Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Tratamiento quirúrgico del carcinoma de Merkel facial avanzado. Presentación de un caso / Surgical treatment of advanced facial Merkel cell carcinoma. A case report

Introducción. El carcinoma de Merkel es un tumor maligno poco frecuente, que afecta principalmente a la población caucásica y cuya etiología guarda relación con el poliomavirus de las células de Merkel. Conlleva mal pronóstico, especialmente en estadios finales. Caso clínico. Se expone el caso de una paciente que presentaba un tumor primario facial de grandes dimensiones, con avanzado grado de extensión, afectación linfática cervical y metástasis parotídea derecha. Fue tratada mediante exéresis de la lesión primaria y cobertura con injerto de piel parcial, linfadenectomía cervical y parotidectomía ipsilateral. Resultados. Se logró mejoría importante en la calidad de vida de la paciente y sobrevida de al menos seis meses. Conclusión. Aunque no está claro el manejo óptimo del carcinoma de Merkel avanzado debido a su mal pronóstico, la cirugía favorece una mejoría en la calidad de vida del paciente y puede tener un papel clave en el manejo del carcinoma de Merkel en los estadios avanzados.

Introduction. Merkel carcinoma is a rare malignant tumor that mainly affects the Caucasian population and whose etiology is related to the Merkel cell polyomavirus. It has a poor prognosis, especially in the final stages. Clinical case. The case of a patient who presented a large primary facial tumor, with an advanced degree of extension, cervical lymphatic involvement and right parotid metastasis is described. She was treated surgically by excision of the primary lesion and coverage with partial skin graft, cervical lymphadenectomy, and ipsilateral parotidectomy. Results. A significant improvement was achieved in the patient's quality of life and survival of at least six months.Conclusion. Although the optimal management of advanced Merkel carcinoma is unclear due to its poor prognosis, surgery improves the patient's quality of life and it can play a key role in the management of Merkel carcinoma in advanced stages.

Neuroendocrine breast carcinoma

ABSTRACT Neuroendocrine breast cancer (NEBC) is a rare and heterogeneous entity. It most commonly presents a luminal phenotype and a worse prognosis. When diagnosed in an advanced stage, metastasis from another neuroendocrine tumor should be excluded. This case features a premenopausal woman with an oligometastatic breast large cell neuroendocrine carcinoma, estrogen receptor (ER) positive, and human epidermal growth factor receptor 2 (HER2) negative. Since the patient was very symptomatic at the presentation of the disease, chemotherapy was started. Complete radiological response of the metastatic disease was achieved, and the patient was then submitted to radical breast surgery and bilateral oophorectomy. She subsequently underwent radiation therapy. Since then and to date, she has been under endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i), with no evidence of malignant disease. Evidence to guide the choice of treatment for these tumors is currently scarce. In cases with oligometastatic disease, radical treatment should be considered. Given that this entity is rare, its reporting should be encouraged.

Carcinoma neuroendocrino de canal anal: presentación de un caso y revisión bibliográfica

Introducción: Los carcinomas neuroendocrinos (NEC) de canal anal son neoplasias extremadamente raras, representando del 1 a 1,6% de la totalidad de los tumores neuroendocrinos (NET). Suelen ser poco diferenciados, muy agresivos y con alta tendencia a metastatizar. Caso clínico: Mujer de 52 años diagnosticada de fisura anal. Durante la esfinterotomía lateral interna (ELI) se evidencia un pólipo milimétrico aparentemente hiperplásico. Biopsia: NEC de alto grado. En el estudio de extensión se observa engrosamiento de la mucosa del canal anal que invade el esfínter interno, sin enfermedad a distancia. Se realiza amputación abdominoperineal laparoscópica donde se objetiva infiltración del tabique rectovaginal, por lo que se realiza resección y vaginoplastia. AP: NEC con estadio PT4B N2A, por lo que se indica quimioterapia adyuvante. Discusión: La presentación clínica de los NEC de canal anal es inespecífica, diferenciándose de otros tumores colorrectales en que hasta el 67% de los pacientes presentan metástasis al diagnóstico, siendo la supervivencia media de 11 meses. Si diagnosticamos un NEC localizado de forma incidental, es fundamental la celeridad en su tratamiento, dada su agresividad.

Introduction: Neuroendocrine carcinomas (NEC) of the anal canal are extremely rare neoplasms, representing 1 to 1.6% of all neuroendocrine tumors (NET). They are usually poorly differentiated, very aggressive and with a high tendency to metastasize. Clinical case: A 52-year-old woman diagnosed with anal fissure. During the LIS, an apparently hyperplastic millimetric polyp is evidenced. Biopsy: high-grade NEC. The imaging study shows thickening of the mucosa of the anal canal that invades the internal sphincter, without metastases. We performed a laparoscopic abdominoperineal amputation, and noticed an infiltration of the rectovaginal septum, so resection and vaginoplasty was performed. Pathology: NEC with stage PT4B N2A, for which adjuvant chemotherapy is indicated. Discussion: The clinical presentation of NEC of the anal canal is nonspecific, differing from other colorectal tumors in that up to 67% of patients have metastases at diagnosis, with a median survival of 11 months. When an incidentally localized NEC is diagnosed, prompt treatment is essential, given its aggressiveness.

