Calcitonin-producing Duodenal Neuroendocrine Tumor: A Case Report and Literature Review.

INTRODUCTION: Neuroendocrine tumors [NETs] exhibit a wide range of clinical presentations, including the production of various hormones. Calcitonin, a sensitive marker for medullary thyroid cancer [MTC], is nonspecific and may be elevated in extra-thyroidal NETs. CASE REPORT: We present the case of a 64-year-old female patient who underwent total thyroidectomy due to a nodule in the isthmus, with a fine-needle aspiration biopsy indicating follicular neoplasia. Pathological examination revealed macro- and micro-nodular thyroid hyperplasia, along with a parathyroid adenoma. During postoperative follow-up, a progressive elevation of calcitonin was observed, reaching 64.2 pg/ml, while carcinoembryonic antigen levels remained normal. Since no MTC foci were found upon reviewing the thyroidectomy specimen, an investigation into the origin of the elevated calcitonin was initiated. Serum chromogranin A and specific neuronal enolase levels were within normal ranges. Tc-99m HYNIC-TOC scintigraphy yielded negative results. Additionally, an upper gastrointestinal endoscopy revealed a submucosal lesion in the second portion of the duodenum, with a biopsy confirming a grade 1 NET. The patient underwent Whipple surgery and hepatic metastasectomy. Postoperatively, a decrease in baseline serum calcitonin levels was observed. Seven years after surgery, she continues specialized monitoring with no biochemical or imaging evidence of disease. CONCLUSION: Serum calcitonin contributes to the diagnosis and monitoring of anterior intestine NETs.

The changes on salivary flow rates, buffering capacity and chromogranin A levels in adults after bariatric surgery.

OBJECTIVES: This study aimed to investigate changes in salivary flow rates, buffering capacity, and salivary chromogranin A (CHGA) levels in adults undergoing bariatric surgery (BS) compared with a non-obese control group. MATERIALS AND METHODS: Salivary analyses were performed on 62 participants aged over 50 years, stratified into two groups matched for age and gender-individuals who had undergone bariatric surgery (BS) (n = 31) and a corresponding healthy control group (n = 31). Before saliva collection, participants completed a comprehensive 11-point visual numerical rating scale (NRS 0-10) xerostomia questionnaire, assessing subjective perceptions of two key aspects: dryness of the oral mucosa and resultant impact on oral functional ability. Three distinct saliva measurements were obtained: unstimulated whole saliva (UWS), stimulated whole saliva (SWS), and unstimulated upper labial saliva (ULS). The buffering capacity of unstimulated saliva was assessed using pH indicator strips, and concentrations of salivary Chromogranin A (CHGA) were quantified in stimulated saliva via enzyme-linked immunosorbent assay (ELISA). RESULTS: After BS, more than 40% of BS group patients reported xerostomia, with 16.1% experiencing only mild symptoms without significant functional impact (p = 0.009). The prevalence of xerostomia and tongue dryness was higher in the BS group compared to the control group (p = 0.028 and p = 0.025, respectively). The comparative analysis unveiled no statistically significant differences in flow rates of unstimulated upper labial saliva (ULS), unstimulated whole saliva (UWS), and stimulated whole saliva (SWS) between the control group and patients who underwent bariatric surgery. However, in patients undergone BS with xerostomia, both ULS and UWS flow rates were significantly lower than in controls with xerostomia (p = 0.014 and p = 0.007, respectively). The buffering capacity was significantly lower in patients undergone BS than in controls (p = 0.009). No differences were found between groups regarding CHGA concentration and output values, nevertheless, higher values of CHGA concentrations were significantly correlated to lower flow rates. CONCLUSION: According to the results, this study suggests that individuals undergoing BS may exhibit altered salivary buffering capacity and reduced unstimulated salivary flows in the presence of xerostomia. Additionally, the findings suggest that elevated concentration of salivary CHGA might be associated, in part, with salivary gland hypofunction. CLINICAL RELEVANCE: The clinical significance of this study lies in highlighting the changes in salivary functions after BS. The identified salivary alterations might be attributed to adverse effects of BS such as vomiting, gastroesophageal reflux, and dehydration. Understanding these changes is crucial for healthcare professionals involved in the care of post-BS patients, as it sheds light on potential oral health challenges that may arise as a consequence of the surgical intervention. Monitoring and managing these salivary alterations can contribute to comprehensive patient care and enhance the overall postoperative experience for individuals undergoing BS.

