Treatment and prognosis of patients of G3 nonfunctional pancreatic neuroendocrine tumors with proliferation index of Ki-67<55% / 中华消化外科杂志

Objective:To investigate the treatment and prognosis of patients of G3 non-functional pancreatic neuroendocrine tumors (pNETs) with proliferation index of Ki-67 <55%.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 G3 non-functional pNETs patients with proliferation index of Ki-67<55% who were admitted to Zhongshan Hospital of Fudan University from April 2014 to April 2020 were collected. There were 11 males and 4 females, aged (58±10)years. All patients underwent radical resection of the primary lesion. Obser-vation indicators: (1) treatment; (2) postoperative pathological characteristics; (3) follow-up. Measure-ment data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. The Pearson correlation analysis was used to verify the correlation between variables. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Log-Rank test was used for survival analysis. Results:(1) Treatment. All 15 G3 nonfunctional pNETs patients underwent radical resection of the primary lesion of pancreas, including 5 cases receiving pancreati-coduodenectomy, 10 cases receiving distal pancreatectomy with splenectomy. There were 5 patients with simultaneous liver oligometastasis who underwent combined segmental (lobectomy) hepatectomy. All 15 patients had negative tumor margin, and the operation time and volume of intraoperative blood loss of 15 patients was 120(90,210)minutes and 200(50,300)mL, respectively. None of patient had complications ≥Ⅲ grade of the Clavien-Dindo classification during the postoperative 30 days. Of the 15 patients, there were 5 cases receiving comprehensive treatment based on CAPTEM chemo-therapy (temozolomide combined with capecitabine), 2 cases receiving local interventional therapy, 2 cases receiving CAPTEM chemotherapy, 1 case receiving local interventional therapy combined with molecular targeted therapy, 1 case receiving local interventional therapy combined with long acting somatostatin therapy, 1 cases receiving long acting somatostatin therapy combined with molecular targeted therapy, and 3 cases without postoperative treatment. (2) Postoperative patholo-gical characteristics. The tumor diameter of 15 patients was 3.3(range, 0.5-6.0)cm. There were 2 cases with tumor diameter <2 cm, 13 cases with tumor diameter ≥2 cm. The number of lymph nodes dissected and number of lymph nodes metastatic was 6(4, 10) and 2(1,3) in 15 patients, respectively, including 12 cases with positive lymph node metastasis. Of the 15 patients, there were 5 cases with tumor invasion of adjacent organ, 5 cases with simultaneous liver metastasis, 8 cases with perineural invasion and 8 cases with vascular invasion. There were 3, 7, and 5 patients with stage Ⅱ, stage Ⅲ, and stage Ⅳ of pathological TNM staging, respectively. The proliferation index of Ki-67 and mitotic count was 32%±9% and (11±9)/10 high power field in the primary lesion of 15 patients, respectively, and there was no correlation between proliferation index of Ki-67 and mitotic count ( P>0.05). (3) Follow-up. All 15 patients were followed up after surgery for (55±24)months. The median survival time of 15 patients was 78(range, 43-113)months, with 1-, 3-, 5-year overall survival rate as 100%, 92%, 62%, respectively. During the follow up, 9 of the 15 patients underwent tumor recurrence, with the recurrence time as 20(14, 44)months. There were 8 patients died of tumor recurrence or metastasis. The median survival time was 86(range, 51-120)months in 5 patients receiving comprehensive treatment based on CAPTEM chemotherapy, versus 53(range, 45-60)months in 10 patients receiving other postoperative adjuvant therapy or without postoperative treatment, showing a significant difference between them ( χ2=4.21, P<0.05). Conclusion:The prognosis of patients of G3 nonfunctional pNETs with proliferation index of Ki-67<55% undergoing radical resection combined with postoperative comprehensive treatment based on CAPTEM chemotherapy in better than that of patients receiving other postoperative adjuvant therapy or without posto-perative treatment.

Effect of lymph node metastasis on the prognosis of patients with G2 phase stage pancreatic neuroendocrine tumors / 国际外科学杂志

