS-FNA con evaluación histopatológica diferida realizada entre los años 2011-2014, en Hospital Clínico UC-Christus. Se evaluaron características clínicas, endosonográficas, diagnóstico histopatológico y número de pases por procedimiento. Todas las EUS-FNA incluyeron citología y block celular para diagnóstico definitivo. RESULTADOS: Se incluyeron en el análisis 59 lesiones pancreáticas sólidas evaluadas con EUS-FNA. Seguimiento prospectivo de 44 EUS-FNA con ROSE, que fueron comparadas con 15 EUS-FNA sin evaluación in situ (retrospectivo). La muestra total incluyó individuos con un promedio de 62,8 años de edad, 54,2% hombres, donde 77,6% de las lesiones se ubicaba en la cabeza pancreática. Endosonográficamente 86,5% de las lesiones eran hipoecoicas y 56,9% tenían márgenes poco definidos. La EUS-FNA fue diagnóstica en 86,2% del total de la muestra. Las EUS-FNA realizadas con ROSE presentaron un mayor rendimiento diagnóstico respecto a las efectuadas sin evaluación in situ (97,7% vs 50%, p < 0,0001). El número de pases por procedimiento fue menor (2,7% vs 5,8%, p < 0,0001) en el grupo con ROSE. No hubo diferencias en complicaciones en ambos grupos. CONCLUSIÓN: La evaluación por citopatólogo in situ de la muestra obtenida por EUS-FNA mejora el rendimiento diagnóstico de las lesiones pancreáticas sólidas. Nuestros hallazgos apoyan el uso de ROSE asociado a EUS-FNA, siendo concordantes con las recomendaciones actuales de utilizar evaluación histopatológica in situ en EUS-FNA, especialmente en centros donde el rendimiento diagnóstico sin uso de ROSE es menor a 90%.

Aumento de detección de lesiones gástricas premalignas mediante protocolo Sydney en comparación con biopsias no protocolizadas / Increased detection of premalignant gastric lesions through Sydney protocol in comparison with non-protocolized gastric biopsies

Introduction: Gastric cancer (GC) is the leading cause of cancer mortality in Chile. The development ofgastric adenocarcinoma its preceded by a histopathologic cascade composed of gastric atrophy, intestinal metaplasia and gastric dysplasia. Sydney protocol has been proposed as the standard method for diagnosingthese conditions. The aim of this research study was to establish whether Sydney protocol increase thedetection of premalignant gastric lesions, as gastric atrophy and intestinal metaplasia, compared to non protocolizedendoscopies/biopsies. Methods: Upper gastroduodenal endoscopies (GDE) from Hospital Clí-nico Universidad Católica de Chile between April-May 2015 and April-May 2016 was analyzed. Patientswith histological study with 18 years-old or older were included. Patients with history of GC or malignantlesions at GDE where excluded. Detection of gastric atrophy, intestinal metaplasia and suggestive findingsof autoimmune gastritis where compared between Sydney protocol and non-protocolized endoscopies/biopsies...

Introducción: El cáncer gástrico (CG) es la principal causa de muertes por cáncer en Chile. El desarrollo del adenocarcinoma gástrico es precedido por una cascada histopatológica (gastritis; atrofia gástrica/AG; metaplasia intestinal/MI). Se ha propuesto la biopsia del cuerpo, ángulo y antro a través del protocolo de Sydney para la búsqueda de estas condiciones. Objetivo: Determinar la diferencia en la detección delesiones premalignas gástricas a través del protocolo de Sydney comparado con el estudio endoscópico habitual. Métodos: Se analizaron las endoscopias digestivas altas (EDA) realizadas en el Centro de Endoscopia Digestiva del Hospital Clínico de la Universidad Católica en los períodos entre abril y mayo del 2015 y 2016. Se incluyeron las EDA de pacientes mayores de 18 años con estudio histológico. Fueron excluidos los pacientes con antecedente personal de CG o lesiones de aspecto maligno macroscópicas. Se comparó la detección de AG, MI y gastritis autoinmune (GA) en el estudio histológico entre los pacientes con protocolo Sydney y el estudio endoscópico no protocolizado...