Investigation of possible relationship between atopic dermatitis and salivary biomarkers, stress, and sleep disorders.

Atopic dermatitis (AD) is a chronic, relapsing, multifactorial inflammatory disease with genetic, environmental, and immunological characteristics. The quality of life and sleep of patients and their families are affected by AD, which triggers stress, described as one of the factors that worsens AD. Salivary biomarkers such as cortisol, alpha-amylase, chromogranin A, and melatonin have been associated with stress and sleep disturbances. Therefore, the evaluation of stress and sleep disorders using salivary biomarkers in AD patients is important. This review aims to describe the possible relationship between atopic dermatitis and stress, sleep disorders, and salivary biomarkers, seeking to contribute to better understanding and clinical management of AD. This descriptive study is characterized as a narrative literature review. A literature search was conducted of studies published in English and Portuguese between January 2012 and October 2022 that are available in electronic media from various databases, such as Scientific Electronic Library Online, Latin American and Caribbean Literature on Health Sciences, and PubMed. AD is associated with different degrees of impact on the lives of individuals who present with the disease. Psychological stress may induce changes in saliva composition and worsen AD; at the same time, the severity of the disease may be associated with emotional impact. Further studies are needed to assess and correlate AD severity, stress, and sleep disturbances with salivary biomarkers in order to better understand this association.

Serum chromogranin A levels are associated with the SYNTAX score in coronary artery disease

SUMMARY OBJECTIVE: In this article, we investigated the association of chromogranin A with coronary artery disease. METHODS: Biochemical parameters and chromogranin A levels obtained from peripheral blood samples during coronary angiography were analyzed in 90 patients. Patients were classified into two groups, namely, SYNergy between PCI with TAXUS and Cardiac Surgery score ≥1 (n=45) and SYNergy between PCI with TAXUS and Cardiac Surgery score=0 (n=45). This is a cross-sectional, prospective study. RESULTS: Serum chromogranin A levels were significantly higher in the group with SYNergy between PCI with TAXUS and Cardiac Surgery score ≥1 compared to the group with SYNergy between PCI with TAXUS and Cardiac Surgery score=0 (1381.5±418.9 ng/mL and 1121.2±290.7 ng/mL, respectively; p=0.002). Serum chromogranin A levels were correlated with SYNergy between PCI with TAXUS and Cardiac Surgery score (r=0.556, p<0.04). ROC analysis showed that the area under the curve for serum chromogranin A levels was 0.687 (p=0.007), and the best cutoff value of 1,131 ng/mL had a sensitivity of 67% and a specificity of 65% for the prediction of coronary artery disease. CONCLUSION: Serum chromogranin A levels were increased in coronary artery disease patients with SYNergy between PCI with TAXUS and Cardiac Surgery score ≥1. Increasing serum chromogranin A levels are proportional to the SYNergy between PCI with TAXUS and Cardiac Surgery score.

Associação da cromogranina a com a ansiedade e o estresse em profissionais de enfermagem

Objetivo: Avaliar a associação da concentração de Cromogranina A com a ansiedade e estresse em profissionais de enfermagem e a associação da ansiedade e estresse com fatores sociodemográficos, epidemiológicos e laborais. Método: Estudo transversal desenvolvido com 210 profissionais de enfermagem de uma instituição hospitalar do Sudeste de Minas Gerais, Brasil, entre 2018/2019, por meio de preenchimento de um questionário de caracterização, do Inventário de Ansiedade de Beck e do Inventário de Sintomas de Stress para Adultos de Lipp, bem como da coleta de saliva dos participantes para verificar a concentração de Cromogranina A dos participantes. Os dados foram analisados de forma descritiva e inferencial, com nível de significância de 5%. Resultados: A maioria dos profissionais apresentou estresse (58,1%) e ansiedade (51,9%). Fatores como faixa etária, número de filhos, tempo de atuação na instituição, carga horária de trabalho, falta de atividade física, uso de medicamentos e outro emprego, aumentaram as chances desses trabalhadores terem ansiedade e estresse em níveis mais altos (P< 0,001). A Cromogranina A apresentou maiores alterações nos profissionais do turno da tarde. Observou-se associação entre o grupo que tinha estresse e ansiedade com a Cromogranina A, no turno da noite, bem como do grupo que tinha apenas ansiedade em horários do turno da manhã (P< 0,05). Conclusão: Os profissionais apresentaram níveis de ansiedade e estresse, que foram associados às alterações da CgA em alguns horários, demonstrando que essa proteína pode ser um possível biomarcador de ansiedade e de estresse.