Objective:To investigate the effect of lymph node metastasis on the prognosis of patients with G2 phase stage pancreatic neuroendocrine neoplasm(pNEN).Methods:A retrospective case control study was conducted to analyze the case data of 368 patients with pancreatic neuroendocrine tumors in G2 phase stage from January 1, 2010 to December 31, 2016 in SEER database, including 174 males and 194 females. According to whether lymph nodes were metastatic, they are divided into lymph node non metastatic (N0) group ( n=272) and lymph node metastatic (N1) group ( n=96). The Kaplan-Meier method and Log-rank test were used to compare the overall survival rate (OS) of patients in the N0 and N1 groups. The COX proportional risk model was used to evaluate whether N stage was an independent risk factor affecting prognosis. Count data were expressed as cases and percentage(%), and Chi-square test was used for comparison between the groups. Results:Among all patients, the OS of patients in the N0 group was better than that of patients in the N1 group. The OS of N0 patients at 1, 3, and 5 years was 96.3%, 92.7%, and 85.6%, respectively, while the OS of N1 patients at 1, 3, and 5 years was 92.6%, 82.1%, and 82.1%, respectively ( P=0.014). Multivariate analysis showed that age ( HR=2.245, 95% CI: 1.126-4.475, P=0.022) and N stage ( HR=0.457, 95% CI: 0.237-0.883, P=0.020) were independent prognostic factors for G2 phase pNEN patients. Conclusion:Lymph node metastasis is one of the independent prognostic factors in patients with G2 phase stage pNEN.

Small cell neuroendocrine carcinoma with adenocarcinoma and high grade squamous intraepithelial neoplasia of the cervix

ABSTRACT Neuroendocrine neoplasm (NEN) of the cervix is a malignant tumor and is classified into low and intermediate-grade neuroendocrine tumor (NET), and high-grade small cell neuroendocrine carcinoma (SCNEC), and large cells neuroendocrine carcinoma (LCNEC). SCNEC of the cervix is an Infrequent tumor with an incidence of less than 1% of all gynecological malignancies. It is characterized by small to medium-sized tumor cells with scant cytoplasm and neuroendocrine differentiation. Most cases of SCNEC of the cervix manifest in pure forms, and only cases show coexisting, non-neuroendocrine component of HPV-associated adenocarcinoma or squamous cell carcinoma. In this report, reviewing the literature, we present one such unique case of SCNEC of the cervix with adenocarcinoma and high-grade squamous intraepithelial neoplasia.

Gastric neuroendocrine tumor: when surgical treatment is indicated? / Tumor neuroendócrino gástrico: quando tratamento cirúrgico está indicado?

ABSTRACT 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.

RESUMO RACIONAL: Os tumores neuroendócrinos gástricos são um grupo heterogêneo de neoplasias produtoras de substâncias bioativas, sendo o seu tratamento variável de acordo com o estadiamento e a classificação, sendo utilizadas técnicas endoscópicas, cirurgias abertas, quimioterapia, radioterapia e fármacos análogos da somatostatina. OBJETIVOS: Identificar e revisar os casos de neoplasia neuroendócrina gástrica submetidos a tratamento cirúrgico. MÉTODOS: Revisão os doentes tratados cirurgicamente de 1983 e 2018. RESULTADOS: Foram incluídos 15 pacientes, com predomínio do sexo feminino (73,33%) e média de idade de 55,93 anos. O sintoma mais comum foi a epigastralgia (93,3%) e o tempo médio do início dos sintomas foi de 10,07 meses. A endoscopia digestiva pré-operatória indicou predomínio de casos com 0 a 1 lesões (60%), de tamanho ≥ 1,5 cm (40%), localizadas em antro gástrico (53,33%), com ulceração (60%), Borrmann 3 (33,33%). A avaliação da peça cirúrgica indicou um predomínio de tumores neuroendócrinos invasivos (60%), com invasão angiolinfática na maioria dos casos (80%). A imuno-histoquímica para cromogranina A foi positiva em 60% dos casos e para sinaptofisina em 66,7%, com índice de Ki-67 predominante entre 0 e 2%. Metástases foram observadas em 20% dos casos. O procedimento cirúrgico mais utilizado foi a gastrectomia subtotal com reconstrução em Y de Roux (53,3%). Recidiva tumoral ocorreu em 20% dos casos e novo tratamento foi necessário em 26,67% dos casos. CONCLUSÕES: Os tumores neuroendócrinos gástricos apresentam baixa incidência na população em geral, e o tratamento cirúrgico está indicado nas lesões avançadas. O estudo de seu manejo ganha importância frente às especificidades de cada caso e a necessidade de conduta adequada para a prevenção de recidivas e complicações.