Pattern & presentation of colorectal cancer in central Sudan, a retrospective descriptive study, 2010-2012.

AIMS & OBJECTIVE: To determine the age and gender distribution and clinical presentation of patients together with histological types of colorectal cancer cases presented to Ibn Sina specialized hospital. PATIENTS AND METHODS: This retrospective study was conducted in Ibn Sina Hospital (Sudan). Seventy three (73) patients of colorectal cancer who presented in the period from January 2010 to December 2012 were included. Data were collected from their hospital records and analyzed using SPSS computer program 17. RESULTS: More than 17 % of the study populations was below the age of 40 years, and 43.84% was below 50 years. The male to female ratio was 1:1.02. Rectal bleeding is the commonest presenting symptom and well differentiated adenocarcinoma is the dominating tumor grade. 8.3 % of patients presented with liver metastasis. CONCLUSION: Colorectal cancer in this study was found more in young age groups with a peak frequency at the fifth and sixth decades.

[Estimation of thyroid cancer incidence in Chile based on pathological reports]. / Epidemiología del cáncer de tiroides en Chile: Resultados del estudio INCATIR.

BACKGROUND: Thyroid cancer (TC) detection is increasing steadily. AIM: To determine the incidence of TC based on pathological reports of thyroidectomies. MATERIAL AND METHODS: Fifty pathology laboratories performing thyroid gland pathological studies were identified. Those that accepted to participate were required to send trimestral reports of all thyroid pathological studies, from March 2011 to February 2012. RESULTS: In the study period, 1309 case of TC were confirmed in 2614 thyroidectomy surgical samples. Considering the susceptible population according to 2012 census, the estimated incidence of TC during 2011 should be higher than 7.86 cases per 100,000 persons/year. Papillary cancer was the most common pathological type in 92% of samples (95% confidence intervals 90-93%). The proportion of microtumors was significantly higher in women than in men and among papillary than in follicular or medullary tumors. Only one fourth of tumors came from thyroidectomies performed in the Ministry of Health network. CONCLUSIONS: The incidence and features of TC in Chile are similar to the figures reported abroad.

Epidemiología del cáncer de tiroides en Chile: Resultados del estudio INCATIR / Estimation of thyroid cancer incidence in Chile based on pathological reports

Background: Thyroid cancer (TC) detection is increasing steadily. Aim: To determine the incidence of TC based on pathological reports of thyroidectomies. Material and Methods: Fifty pathology laboratories performing thyroid gland pathological studies were identified. Those that accepted to participate were required to send trimestral reports of all thyroid pathological studies, from March 2011 to February 2012. Results: In the study period, 1309 case of TC were confirmed in 2614 thyroidectomy surgical samples. Considering the susceptible population according to 2012 census, the estimated incidence of TC during 2011 should be higher than 7.86 cases per 100,000 persons/year. Papillary cancer was the most common pathological type in 92% of samples (95% confidence intervals 90-93%). The proportion of microtumors was significantly higher in women than in men and among papillary than in follicular or medullary tumors. Only one fourth of tumors came from thyroidectomies performed in the Ministry of Health network. Conclusions: The incidence and features of TC in Chile are similar to the figures reported abroad.

Perfil de metilación de genes supresores de tumores APAF1, ASSP1, p73 y FHIT en pacientes con leucemia linfoblástica aguda infantil / Detection of hypermethylation in tumor suppressor genes APAF1, ASSP1, p73 and FHIT in childhood acute lymphoblastic leukemia