Objective: To evaluate the association of Chromogranin A concentration with anxiety and stress in nursing professionals and the association of anxiety and stress with sociodemographic, epidemiological, and occupational factors. Materials and Methods: Cross-sectional study carried out with 210 nursing professionals from a hospital in the southeast of the state of Minas Gerais, Brazil, between 2018 and 2019, by completing a characterization questionnaire, the Beck Anxiety Inventory and the Lipp's Stress Symptoms Inventory for Adults, as well as the collection of saliva from the participants to verify the concentration of Chromogranin A. Data were analyzed descriptively and inferentially, with a significance level of 5%. Results: Most of the professionals had stress (58.1%) and anxiety (51.9%). Factors such as age group, number of children, time working in the institution, workload, lack of physical activity, use of medication and having other jobs, increased the likelihood of these workers experiencing higher levels of anxiety and stress (P< 0.001). Chromogranin A showed greater changes among the nursing professionals working the evening shift. A relationship was observed between the group that presented stress and anxiety with Chromogranin A, during the night shift, as well as the group that presented only anxiety during the morning shift (P< 0.05). Conclusion: Nursing professionals showed levels of anxiety and stress that were associated with changes in CgA at certain times, demonstrating that this protein may be a possible biomarker of anxiety and stress.

Objetivo: Evaluar la asociación de la concentración de Cromogranina A con la ansiedad y el estrés en profesionales de enfermería y la asociación de la ansiedad y el estrés con factores sociodemográficos, epidemiológicos y laborales. Método: Estudio transversal desarrollado con 210 profesionales de enfermería de un hospital del Sudeste de Minas Gerais, Brasil, entre 2018/2019, mediante la realización de un cuestionario de caracterización, el Inventario de Ansiedad de Beck y el Inventario de Síntomas de Estrés para Adultos de Lipp, así como la recolección de saliva de los participantes para verificar la concentración de Cromogranina A de los participantes. Los datos fueron analizados de forma descriptiva e inferencial, con un nivel de significancia del 5%. Resultados: La mayoría de los profesionales tenían estrés (58,1%) y ansiedad (51,9%). Factores como grupo de edad, número de hijos, tiempo de trabajo en la institución, carga de trabajo, falta de actividad física, uso de medicamentos y otros empleos, aumentaron las posibilidades de que estos trabajadores tuvieran ansiedad y estrés en niveles más altos (P< 0,001). La Cromogranina A mostró mayores cambios en los profesionales del turno vespertino. Se observó asociación entre el grupo que presentó estrés y ansiedad con Cromogranina A, en el turno de la noche, así como el grupo que presentó únicamente ansiedad en el turno de la mañana (P< 0,05). Conclusión: Los profesionales presentaron niveles de ansiedad y estrés, que se asociaron con cambios en la CgA en determinados momentos, demostrando que esa proteína puede ser un posible biomarcador de ansiedad y estrés.

Assessment of child's dental anxiety/fear and stress during dental treatment: a systematic review by CEDACORE

Abstract: There is a lack of evidence on the correlation between salivary biomarkers and subjective measures of dental fear and anxiety in children. This systematic review aimed to retrieve the scientific evidence comparing the results of dental anxiety measured by salivary biomarkers with patient-reported outcomes in pediatric dental setting. The PECOS was as follows: population: pediatric patients aged ≤ 18 years; exposure: patient-reported outcome measures, such as scales and/or questionnaires; comparator: salivary biomarkers; outcome: anxiety, fear, phobia or stress during dental treatment; study design: observational studies or controlled trials. Electronic searches were conducted in PubMed, Scopus, Web of Science, and Ovid databases. Studies that compared scales/questionnaires and salivary biomarkers for the evaluation of dental anxiety, fear, and stress in children/adolescents during dental treatment were included. Certainty of evidence was assessed with GRADE. Risk of bias of the included studies was assessed with the Cochrane tool or the University of Adelaide tool. From the 314 studies identified, eight were included. Participants' age ranged from three to 13 years. The most used salivary biomarkers and instruments were cortisol and the Dental Subscale of the Children's Fear Survey Schedule, respectively. Most studies showed a weak correlation between objective and subjective measures. The main issues regarding bias were on allocation concealment, blinding of assessors, follow up, and exposure assessment. Certainty of evidence was low/very low. Evidence of salivary biomarkers and patient-reported outcome measures to investigate anxiety, fear and stress in children during in the dental environment is limited. There was no correlation between subjective and objective measures in almost all included studies.