Aspectos anatomo-clínicos de un caso de neoplasia sólida seudopapilar de páncreas: (tumor de Frantz) / Solid pseudopapillary neoplasm of the pancreas: (Frantz´s tumor) anatomo-clinical aspects / Aspectos anátomo-clínicos de um caso de neoplasia sólida pseudopapilar do pâncreas: (tumor de Frantz)

El tumor pseudopapilar de páncreas, conocido como tumor de Frantz, es excepcional; comprende entre el 0.2 y 2.7 % de los carcinomas de páncreas. Su etiología es desconocida y predomina en mujeres jóvenes. Son tumores de bajo potencial maligno, que cursan asintomáticos y dan síntomas por compresión regional: dolor gravativo y/o masa abdominal palpable. La probabilidad de una forma definidamente maligna es de 15 %. Anatómicamente se localizan con mayor frecuencia en la cola del páncreas, seguido por la cabeza y el cuerpo. El tratamiento es la resección quirúrgica y su pronóstico es excelente, con sobrevida a 5 años de casi 100 %. El diagnóstico es anátomo-patológico, considerando el aspecto microscópico y el perfil inmunohistoquímico. Se presenta un caso de una mujer de 21 años, en la cual se realizó una cirugía de excéresis completa del tumor y que se mantiene a asintomática a 24 meses de operada.

Pseudo papillary tumor of the pancreas, also called Frantz´s tumor, is a very rare disease; between 0.2 and 2.7 % of pancreatic carcinomas. Ethiology is unknown; is observed in young women. It´s a tumors with low malignant potential, usually of asymptomatic evolution by long time and the symptoms are due to regional compression: pain or abdominal mass. The possibility of a malignant form is around 15 %. Anatomically, they are most frequently located in the tail of the pancreas, followed by the head and body. The treatment is the surgical resection; with an excellent prognosis and a 5-year survival almost 100 %. The diagnosis is with pathological study, considering the microscopic appearance and the immunohistochemical profile. Its perform an analysis of the literature and once case of a 21 years old, woman is reported. A complete resection surgery of the tumor was performed and remains asymptomatic at 24 months of follow-up.

O tumor pseudopapilar do pâncreas, conhecido como tumor de Frantz, é excepcional; compreende entre 0,2 e 2,7 % dos carcinomas pancreáticos. Sua etiologia é desconhecida e predomina em mulheres jovens. São tumores de baixo potencial maligno, que são assintomáticos e apresentam sintomas devido à compressão regional: dor intensa e/ou massa abdominal palpável. A probabilidade de uma forma definitivamente maligna é de 15 %. Anatomicamente, eles estão localizados com mais frequência na cauda do pâncreas, seguido pela cabeça e corpo. O tratamento é a ressecção cirúrgica e seu prognóstico é excelente, com sobrevida em 5 anos de quase 100 %. O diagnóstico é anátomo-patológico, considerando o aspecto microscópico e o perfil imuno-histoquímico. Apresenta-se o caso de uma mulher de 21 anos submetida a cirurgia de excisão completa do tumor e que permanece assintomática 24 meses após a cirurgia.

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.

Application of C-type incision to endoscopic submucosal dissection for the treatment of rectal neuroendocrine tumors / 中华消化内镜杂志

Objective:To evaluate the clinical efficacy of C-type endoscopic submucosal dissection (C-ESD) for rectal neuroendocrine tumors (NEN).Methods:The retrospective analysis was performed on data of 55 patients who underwent ESD for rectal NEN at the Department of Endoscopy in Quanzhou First Hospital from January 2018 to July 2021. Patients were divided into the C-ESD group ( n=28) and the conventional ESD group ( n=27). The dissection time, the dissection speed, the number of submucosal injections, the enbloc resection rate, the curative resection rate and the rate of postoperative complications of the two groups were compared. Results:There were no statistically significant differences in basic information between the two groups ( P>0.05). The dissection time was 13.8±4.2 min in the C-ESD group and 19.9±3.9 min in the conventional ESD group with statistically significant difference ( t=5.649, P<0.001). The dissection speed in the C-ESD group was 0.08±0.04 cm 2/min, which was faster than 0.06±0.04 cm 2/min in the conventional ESD group ( t=2.218, P=0.031). The number of submucosal injections in the C-ESD group was less than that in the conventional ESD group [2 (1, 2) VS 3 (2, 3), Z=-8.701, P<0.001]. The lesions were enbloc resected in both groups. The curative resection rate in the C-ESD group was 100.0% (28/28) and 88.9% (24/27) in the conventional ESD group with statistically significant difference ( P=0.011). There were 7 cases of postoperative complications in the conventional ESD group, including 1 delayed bleeding, 5 delayed perforation and 1 muscularis propria injury, while no postoperative complications occurred in the C-ESD group ( P=0.004). Conclusion:C-ESD is a safe and effective treatment strategy for colorectal NEN, which can shorten the dissection time, improve the dissection speed, reduce the number of submucosal injections, improve the curative resection rate, and reduce complications.