La leucemia linfoblástica aguda (LLA), es la neoplasia mas frecuente en la población infantil. Se manifiesta por una perdida de diferenciación de progenitores linfoides produciendo un aumento de células inmaduras. La hipermetilación en la región promotora de genes supresores de tumores (GST) puede producir un silenciamiento génico que le proporciona a la célula leucémica una ventaja proliferativa o la previene de la apoptosis. Se estudia el estado de hipermetilación de 4 GST involucrados en la apoptosis: APAF1, ASPP1, p73 y FHIT y su asociación con la sobrevida de pacientes menores de 15 años con diagnóstico de LLA. Se analizaron 38 muestras de médula ósea mediante modificación con bisulfito del ADN y reacción en cadena de la polimerasa especifica de metilación (MSP). El rango de edad al diagnóstico fue de 10 meses a 13,8 años. La sobrevida global fue de 69 por ciento a los 5 años. El 81,5 por ciento de los pacientes tuvo al menos un gen hipermetilado. La frecuencia de metilación observada fue: APAF1 68,4 por ciento, FHIT 56,4 por ciento, p73 42 por ciento y ASPP1 18,4 por ciento. La asociación entre hipermetilación y grupo <5 años y 5 años fue: Global p=0,20, APAF1 p=0,03, FHIT p=0,51, p73 p=0,51 y ASPP1 p=0.67. Las curvas de sobrevida se calcularon según frecuencia de hipermetilación de cada gen: APAF1 p=0,05, FHIT p=0,31, p73 p=0,98 y ASPP1 p=0,82. La alta frecuencia de hipermetilación obtenida reafirma la participación de la metilación en la región promotora de GST en la patogénesis de la LLA. La hipermetilación del gen APAF1 fue muy frecuente y se asoció significativamente a la sobrevida del grupo de estudio, mostrando a este gen como un factor predictivo de mal pronostico en pacientes con LLA.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. It is manifested by a loss of differentiation of lymphoid progenitors, producing an increase of immature cells. Hypermethylation in promoter region of tumor suppressor genes (GST) may produce a gene silencing that provides a leukemic cell a proliferative advantage or prevent apoptosis. We studied the hypermethylation status of 4 GST involved in apoptosis: APAF1, ASPP1, p73 and FHIT and its association with survival of patients <15 years diagnosed with ALL. We analyzed 38 samples of bone marrow by DNA bisulfite modification and chain reaction methylation-specific polymerase (MSP). The mean age at diagnosis was 10 months to 13.8 years. Overall survival was 69 percent at 5 years. 81.5 percent of patients had at least one hypermethylated gene. The frequency observed was: APAF1 68.4 percent, 56.4 percent FHIT, p73 ASPP1 42 percent and 18.4 percent. The association between hypermethylation and group <5 years and 5 years was: Global p = 0.20, APAF1 p = 0.03, FHIT p = 0.51, p73 p = 0.51, ASPP1 p = 0.67. Survival curves were calculated by frequency of hypermethylation of each gene: APAF1 p = 0.05, p = 0.31 FHIT, p73 p = 0.98 and ASPP1 p = 0.82. The high frequency of hypermethylation obtained confirms enrollment of methylation in the promoter region of GST in the pathogenesis of ALL. APAF1 gene hypermethylation was very frequent and was significantly associated with survival in the study group, showing this gene as a predictor of poor prognosis in patients with ALL.

Infección por el virus del papiloma humano en el hombre y su relación con el cáncer: estado actual y prospectivas / Human papillomavirus infection in men and its relation with cancer: Current status and prospectics

Introducción. El virus del papiloma humano (HPV por sus siglas en inglés) es una de las infecciones de transmisión sexual más frecuentes en el mundo y es descrito como el principal agente causal del cáncer cervicouterino (99,7%). En mujeres existe abundante información sobre esta infección, mientras que sus características en población masculina son poco conocidas. Material y método. Se realizó una búsqueda de bibliografía actualizada de la infección por HPV en hombres y su relación con distintos tipos de cáncer. Resultados. La infección por HPV en hombres podría estar asociada a tumores de piel, región perianal, amígdala, orofaringe, laringe, esófago, próstata y uretra. La infección por HPV generalmente es silente, por lo cual no produce síntomas o signos clínicos evidentes, provocando que un gran número de personas estén infectadas sin saberlo, lo cual constituye un problema tanto para el hombre como para su pareja sexual. Los estudios de prevalencia muestran que las zonas de mayor presencia del virus son en poblaciones jóvenes de África y América Latina, donde los programas de vacunación contra este virus tardarán en concretarse. Discusión. Es importante incorporar métodos diagnósticos para HPV en la población masculina e incrementar la vacunación de esta. Asimismo, el control periódico de la población de hombres infectados por la asociación entre HPV y cáncer es crucial, especialmente en las áreas anatómicas asociadas a las enfermedades de transmisión sexual (AU)

