Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile.

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.

Divertículo de Meckel con tumor neuroendocrino: presentación inusual / Meckel's diverticulum with neuroendocrine tumor: unusual presentation

El divertículo de Meckel es una malformación congénita que suele presentarse como un hallazgo incidental asintomático. Puede complicarse por procesos inflamatorios o tumores, cursando con sintomatología abdominal sumamente inespecífica, lo que complica su diagnóstico oportuno. Aunque la incidencia de neoplasias malignas en estos divertículos es baja, los tumores neuroendocrinos son los más representativos. Presentamos el caso de una paciente de 72 años que consultó por dolor abdominal y deposiciones melénicas, con múltiples nódulos intrahepáticos sugestivos de tumores neuroendocrinos y hallazgo intraoperatorio incidental de diverticulitis aguda de Meckel con metástasis peridiverticular de un tumor neuroendocrino. (AU)

Meckel's diverticulum is a congenital malformation that usually presents as an incidental finding. It can be complicated by inflammatory processes or tumors, with non-specific abdominal symptoms which delay its timely diagnosis. Although the incidence of malignant neoplasms in these diver-ticula is low, neuroendocrine tumors are the most representative. We present the case of a 72-year-old female patient who consulted for abdominal pain and melenic bowel movements, with multiple intrahepatic nodules suggestive of neuroendocrine tumors and an incidental intraoperative finding of acute Meckel's diverticulitis with peridiverticular metastasis of a neuroendocrine tumor. (AU)

Breakthrough Symptoms Remain an Unmet Need in Symptomatic Patients With Neuroendocrine Tumors and Carcinoid Syndrome.

OBJECTIVES: The aims of the study were to assess the effects of breakthrough carcinoid syndrome symptoms on well-being in neuroendocrine tumor (NET) patients insufficiently controlled on long-acting somatostatin analog (SSA) and to assess patient experience with treatment options, physician communication, and disease information sources. METHODS: This study surveyed US NET patients from 2 online communities, experiencing at least one symptom, by utilizing a 64-item questionnaire. RESULTS: One hundred patients participated: 73% female, 75% age 56 to 75 years, and 93% White. Primary tumor distribution was as follows: gastrointestinal NET (n = 55), pancreatic NET (n = 33), lung NET (n = 11), and other NET (n = 13). All patients were actively treated with one long-acting SSA and experiencing breakthrough symptoms: diarrhea, flushing, or other (13% experienced one, 30% two, 57% greater than two). More than one third of treated patients experienced carcinoid-related symptoms daily. Sixty percent of respondents reported not having short-acting "rescue" treatment available, impacting well-being though anxiety or depression (45%), trouble exercising (65%), sleeping (57%), employment (54%), and maintaining friendships (43%). CONCLUSIONS: Breakthrough symptoms remain an unmet need, even in treated patients with NETs. Though still relying on physicians, NET patients are now also using the Internet. Improved awareness of optimal SSA use may improve syndrome control.

SEOM-GETNE clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2022).

Neuroendocrine neoplasms (NENs) are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise mainly due to an improvement on diagnostic techniques and awareness. Earlier detection, along with steadfast improvements in therapy, has led to better prognosis over time for advanced gastrointestinal and pancreatic neuroendocrine tumors. The aim of this guideline is to update evidence-based recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification, and therapeutic options, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are reviewed and discussed, and treatment algorithms to guide therapeutic decisions are provided.

Clinical presentation and recurrence of pituitary neuroendocrine tumors: results from a single referral center in Colombia.

INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. SUBJECTS AND METHODS: A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12 month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10 years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. RESULTS: Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). CONCLUSION: Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.

An Overview of Pituitary Neuroendocrine Tumors (PitNET) and Algorithmic Approach to Diagnosis.

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.

Neuroendocrine Neoplasms of the Pancreas: Diagnostic Challenges and Practical Approach.

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.