Clinical characteristics and prognosis of duodenal neuroendocrine neoplasms / 中华普通外科杂志

Objective:To investigate the clinical characteristics and prognosis of duodenal neuroendocrine neoplasms.Methods:The clinical data of 35 patients with duodenal neuroendocrine neoplasms admitted to Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from Jan 2012 to Dec 2021 were retrospectively analyzed. The differences of clinical characteristics between periampullary and non-periampullary duodenal neuroendocrine neoplasms were analyzed. Kaplan-Meier curve was used for survival analysis, and the clinical factors affecting the prognosis were analyzed.Results:Of the 35 patients, 30 underwent tumor resection, 7 (23%) developed different degree of complications after operation and were improved and discharged after intervention. A total of 5 patients died during the follow-up period. Only 1 of 30 patients who underwent tumor resection died 30 months after operation due to disease progression, and the others had no recurrence or metastasis. Univariate analysis showed that tumor size, tumor grade, and tumor location were associated with the prognosis of patients (all P<0.05), and multivariate analysis showed that patients with tumors located.Away from the ampulla had a significantly better prognosis than those located around the duodenal ampulla ( P<0.01). Conclusions:Patients with duodenal neuroendocrine neoplasms have a good prognosis after complete resection; patients with duodenal neuroendocrine neoplasms located around the ampulla of Vater have a relatively poor prognosis compared with those away from the area of ampulla.

Hipercortisolismo severo e hipocalemia recurrente / Severe hypercortisolism and recurring hypocalemia

RESUMEN El síndrome de Cushing endógeno deriva de un aumento crónico, inapropiado y sostenido de glucocorticoides principalmente como respuesta al exceso en las concentraciones séricas elevadas de la hormona adrenocorticotropa (ACTH) desde un tumor adenohipofisiario, enfermedad de Cushing; o producida de forma ectópica por tumores neuroendocrinos. El Cushing suprarrenal se origina por tumores de la corteza adrenal que producen de forma autónoma cortisol y es independiente de ACTH. El curso clínico, tratamiento, pronóstico y posibles complicaciones dependen de identificar de forma correcta la lesión desencadenante; situación que en múltiples ocasiones resulta en una experiencia retadora para los clínicos. Se presenta el caso de una mujer de 62 años, ingresada por síntomas constitucionales con hipocaliemia severa de difícil corrección e hipercortisolismo severo.

ABSTRACT Endogenous Cushing syndrome derives from a chronic, inappropriate, and sustained increase in glucocorticoids, mainly in response to remarkably high serum concentrations of adrenocorticotropic hormone (ACTH) secreted from an adenohypophyseal tumor, Cushing's disease, or due to ectopic production by neuroendocrine tumors. Adrenal Cushing's disease is caused by tumors of the adrenal cortex that autonomously produce cortisol and this is independent from ACTH action. Clinical course, treatment, prognosis, and possible complications depend on correctly identifying the triggering lesion; this situation frequently becomes a challenging experience for clinicians. We present the case of a 62-year-old woman, admitted for constitutional symptoms with severe hypokalemia that was difficult to correct and severe hypercortisolism.

Clinical related factors to neuroendocrine tumors in Ecuadorian patients: a logistic biplot approach / Factores clínicos asociados a tumores neuroendocrinos en pacientes ecuatorianos: un análisis biplot logístico

Abstract Neuroendocrine tumors (NETs) are relative rare, affecting neuroendocrine cells throughout the body. Most tumors are diagnosed at advanced stages. NETs prevalence has increased in the last years but there is little data available in developing countries. The aim of this study was to describe symptoms associated with NETs in patients of the Society for the Fight Against Cancer (SOLCA) in Ecuador from 2005 to 2020; using logistic biplots, in a hospital database, generating binary responses (presence/absence) relevant to this study. The results showed that the mean age was 59 and the study showed no difference in prevalence between genders. NETs were mainly found in lungs (19%), followed by stomach (18%) and skin (9%). Most patients had pathological diagnosis G2 and G3 (30% and 70%, respectively). Symptoms as cough, dyspnea, weight loss, diarrhea, constipation, abdominal pain, dyspepsia, hypertensive crisis, distended abdomen and intestinal obstruction had p values <0.05. Additionally, the statistical analysis showed that cough and intestinal obstruction were also common, bearing in mind that patients had most frequent NETs in the lungs and skin. In summary, our results indicate that symptoms of NETs patients were positively associated with lung and skin. Further investigation is needed focusing on the type of NETs and their symptoms in order to establish an early marker for diagnosis.