Introduction. Human papillomavirus (HPV) is one of most frequent sexually transmitted infections worldwide. It has been described as the principal agent for cervical uterine carcinoma (99.7%). There is abundant information on this infection in women, however, its characteristics in the male population still remains unclear. Materials and methods. A search of updated bibliography on HPV infection in males and its relationship with several forms of cancer was conducted. Results. HPV infection in men could be associated to skin, perianal, tonsils, oropharynx, pharynx, esophagus, prostate and urethra carcinoma. HPV infection is usually silent, so that there are no clear symptoms or clinical signs. Therefore, there are many infected people who are unaware that they have HPV infection. This is a problem for men as well as their sexual partner. Prevalence studies show that the areas having the greatest presence of the HPV virus are in the young populations of Africa and Latin America. This is where the vaccine programs against this virus are slow in materializing. Discussion. It is important to incorporate diagnosis methods in male population and to increase HPV vaccine in men. Furthermore, periodic control of the HPV-infected male population is crucial, especially in the anatomical areas associated to sexual transmission diseases (AU)

Prevalencia de enfermedad diverticular del apéndice cecal en pacientes apendicectomizados por apendicitis aguda / Diverticular disease of the appendix in appendectomies

Introduction: Diverticular disease of the appendix is an infrequent finding in the study of surgical specimens from patients operated on for clinically suspected acute appendicitis. Our aim was to determine the prevalence of diverticular disease of the appendix in patients who underwent appendectomies based on the clinical diagnosis of acute appendicitis. Material and Method: Design: Cross-sectional study. Inclusion criteria: Patients who underwent appendectomies based on a clinical diagnosis of acute appendicitis. Studyperiod: january 2000 to december 2008. Sampling: Non-probabilistic sampling of consecutive cases. Methodology: A review was conducted of the clinical records and surgical specimens from patients who underwent appendectomies based on a clinical diagnosis of acute appendicitis. Results: Within the study period, 11.472 appendectomies were performed based on a clinical diagnosis of acute appendicitis. Ninety-four patients presented diverticular disease of the appendix (0.8 percent). The median age was 40 years and 62.8 percent were male. The disease appeared as: appendicular diverticulitis (45.7 percent), appendicular diverticulosis with acute appendicitis (28.7 percent), appendicular diverticulitis with acute appendicitis (17.0 percent), appendicular diverticulosis (5.3 percent), and appendicular pseudodiverticulosis with acute appendicitis (3.2 percent). Operative morbidity was 12.7 percent. One patient presented an adenocarcinoma of the appendix associated with diverticular disease. Conclusion: The prevalence of diverticular disease of the appendix is low in our population and the characteristics are different to reported by other authors.

Introducción: La enfermedad diverticular del apéndice cecal es un hallazgo infrecuente en apendicectomizados por sospecha clínica de apendicitis aguda. Nuestro objetivo es evaluar la prevalencia de enfermedad diverticular del apéndice cecal en pacientes apendicectomizados por sospecha clínica de apendicitis aguda. Material y Método: Diseño de estudio: Estudio de corte transversal. Criterios de inclusión: Pacientes apendicectomizados por sospecha clínica de apendicitis aguda. Período de estudio: enero de 2000 a diciembre de 2008. Muestreo: No probabilístico de casos consecutivos. Metodología: Se realizó una revisión de los registros clínicos y de las piezas quirúrgicas de los pacientes sometidos a apendicectomía por diagnóstico clínico de apendicitis aguda. Resultados: Se estudiaron 11.472 apendicectomías. Noventa y cuatro pacientes presentaron enfermedad diverticular del apéndice (0,8 por ciento). La mediana de edad fue 40 años y el 62,8 por ciento fue género masculino. La enfermedad se presentó como: diverticulitis apendicular (45,7 por ciento), diverticulosis apendicular con apendicitis aguda (28,7 por ciento), diverticulitis apendicular con apendicitis aguda (17,0 por ciento), diverticulosis apendicular (5,3 por ciento) y pseudodiverticulosis apendicular con apendicitis aguda (3,2 por ciento). La morbilidad operatoria fue 12,7 por ciento. Un paciente presentó un adenocarcinoma del apéndice cecal asociado a la enfermedad diverticular del apéndice. Conclusión: La prevalencia de enfermedad diverticular del apéndice cecal es baja en nuestra población y con características que difieren a lo reportado por otros autores.

