RESUMEN
Pituitary neuroendocrine tumors (PitNET) are known to be variably infiltrated by different immune cells. Nonetheless, their role in pituitary oncogenesis has only begun to be unveiled. The immune microenvironment could determine the biological and clinical behavior of a neoplasm and may have prognostic implications. To evaluate the expression of immune-related genes and to correlate such expression with the presence of infiltrating immune cells in forty-two PitNETs of different lineages, we performed whole transcriptome analysis and RT-qPCR. Deconvolution analysis was carried out to infer the immune cell types present in each tumor and the presence of immune cells was confirmed by immunofluorescence. We found characteristic expression profiles of immune-related genes including those encoding interleukins and chemokines for each tumor lineage. Genes such as IL4-I1, IL-36A, TIRAP, IL-17REL, and CCL5 were upregulated in all PitNETS, whereas IL34, IL20RA, and IL-2RB characterize the NR5A1-, TBX19-, and POU1F1-derived tumors, respectively. Transcriptome deconvolution analysis showed that M2 macrophages, CD4+ T cells, CD8+ T cells, NK cells, and neutrophils can potentially infiltrate PitNET. Furthermore, CD4+ and CD8+ T cells and NK cells infiltration was validated by immunofluorescence. Expression of CCL18, IL-5RA, and HLA-B as well as macrophage tumor infiltration could identify patients who can potentially benefit from treatment with immune checkpoint inhibitors.
Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Transcriptoma , Microambiente Tumoral , Humanos , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/inmunología , Neoplasias Hipofisarias/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/inmunología , Tumores Neuroendocrinos/patología , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica/métodos , Masculino , Femenino , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , AdultoAsunto(s)
Adenoma , Neoplasias del Oído , Oído Medio , Humanos , Neoplasias del Oído/cirugía , Neoplasias del Oído/patología , Neoplasias del Oído/diagnóstico por imagen , Oído Medio/diagnóstico por imagen , Oído Medio/cirugía , Oído Medio/patología , Adenoma/cirugía , Adenoma/diagnóstico por imagen , Adenoma/patología , Endoscopía , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Femenino , Tomografía Computarizada por Rayos X , Masculino , Persona de Mediana EdadRESUMEN
GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion.
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Acromegalia , Neoplasias Hipofisarias , Humanos , Acromegalia/genética , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , MicroARNs/genéticaAsunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Tumores Neuroendocrinos , Humanos , Ampolla Hepatopancreática/cirugía , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/patología , Esfinterotomía Endoscópica/métodos , Masculino , FemeninoRESUMEN
BACKGROUND: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America. AIM: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs. METHODS: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile. RESULTS: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex. CONCLUSIONS: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes.
Asunto(s)
Hospitales Universitarios , Neoplasias Intestinales , Intestino Delgado , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios Retrospectivos , Chile/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Pronóstico , Anciano , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/patología , Neoplasias Intestinales/diagnóstico , Intestino Delgado/patología , Adulto , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/diagnóstico , Anciano de 80 o más Años , Tasa de Supervivencia , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adulto Joven , Linfoma/epidemiología , Linfoma/diagnóstico , Linfoma/patologíaRESUMEN
BACKGROUND: Gastric neuroendocrine tumors are a heterogeneous group of neoplasms that produce bioactive substances. Their treatment varies according to staging and classification, using endoscopic techniques, open surgery, chemotherapy, radiotherapy, and drugs analogous to somatostatin. AIMS: To identify and review cases of gastric neuroendocrine neoplasia submitted to surgical treatment. METHODS: Review of surgically treated patients from 1983 to 2018. RESULTS: Fifteen patients were included, predominantly female (73.33%), with a mean age of 55.93 years. The most common symptom was epigastric pain (93.3%), and the mean time of symptom onset was 10.07 months. The preoperative upper digestive endoscopy (UDE) indicated a predominance of cases with 0 to 1 lesion (60%), sizing ≥1.5 cm (40%), located in the gastric antrum (53.33%), with ulceration (60%), and Borrmann III (33.33%) classification. The assessment of the surgical specimen indicated a predominance of invasive neuroendocrine tumors (60%), with angiolymphatic invasion in most cases (80%). Immunohistochemistry for chromogranin A was positive in 60% of cases and for synaptophysin in 66.7%, with a predominant Ki-67 index between 0 and 2%. Metastasis was observed in 20% of patients. The surgical procedure most performed was subtotal gastrectomy with Roux-en-Y reconstruction (53.3%). Tumor recurrence occurred in 20% of cases and a new treatment was required in 26.67%. CONCLUSIONS: Gastric neuroendocrine tumors have a low incidence in the general population, and surgical treatment is indicated for advanced lesions. The study of its management gains importance in view of the specificities of each case and the need for adequate conduct to prevent recurrences and complications.