Neoplasias neuroendócrinas em pacientes jovens: perfil epidemiológico, aspectos clínicos e fatores prognósticos / Neuroendocrine neoplasms in young patients: epidemiological profile, clinical aspects and prognostic factors

INTRODUÇÃO: As neoplasias neuroendócrinas (NENs) são doenças raras, principalmente em pacientes jovens. No entanto, uma percepção de aumento no número de casos de NENs de início jovem (18-40 anos) (YONEN) foi observada em nossa prática clínica. Os dados sobre o perfil epidemiológico dos YONENs são escassos na literatura mundial. Assim, este estudo tem como objetivo avaliar a frequência e os aspectos clínicos e prognósticos dos YONENs em comparação aos NENs de início tardio (> 40 anos) (LONEN). MÉTODOS: Realizamos uma análise retrospectiva de pacientes consecutivos com diagnóstico de NEN gastroenteropancreáticos e de primário oculto tratados de 2010 a 2018 no AC Camargo Cancer Center, localizado em São Paulo, Brasil. Análises descritivas foram usadas para resumir as características dos pacientes, por grupos de YONENs e LONENs. As diferenças de variáveis binárias entre os grupos foram avaliadas pelo teste exato de Fisher ou teste do qui-quadrado de Pearson, e o método de Kaplan-Meier foi usado para estimar a sobrevida livre de progressão (SLP) e a sobrevida global (SG) entre os pacientes metastáticos ao diagnóstico. Fatores prognósticos foram avaliados usando análise de Cox univariada e multivariada. Um valor de p<0,05 foi considerado significativo na análise multivariada. RESULTADOS: De janeiro/2010 a dezembro/2018, 456 pacientes foram incluídos, 90 (19,7%) eram pacientes YONEN e 366 (80,3%) pacientes LONEN, com idade mediana de 35 anos e 56 anos, respectivamente. A origem mais comum foi midgut (150, 32,9%), seguido de pâncreas (121, 26,5%). Pacientes YONEN eram mais frequentemente não tabagistas (p=0,001), tinham menos comorbidades (p=0,001), menos segundas neoplasias (p=0,003), eram mais sintomáticos ao diagnóstico (p=0,001) e apresentavam mais tumores neuroendócrinos bem diferenciados (p=0,005) em comparação com pacientes LONEN. Pacientes YONEN também tiveram maior frequência de síndromes genéticas conhecidas (6,7% vs. 3,0%). Ao diagnóstico, 16 (17,8%) pacientes YONEN e 109 (29,8%) pacientes LONEN eram metastáticos (p=0,02). Dos pacientes com doença localizada, 4 (5,4%) dos YONEN e 13 (5,8%) dos LONEN apresentaram recidiva à distância. Não houve diferença na SG de acordo com as faixas etárias, considerando todos os estádios. No subgrupo metastático, pacientes YONEN apresentaram SLP mediana numericamente inferior em comparação a pacientes LONEN (11,3 vs. 24,3 meses, p=0,16). Na análise multivariada ajustada, YONEN não foi independentemente associado com SLP mediana inferior (Hazard Ratio: 1,736, intervalo de confiança de 95%: 0,980-3,075, p=0,059). CONCLUSÕES: Este estudo apresentou uma das maiores coortes de pacientes YONEN conhecidos na literatura. Este grupo demonstrou algumas características clínicas e prognósticas distintas, com maior frequência de tumores neuroendócrinos bem diferenciados e menos doença metastática ao diagnóstico. Um maior entendimento da biologia tumoral desses pacientes é necessário.