[Prevalence of the drug consumption among Chilean university students]. / Estudio cuantitativo del consumo de drogas y factores sociodemográficos asociados en estudiantes de una universidad tradicional chilena.

BACKGROUND: Drug abuse is one of the main public health problems and mostly involves young people. AIM: To determine the prevalence of drug consumption among university students and its associated social factors. MATERIAL AND METHODS: A questionnaire exploring consumption of drugs and social-demographic, economic and religious variables, was applied to 1577 third year students aged 22 ± 2 years (54% females) of a public university. RESULTS: Sixty eight percent of the students were of middle socioeconomic class, 71 % belonged to some religion and 29% declared themselves as agnostic. Ninety six percent drank alcohol at least once and 29% never smoked. Among illicit drugs, marijuana was consumed by 22% followed by cocaine in 5.3%o, hallucinogenic drugs in 2.6 % >, inhalants in 2.3% > and cocaine free base in 1.4%). Six percent consumed stimulants and 13.8%>, sedatives. A higher economic income facilitated drug consumption and the adscription to a religion was protective against it. CONCLUSIONS: Alcohol is the most commonly consumed drug, and is the substance that generates more problems to students.

Compromiso ganglionar extracapsular en pacientes con cáncer gástrico: determinación del valor pronóstico / Prognostic value of extracapsular lymph node involvement among patients with gastric cancer

Background: Extracapsular lymph node involvement has a negative prognosis in malignant tumors. Aim: To assess the prognostic importance of extracapsular lymph node involvement in patients with gastric cancer with lymph node metastases. Material and Methods: Clinical and morphological features and survival of patients with gastric cancer and lymph node involvement operated between 1986 and 2003, were analyzed. Patients with and without extracapsular involvement were compared. Results: During the study period, 459 gastrectomies were performed, 312 patients (68 percent) had lymph node involvement and 144 (31 percent) had extracapsular involvement. Patients with and without extracapsular involvement were followed for a median of 10 (range 1 to 120) and 41 (range 1 to 193) months, respectively. Five years actuarial survival for patients with and without extracapsular involvement was 23 and 40 percent respectively. Extracapsular lymph node involvement and level of wall infiltration were identified as prognostic factors using a multivariate analysis. Conclusions: Extracapsular lymph node involvement is an independent risk factor for mortality among patients with gastric cancer.

Estudio cuantitativo del consumo de drogas y factores sociodemográficos asociados en estudiantes de una universidad tradicional chilena / Prevalence of the drug consumption among Chilean university students

Background: Drug abuse is one of the main public health problems and mostly involves young people. Aim: To determine the prevalence of drug consumption among university students and its associated social factors. Material ana Methods: A questionnaire exploring consumption of drugs and social-demographic, economic and religious variables, was applied to 1577 third year students aged 22 ±2 years (54 percent females) of a public university. Results: Sixty eight percent of the students were of middle socioeconomic class, 71 percent belonged to some religion and 29 percent declared themselves as agnostic. Ninety six percent drank alcohol at least once and 29 percent never smoked. Among illicit drugs, marijuana was consumed by 22 percent followed by cocaine in 5.3 percento, hallucinogenic drugs in 2.6 percent>, inhalants in 2.3 percent> and cocaine free base in 1.4 percent). Six percent consumed stimulants and 13.8 percent>, sedatives. A higher economic income facilitated drug consumption and the adscription to a religion was protective against it. Conclusions: Alcohol is the most commonly consumed drug, and is the substance that generates more problems to students.

