Síndrome de feocromocitoma-paraganglioma de tipo 5 como causa de hipertensión arterial en una paciente colombiana: reporte de caso / Pheochromocytoma/paraganglioma type 5 syndrome as a cause of secondary hypertension in a Colombian patient: case report

El feocromocitoma es un tumor derivado de las células de la cresta neural con la capacidad de producir sustancias simpaticomiméticas y, por ende, un cuadro clínico particular. Causa menos del 1 % de los casos de hipertensión arterial sistémica y su incidencia se estima entre 0,4 y 0,6 casos por 100.000 personas cada año, con una supervivencia media de siete años. De todos los tumores sólidos, el feocromocitoma tiene un mayor componente genético, que puede heredarse hasta en el 40 % de los casos. Una vez diagnosticada la enfermedad, se debe definir el tratamiento y el pronóstico, en parte condicionados por las variantes genéticas asociadas, en especial RET, SDHx, VHL y NF1.Se presenta el caso de una mujer joven con dolor abdominal e hipertensión arterial sistémica, a quien se le diagnosticó feocromocitoma. Al secuenciar el exoma, se identificó una variante patogénica extremadamente rara y de reciente descubrimiento: SDHA: c.1A>C (p.Met1Leu). La paciente respondió adecuadamente al tratamiento quirúrgico y continuó en seguimiento sin recurrencias.El abordaje diagnóstico de los pacientes con feocromocitoma comienza con la sospecha clínica, seguida de la medición de determinados metabolitos en sangre y orina, y, finalmente, los estudios de imagenología. Los desarrollos tecnológicos actuales permiten la aplicación de la medicina de precisión en este campo. En este caso de feocromocitoma, se identificó un componente genético importante que no solo afecta al paciente, sino también, a sus familiares. La tamización adecuada del caso índice permite identificar mutaciones y caracterizar mejor la enfermedad.

Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes.We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences.The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

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)

Complete and sustained response after peptide receptor radionuclide therapy in a 66-year-old Filipino male with metastatic pancreatic neuroendocrine tumor: A case report

@#The introduction of peptide receptor radionuclide therapy (PRRT) to the Philippines has allowed for novel approaches in the management of neuroendocrine tumors (NETs). This case report details the management of a 66-year-old Filipino man diagnosed with metastatic pancreatic NET after biopsy and staging with Ga-68 DOTATATE PET-CT. After poor response to somatostatin analogue therapy, the patient was advised to undergo PRRT. Upon completing four cycles of PRRT with Lu-177 DOTATATE, the metastatic hepatic lesions showed resolution and the pancreatic tail tumor exhibited regression, allowing the patient to undergo surgical resection of the primary tumor. On follow-up, he was declared to be in remission with good quality of life and no imaging evidence of recurrence. The case underscores the diagnostic and therapeutic utility of radiolabeled somatostatin analogues along with the importance of a multidisciplinary approach in the management of an initially unresectable metastatic pancreatic NET

Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States / 中华医学杂志(英文版)

BACKGROUND@#Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period.@*METHODS@#Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States.@*RESULTS@#The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas.@*CONCLUSIONS@#The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.

Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways / 中华医学杂志(英文版)

BACKGROUND@#Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.@*METHODS@#We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs.@*RESULTS@#The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling.@*CONCLUSION@#We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.

Plurihormonal PIT1-lineage pituitary neuroendocrine tumors: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast / 医学前沿

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

Liver transplant for metastatic neuroendocrine tumors: a single-center report / Transplante de fígado para tumores neuroendócrinos metastáticos: série de casos

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.

Chinese expert consensus on gastroenteropancreatic neuroendocrine neoplasms (2022 edition) / 中华肿瘤杂志

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are highly heterogeneous tumors. According to the 2019 World Health Organization classification and grading criteria for neuroendocrine neoplasms of the gastrointestinal tract and hepatopancreatobiliary organs, GEP-NENs include well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). GEP-NETs may present as hormonally functioning or nonfunctioning tumors and may have distinct clinical features based on their sites of origin. The Expert Committee of Neuroendocrine Tumors, Chinese Society of Clinical Oncology revised and updated the 2016 version of Chinese expert consensus on GEP-NENs. The update the consensus includes the epidemiology, clinical manifestations, biochemical and imaging examinations, pathological features, and treatment and follow-up of GEP-NENs.