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)

Ileum neuroendocrine tumor: Case report and literature review

Ileal neuroendocrine tumors are rare primary epithelial neoplasm arising from enterochromaffin cells. A 65-year-old male presented with complaints of recurrent abdominal pain of 1 year duration. The pain was more aggravated in last 7 days associated with vomiting, loss of appetite and diarrhea. On radioimaging ultrasonography finding impression of small bowel mass lesion suggestive of ileac carcinoid tumor with ischemic bowel disease was given. Computerized tomograph abdomen pelvis showed a welldefined hypodense, round, hetergenous, enhancing mass measuring 2.6x1.6x1.2 cm., showing arterial enhancement in mesentery in close relation to ileum and metastatic lymph node mass- indicating likeness of neuroendocrine tumor. The surgical resection of ileum with mass and enlarged mesenteric nodes were done. On gross examination ileum specimen on cut open showed multiple, irregular mucosal thickenings with foci of ulceration. The submocosa showed single, circumscribed, round tumor measuring 3 x 2.5x1.5 cm. Cut section of tumor was yellowish, tan, well circumscribed and solid. The mesenteric lymph nodes were enlarged. The microscopic examination ileum showed a tumor composed of uniform, round cells having to oval nuclei with salt and pepper chromatin. Tumor cells were arranged in trabecular, nests, ribbons and in areas pseudo glandular pattern. Increased mitotic activity was noted (4/10 high power field). Mesenteric lymph nodes were involved by tumor. On histopathology reported as Well-differentiated neuroendocrine tumors (NET), G2, intermediate grade of ileum. The immunohistochemical stain were positive for synaptophysin, chromogranin A. The Ki-67 expression was <1%. Herewith we are presenting rare case of well-differentiated neuroendocrine tumor NET, G2, intermediate grade of ileum for its clinical, radio imaging ,pathological features and management.

Small cell neuroendocrine carcinoma with primary orbital involvement – The unseen, and a review of literature

Neuroendocrine neoplasms are derived from the epithelial lineages mainly of respiratory tract, with predominant neuroendocrine differentiation. There are only a handful of documented cases of paranasal small cell neuroendocrine carcinomas (SNEC) with primary orbital involvement. Here, the authors describe a 33-year-old male patient with rapidly progressive swelling of the right lower lid with proptosis since 4 weeks. On contrast-MRI orbit, an ill-defined multilobulated mass measuring 3.6 × 3.1 cm with intense homogenous enhancement was seen in the right retrobulbar space involving the right ethmoid sinus. On incisional biopsy, a poorly differentiated mass containing numerous small round blue cells and scanty intervening stroma with prominent necrosis and apoptosis was seen. Immunohistochemistry was strongly positive for synaptophysin. He was diagnosed as a case of SNEC and received chemotherapy, with good response till date of 9 months of follow up. The authors present a literature review and describe challenges in management of a primary orbital SNEC.

Clinical imaging features and prognosis of von Hippel-Lindau syndrome associated with pancreatic lesions / 中华消化外科杂志

Objective:To investigate the clinical imaging features and prognosis of von Hippel-Lindau (VHL) syndrome associated with pancreatic lesions.Method:The retrospective case-control study was conducted. The clinicopathological data of 161 patients with VHL syndrome who were admitted to Peking University First Hospital from September 2010 to August 2022 were collected. There were 83 males and 78 females, with age of onset as 27.0(range, 8.0-66.0)years. Observation indicators: (1) imaging results of VHL syndrome associated with pancreatic lesions; (2) clinical characteristics of VHL syndrome associated with pancreatic lesions; (3) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions; (4) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic neuroendocrine neoplasms (pNENs). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Results:(1) Imaging results of VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, there were 151 patients associated with pancreatic lesions and 10 patients not associated with pancreatic lesions. Of the 151 patients with VHL syndrome associated with pancreatic lesions, there were 136 patient with pancreatic cystic lesions and 34 patients with pNENs, 22 patients with both pNENs and pancreatic cystic lesions, and the type of pancreatic lesions could not be accurately determined in 3 cases. (2) Clinical characteristics of VHL syndrome associated with pancreatic lesions. The age of onset in 151 patients with VHL syndrome associated with pancreatic lesions was 33.0(range, 14.0-68.0)years. Cases with gene site mutation of exon 1, exon 2, exon 3 and other types of gene site was 51, 16, 43 and 41, respectively. There were 116 patients of VHL type 1 and 35 patients of VHL type 2. There were 92 patients with family history of VHL syndrome and 59 patients without family history of VHL syndrome. There were 127 patients combined with renal cell carcinoma, 112 patients combined with central nervous system lesions, 46 patients combined with retinal hemangioblastoma. Patients may combined with multiple lesions. (3) Comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions. The age of onset, VHL syndrome type (VHL1 type, VHL2 type) and cases combined with renal cell carcinoma were 32.5(range, 14.0-68.0)years, 110, 26 and 115 in 136 patients with VHL syndrome associated with pancreatic cystic lesions, versus 22.0(range, 8.0-64.0)years, 13, 12 and 14 in 25 patients with VHL syndrome not associated with pancreatic cystic lesions, showing significant differences in the above indicators between them ( Z=-3.384, χ2=9.770, 10.815, P<0.05). (4) Comparison of clinicopathological factors in patients with VHL syndrome associated with pNENs. The age of onset, gene mutation sites (exon 1, exon 2, exon 3, other types of gene site) and VHL syndrome type (VHL1 type, VHL2 type) were 33.5(range, 14.0-64.0)years, 12, 5, 14, 3 and 18, 16 in 34 patients with VHL syndrome associated with pNENs, versus 27.0(range, 9.0-66.0)years, 41, 12, 32, 42 and 105, 22 in 127 patients with VHL syndrome not associated with pNENs, showing significant differences in the above indicators between them ( Z=-4.030, χ2=8.814, 13.152, P<0.05). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, 3 patients underwent surgical treatment, and the remaining patients were followed up. All 161 patients with VHL syndrome were followed up for 6 (range, 1-12)years, in which 15 patients died and 146 patients alive during the follow-up. The follow-up time of 3 patients undergoing surgical treatment was 4, 14, 9 years, respectively, and all of them were alive. Conclusions:The clinical imaging features of pancreatic lesions related to VHL syndrome are cystic lesions and pNENs, which with the characteristics of multiple lesions and benign tumors. Such patients usually do not requiring surgical treatment and have good prognosis.