BACKGROUND: Neuroendocrine neoplasms (NENs) comprise a rare disease, mainly in young patients. However, an increase in the number of cases in young-onset (18-40 years old) NENs (YONEN) has been observed in our clinical practice. The data about YONENs epidemiological profiles are scarce; thus, this study aims to assess the frequency and clinical aspects of YONEN in comparison to late-onset (>40 years old) NENs (LONEN). METHODS: We performed a retrospective analysis of all consecutive patients diagnosed with gastroenteropancreatic or unknown primary NENs treated from 2010 to 2018 at AC Camargo Cancer Center, a large cancer center located in São Paulo, Brazil. Descriptive analysis was used to summarize patients characteristics, by groups of YONENs and LONENs. Differences between groups were assessed by the Fisher exact test or Pearson chi-square test, and the Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) among the metastatic patients. Prognostic factors were assessed using univariate and multivariate Cox analysis. A p value <0.05 was considered significant. RESULTS: A total of 456 patients were enrolled: the most common origin was midgut (150, 32.9%) followed by pancreas (121, 26.5%). YONEN occurred in 90 (19.7%) patients: they were more likely to be non-smokers (p=0.001), had less omorbidities (p=0.001), less second neoplasms (p=0.003), were more symptomatic at diagnosis (p=0.001) and had more frequently NENs of well differentiated histology (p=0.005) in comparison with LONEN patients. YONEN patients also had a higher frequency (6.7% vs. 3.0%) of known genetic syndromes. At diagnosis, 16 (17.8%) YONEN patients and 109 (29.8%) LONEN patients were metastatic (p=0.02). About the patients with localized disease, 4 (5.4%) of the YONEN and 13 (5.8%) of the LONEN had distant recurrence (p=0.575). There was no difference in OS according to age groups, considering all stages. In the metastatic subgroup, YONEN patients had a numerically lower median PFS compared to LONEN patients (11.3 vs. 24.3 months, p=0.164). In adjusted multivariate analysis, YONEN was not independently associated with lower median PFS (Hazard Ratio: 1.736, 95% confidence interval: 0.980-3.075, p=0.38). CONCLUSIONS: This study presented one of the largest cohorts of YONEN patients known in the literature. This group demonstrated some distinct clinical and prognostic features, with a higher frequency of well-differentiated neuroendocrine tumors and less metastatic disease at diagnosis. A greater understanding of the tumor biology of these patients is necessary.

Clinical characteristics of 662 patients with pancreatic neuroendocrine tumors receiving antitumoral therapy.

Pancreatic neuroendocrine neoplasia constitute an important subentity of the gastroenteropancreatic neuroendocrine neoplasms accounting for up to 15% of all neuroendocrine neoplasm. Prognosis and oncological behavior of pancreatic neuroendocrine tumors (pNETs) is extremely heterogenous and dependent on the specific tumor stage and differentiation. However, systematic data on the specific epidemiology of pNET are scarce. We identified 662 patients with pNET within the Oncology Dynamics database (IQVIA). Patients were derived from 4 European countries (Germany, France, UK, Spain), 3 Asian countries (Japan, China, South Korea) and 2 South American countries (Mexico and Brazil) and with regard to major patient and tumor related characteristics including patients' age, sex, tumor stage, tumor grading, and differentiation. The mean age of the study cohort was 62 years (SD 12 years) with 53.9.1% of all patients being male. The majority of patients had an Eastern co-operative of Oncology Group 1 performance status (63.3%). The most common Union international contre le cancer tumor stage was stage IV (85%) with liver metastases (89.0%) representing the most common site of extra-pancreatic tumor manifestation. The majority of all patients displayed well or moderate tumor differentiation (9.6% of patients had a Ki-67 expression below 2%. 67.6% of pNET patients had a Ki-67 expression between 2 and 20% and 22.8% of patients showed an expression above 20%). At time point of diagnoses, 93.1% of patients were classified as inoperable. Of note, 93.9 % of patients received systemic anti-tumoral therapy in palliative intention, while treatment was administered in 1.4 % of cases in neoadjuvant and in 4.7% of cases in in an adjuvant setting. Biological therapy was applied to 39.4% of patients, followed by targeted therapies (31.4%) and chemotherapy. Pancreatic neuroendocrine neoplasia are diagnosed in advanced tumor stages, globally. Systemic treatment was the most commonly used treatment modality. Such data may help to better understand the specific epidemiology of pNET worldwide.

Proposing Specific Neuronal Epithelial-to-Mesenchymal Transition Genes as an Ancillary Tool for Differential Diagnosis among Pulmonary Neuroendocrine Neoplasms.

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.

Neutrophil to lymphocyte ratio as a prognosis biomarker of PRRT in NET patients.

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.

Clinicopathological and molecular profile of grade 3 gastroenteropancreatic neuroendocrine neoplasms.

The 2019 Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3 NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3 NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3 NET, with a 23% change in diagnosis. Median overal survival for G3 NET and NEC patients was 55.6 and 11.9 months, respectively (hazard ratio = 2.78 [95% confidence interval = 1.09-7.11], p = .042), which was confirmed by an adjusted analysis (hazard ratio = 2.90 NEC vs. G3 NET; p = .03). NGS was performed in 32 cases: 21 NEC and 11 G3 NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3 NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors.