Tumor neuroendócrino gástrico: relato de caso e revisão de literatura / Gastric neuroendocrine tumor: case report and literature review / Tumor neuroendocrino gástrico: reporte de caso y revisión de la literatura

Este artigo consiste em um estudo de caso de paciente do sexo masculino, 40 anos, com diarreia e perda ponderal significativa iniciada sete meses depois da sua admissão no Hospital Geral Roberto Santos. O paciente não apresentava alterações significativas no exame físico e as investigações clínicas e laboratoriais foram inexpressivas. Foram realizados estudos endoscópicos e anatomopatológicos, confirmando o diagnóstico de neoplasia neuroendócrina gástrica. Os achados histopatológicos evidenciaram um tumor bem diferenciado do tipo dois, sendo uma neoplasia rara de bom prognóstico. O paciente foi submetido a gastrectomia segmentar de corpo gástrico e evoluiu com melhora clínica da diarreia. Ele recebeu alta hospitalar e segue em acompanhamento com os serviços de gastroenterologia e endocrinologia.

This study reports the case of a 40-year-old male patient presenting with diarrhea and significant weight loss initiated seven months before admission at the Hospital Geral Roberto Santos. The patient showed no significant changes in the physical examination, and clinical and laboratory investigations were inexpressive. Gastric neuroendocrine neoplasia was diagnosed by endoscopic and anatomopathological studies. Histopathological findings showed a well-differentiated type 2 tumor ­ a rare neoplasm with a good prognosis. The patient underwent segmental gastrectomy of the gastric body, evolving with clinical improvement of diarrhea. He was discharged from the hospital and is being followed by gastroenterology and endocrinology services.

Paciente del sexo masculino, 40 años, con diarrea y pérdida significativa de peso, que inició siete meses después de su ingreso en el Hospital Geral Roberto Santos. El paciente no presentó cambios significativos en la exploración física y las investigaciones clínicas y de laboratorio fueron inexpresivas. Se realizaron estudios endoscópicos y anatomopatológicos que confirmaron el diagnóstico de neoplasia neuroendocrina gástrica. Los hallazgos histopatológicos mostraron un tumor tipo 2 bien diferenciado, que es una neoplasia poco frecuente y de buen pronóstico. El paciente fue sometido a gastrectomía segmentaria del cuerpo gástrico y evolucionó con mejoría clínica de la diarrea. Fue dado de alta del hospital y aún está en seguimiento con los servicios de gastroenterología y endocrinología.

Tumor neuroendocrino de colon derecho en un paciente con colitis ulcerativa: a propósito de un caso / Right colon neuroendocrine tumor in a patient with ulcerative colitis: A case study

Resumen Los tumores neuroendocrinos del colon son relativamente raros en comparación con el carcinoma colorrectal esporádico; su incidencia es muy baja y la localización más frecuente es en el ciego, colon sigmoideo y recto. Se describe con poca frecuencia la asociación de tumor neuroendocrino con la colitis ulcerativa debido a la inflamación crónica que conduce a la diferenciación de células neuroendocrinas a partir de células multipotenciales en el epitelio displásico, que puede ser responsable del desarrollo de carcinomas neuroendocrinos colorrectales. La presentación del caso se trata de un paciente de 57 años de edad con colitis ulcerativa con cuadro de dolor abdominal, pérdida de peso y diarreas líquidas con moco. En el examen físico presentó una lesión endurecida en el marco colónico derecho con tomografía de lesión neoplásica en el colon ascendente y en su hospitalización presentó un cuadro de oclusión intestinal, por lo que se le realizó una hemicolectomía más ileostomía, cuyo resultado en la biopsia fue un tumor neuroendocrino G3 de células grandes en el colon ascendente. En este artículo se revisan de forma práctica los aspectos relacionados con la fisiopatología, diagnóstico y tratamiento de la asociación de estas dos patologías.

Abstract Neuroendocrine colon tumors are relatively unknown compared with sporadic colorectal cancer; its incidence is low, and it is generally located in the cecum, sigmoid colon, and rectum. The existing relation between neuroendocrine tumors and ulcerative colitis is not frequently described due to the chronic inflammation that leads to neuroendocrine cell differentiation from multipotential cells in the dysplastic epithelium, which can be responsible for colorectal neuroendocrine carcinomas development. The study refers to the case of a patient of 57 years old with ulcerative colitis, abdominal pain, weight loss, and liquid diarrhea with mucus. Physical examination revealed a hardened lesion in the right colonic framework with the tomography of a neoplastic lesion in the ascending colon. When the patient was hospitalized, he developed an intestinal obstruction. A hemicolectomy plus ileostomy procedure was performed resulting in a large cell G3 neuroendocrine tumor in the ascending colon revealed in the biopsy. In this article, the aspects related to the pathophysiology, diagnosis, and treatment of the association of these two pathologies are reviewed in a practical way.