Cáncer de la vesícula biliar: estudios necesarios para el diseño de estrategias de prevención y diagnóstico precoz / Gallbladder cancer: necessary studies to design strategies for prevention and early diagnosis

Chile tiene la mayor tasa de incidencia de cáncer de vesícula biliar (CVB) en el mundo (> 30 por 100.000). Siendo la principal causa de muerte por cáncer entre las mujeres chilenas. Para diseñar estrategias de prevención y diagnóstico precoz del CVB hay que entender los factores etiológicos del proceso carcinogénico vesicular. Hay consenso que para el desarrollo de este cáncer concurren factores -genéticos, hormonales, infecciones crónicas, e inflamaciones crónicas asociadas a litiasis vesicular; y también que este cáncer ocurre en condiciones de pobreza. Desafortunadamente es insuficiente el conocimiento sobre la carcinogénesis vesicular, sobre el mecanismo de acción de los factores de riesgo clásicos y sobre cuáles son relevantes en la iniciación y promoción del CVB. En este artículo centramos la discusión en la litiasis vesicular, considerado el principal factor de riesgo del CVB. Se analiza las estrategias de prevención y control y se discuten los programas actuales. Finalmente se presentan dos estudios sobre factores de riesgo y de susceptibilidad para CVB que están siendo implementados en Chile.

Chile has the highest gallbladder cancer (GBC) incidence rate in the world (>30 per 100,000 person-years) and is the leading cause of cancer deaths among Chilean women. To design strategies of prevention and early diagnosis of GBC we must understand the etiological factors of the gallbladder carcinogenic process; There is consensus that in the development of this cancer concurs genetic and hormonal factors, infection, and chronic inflammation associated with lithiasis; and that is strongly associated with poverty conditions; But unfortunately there is not enough information about this process or how the classic risk factors associated play a role in its development. There is also no information on which are important in the initiation and promotion of GBC. In this article we focus the discussion in gallstones, considered the main risk factor for GBC. We analize some strategies of prevention and control and discuss some aspects of the current program. Finally we will point out two studies on risk factors and genetic susceptibility to GBC that are being implemented in Chile.

Carcinoma epidermoide oral y orofaríngeo: estudio clínico-patológico / Oral and oropharingeal squamous cells carcinoma: clinico-pathological study

Introduction: Oral cancer is a common disease in many parts of the world, in Chile only accounts for 1.6 percent of all cancers. The majority is squamous cell carcinoma with important clinical, epidemiological and pathological differences between lip, oral and orofaringeal locations. Objective: To analyze clinical and pathological characteristics of oral and oropharingeal squamous cell carcinoma in Temuco, Chile. Materials and Methods: A descriptive, retrospective study of all diagnosed cases in 15 years (1994 and 2008). The patients were analyzed according to gender, age; and the tumors were classified based on anatomic location, size, macroscopical findings and degree of differentiation. Results: We found 93 carcinomas, with male to female ratio of 5:1, average age 67 years. Patients under 50 years accounted for only 8 percent of cases. The most common sites were lower lip, tongue and gingiva, with an average size of 28 mm, which increased towards orofarinx and more than half were moderately differentiated. Conclusions: In our region, this carcinoma most often affects the seventh decade of life and male population and has similar characteristics to those in other countries which is predominantly. The size at diagnosis is significant. The detection of some differences in the group with mapuche surnames warrants a study with a larger number of cases.