Associação do polimorfismo genético da Cromogranina A com pacientes portadores de câncer de tireoide / Association of chrogranin A (CHGA) genetic polymorphism with patients with thyroid câncer / Asociación del polimorfismo genético de la crogranina A (CHGA) con pacientes con cáncer de tiroides

Objetivo: Descrever a presença do polimorfismo da região codante do gene CHGA Glu264Asp e associa-lo com as características clinicas da doença. Método: Trata-se de um estudo transversal, descritivo e de caso controle para investigar o polimorfismo da CHGA Glu264Asp por meio de amostras de sangue de 53 indivíduos sendo o grupo caso, formado por 23 pacientes, de ambos os sexos, que sofreram a tireoidectomia e foram submetidos ao tratamento com o Radiofármaco Iodeto de Sódio (I131). Para a genotipagem foi utilizada a técnica PCRRFLP. Foi adotado o nível de significância de 5%. Resultados: Houve diferença estatística significativa na distribuição alélica entre indivíduos com câncer papilífero da tireoide e os sadios. Com tudo, a presença do alelo G é um fator de risco para o câncer papilífero da tireoide. Observou-se uma correlação entre o genótipo GG com o aumento do nível de TSH em pacientes que apresentavam essa patologia. Conclusão: Demostrou-se que o alelo selvagem pode ser um fator de risco para o desenvolvimento da neoplasia tireoidiana do tipo papilar. Por ser uma doença de etiologia multifatorial, são necessários outros estudos em populações diferentes para melhor compreensão da doença.

Objective: To describe the presence of polymorphism of the codante region of the CHGA Glu264Asp gene and to associate it with the clinical characteristics of the disease. Method: This is a cross-sectional, descriptive and case-control study to investigate chga glu264Asp polymorphism through blood samples from 53 individuals, consisting of 23 patients of both sexes who underwent thyroidectomy and underwent treatment with the Radiopharmaceutical Sodium Iodide (I131). Pcr-RFLP technique was used for genotyping. The significance level of 5% was adopted. Results: There was a statistically significant difference in the allelic distribution between individuals with papillary thyroid cancer and healthy individuals. With everything, the presence of the G alllet is a risk factor for papillary thyroid cancer. A correlation was observed between the GG genotype and the increased level of TSH in patients with this pathology. Conclusion: It was shown that the wild allomay be a risk factor for the development of the thyroid neoplasm of the papilar type. As it is a disease of multifactorial etiology, further studies in different populations are needed to better understand the disease

Objetivo: Describir la presencia de polimorfismo de la región codante del gen CHGA Glu264Asp y asociarlo con las características clínicas de la enfermedad. Método: Estudio transversal, descriptivo y de casos y controles para investigar el polimorfismo chga glu264Asp a través de muestras de sangre de 53 individuos, constituido por 23 pacientes de ambos sexos sometidos a tiroidectomía y tratamiento con yoduro de sodio radiofarmacéutico (I131). Se utilizó la técnica Pcr-RFLP para el genotipado. Se adoptó el nivel de significancia del 5%. Resultados: Hubo una diferencia estadísticamente significativa en la distribución alélica entre individuos con cáncer papilar de tiroides e individuos sanos. Con todo, la presencia del Gallete G es un factor de riesgo para el cáncer papilar de tiroides. Se observó una correlación entre el genotipo GG y el aumento del nivel de TSH en pacientes con esta patología. Conclusión: Se demostró que el aloplasma silvestre puede ser un factor de riesgo para el desarrollo de la neoplasia tiroidea del tipo papilar. Como es una enfermedad de etiología multifactorial, se necesitan más estudios en diferentes poblaciones para comprender mejor la enfermedad