Resumen Los tumores neuroendocrinos (TNE) son relativamente raros y afectan a las células neuroendocrinas de todo el cuerpo. La mayoría de los tumores se diagnostican en etapas avanzadas. La prevalencia de los TNE ha aumentado en los últimos años, pero hay pocos datos en los países en desarrollo. El objetivo de este estudio fue determinar los síntomas asociados a los TNE en pacientes de la Sociedad de Lucha contra el Cáncer (SOLCA) en Ecuador entre 2005 y 2020, utilizando biplots logísticos en una base de datos hospitalaria, generando respuestas binarias (presencia / ausencia) relevantes para este estudio. Los resultados mostraron que la edad promedio era de 59 años y el estudio no encontró diferencias en la prevalencia entre géneros. Los TNE se encontraron con mayor frecuencia en los pulmones (19%), seguidos del estómago (18%) y piel (9%). La mayoría de los pacientes tenían diagnóstico patológico G2 y G3 (30% y 70% respectivamente). Los síntomas como tos, disnea, pérdida de peso, diarrea, estreñimiento, dolor abdominal, dispepsia, crisis hipertensiva, abdomen distendido y obstrucción intestinal tuvieron valores de p <0,05. Además, el análisis estadístico mostró que la tos y la obstrucción intestinal también eran comunes, teniendo en cuenta que los pacientes tenían TNE más frecuentes en los pulmones y la piel. En resumen, nuestros resultados indican que los síntomas de los pacientes con TNE se asociaron positivamente con los pulmones y la piel. Se necesitan más investigaciones que se centren en el tipo de TNE y sus síntomas a fin de establecer un marcador más temprano para el diagnóstico.

O prognóstico dos diferentes subtipos de carcinomas de esôfago neuroendócrinos: um estudo de base populacional / The prognosis of the different esophageal neuroendocrine carcinoma subtypes: a population-based study

ABSTRACT Background Neuroendocrine neoplasms are extremely rare and account for 0.4% to 2% of all malignant esophageal neoplasms. The burden of the neuroendocrine histological type on the patients' prognosis and survival is poorly debated. This study aimed to compare the survival rates of primary neuroendocrine neoplasms compared with adenocarcinoma and squamous cell carcinoma of the esophagus. Methods This is a retrospective cohort from the Surveillance, Epidemiology, and End Results Program database. Overall survival and cancer-specific survival were evaluated with Kaplan-Meier curves and logrank tests. Proportional Cox regression models were used to evaluate variables related to overall survival. Results After eligibility criteria, 66,528 patients were selected. The mean follow-up was 22.6 months (SD 35.6). Adenocarcinoma was predominant (62%), followed by squamous cell carcinoma (36%). Large cell carcinoma, small cell carcinoma, and mixed adenoneuroendocrine carcinoma each account for less than 1% each. On the long-term overall survival analysis, esophageal adenocarcinoma showed a better prognosis than all the other histologic types (P-value for logrank test <0.001). With adenocarcinoma as a reference, HR was 1.32 for large cell carcinoma (95%CI 1.2 to 1.45) and 1.37 for small cell carcinoma (95%CI 1.23 to 1.53). The HR was 1.22 for squamous cell carcinoma (95%CI: 1.2 to 1.24); and 1.3 for adenoneuroendocrine carcinoma (95%CI 1.01 to 1.66). For multivariate Cox regression analysis, besides age and stage, the neuroendocrine subtypes large cell carcinoma and small cell carcinoma were considered independent prognostic variables. Conclusion In the esophagus, large cell carcinoma and small cell carcinoma show poorer long-term survival rates than squamous cell carcinoma and adenocarcinoma.

RESUMO Contexto As neoplasias neuroendócrinas são extremamente raras e representam 0,4% a 2% de todas as neoplasias malignas do esôfago. A determinação prognóstica e avaliação de sobrevida para o tipo histológico neuroendócrino é pouco debatida. Este estudo teve como objetivo comparar as taxas de sobrevida de neoplasias neuroendócrinas primárias comparadas com adenocarcinoma e carcinoma espinocelular de esôfago. Métodos Este é um estudo coorte retrospectivo do banco de dados do Surveillance, Epidemiology, and End Results Program. A sobrevida global e a sobrevida específica do câncer foram avaliadas com curvas de Kaplan-Meier e testes de logrank. Modelos de regressão de Cox proporcional foram utilizados para avaliar as variáveis relacionadas à sobrevida global. Resultados Após critérios de elegibilidade, foram selecionados 66,528 pacientes. O seguimento médio foi de 22,6 meses (DP 35,6). O adenocarcinoma foi predominante (62%), seguido pelo carcinoma espinocelular (36%). Carcinoma de grandes células, carcinoma de pequenas células e carcinoma adenoneuroendócrino misto representam menos de 1% cada. Na análise de sobrevida global, o adenocarcinoma de esôfago apresentou um prognóstico melhor do que todos os outros tipos histológicos (P valor para teste de logrank < 0,001). Com adenocarcinoma como referência, HR foi de 1,32 para carcinoma de grandes células (IC95% 1,2 a 1,45) e 1,37 para carcinoma de pequenas células (IC95% 1,23 a 1,53). O HR foi de 1,22 para carcinoma espinocelular (IC95%: 1,2 a 1,24); e 1,3 para carcinoma adenoneuroendócrino (IC95% 1,01 a 1,66). Para a análise multivariada da regressão de Cox, além da idade e do estadiamento, os subtipos neuroendócrinos carcinoma de grandes células e carcinoma de pequenas células foram considerados variáveis prognósticas independentes. Conclusão No esôfago, o carcinoma de grandes células e o carcinoma de pequenas células apresentam menores taxas de sobrevida a longo prazo do que o carcinoma espinocelular e o adenocarcinoma.