[Update on neuroendocrine tumors]. / Tumores Neuroendocrinos: un desafío transversal.

Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.

Clinicopathological and Prognostic Significance of CD47 Expression in Lung Neuroendocrine Tumors.

BACKGROUND: Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation. Recent clinical trials have indicated that inhibition of CD47 with anti-CD47 antibodies exerts a promising antitumor effect against several human malignancies, including NSCLC, melanoma, and hematologic malignancies. However, the clinical relevance of CD47 expression in LNET has remained unclear. METHODS: We performed a retrospective study in which we analyzed tumor biopsies from 51 patients with a confirmed diagnosis of LNET that received treatment at our hospital. Then, we analyzed if there was any correlation between CD47 expression with any clinical or pathological characteristic. We also analyzed the prognostic significance of CD47, assessed as progression-free survival and overall survival. RESULTS: A total of 51 patients with LNET were enrolled in our study. The mean age at diagnosis was 57.6 (±11.6) years; 30 patients were women (59%). 27.5% of patients were positive for CD47 expression, and 72.5% of patients showed a CD47 expression of less than 1% and were considered as negatives. In patients with high-grade tumors (this time defined as Ki-67 > 40%), the positive expression of CD47 was strongly associated with an increased PFS. Albeit, these differences did not reach statistical significance when analyzing OS. CONCLUSION: Contrary to what happens in a wide range of hematologic and solid tumors, a higher expression of CD47 in patients with LNET is associated with a better progression-free survival, especially in patients with a Ki-67 ≥ 40%. This "paradox" remains to be confirmed and explained by larger studies.

Tumores Neuroendocrinos: un desafío transversal / Update on neuroendocrine tumors

Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma.

ABSTRACT: This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management and surveillance of metastatic and unresectable pheochromocytoma and paraganglioma held on October 2 and 3, 2019. The panelists consisted of endocrinologists, medical oncologists, surgeons, radiologists/nuclear medicine physicians, nephrologists, pathologists, and radiation oncologists. The panelists performed a literature review on a series of questions regarding the medical management of metastatic and unresectable pheochromocytoma and paraganglioma as well as questions regarding surveillance after resection. The panelists voted on controversial topics, and final recommendations were sent to all panel members for final approval.

Primary thymus tumors: retrospective case analysis at a reference center in Latin America, 2011-2019.

BACKGROUND: Thymic tumors are unusual neoplasms, representing 0.2 to 1.5% of tumors in humans, but correspond to 20% of mediastinal tumors and 50% of those that occur in the anterior mediastinum. They tend to appear around the fourth and fifth decades of life without gender predilection. Up to 30% of patients are asymptomatic, therefore many are incidentally diagnosed. Radical thymectomy is the treatment of choice with high survival rates when detected in the early stages. METHODS: This was a retrospective descriptive study, including 18 adult patients' diagnosis of thymic neoplasm, who were managed with surgical resection from 2011 to 2019. Information about demographics, clinical characteristics, imaging findings, surgical and medical management, plus histological findings was obtained and reported. RESULTS: 18 patients with thymic tumors were included, of which specific histologic studies reveled thymomas, carcinomas, neuroendocrine tumors, thymolipoma and thymic cyst. Mean age was 52.7 years, with a predominance of male population. The main symptom was dyspnea, followed by cough and chest pain. Paraneoplastic syndromes such as myasthenia gravis, aplastic anemia and Cushing syndrome were reported. 89% of cases were treated by radical thymectomy alone, while only 2 cases required chemotherapy and radiotherapy. There were no surgical complications. Mean hospital stay length was 11. 9 days, with only 1 mortality during hospital admission. 5-year survival rate was 81%. CONCLUSIONS: The treatment of choice is radical thymectomy, which has been shown to positively impact patient mortality. Early detection is key to improve patient outcomes.