Laboratory variables as predictors of progression in gastroenteropancreatic neuroendocrine tumors in different lines of antineoplastic treatments

ABSTRACT Objective: To determine the association of red cell blood counts, and liver panel tests to predict outcomes in patients with gastroenteropancreatic neuroendocrine tumors who underwent systemic antineoplastic treatments. Methods: Patients with gastroenteropancreatic neuroendocrine tumors in systemic treatment were assessed according to laboratory tests within the same period. Progression free survival was determined by the period between the beginning of treatment and the date of progression. We used conditional models (PWP model) to verify the association between laboratory tests and tumor progression. The level of significance used was 5%. Results: A total of 30 treatments given to 17 patients in the intention-to-treat population were evaluated. Treatment included octreotide, lanreotide, everolimus, lutetium, and chemotherapy. We had statistically significant results in chromogranin A, neutrophils and platelets-to-lymphocyte ratio. The risk of progression increases by 2% with the addition of 100ng/mL of chromogranin A (p=0.034), 4% with the increase of 100 neutrophil units (p=0.006), and 21% with the addition of 10 units in platelets-to-lymphocyte ratio (p=0.002). Conclusion: Chromogranin A, neutrophils and platelets-to-lymphocyte ratio were associated with disease progression during systemic treatment in gastroenteropancreatic neuroendocrine tumors. Further prospective studies with larger cohorts are necessary to validate our findings.

Study of the ultrastructure of Enterococcus faecalis and Streptococcus mutans incubated with salivary antimicrobial peptides.

OBJECTIVES: Enterococcus faecalis has been associated with root canal infections, while Streptococcus mutans has a central role in the etiology of dental caries. One of the main reasons of endodontic failure has been associated to the presence of E. faecalis and the formation of biofilms. S. mutans inhabits the oral cavity, specifically the dental plaque, which is a multispecies biofilm formed on the hard surfaces of the tooth. The biofilm formation is the main factor determining the pathogenicity of numerous bacteria. Natural antimicrobial peptides in the saliva protect against pathogenic bacteria and biofilms. The aim of this study was to assess the ultrastructural damage induced by salivary peptides in bacteria involved in biofilms has not been previously studied. MATERIAL AND METHODS: Enterococcus faecalis and S. mutans incubated with cystatin C, chromogranin A, or histatin 5 were morphologically analyzed and counted. The ultrastructural damage was evaluated by transmission electron microscopy (TEM). RESULTS: A decrease in bacterial numbers was observed after incubation with cystatin C, chromogranin A, or histatin 5, compared to the control group (P < 0.001). Ultrastructural damage in E. faecalis and S. mutans incubated with salivary peptides was found in the cell wall, plasma membrane with a decreased distance between the bilayers, a granular pattern in the cytoplasm, and pyknotic nucleoids. CONCLUSIONS: This study demonstrated that salivary peptides exert antibacterial activity and induce morphological damage on E. faecalis and S. mutans. Knowledge on the ultrastructural damage inflicted by salivary antimicrobial peptides on two important bacteria causing dental caries and root canal infections could aid the design of new therapeutic approaches to facilitate the elimination of these bacteria.

Association of the CHGA gene polymorphism in patients with hemorrhagic stroke and/or aneurysm / Associação do polimorfismo do gene CHGA em pacientes com acidente vascular encefálico hemorrágico e/ou aneurisma

ABSTRACT Introduction: Cerebrovascular diseases have been associated with several genes. Chromogranin A (CHGA) has been used as maker in cardiovascular disease. Therefore, evaluating the polymorphism and verifying its association with this pathology is very important to better understand this disease. Objective: The aim of this study was to identify the association between coding region polymorphism in -264 position of the CHGA gene (Glu264Asp) and hemorrhagic stroke (HS)/aneurysm in the Federal District, Brazil. Methods: This is a population-based case-control, involving 45 cases with HS and/or aneurysm. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used for genotyping these samples. A significance level of 5% was adopted. Results: The absence of the CC genotype the Glu264Asp CHGA polymorphism in the study participants and the significant presence of the GC heterozygote genotype were observed in this study. However, the distribution of genotypes did not differ statistically in the groups. Conclusion: The Glu264Asp CHGA polymorphism does not seem to contribute to the genesis of the CHGA protein expression in this patients group, but to understand whether or not there is a possible association of the pathology in question and whether the mutation will contribute in the gene therapy and thus to improve patients' quality of life.