International trends in pulmonary neuroendocrine cancer studies:a scientometric study

ABSTRACT 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.

Pancreatoduodenectomy in patient with von hippel-lindau disease: a literature review / Pancreaticoduodenectomia em paciente com doença de von hippel-lindau - revisão da literatura

ABSTRACT BACKGROUND: The von Hippel-Lindau disease is a highly penetrant autosomal dominant syndrome characterized by tumor predisposition in different organs. AIM: This study aimed to describe a case of a pancreatoduodenectomy for a 30-year-old male patient with von Hippel-Lindau disease. METHODS: We present a case study and the literature review aiming at the state-of-the-art management of a patient with pheochromocytoma, capillary hemangioblastoma in the peripheral retina, and two neuroendocrine tumors in the pancreas. RESULTS: A larger pancreatic lesion was located in the uncinate process, measuring 31 mm. The smaller lesion was located in the proximal pancreas and was detected only on the positron emission tomography-computed tomography scan with DOTATOC-68Ga. Genetic investigation revealed a mutation in the locus NM_000551.3 c.482G>A (p.Arg161Gln) of the Von Hippel-Lindau Human Suppressor gene. The uncinate process tumor was larger than 30 mm and the patient had a mutation on exon 3; therefore, we indicated a pancreatoduodenectomy involving the proximal pancreas to resect both tumors en bloc. During the postoperative period, the patient presented a peripancreatic fluid collection, which was treated as a grade B pancreatic fistula with clinical resolution of the complication. On postoperative day 21, he was discharged home. CONCLUSION: The management of patients with von Hippel-Lindau disease and pancreatic neuroendocrine tumors is complex and must be centered on tertiary institutions with a large volume of pancreatic surgery. Although the current literature assists in decision-making in most situations, each step of the treatment requires analysis and discussion between different medical specialties, including surgeons, clinicians, radiologists, and anesthesiologists.

RESUMO RACIONAL: A doença de von Hippel Lindau é uma síndrome autossômica dominante que se caracteriza por maior incidência de tumores em diferentes órgãos. OBJETIVO: Descrever um caso de pancreatoduodenectomia em paciente do sexo masculino de 30 anos com von Hippel Lindau. MÉTODO: Apresentamos o caso e a revisão da literatura realizada para otimizar o manejo do paciente, que apresentava feocromocitoma, hemangioblastoma capilar na retina periférica e dois tumores neuroendócrinos no pâncreas. RESULTADOS: O maior tumor pancreático localizava-se no processo uncinado medindo 31 mm. A lesão menor estava localizada no corpo proximal do pâncreas e foi detectada apenas na tomografia computadorizada por emissão de pósitrons com DOTATOC-68Ga. A investigação genética revelou uma mutação no locus NM_000551.3 c.482G>A (p.Arg161Gln) do gene supressor humano de Von Hippel-Lindau. O tumor no processo era maior que 30mm e o paciente apresentava mutação no exon 3. Indicamos pancreatoduodenectomia envolvendo o corpo proximal do pâncreas para ressecar em bloco ambos os tumores. No pós-operatório o paciente apresentou coleção líquida peripancreática que foi tratada como fístula pancreática grau B, com resolução clínica da complicação. Ele recebeu alta hospitalar no vigésimo primeiro dia pós-operatório. CONCLUSÕES: o manejo de pacientes com doença de von Hippel Lindau e tumores neuroendócrinos pancreáticos é complexo e deve ser centrado em instituições terciárias com grande volume de cirurgia pancreática. Embora a literatura atual auxilie na tomada de decisão na maioria das situações, cada etapa do tratamento requer análise e discussão entre diferentes especialidades médicas, incluindo cirurgiões, clínicos, radiologistas e anestesiologistas.