Reactivos de inmunohistoquímica para diagnóstico diferencial de cáncer de cabeza y cuello, estómago, páncreas y tumores neuroendocrinos / Immunohistochemical reagents for differential diagnosis of head and neck cancer, stomach, pancreas and neuroendocrine tumors

INTRODUCCIÓN: El Departamento de Equipo Funcional de Patología Quirúrgica y Necropsia del Instituto Nacional de Enfermedades Neoplásicas, en relación a nuevos reactivos de inmunohistoquímica para diagnóstico oncológico, ha solicitado la opinión técnica de la UFETS. En relación con el cáncer de cabeza y cuello: El carcinoma de la línea media NUT (Nuclear protein in testis) es altamente agresivo y esta normalmente confinada a las células germinales del testículo y ovario, sin embargo, surge con mayor frecuencia en el tórax y cabeza y cuello. Así mismo, Galectina-3 pertenece a la familia de lectinas que se unen a beta galactósido y está involucrada en la adhesión celular, la cual puede expresarse en el carcinoma tiroideo y diferenciarlo de lesiones tiroideas benignas. 3. En relación con el cáncer de estómago/páncreas/tumores neuroendocrinos del sistema gastrointestinal: La Proteína 1 homeobox1 pancreática y duodenal (PDX-1) es un gen que tiene un rol determinantemente regulador durante la formación del páncreas embrionario y juega un papel en la diferenciación del páncreas exocrino y regula la función de las células beta en el páncreas maduro. La Tripsina es la forma activa del tripsinógeno, enzima involucrada en el metabolismo de proteínas, que es producida por las células acinares del páncreas exocrino, siendo útil para carcinoma de páncreas con diferenciación acinar. La Quimiotripsina es una enzima involucrada en el metabolismo de proteínas, que es producida por células acinares del páncreas exocrino. Útil para carcinoma páncreas con diferenciación acinar. ESTRATEGIA DE BÚSQUEDA DE INFORMACIÓN: PREGUNTA CLÍNICA: Cáncer de Cabeza y Cuello: En la población con cáncer de cabeza y cuello, ¿Cuál es la utilidad de los marcadores Galectina 3/NUT como diagnóstico oncológico? Cáncer de Estómago/Pancreas/Tumores Neuroendocrinos del Sistema Gastrointestinal: En la población con cáncer de estómago/páncreas/tumores neuroendocrinos, ¿Cuál es la utilidad de los marcadores de PDX-1/Tripsina/Quimiotripsina como diagnóstico oncológico? B. RECOLECCIÒN DE LOS MANUSCRITOS A REVISAR: Tipos de estudios: La estrategia de búsqueda sistemática de información científica para el desarrollo del presente informe se realizó siguiendo las recomendaciones de la Pirámide jerárquica de la evidencia propuesta por Haynes y se consideró los siguientes estudios: Sumarios y guías de práctica clínica. Revisiones sistemáticas y/o meta-análisis. Ensayos Controlados Aleatorizados (ECA). Estudios Observacionales (cohortes, caso y control, descriptivos) No hubo limitaciones acerca de la fecha de publicación o el idioma para ningún estudio. Fuentes de información: De acceso libre o Bases de datos: Pubmed Fecha de búsqueda: La búsqueda sistemática se limitó a estudios publicados en los últimos 10 años. DISCUSIÓN: Tomando los criterios para un marco de valor de la Health Technology Assessment International (2018)12 para la toma de decisiones y formulación de la recomendación, se describe: La calidad de evidencia evaluada con metodología GRADE para NUT y Galactin-3 fue moderada, y para PDX-1 fue baja la calidad de evidencia, en la evaluación de la calidad de evidencia se ha considerado las limitaciones de las RS (heterogenidad, imprecisión), y las limitaciones en estudios observacionales (inician con calidad baja). Esta valoración de la calidad indica que los valores diagnósticos encontrados pueden ser sustancialmente diferentes al efecto que pueda tener en el mundo real. La magnitud del beneficio es a favor, pues considerando que no existen pruebas en INEN que evalúen las patologías solicitadas (cáncer cuello y tiroides; cáncer páncreas, y pueden ser beneficiosos. Además la alta sensibilidad y especificidad permitiría captar a pacientes con estas patologías. El impacto económico de esta prueba para el INEN es incierto, es