RESUMEN Introducción: Enfermedades cerebrovasculares han sido vinculadas a diversos genes. La cromogranina A (CgA) es utilizada como un marcador en enfermedades cardiovasculares. Por consiguiente, evaluar el polimorfismo y verificar la asociación con esa patología es muy importante para la mejor comprensión de la enfermedad. Objetivo: El enfoque del ensayo fue identificar la asociación entre el polimorfismo en la región codificante en la posición -264 del gen CHGA (Glu264Asp) y el accidente cerebrovascular hemorrágico (ACVH)/aneurisma en Distrito Federal, Brasil. Métodos: Estudio de caso-control de base poblacional, involucrando 45 casos con ACVH y/o aneurisma. Para el genotipaje de las muestras, se utilizó la técnica de laboratorio reacción en cadena de la polimerasa-polimorfismos en la longitud de los fragmentos de restricción (PCR-RFLP). Nivel de significación elegido: 5%. Resultados: Ausencia del genotipo CC del polimorfismo Glu264Asp CHGA en los participantes del ensayo y presencia significativa del genotipo heterocigoto GC. Sin embargo, la distribución de los genotipos no difirió estadísticamente en los grupos. Conclusión: El polimorfismo Glu264Asp CHGA parece no contribuir para la génesis de la expresión de la proteína CgA en este grupo de pacientes, pero revelar si existe o no una posible asociación de la patología en cuestión y si la mutación contribuirá para la terapia genética y mejorará la calidad de vida de los pacientes.

RESUMO Introdução: Doenças cerebrovasculares têm sido ligadas a diversos genes. A cromogranina A (CHGA) é utilizada como um marcador em doenças cardiovasculares. Portanto, avaliar o polimorfismo e verificar a associação com essa patologia é muito importante para melhor compreensão dessa doença. Objetivo: O foco do estudo foi identificar a associação entre o polimorfismo na região codante posição -264 do gene CHGA (Glu264Asp) e o acidente vascular encefálico hemorrágico (AVEH)/aneurisma no Distrito Federal, Brasil. Métodos: Estudo caso-controle de base populacional, envolvendo 45 casos com AVEH e/ou aneurisma. Para a genotipagem dessas amostras, utilizou-se a técnica laboratorial reação em cadeia da polimerase-polimorfismo de comprimento de fragmento de limitação (PCR-RFLP). Nível de significância de 5% foi adotado. Resultados: A ausência do genótipo CC do polimorfismo Glu264Asp CHGA nos participantes do estudo e a presença significativa do genótipo heterozigoto GC foram verificadas. No entanto, a distribuição dos genótipos não diferiu estatisticamente nos grupos. Conclusão: O polimorfismo Glu264Asp CHGA parece não contribuir para a gênese da expressão da proteína CHGA nesse grupo de pacientes, mas revela se existe ou não uma possível associação da patologia em questão e se a mutação contribuirá para a terapia gênica e melhorará a qualidade de vida dos pacientes.

Biogenesis of the Insulin Secretory Granule in Health and Disease.

The secretory granules of pancreatic beta cells are specialized organelles responsible for the packaging, storage and secretion of the vital hormone insulin. The insulin secretory granules also contain more than 100 other proteins including the proteases involved in proinsulin-to insulin conversion, other precursor proteins, minor co-secreted peptides, membrane proteins involved in cell trafficking and ion translocation proteins essential for regulation of the intragranular environment. The synthesis, transport and packaging of these proteins into nascent granules must be carried out in a co-ordinated manner to ensure correct functioning of the granule. The process is regulated by many circulating nutrients such as glucose and can change under different physiological states. This chapter discusses the various processes involved in insulin granule biogenesis with a focus on the granule composition in health and disease.

Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective.

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.

Just another metastatic carcinoid tumour to the uveal tract.