Introducción: El cáncer oral es una enfermedad frecuente en muchas partes del mundo, en Chile corresponde al 1,6 por ciento del total de cánceres. La gran mayoría corresponde a carcinoma epidermoide, con importantes diferencias clínicas, epidemiológicas y patológicas entre las localizaciones labial, intraoral y orofaríngea. Objetivo: Analizar las características clínicas y patológicas del carcinoma epidermoide oral y orofaríngeo en Temuco, Chile. Material y Método: Estudio descriptivo, retrospectivo de todos los casos diagnosticados en 15 años (1994 y 2008), en el Hospital Regional de Temuco. Los pacientes fueron analizados de acuerdo a género, edad, y los tumores fueron clasificados basados en su localización anatómica, tamaño, características macroscópicas y grado de diferenciación. Resultados: Se encontraron 93 carcinomas, con relación hombre:mujer de 5:1, edad promedio 67 años. Pacientes menores a 50 años correspondían sólo al 8 por ciento de los casos. Las localizaciones más frecuentes fueron labio inferior, lengua y encía, con un tamaño promedio de 28 mm, el que aumentó hacia la orofarinx, más de la mitad eran moderadamente diferenciados. Conclusiones: En nuestra región, este carcinoma afecta con mayor frecuencia a la séptima década de la vida y a población masculina y posee características similares a las descritas en otros países donde predomina la raza blanca. El tamaño al diagnóstico es considerable. La detección de algunas diferencias en el grupo con apellidos mapuches amerita un estudio con un mayor número de casos.

Cáncer gástrico sin compromiso ganglionar linfático (pN0): características demográfico-patológicas y factores pronósticos / Prognostic factors for gastric cancer without lymph node involvement

Background: The absence of lymph node involvement (N0) in gastric cancer is associated with a better survival. However some N0 gastric tumors still have a bad prognosis. Aim: To study demographic and morphological variables associated with prognosis in N0 gastric carcinoma. Material and Methods: Review of pathologica records of a regional general hospital, identifying patients with a N0 gastric cancer surgically excised between 1986 and 2003. Results: In the study period, 459 gastrectomies were performed for gastric cancer and in 32 percent, the tumor was devoid of lymph node involvement. These later patients were followed for a median of 64 months with a 71 percent fve years actuarial survival. Bivariate analysis identifed age, tumor size, gastric wallinfiltration, pathological type according to Lauren and Ming, lymphovascular involvement, number of lymph nodes excised and TNM stage as prognostic values Multivariate analysis disclosed the level of gastric wallinfiltration, the presence of a poorly differentiated tumor, lymphatic vascular involvement, number of excise lymph nodes and tumor size as independent prognostic factors. Conclusions: N0 gastric tumors are found in 32 percent of gastrectomies for gastric cancer and have a 71 percent fve years actuarial survival. Gastric wallinfiltration, pathological degree of differentiation tumor size and lymphovascular involvement are independent prognostic factors.

Factores asociados al pronóstico de pacientes operados por cáncer gástrico avanzado / Pathological factors associated with survival in advanced gastric cancer

Background: The degree of tumor infiltration and lymph node involvement are the most relevant pathological features to determine prognosis of advanced gastric cancer. Aim: To determine the association between clinical and pathological features of advanced gastric cancer and patient survival. Material and Methods: The pathological records of patients with advanced gastric cancer subjected to gastrectomy and lymph node excision between 1986 and 2007 were analyzed. Follow up was performed according to data in the clinical records and death certificates obtained at the Chilean National Death Registry. The main outcome analyzed was survival after surgery. Results: The records of 299 patients aged 62 +/- 11 years (68 percent males), were analyzed. Mean follow up ranged from 1 to 206 months. Five and 10 years actuarial survival was 39 and 34 percent, respectively. The pathological predictors of survival were microscopic tumor stage, tumor size and location, Bormann classification, infiltration level, degree of differentiation, pathological type of tumor according to Lauren, Ming y Nakamura, lymph node involvement and the absence of residual tumor after surgical excision. Conclusions: The pathological study of the surgical piece in advanced gastric cancer has important prognostic implications.