Linfoma de Hodgkin anal primario y tumor neuroendocrino intestinal sincrónicos: a propósito de un caso y revisión de la literatura / Primary rectal Hodgkin's lymphoma and synchronous small bowel neuroendocrine tumor: Case report and literature review

Resumen La localización extranodal gastrointestinal del linfoma de Hodgkin comprende el 5% de todos los linfomas. Dentro de este grupo, el linfoma anal primario representa menos del 0,05%, siendo por tanto una entidad extremadamente rara. Por otro lado, los tumores neuroendocrinos son un grupo heterogéneo de neoplasias relativamente poco frecuentes, pero de localización fundamentalmente digestiva. La asociación entre un linfoma de Hodgkin de localización anal y un tumor neuroendocrino intestinal no ha sido descrita previamente en la literatura, pero no es en absoluto raro que los tumores neuroendocrinos puedan coexistir con otro tipo de neoplasias. Los autores presentan el caso infrecuente de presentación de linfoma Hodgkin de localización anal asociado a un tumor neuroendocrino intestinal en una paciente mujer de 74 años, describiéndose la clínica, resultados de pruebas complementarias y tratamiento recibido.

Abstract Extranodal gastrointestinal Hodgkin's lymphoma comprises 5% of all lymphomas. In this group, primary rectal lymphoma represents less than 0.05%; thus, it is an extremely rare entity. On the other hand, neuroendocrine tumors are a heterogeneous group of infrequent neoplasms, mainly of digestive location. The association between a rectal Hodgkin's lymphoma and an intestinal neuroendocrine tumor has not been previously described in the literature, but it is not at all uncommon for neuroendocrine tumors to coexist with other types of neoplasms. The authors present a rare case of rectal Hodgkin's lymphoma associated with an intestinal neuroendocrine tumor in a 74-year-old female patient, describing the symptoms, complementary test results, and treatment.

Neoplasias neuroendocrinas del intestino: serie de casos / Intestinal neuroendocrine tumors: case series

RESUMEN: Los tumores neuroendocrinos (TNE) intestinales representan el mayor porcentaje de este tipo de lesiones a nivel del aparato digestivo. El tratamiento de elección es la extirpación de la lesión primaria y sus linfonodos regionales. El objetivo de este estudio es reportar el resultado de pacientes portadores de TNE intestinales, tratados quirúrgicamente, en términos de morbilidad postoperatoria (MPO) y mortalidad. Serie de casos de pacientes con TNE intestinales intervenidos de forma consecutiva en Clínica RedSalud Mayor Temuco, entre 2006 y 2020. Las variables resultado fueron MPO y mortalidad. Otras variables de interés fueron localización y diámetro del tumor, tipo de cirugía y estancia hospitalaria. Se utilizó estadística descriptiva. Se trató a 11 pacientes (54,5 % mujeres), con una mediana de edad de 56 años. El 54,5 % de los tumores se localizó en yeyuno-íleon. La mediana del diámetro tumoral, tiempo quirúrgico y estancia hospitalaria fueron 2 cm, 75 min y 4 días, respectivamente. El tipo de resección más frecuente fue hemicolectomía derecha (63,6 %). La MPO fue 9,1 % (seroma en un paciente). No hubo reintervenciones ni mortalidad operatoria. Con una mediana de seguimiento de 18 meses, no se verificaron recurrencias. Los resultados reportados en relación a MPO y mortalidad, son adecuados en relación con la evidencia publicada.

SUMMARY: Intestinal neuroendocrine tumors (INETs) represent the highest percentage of this type of lesion in the digestive system. The treatment of choice is removal of the primary lesion and its regional lymph nodes. The aim of this study is to report the results of patients with INETs treated surgically, in terms of postoperative morbidity (POM) and mortality. Series of cases of patients with intestinal INETs operated consecutively at Clínica RedSalud Mayor Temuco, between 2006 and 2020. Result variables were POM and mortality. Other variables of interest were location and diameter of the tumor, type of surgery, and hospital stay. Descriptive statistics were used. Eleven patients (54.5 %) were treated, with a median age of 56 years. 54.5 % of the tumors were located in the jejunum-ileum. The median tumor diameter, surgical time, and hospital stay were 2 cm, 75 min, and 4 days, respectively. The most frequent type of resection was right hemicolectomy (63.6 %). The MPO was 9.1 % (seroma in one patient). There were no reoperations or operative mortality. With a median follow-up of 18 months, there were no recurrences. Reported results in relation to POM and mortality are adequate in relation to the published evidence.