We describe the clinic, image, and histopathologic features of a well differentiated neuroendocrine carcinoma (carcinoid tumour) metastatic to choroid and ciliary body in a 52-year-old Mexican Mestizo man. The ophthalmologic examination showed an inferior choroidal mass accompanied by exudative retinal detachment. Ultrasound B-Scan study revealed a diffuse thickened choroid with overlying serous retinal detachment, ultrasound A-Scan revealed a high internal reflectivity solid lesion. Ultrasound biomicroscopy (UBM) evidenced a dome shaped ciliary body mass, presumptive diagnosis was uveal tract metastatic disease. Scleral flap choroidal incisional biopsy was performed. Microscopic evaluation demonstrated a hypercellular lesion replacing choroid, composed by cohesive oval-round cells with finely granular chromatin arranged in organoid pattern. Immunohistochemical reactions were Pankeratin AE1/AE3 (+), Cytokeratin CK5/6 (+), Chromogranin A (+), Ki67 (20%), typical well differentiated neuroendocrine carcinoma (carcinoid tumour) was diagnosed. Patient had a mediastinal carcinoid diagnosed 3 years earlier. Metastatic cancer to the eye is perhaps the leading cause of intraocular tumour, despite this fact metastases are rarely seen by the ophthalmologist while the patient is alive. Intraocular metastasis should be considered in the presence of ciliary body or/and choroidal amelanotic or pigmented mass and serous retinal detachment in a patient with history of carcinoid tumor, althought its low frequency (2.2%).

Hiperplasia neuroendocrina en colitis linfocitica y colitis ulcerativa / Neuroendocrine hiperplasia in linfocitic and ulcerative colitis

Introducción: Algunos autores han demostrado incremento de células neuroendócrinas en colitis microscópica y colitis ulcerativa. Objetivo: El objetivo del presente estudio fue evaluar la presencia de células neuroendócrinas en colitis linfocítica, colitis colagenosa y colitis ulcerativa en comparación a controles. Materiales y métodos: Se usó inmunohistoquímica para identificar a las células neuroendócrinas a través del marcador cromogranina A. El estudio incluyó 10 casos de cada diagnóstico de colitis linfocítica, colitis colagenosa y colitis ulcerativa. Resultados: Se encontró diferencia estadísticamente significativa en el conteo de células neuroendocrinas en colitis linfocítica (p=0,019104) y colitis ulcerativa en comparación con los controles (p=0,0077). En colitis colagenosa, se encontró un incremento de células neuroendocrinas pero no pudimos demostrar diferencias estadísticamente significativa. Conclusión: Se demostró hiperplasia de células neuroendocrinas en colitis linfocítica y colitis ulcerativa, lo que confirma lo reportado por los pocos estudios anteriores realizados sobre el tema.

Introduction: Some authors have found increase of neuroendocrine cells in microscopic colitis and ulcerative colitis. Objective: The aim of this study is to evaluate the presence of neuroendocrine cells in ulcerative colitis and lymphocytic colitis and collagenous colitis. Materials and methods: Immunohistochemistry was performed to identify neuroendocrine cells through marker chromogranin A (CgA). The study included 10 cases of each diagnosis of Lymphocytic colitis, collagenous colitis and ulcerative colitis. Results: There was statistically significant difference in the count of neuroendocrine cells, between lymphocytic colitis and control (p=0.019104), and between ulcerative colitis and controls (p=0.0077). In collagenous colitis there was an increase in neuroendocrine cells but we failed to find statistical differences. Conclusion: We could observe neuroendocrine cell hyperplasia in lymphocytic colitis and ulcerative colitis compared with controls, which confirm previous studies.

The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium.

The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal EEC lineage during inflammation.

Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A.

OBJECTIVES: The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. MATERIALS AND METHODS: Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P < 0.001, respectively). CHGA gene variants (T-415C and Glu264Asp) revealed significant differences between diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P < 0.05). CONCLUSIONS: T2DM causes abnormalities in the function of salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. CLINICAL RELEVANCE: Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.

"Unclassical" Combination of Smell Dysfunction, Altered Abdominal Nociception and Human Hypertension Associated "Classical" Adrenal-Augmentation.