Introducción: El estudio de la pieza operatoria de pacientes resecados por cáncer gástrico (CG) ha permitido identificar variables anatomo-patológicas con valor pronóstico en la supervivencia (SV) y recurrencia de estos pacientes, siendo el compromiso ganglionar linfático y nivel de infiltración tumoral, los factores más relevantes identificados. El objetivo de este estudio es determinar asociación entre variables clínicas y morfológicas con la SV de pacientes resecados por CG avanzado (CGA). Material y Método: Estudio de cohorte retrospectiva. Se estudiaron variables clínicas y morfológicas de 299 pacientes operados por CGA entre enero de 1986-diciembre de 2001. Los datos fueron obtenidos desde la Unidad de Anatomía Patológica del Hospital Hernán Henríquez Aravena de Temuco. Se aplicó estadística descriptiva y analítica; confección de curvas de supervivencia, y finalmente se aplicaron modelos de regresión logística para realizar ajuste, calcular odds ratios y sus respectivos intervalos de confianza de 95 por ciento. Resultados: La cohorte tuvo una mediana de edad de 63 años y el 68 por ciento de ella correspondió al género masculino. Con una mediana de seguimiento de 21 meses (1 a 206), se observó una SV actuarial global a 5 y 10 años de 39 por ciento y 34 por ciento respectivamente. En el análisis bivariado, se verificó asociación con la SV en: etapa tumoral macroscópica, localization y tamaño tumoral, tipo según Bormann, nivel de infiltración, grado de diferenciación histológico, tipo histológico según Lauren, Ming y Nakamura, estado ganglionar linfático (N), estadio TNM y resultado de la resección realizada. Conclusiones: Las variables mencionadas deben ser cuidadosamente evaluadas al momento de decidir terapias en pacientes con CGA.

Factores morfológicos asociados al pronóstico de pacientes operados por cáncer gástrico incipiente / Pathological features associated with survival in early gastric cancer

Background: Early gastric cancer corresponds to those tumors that only involve mucosa and submuco-sa. It is associated with a high survival rate. Aim: To determine pathological factors associated with survival in early gastric cancer. Material and Methods: Analysis of pathological records of 106 patients, with a median age of 63 years (60 percent> males), subjected to a gastrectomy for early gastric cancer. Follow up was performed according to data in the clinical records and death certificates obtained at the Chilean National Death Registry. Results: Five years global survival of patients was 91 percento. Lymph node involvement was more common among tumors bigger than 35 mm, with a low degree of differentiation and among those tumors classified as diffuse according to Lauren. Survival was significantly lower for bigger tumors, those with of a low degree of differentiation, diffuse tumors according to Lauren and those with lymph node involvement. Conclusions: Early gastric cancer has a high five years survival. Bigger tumors, those with a low degree of differentiation and those with lymph node involvement are associated with lower survival rates.

Introducción: El cáncer gástrico incipiente (CGI) es aquel que compromete la mucosa o submucosa gástrica independientemente del compromiso ganglionar linfático, estimándose su prevalencia en Chile inferior al 20 por cientoo. El objetivo de este estudio es determinar prevalencia de CGI y asociación de variables biode-mográficas y morfológicas con la supervivencia (SV) de pacientes resecados por CGI. Material y Método: Estudio de cohorte retrospectiva. Se estudiaron variables biodemográficas y morfológicas de 106 pacientes resecados por CGI entre 1986-2007. Se aplicó estadística descriptiva y analítica; confección de curvas de SV, y finalmente se aplicaron modelos de regresión logística para realizar ajuste, calcular odds ratio y sus respectivos intervalos de confianza de 95 por ciento. Resultados: 15 por ciento correspondió a CGI. La mediana de edad fue 63 años y el 60 por ciento correspondió a género masculino con una SV global a 5 años de 91 por ciento. Se observaron diferencias estadísticas significativas entre tumores mucosos y submucosos en cuanto a la localización tumoral y compromiso linfonodal junto con presentarse el compromiso nodal más frecuentemente en tumores > 35mm poco diferenciados y difusos de Lauren. El análisis multivariado identificó como factores asociados a la SV: tamaño tumoral, grado de diferenciación histológica en su variedad poco diferenciado, tipo difuso de Lauren y compromiso ganglionar linfático. Conclusiones: Se verificó una prevalencia de CGI de 15 por ciento, los que resecados presentan SV de 91 por ciento a 5 años. El compromiso linfonodal es un factor asociado a la SV; y además, se relaciona con tamaño tumoral, tipo histológico según Lauren, grado de diferenciación histológico y nivel de infiltración.