Seguimento de longo prazo de pacientes com tumor neuroendócrino da papila duodenal submetidos à papilectomia endoscópica: série de casos e revisão da literatura / Long-term follow-up of patients undergoing endoscopic papillectomy for papillary neuroendocrine tumor: a case series and literature review

ABSTRACT BACKGROUND: Duodenal papilla neuroendocrine tumors (DP-NET) are rare. Surgical therapy may be recommended for their treatment. However, they have high rates of morbidity and mortality. Endoscopic papillectomy (EP) is safe and effective for complete resection of tumors at this site. OBJECTIVE: This study aimed to describe a case series of DP-NETs resected by EP and perform a literature review. METHODS: A series of patients with DP-NETs underwent EP as primary treatment between Jan/2008 and Mar/2020 at a tertiary referral center. A comprehensive search was made on the MEDLINE primary electronic database. The search strategy was designed to find all articles related to DP-NETs published in the literature. RESULTS: Six patients underwent EP for presenting DP-NETs, four of whom were women (mean age, 63 years). The mean diameter of DP-NETs was 1.6±0.3 cm. Four of six patients were followed up, one of whom suffered relapse at the resection site after 3 months and was referred to surgery (pT3n1b) and the remaining three patients experienced no endoscopic or histological recurrence during follow-up periods of 10, 7, and 4 years, respectively. Eighteen articles were found in the literature search in MEDLINE. The articles included case reports of endoscopically treated DP-NETs. CONCLUSION: EP is safe and effective for DP-NETs that are ≤20 mm, confined to the submucosal layer, well-differentiated, and without local or remote metastasis. Adequate endoscopic follow-up and definitive surgical treatment in the presence of relapse are necessary.

RESUMO CONTEXTO: Tumores neuroendócrinos da papila duodenal (TNE-PD) são raros. A cirurgia deve ser recomendada para o tratamento. No entanto, apresentam altas taxas de morbimortalidade. A papilectomia endoscópica (PE) é segura e eficaz para a ressecção completa de tumores nesta região. OBJETIVO: Descrever uma série de casos de TNEs-PD ressecados por PE e realizar uma revisão da literatura. MÉTODOS: Pacientes com TNEs-PD submetidos a PE como tratamento primário com intenção curativa entre jan/2008 e mar/2020 em um centro de referência terciário foram estudados. Uma pesquisa abrangente foi feita no MEDLINE. A estratégia de busca foi desenhada para encontrar todos os artigos relacionados a TNEs-PD publicados na literatura, que haviam sido submetidos a PE. RESULTADOS: Seis pacientes foram submetidos a PE por apresentar TNEs-PD, sendo quatro mulheres, com média de idade de 66 anos (22-96). O diâmetro médio dos TNEs-PD foi de 1,8±0,4 cm. Quatro dos seis pacientes foram acompanhados, um dos quais sofreu recidiva no local da ressecção após 3 meses e foi encaminhado para cirurgia (pT3n1b), e os três pacientes restantes não apresentaram recorrência endoscópica ou histológica durante os períodos de acompanhamento de 10, 7 e 4 anos, respectivamente. Dezoito artigos foram encontrados no MEDLINE. Os artigos incluíram relatos de casos de TNEs-PD tratados pela PE. CONCLUSÃO: A PE é segura e eficaz para TNEs-PD ≤20 mm, confinados à camada submucosa, bem diferenciados e sem metástases locais ou remotas. Acompanhamento endoscópico adequado e tratamento cirúrgico definitivo na vigência de recidiva são necessários.

Ressecção endoscópica sob imersão d'água de pequenos tumores neuroendócrinos retais / Underwater endoscopic mucosal resection for small rectal neuroendocrine tumors