We report a 33-year-old female patient, who arrived to the emergency ward with an abdominal pain that suddenly started 10 days before admission. Simultaneously, the patient developed sudden arterial hypertension and smell disturbances. Conventional medical treatment for pain and arterial hypertension was effortless. Laboratory tests ruled out pancreatitis. Metanephrines in her urine were also normal. A dual-phase intravenous contrast computed tomography of the abdomen showed a large mass within left adrenal gland. Adrenocortical adenoma was diagnosed. The mass was not hypervascularized but positive for synaptophysin and chromogranin A. Importantly, these proteins are heavily involved with acetylcholine metabolism. The triad of olfactory disorders, pain and arterial hypertension normalized after surgically extracting the adrenal mass. To our knowledge, this medical case is the first reported patient exhibiting immediate recovery of such unclassical triad of local and remote findings. The function and dysfunction of key nanocholinergic pathways involved with smell, blood pressure and nociception would explain the pathophysiology of this unique medical case.

Carcinoma anficrino de glándula mamaria. Reporte de un caso inusual / Breast amphicrine carcinoma. Report of an unusual case

Los tumores anficrinos de la glándula mamaria son lesiones duales muy poco frecuentes con diferenciación epitelial y neuroendocrina de una misma célula. Nosotros presentamos el caso de una mujer con masa en el seno derecho. El estudio histopatológico mostró un tumor maligno constituido por células pequeñas entremezcladas con algunas células con aspecto en anillo de sello. El uso de anticuerpos monoclonales mostró inmunoreactividad para marcadores epiteliales y neuroendocrinos en las células malignas. Estas características permitieron hacer el diagnóstico de un tumor anficrino basado en la expresión en la misma célula de marcadores epiteliales y neuroendocrinos. El diagnóstico diferencial debe realizarse con los tumores de colisión o con metástasis. La interpretación rigurosa de la inmunohistoquímica en las células neoplásicas en un tumor anficrino es útil para distinguir esta entidad de otras patológicas con características morfológicas similares.

Amphicrine tumours of the mammary gland are very rare dual lesions with epithelial and neuroendocrine differentiation in the same cell. We report the case of a woman with a mass in the right breast. The histopathology study showed a malignant tumour formed by small cells inter-mixed with some cells with a signet ring appearance. The use of antibodies showed immunoreactivity for epithelial and neuroendocrine markers in the malignant cells. These characteristics enable the diagnosis of an amphicrine tumour, based on the expression of epithelial and neuroendocrine markers in the same cell. The differential diagnosis must be made with collision tumours or with metastasis. The rigorous interpretation of the immunohistochemistry in the malignant cells in an amphicrine tumour is useful in order to distinguish this tumour from other diseases with similar morphological characteristics.

Síndrome Carcinoide: Presentación de caso y revisión de la literatura / Carcinoid syndrome: case report and literature review

Se presenta el caso de una mujer de 63 años de edad, con cuadro clínico crónico de un año de evolución caracterizado por diarrea esteatorreica, asociado a episodios de dolor abdominal difuso, tipo cólico, “sensación de bochornos” y enrojecimiento en cara y tronco superior. El abordaje diagnóstico de la diarrea crónica es un reto para los médicos generales y especialistas, más aún, cuando se acompaña de manifestaciones inespecíficas como dolor abdominal y la presencia de “bochornos”. La coexistencia de varios de los anteriores síntomas, obliga a descartar diversas patologías que representan alta morbimortalidad para el paciente. El síndrome de intestino irritable, el feocromocitoma, el hipertiroidismo, el síndrome carcinoide, entre otras, son patologías a excluir en todo caso. El presente artículo pretende brindar el diagnóstico diferencial de las patologías que presentan dichos síntomas, buscando conducir al lector hasta el diagnóstico definitivo de la paciente.

A 63-year-old woman reported a chronic clinical evolution of one year characterized by steatorrhea, associated with episodes of diffuse abdominal pain, cramping and “hot flashes” also redness on the face and upper trunk . The diagnostic approach of chronic diarrhea is a challenge for physicians and specialists, especially, when accompanied by nonspecific manifestations such as abdominal pain and the presence of “hot flashes”. The coexistence of several of these symptoms must be ruled various pathologies that represent high morbidity and mortality for the patient. Irritable bowel syndrome, pheochromocytoma, hyperthyroidism, carcinoid syndrome, among others, are conditions to exclude in any case. This article aims to provide the differential diagnosis of the diseases that have these symptoms, seeking to lead the reader to the definitive diagnosis of the patient.

Diagnostic work-up of gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.