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Tumores Neuroendocrinos , Neoplasias Gástricas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Recurrencia Local de Neoplasia , Gastrectomía/métodos , Anastomosis en-Y de Roux , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS: To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS: A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS: During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS: Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.
Asunto(s)
Neoplasias Hepáticas , Trasplante de Hígado , Tumores Neuroendocrinos , Femenino , Humanos , Masculino , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Trasplante de Hígado/métodos , Estudios Retrospectivos , Supervivencia sin EnfermedadRESUMEN
Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.
Asunto(s)
Mutación de Línea Germinal , Tumores Neuroendocrinos , Adulto Joven , Humanos , Mutación , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Pérdida de Heterocigocidad , Predisposición Genética a la Enfermedad , Proteína de la Xerodermia Pigmentosa del Grupo DRESUMEN
The diagnostic algorithm and nomenclature of pituitary neuroendocrine tumors have evolved over the past decade, beginning with simpler categorical schemes focused on histomorphologic features and moving to a more sophisticated lineage-specific categorization. This contemporary overview highlights a multimodal approach to pituitary neuroendocrine tumors with a focus on changes in nomenclature, classification, and subclassification; including, brief comments on treatment, and new guidelines for genetic screening, particularly for young patients with such neoplasms.
Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/genéticaRESUMEN
Most pancreatic neuroendocrine neoplasms are slow-growing, and the patients may survive for many years, even after distant metastasis. The tumors usually display characteristic organoid growth patterns with typical neuroendocrine morphology. A smaller portion of the tumors follows a more precipitous clinical course. The classification has evolved from morphologic patterns to the current World Health Organization classification, with better-defined grading and prognostic criteria. Recent advances in molecular pathology have further improved our understanding of the pathogenesis of these tumors. Various issues and challenges remain, including the correct recognition of a neuroendocrine neoplasm, accurate classification and grading of the tumor, and differentiation from mimickers. This review focuses on the practical aspects during the workup of pancreatic neuroendocrine neoplasms and attempts to provide a general framework to help achieve an accurate diagnosis, classification, and grading.
Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Pronóstico , Organización Mundial de la Salud , Clasificación del TumorRESUMEN
We describe a case of a gastric neuroendocrine tumor (NET) in a patient with a history of long- term proton pump inhibitor (PPI) use. A 29- year- old man using PPI for the last 10 years due to gastroesophageal reflux disease developed progressive bouts of heartburn. Upper gastrointestinal endoscopy localized an elevated lesion with central depression in the greater curvature of gastric body. Lesion biopsies revealed a well- differentiated neuroendocrine tumor. Despite PPIs have a well- established safety profile, concerns have been raised about a potential relationship between PPI- induced hypergastrinemia and the development of neuroendocrine tumors.
Asunto(s)
Reflujo Gastroesofágico , Tumores Neuroendocrinos , Neoplasias Gástricas , Masculino , Humanos , Adulto , Inhibidores de la Bomba de Protones/efectos adversos , Tumores Neuroendocrinos/inducido químicamente , Tumores Neuroendocrinos/patología , Neoplasias Gástricas/inducido químicamente , Neoplasias Gástricas/patologíaRESUMEN
ABSTRACT BACKGROUND: Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS: To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS: A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS: During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS: Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.