Multiple neuroendocrine neoplasia in a patient with type i neurofibromatosis (nf1): report of a new mutation (nf1, exons 2-30 deletion) and literature review / Neoplasia neuroendócrina múltipla em doente com neurofibromatose tipo 1 (nf1). descrição de uma nova mutação e revisão da literatura

ABSTRACT BACKGROUND: Plexiform neurofibromas represent a common neoplasia of type 1 neurofibromatosis in which neurofibromas arise from multiple nerves involving connective tissue and skin and rarely affect the colon and rectum. Co-occurrence of plexiform neurofibromas, neuroendocrine tumors with primary involvement of the rectum, and medullary thyroid carcinoma in patients with neurofibromatosis type 1 is a previously undescribed condition. The aim of this manuscript was to present a case of primary plexiform neurofibroma and neuroendocrine tumors of the upper rectum in a patient with neurofibromatosis type 1 whose genetic sequencing found a novel mutation in the neurofibromatosis type 1 gene and to review the literature. CASE REPORT: A 49-year-old woman with a familial history of neurofibromatosis type 1 complained of abdominal cramps for 6 months. She had previously been submitted for a total thyroidectomy due to medullary thyroid carcinoma. She was submitted to a colonoscopy, which identified a submucosa lesion located in the upper rectum. The patient was referred for a laparoscopic rectosigmoidectomy, and the histopathological study of the surgical specimen identified two different tumors. An immunohistochemical panel was done for histopathological confirmation of the etiology of both lesions. The results of the panel showed intense immunoexpression of S100 protein in the largest and superficial lesion, as well as positivity for chromogranin and synaptophysin in the minor and deep lesion confirming the diagnosis of rectal plexiform neurofibromas concomitant with neuroendocrine tumors. The proliferative activity rate using Ki-67 antibodies showed that both tumors had a low rate of mitotic activity (<1%). Genetic sequence panel identified an undescribed mutation in the neurofibromatosis type 1 gene (deletion, exons 2-30). The patient's postoperative evolution was uneventful, and she remains well, without recurrence, 3 years after surgery. CONCLUSION: The co-occurrence of medullary thyroid carcinoma, plexiform neurofibromas, and neuroendocrine tumors of the rectum in patients with neurofibromatosis type 1 is an exceptional and undescribed possibility, whose diagnosis can be confirmed by the immunohistochemical staining and genetic panel.

RESUMO RACIONAL: Os neurofibromas plexiformes representam uma neoplasia frequente na neurofibromatose tipo 1 onde os neurofibromas surgem de múltiplos nervos envolvendo, também, o tecido conjuntivo e a pele raramente acometendo o cólon e o reto. A co-ocorrência de neurofibromas plexiformes, tumores neuroendócrinos, com envolvimento primário do reto, e carcinoma medular de tireoide em pacientes com neurofibromatose tipo 1 é uma condição ainda não descrita. O objetivo deste manuscrito é descrever um caso de neurofibromas plexiformes e tumores neuroendócrinos primários do reto superior, em paciente com neurofibromatose tipo 1, cujo sequenciamento genético identificou uma nova mutação no gene neurofibromatose tipo 1 e revisar a literatura sobre o tema. DESCRIÇÃO DO CASO: Mulher de 49 anos, com história familiar de neurofibromatose tipo 1 queixava-se de cólicas abdominais há seis meses. Tinha sido previamente submetida a tireoidectomia total por carcinoma medular de tireoide. Foi submetida a colonoscopia, que identificou lesão submucosa localizada no reto superior. A doente foi encaminhada para retossigmoidectomia laparoscópica, cujo estudo histopatológico do espécime cirúrgico identificou dois tumores distintos. Realizou-se painel imuno-histoquímico para confirmação histopatológica da etiologia de ambas as lesões. O resultado do painel mostrou intensa imunoexpressão da proteína S-100 da lesão superficial e de maior tamanho,e positividade para cromogranina e somatofisina da lesão mais profunda e de menores dimensões confirmando o diagnóstico de neurofibromas plexiformes retal e tumores neuroendócrinos. O índice de atividade proliferativa utilizando o anticorpo ant-Ki-67 mostrou que ambos os tumores apresentavam baixa índice mitótico (<1%). O painel genético identificou mutação no gene neurofibromatose tipo 1 (deleção, exons 2-30) ainda não descrita. A doente apresentou evolução pós-operatória sem intercorrências, permanecendo bem, sem recorrência, três anos após a cirurgia. CONCLUSÕES: A co-ocorrência de carcinoma medular de tireoide, neurofibromas plexiformes e tumores neuroendócrinos do reto em pacientes com neurofibromatose tipo 1 é uma possibilidade excepcional e ainda não descrita, cujo diagnóstico pode ser confirmado pela coloração imuno-histoquímica e painel genético.