necesario realizar un análisis de impacto presupuestario para estimar cuantitativamente el gasto sanitario del uso de esta prueba en la población con cáncer de tumores sólidos localmente avanzado y metastásicos. La incorporación de esta tecnología supone un impacto probablemente positivo en la equidad al considerar que poblaciones con enfermedades frecuentes y poco frecuentes puedan ser atendidos y diagnosticados para un tratamiento adecuado, evitando el infradiagnóstico. Cáncer de cabeza y cuello: Los estudios que evaluaron NUT y Galactin-3, evaluaron en población con cáncer de cabeza y cuello. En NUT evaluaron la inmunohistoquímica(fijados en parafina) comparado con Fish. Encontraron que los tumores teñidos con NUT fueron principalmente carcinomas de aringe, cavidad oral y pulmón. Los tumores que fueron positivos revelaron típicamente una fuerte reactividad nuclear difusa (> 90%) en un patrón moteado, mientras que los casos negativos carecían de reactividad nuclear. La sensibilidad y especificidad de NUT fue 87% y 100% para diferenciar carcinomas de línea media NUT de otros tumores de células no germinales. En Galactina-3 se encontró un MA que evaluó la confiabilidad histológica de galectina3 para identificación de cáncer de tiroides. Este MA realizó una búsqueda en base de datos hasta mayo del 2017. Incluyeron 52 artículos originales (todos retrospectivos). La sensibilidad de Galectina-3 fue del 87% (IC 95: 86% a 88%) y la especificidad del 87% (IC 95%: 86% a 88%). Concluyen que con estos datos se muestra una alta confiabilidad de Galectina-3 para el cáncer de tiroides en histología, y distinguirlo de tumores de tiroides benignos. Este MA presentó heterogeneidad (85% y 93%, para sensibilidad y especificidad) así como sesgo de publicación significativo El departamento solicitante añadió que Galactina-3 y junto con el marcador I67 refuerza el diagnóstico para carcinoma tiroideo y carcinoma de paratiroides. Cáncer de estómago/páncreas/tumores neuroendócrinos: El estudio que evalúa el uso de PDX-1 analizó su uso en tumores neuroendocrinos (TNE) y no TNE de diferente localización y origen histogenético. PDX-1 fue positivo en tres de cuatro TNE pancreáticos, presente en todos los insulinomas, gastrinomas y somastotatinomas. PDX-1 fue negativo en otros cánceres que no eran de origen gástricos. La expresión de PDX-1 es muy sensible para la mayoría de los TNE pancreáticos y no es positiva cuando no son tumores de origen pancreáticos. En un estudio se evaluó tripsina y quimiotripsina encontró que estas dos pruebas pueden detectar hasta un 95% de carcinoma acinar pancreático, sin embargo, el nivel de confianza de este artículo es de baja calidad pues es una revisión narrativa. El departamento solicitante añadió que el PDX-1 un cáncer primario metastásico no conocido, puede determinar si el origen es de origen neuroendocrino pancreático y diferenciarlo de uno de origen colónico o de apéndice. Tripsina y quimiotripsina. CONCLUSIONES: Dentro de la búsqueda, se encontró evidencia del uso de los marcadores para cáncer de cabeza y cuello (NUT y galectina-3) y en cáncer de estómago/páncreas/tumores neuroendocrinos (PDX-1, tripsina y quimiotripsina). NUT logró tener una sensibilidad del 87% y especificidad del 100% para detección de carcinoma de linea media NUT. Galectina-3 para identificación de cáncer de tiroides obtuvo una sensibilidad de 87% y especificidad del 87%. Un estudio evidenció que el uso de PDX-1 es útil para diagnóstico de tumores neuroendocrinos pancreáticos. El diagnóstico de carcinoma acinar pancreático, el uso de tripsina y quimotripsina fueron reactivos en el 95% de los casos y, según se informa, la combinación es la más sensible para el diagnóstico de esta patología. Los estudios encontrados tienen como principal limitación el no ser comparado con pruebas estándares, y ser estudios observacionales descriptivos. Se recomienda que los reactivos solicitados, de incorporarse deban tener un registro SISMED. Por lo expuesto, la UFETS en consenso con el Comité de ETS, emite opinión favorable para el uso de la tecnología del marcador PDX-1.