RESUMO RACIONAL: Os tumores neuroendócrinos são neoplasias raras de comportamento biológico incerto. O fígado é um local comum de metástase, ocorrendo em 50% dos pacientes com doença metastática. OBJETIVOS: Analisar casuística de transplante hepático por metástases de tumores neuroendócrinos. MÉTODOS: Estudo descritivo retrospectivo com revisão de prontuários de pacientes submetidos a transplante hepático por metástases de tumores neuroendócrinos em um único centro no Nordeste do Brasil durante 20 anos (janeiro de 2001 a dezembro de 2021). RESULTADOS: Durante o período analisado, foram realizados 2.000 transplantes hepático, sendo 11 indicados por metástases hepáticas de tumores neuroendócrinos. A média de idade ao diagnóstico foi de 45,09±14,36 anos (26-66 anos) e 72,7% dos casos eram do sexo feminino. O local do tumor primário mais comum foi o trato gastrointestinal (64% dos casos). Após detalhada investigação, três pacientes não tiveram o local do tumor primário identificado (27%). A sobrevida global um mês e após um ano do transplante foi de 90 e 70%, respectivamente. A sobrevida após 5 anos foi de 45,4%. A taxa de sobrevida livre de doença foi de 72,7% no primeiro ano e 36,3% em cinco anos. CONCLUSÕES: O transplante hepático é uma modalidade de tratamento com bons resultados de sobrevida global e sobrevida livre de doença, em pacientes selecionados com metástases hepáticas irressecáveis de tumores neuroendócrinos. No entanto, a seleção rigorosa dos pacientes é necessária para obter melhores resultados e o momento ideal para a indicação do transplante ainda é um tema controverso na literatura.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Trasplante de Hígado/métodos , Tumores Neuroendocrinos/cirugía , Neoplasias Hepáticas/secundario , Estudios Retrospectivos , Tumores Neuroendocrinos/patología , Supervivencia sin EnfermedadRESUMEN
Pulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological parameters, resulting in considerable overlapping among PNENs, which may result in important challenges for clinicians' decisions in the case of small biopsies. Since PNENs originate from the neuroectodermic cells, epithelial-to-mesenchymal transition (EMT) gene expression shows promise as biomarkers involved in the genotypic transformation of neuroectodermic cells, including mutation burden with the involvement of chromatin remodeling genes, apoptosis, and mitosis rate, leading to modification in final cellular phenotype. In this situation, additional markers also applicable to biopsy specimens, which correlate PNENs subtypes with systemic treatment response, are much needed, and current potential candidates are neurogenic EMT genes. This study investigated EMT genes expression and its association with PNENs histotypes in tumor tissues from 24 patients with PNENs. PCR Array System for 84 EMT-related genes selected 15 differentially expressed genes among the PNENs, allowing to discriminate TC from AC, LCNEC from AC, and SCLC from AC. Functional enrichment analysis of the EMT genes differentially expressed among PNENs subtypes showed that they are involved in cellular proliferation, extracellular matrix degradation, regulation of cell apoptosis, oncogenesis, and tumor cell invasion. Interestingly, four EMT genes (MAP1B, SNAI2, MMP2, WNT5A) are also involved in neurological diseases, in brain metastasis, and interact with platinum-based chemotherapy and tyrosine-kinase inhibitors. Collectively, these findings emerge as an important ancillary tool to improve the strategies of histologic diagnosis in PNENs and unveil the four EMT genes that can play an important role in driving chemical response in PNENs.
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Tumor Carcinoide , Carcinoma Neuroendocrino , Neoplasias Pulmonares , Tumores Neuroendocrinos , Humanos , Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Carcinoma Neuroendocrino/genética , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/genética , Tumor Carcinoide/patologíaRESUMEN
INTRODUCTION: Pulmonary neuroendocrine tumors account for approximately 20% of all primary lung tumors. Few studies summarize the current body of pulmonary neuroendocrine tumors studies worldwide. OBJECTIVE: A quantitative scientometric analysis was conducted to evaluate the development of applications and innovations and to analyze their contribution to various areas of improvement in treatment and diagnosis of pulmonary neuroendocrine tumors. METHODS: We searched for studies published in the last 20 years in the databases United States National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Scopus, and Web of Science, using the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'typical pulmonary carcinoid', 'atypical pulmonary carcinoid', 'pulmonary carcinoid and diagnosis', 'pulmonary carcinoid and treatment', 'pulmonary carcinoid and epidemiology' and 'pulmonary carcinoid and prognosis'. RESULTS: Our results showed the number of publications increased significantly over the study period and was strongly associated with the economic or financial situation of the publications' countries of origin. We observed a predominance of studies on histological diagnosis compared to treatment, and among the studies related to treatment, a predominance of retrospective studies relative to prospective studies was found. CONCLUSION: Based on the published literature, we concluded research on pulmonary neuroendocrine tumors still seems to be incipient, because it favors studies related to histological characterization of the disease, and therapeutic studies are still predominantly of a retrospective nature.