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

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

Application of rubber band traction to endoscopic submucosal dissection / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of rubber band traction-assisted endoscopic submucosal dissection (ESD).Methods:A total of 49 patients with rectal endocrine tumor who underwent ESD at Beijing Friendship Hospital Affiliated to Capital Medical University from January 2016 to December 2019 were reviewed. Thirty-two patients who underwent traditional ESD from January 2016 to May 2018 were assigned to the non-traction group. Seventeen patients who underwent the operation with a rubber band as auxiliary traction from June 2018 to December 2019 were assigned to the traction group. Basic information, ESD procedure time, complications were compared between the two groups.Results:There were no significant differences in age, gender or lesion size between the traction group and the non-traction group ( P>0.05). The ESD operation time of the traction group was significantly shorter than that of the non-traction group (13.76±5.71 min VS 22.99±10.32 min, t=-3.408, P=0.001). There were no postoperative complications in the traction group, but 3 cases of perforation occurred in the non-traction group. There was no significant difference in the incidence of perforation between the two groups ( P=0.542). Conclusion:Rubber band traction can safely improve the efficiency of ESD.

Clinical value of 18F-FDG PET/CT imaging in non-functional pancreatic neuroendocrine neoplasms / 中华核医学与分子影像杂志

Objective:To analyze 18F-FDG PET/CT imaging features of non-functional pancreatic neuroendocrine neoplasms (NF-pNENs) and investigate its correlation with pathology and prognosis. Methods:A total of 35 cases (17 males, 18 females; age (51±12) years) of pathologically confirmed NF-pNENs who underwent pretherapeutic 18F-FDG PET/CT from January 2011 to July 2017 in Peking Union Medical College Hospital were retrospectively enrolled. Clinical data were collected and patients were followed up. PET/CT parameters including number and maximum diameter of lesions, SUV max and pancreatic tumor-to-liver ratio (T/L) were measured. Mann-Whitney U test and Kruskal-Wallis rank sum test, Spearman correlation analysis were used to analyze the data. Results:Among the included 35 NF-pNENs patients (G1, n=6; G2, n=21; G3, n=8) with maximum diameter of 3.0(2.1, 6.1) cm and SUV max of 5.5(4.0, 8.9), 32 were positive in PET/CT. There were 1 patient with cystic, 2 with calcification and 3 with dilatation of pancreaticobiliary duct. Among 10 patients with metastases, 8 revealed multiple liver metastases. There was statistical difference of T/L among G1-G3 tumor (1.23(0.60, 2.00), 3.05(1.80, 4.00), 3.90(1.90, 7.60); H=8.29, P=0.016), but there were no statistical differences of SUV max or maximum diameter among G1-G3 tumor ( H values: 4.34, 3.37, P values: 0.114, 0.186). There was a significant correlation between T/L (2.78(1.48, 3.94)) and Ki-67 index (8.0(3.0, 20.0); rs=0.631, P<0.001). Among 27 patients with available follow-up results, T/L in patients with complete remission or stable disease ( n=20) was statistically lower than that in patients with progressive disease or death ( n=7) (2.1(1.2, 3.2) vs 7.5(3.4, 13.4); z=-3.37, P=0.001). Conclusions:18F-FDG PET/CT can detect primary and metastatic lesions of NF-pNENs. T/L can better reflect the proliferative activity based on Ki-67 index than SUV max and it may be favorable on prognostic value.

Progress in diagnosis and treatment of thymic neuroendocrine tumors / 中国胸心血管外科临床杂志

@#Thymic neuroendocrine tumors (TNETs) are a series of rare diseases with aggressive biology and poor prognosis. Clinical manifestations of TNETs are atypical, and ectopic secretion of adrenocorticotropic hormone can be found in some cases, resulting in associated endocrine symptoms. Due to the low morbidity and strong heterogeneity, it’s difficult to diagnose, treat and obtain new treatment regimen. Early complete surgical resection is an effective treatment. For advanced cancer, clinical trials of new drugs are expected to improve the survival of patients.

Progress of the pathogenesis in Merkel cell carcinoma / 肿瘤研究与临床

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, which is named for its ultrastructure and immunophenotype similar to Merkel cells in the skin. It has been found that the integration of MCC with the oncogenic Merkel cell polyomavirus (MCPyV) may drive tumorigenesis or cause somatic mutations to the development of MCC because of ultraviolet ray-induced DNA damage. However, the pathogenesis of MCC is still unclear. This article introduces the current research progress of the pathogenesis of MCC, hoping to provide theoretical guidance for follow-up researches.