ABSTRACT BACKGROUND: A common site of neuroendocrine tumors (NETs) is the rectum. The technique most often used is endoscopic mucosal resection with saline injection. However, deep margins are often difficult to obtain because submucosal invasion is common. Underwater endoscopic mucosal resection (UEMR) is a technique in which the bowel lumen is filled with water rather than air, precluding the need for submucosal lifting. OBJECTIVE: This study aimed to evaluate the efficacy and safety of UEMR for removing small rectal neuroendocrine tumors (rNETs). METHODS: Retrospective study with patients who underwent UEMR in two centers. UEMR was performed using a standard colonoscope. No submucosal injection was performed. Board-certified pathologists conducted histopathologic assessment. RESULTS: UEMR for small rNET was performed on 11 patients (nine female) with a mean age of 55.8 years and 11 lesions (mean size 7 mm, range 3-12 mm). There were 9 (81%) patients with G1 rNET and two patients with G2, and all tumors invaded the submucosa with only one restricted to the mucosa. None case showed vascular or perineural invasion. All lesions were removed en bloc. Nine (81%) resections had free margins. Two patients had deep margin involvement; one had negative biopsies via endoscopic surveillance, and the other was lost to follow-up. No perforations or delayed bleeding occurred. CONCLUSION: UEMR appeared to be an effective and safe alternative for treatment of small rNETs without adverse events and with high en bloc and R0 resection rates. Further prospective studies are needed to compare available endoscopic interventions and to elucidate the most appropriate endoscopic technique for resection of rNETs.

RESUMO CONTEXTO: Um local comum de tumores neuroendócrinos (TNEs) é o reto. A técnica mais utilizada é a ressecção endoscópica da mucosa com injeção de solução salina. No entanto, as margens profundas costumam ser difíceis de ressecar porque a invasão da submucosa é comum. A ressecção endoscópica sob imersão d'água (RESI) é uma técnica em que o lúmen intestinal é preenchido com água em vez de ar, evitando a necessidade de elevação submucosa. OBJETIVO: Este estudo teve como objetivo avaliar a eficácia e segurança da RESI para a remoção de pequenos TNEs retais (rTNEs). MÉTODOS: Estudo retrospectivo com pacientes que realizaram RESI em dois centros. RESI foi realizada usando um colonoscópio padrão. Nenhuma injeção submucosa foi realizada. Patologistas certificados conduziram avaliação histopatológica. RESULTADOS: RESI foi realizada para pequenos rTNEs em 11 pacientes (nove mulheres) com média de idade de 55,8 anos e 11 lesões (tamanho médio de 7 mm, variando de 3-12 mm). Havia 9 (81%) pacientes com G1 rTNEs e dois pacientes com G2, sendo que todos os tumores invadiam a submucosa sendo apenas um restrito a mucosa. Nenhum caso mostrou invasão vascular ou perineural. Todas as lesões foram removidas em bloco. Nove (81%) ressecções tiveram margens livres. Dois pacientes tiveram envolvimento de margens profundas; um teve biópsias negativas por meio de vigilância endoscópica e o outro perdeu o acompanhamento. Não ocorreram perfurações ou sangramento tardios. CONCLUSÃO: A RESI parece ser uma alternativa eficaz e segura para o tratamento de pequenos rTNEs sem eventos adversos e com altas taxas de ressecção em bloco e R0. Mais estudos prospectivos são necessários para comparar as intervenções endoscópicas disponíveis e para elucidar a técnica endoscópica mais adequada para ressecção de rTNEs.

Appendiceal Neuroendocrine Tumours - Experience of One Service / Tumores neuroendócrinos do apêndice - Experiência de um serviço

Abstract Tumours of the appendix are rare and tend to be diagnosed incidentally, in cases of acute appendicitis. For some authors, appendiceal neuroendocrine tumours (ANETs) are the most frequent neoplasm of the appendix, observed in 0.3% to 0.9% of cases acute appendicitis. The present is a unicentric retrospective study conducted between January 2005 and March 2017. Out of a total of 3,007 surgeries for appendiceal pathologies performed in the adult population at the hospital where the present study was conducted, there were 70 (2.33%) malignant cases, 20 (28.6%) of which were ANETs. The patients had a median age of 44 years (range: 18 to 85 years), and were predominantly women (there were 1.9 times more women than men). In 16 cases (80%), a simple appendicectomy was performed (1 patient was submitted to a right hemicolectomy later). The cases of ANETs had a good prognosis in our series: 85% of the patients are either alive today or were alive after 5 years of follow-up. Despite the fact that ANETs are described as the most frequent tumor of the appendix, this was not confirmed in our series, in which they only represented 28.6% of the cases; adenocarcinoma was the most frequent tumor (65.7%) among our sample.