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Tumor Carcinoide , Carcinoma Neuroendocrino , Neoplasias Pulmonares , Tumores Neuroendocrinos , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Tumor Carcinoide/terapia , Neoplasias Pulmonares/terapia , Tumores Neuroendocrinos/patologíaRESUMEN
The pituitary is a master gland responsible for the modulation of critical endocrine functions. Pituitary neuroendocrine tumours (PitNETs) display a considerable prevalence of 1/1106, frequently observed as benign solid tumours. PitNETs still represent a cause of important morbidity, due to hormonal systemic deregulation, with surgical, radiological or chronic treatment required for illness management. The apparent scarceness, uncommon behaviour and molecular features of PitNETs have resulted in a relatively slow progress in depicting their pathogenesis. An appropriate interpretation of different phenotypes or cellular outcomes during tumour growth is desirable, since histopathological characterization still remains the main option for prognosis elucidation. Improved knowledge obtained in recent decades about pituitary tumorigenesis has revealed that this process involves several cellular routes in addition to proliferation and death, with its modulation depending on many signalling pathways rather than being the result of abnormalities of a unique proliferation pathway, as sometimes presented. PitNETs can display intrinsic heterogeneity and cell subpopulations with diverse biological, genetic and epigenetic particularities, including tumorigenic potential. Hence, to obtain a better understanding of PitNET growth new approaches are required and the systematization of the available data, with the role of cell death programs, autophagy, stem cells, cellular senescence, mitochondrial function, metabolic reprogramming still being emerging fields in pituitary research. We envisage that through the combination of molecular, genetic and epigenetic data, together with the improved morphological, biochemical, physiological and metabolically knowledge on pituitary neoplastic potential accumulated in recent decades, tumour classification schemes will become more accurate regarding tumour origin, behaviour and plausible clinical results.
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Tumores Neuroendocrinos , Neoplasias Hipofisarias , Senescencia Celular , Humanos , Tumores Neuroendocrinos/patología , Hipófisis/metabolismo , Neoplasias Hipofisarias/patología , Transducción de SeñalRESUMEN
PURPOSE: Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE is a palliative therapeutic option for advanced Neuroendocrine Tumors (NETs). Prognostic factors can predict long-term outcomes and determine response to therapy. Among those already explored, biomarkers from full blood count, including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) has shown value for other solid tumors and for NETs patients submitted to other forms of therapy. However, its relation to PRRT response and patients' prognosis is still to be determined. METHODS: Medical records from 96 patients submitted to PRRT between 2010 and 2017 were reviewed, median NLR and PLR were calculated from baseline flood blood count and dichotomized as high or low. Progression-free survival (PFS) and Overall Survival (OS) were calculated. RESULTS: NLR and PLR median values were 1.8 and 123, respectively. Patients with low NLR had a significantly longer OS (estimated median of 77.5 months, 95% CI: 27.3-127.7) when compared to patients with high NLR (estimated median of 47.7 months, 95% CI: 34.7-60.8); p = 0.04. Patients with low NLR had a trend toward a longer median PFS when compared to patients with high NLR [estimated medians of 77 months (95% CI: 27.3-127.7), and 47.7 months, (95% CI: 34.7-60.7)], respectively, p = 0.08. CONCLUSION: Patients with advanced-stage NET with NLR higher than 1.8 have worse long term clinical outcomes after PPRT. Larger studies are needed to validate the optimal cutoff for this biomarker.
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Tumores Neuroendocrinos , Neutrófilos , Biomarcadores , Humanos , Recuento de Linfocitos , Linfocitos/patología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Tomografía de Emisión de Positrones , Pronóstico , Cintigrafía , Estudios RetrospectivosRESUMEN
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.
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Antineoplásicos , Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Antineoplásicos/uso terapéutico , Cromogranina A/uso terapéutico , Humanos , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/patología , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Incidence of pancreatic neuroendocrine tumors (pNETS) seems to be rising over the years, with many cases incidentally diagnosed. Surgery and active surveillance are current treatment modalities for small pNETS. We review our institutional series and compare outcomes for small asymptomatic and nonfunctioning tumors. METHODS: This retrospective cohort study included patients with 2 cm or less and well differentiated pNETS at a single Brazilian Cancer Center. From 2002 to 2020, patients received active surveillance or surgery as a treatment strategy. Short and long-term results were compared. RESULTS: Sixty-four patients were included, 41 in surgical strategy and 23 in the active surveillance approach. Baseline group characteristics were comparable. More patients on active surveillance underwent abdominal magnetic resonance imaging (MRI) and had tumors located in the pancreatic head (41% vs. 17%, p = 0.038). Minimally invasive procedure was chosen in 80.1% of the surgical patients. No patient died after surgery. Median follow-up period was 38.6 and 46.4 months for active surveillance and surgery cohorts, respectively. No difference in disease progression rate was observed. CONCLUSION: Both approaches seem to be safe for small pNETs. Long-term outcome and quality of life should be considered when discussing such options with patients.
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Tumores Neuroectodérmicos Primitivos , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Brasil/epidemiología , Estudios de Cohortes , Humanos , Tumores Neuroendocrinos/patología , Pancreatectomía/métodos , Neoplasias Pancreáticas/patología , Calidad de Vida , Estudios Retrospectivos , Espera VigilanteRESUMEN
Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.