Resumo Tumores do apêndice são raros, e tendem a ser diagnosticados de forma incidental, em casos de apendicite aguda. Para alguns autores, tumores neuroendócrinos do apêndice (TNEAs) são as neoplasias mais frequentes do apêndice, e são observados em 0,3 a 0,9% de todos os casos agudos de apendicite. Este é um estudo monocêntrico e retrospectivo realizado entre janeiro de 2005 e março de 2017. Entre umtotal de 3.007 cirurgias para patologias do apêndice realizadas na população adulta no hospital em que o estudo foi conduzido, houve 70 (2,33%) casos de malignidade, 20 (28,6%) dos quais eram TNEAs. Os pacientes tinham uma idade média de 44 anos (gama: 18-85 anos), e eram predominantemente mulheres (havia 1,9 vezes mais mulheres do que homens). Em 16 casos (80%), realizou-se uma simples apendicectomia (1 paciente foi submetido a uma hemicolectomia direita mais tarde). Os casos de TNEAs tiveram um bom prognóstico em nossa série: 85% dos pacientes estão vivos hoje, ou estavam após um seguimento de 5 anos. Apesar de os TNEAs serem descritos como os tumores mais frequentes do apêndice, isso não foi confirmado nesta série, na qual eles representaram apenas 28,6% dos casos; adenocarcinoma foi o tumor mais frequente (65,7%) emnossa amostra.

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.

Cirugía radioguíada con análogos de somatostatina radiomarcados en tumores neuroendocrinos: reporte de caso / Radioguided surgery with radiolabeled somatostatin analogues in neuroendocrine tumors: Case report

Resumen Introducción: El mejor tratamiento para los tumores neuroendocrinos es la resección completa del tumor, los ganglios, e inclusive en casos seleccionados, las metástasis a distancia. En ocasiones, el tumor primario es pequeño y de difícil localización preoperatoria o sus recaídas pueden ser difíciles de localizar en el terreno de fibrosis por cirugías o tratamientos previos. La cirugía radioguíada ofrece una opción adicional de localización intraoperatoria que hasta ahora no ha sido muy utilizada en tumores neuroendocrinos. Presentación del caso: Paciente de 59 años con antecedente de resección atípica de duodeno y páncreas por tumor neuroendocrino grado 2 del duodeno un año antes. En la tomografía por emisión de positrones/tomografía computarizada (PET/CT) 68Ga-DOTANOC se encontró un ganglio con sobreexpresión de receptores de somatostatina en el mesenterio, sin otras lesiones a distancia. Por los antecedentes quirúrgicos y la dificultad de visualizar la lesión en las imágenes anatómicas (resonancia magnética [RM]) se decidió realizar la cirugía radioguíada. En el preoperatorio se administraron 15 mCi de tecnecio 99 metaestable-hidrazinonicotinilo-Tyr3-octreotida (99mTc-HYNIC-TOC) y se verificó la buena captación en el ganglio. En cirugía, luego de la disección inicial se utilizó la sonda gamma, que detectó una actividad 5 veces mayor en el ganglio, comparado con los tejidos vecinos, lo que permitió su localización y resección. La evolución fue adecuada y un año después no hay evidencia de recaídas. Conclusión: La cirugía radioguíada no ha sido muy utilizada en la localización intraoperatoria de tumores neuroendocrinos, pero es una buena alternativa en casos seleccionados, como el presentado en este artículo, y permite la detección intraoperatoria y su resección completa.

Abstract Introduction: The best treatment for neuroendocrine tumors is complete resection of the tumor, lymph nodes, and even distant metastases in selected cases. Sometimes, the primary tumor is small and difficult to detect before surgery, or its relapses may be difficult to locate in the fibrosis field due to previous surgeries or treatments. Although radioguided surgery allows for additional intraoperative localization, it has yet to be widely used in neuroendocrine tumors. Case report: A 59-year-old patient with a history of atypical resection of duodenum and pancreas due to grade 2 neuroendocrine tumor of the duodenum one year earlier. On 68Ga-DOTANOC PET/CT, a node with somatostatin receptor overexpression was found in the mesentery, with no other distant lesions. Due to the surgical history and the difficulty in visualizing the lesion on anatomical images (MRI), it was decided to perform the radioguided surgery. During the preoperative period, 15 mCi of 99mTc-HYNIC-TOC were administered verifying good uptake in the ganglion. Following the initial dissection, a gamma probe was used, detecting 5 times more activity in the ganglion than in adjacent tissues, allowing for localization and resection. The patient's progress was satisfactory, and one year later there is no evidence of relapse. Conclusion: Although radioguided surgery is not commonly used in the intraoperative location of neuroendocrine tumors, it is a viable option in some situations, such as the one presented here, because it allows for intraoperative detection and full resection.