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.

Construction and application value of CT based radiomics model in predicting the prognosis of patients with gastric neuroendocrine neoplasm / 中华消化外科杂志

Objective:To construct of a computed tomography (CT) based radiomics model for predicting the prognosis of patients with gastric neuroendocrine neoplasm (GNEN) and inves-tigate its application value.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 182 patients with GNEN who were admitted to 2 medical centers, including the First Affiliated Hospital of Zhengzhou University of 124 cases and the Affiliated Cancer Hospital of Zhengzhou University of 58 cases, from August 2011 to December 2020 were collected. There were 130 males and 52 females, aged 64(range, 56-70)years. Based on random number table, all 182 patients were divided into the training dataset of 128 cases and the validation dataset of 54 cases with a ratio of 7:3. All patients underwent enhanced CT examination. Observation indicators: (1) construction and validation of the radiomics prediction model; (2) analysis of prognostic factors for patients with GNEN in the training dataset; (3) construction and evaluation of the prediction model for prognosis of patients with GNEN. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and the chi-square test, corrected chi-square test or Fisher exact probability were used for comparison between groups. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. The R software (version 4.0.3) glmnet software package was used for least absolute shrinkage and selection operator (LASSO)-COX regression analysis. The rms software (version 4.0.3) was used to generate nomogram and calibration curve. The Hmisc software (version 4.0.3) was used to calculate C-index values. The dca.R software (version 4.0.3) was used for decision curve analysis. Results:(1) Construction and valida-tion of the radiomics prediction model. One thousand seven hundred and eighty-one radiomics features were finally extracted from the 182 patients. Based on the feature selection using intra-group correlation coefficient >0.75, and the reduce dimensionality using LASSO-COX regression analysis, 14 non zero coefficient radiomics features were finally selected from the 1 781 radiomics features. The radiomics prediction model was constructed based on the radiomics score (R-score) of these non zero coefficient radiomics features. According to the best cutoff value of the R-score as -0.494, 128 patients in the training dataset were divided into 64 cases with high risk and 64 cases with low risk, 54 patients in the validation dataset were divided into 35 cases with high risk and 19 cases with low risk. The area under curve (AUC) of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the training dataset was 0.83[95% confidence interval ( CI ) as 0.76-0.87, P<0.05], 0.84(95% CI as 0.73-0.91, P<0.05), 0.91(95% CI as 0.78-0.95, P<0.05), respectively. The AUC of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the validation dataset was 0.84(95% CI as 0.75-0.92, P<0.05), 0.84 (95% CI as 0.73-0.91, P<0.05), 0.86(95% CI as 0.82-0.94, P<0.05), respectively. (2) Analysis of prognostic factors for patients with GNEN in the training dataset. Results of multivariate analysis showed gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression were independent factors influencing prognosis of patients with GNEN in the training dataset ( P<0.05). (3) Construction and evaluation of the prediction model for prognosis of patients with GNEN. The clinical prediction model was constructed based on the independent factors influen-cing prognosis of patients with GNEN including gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression. The C-index value of clinical prediction model in the training dataset and the validation dataset was 0.86 (95% CI as 0.82-0.90) and 0.80(95% CI as 0.72-0.87), respectively. The C-index value of radiomics prediction model in the training dataset and the validation dataset was 0.80 (95% CI as 0.74-0.86, P<0.05) and 0.75(95% CI as 0.66-0.84, P<0.05), respectively. The C-index value of clinical-radiomics combined prediction model in the training dataset and the validation dataset was 0.88(95% CI as 0.85-0.92) and 0.83 (95% CI as 0.77-0.89), respectively. Results of calibration curve show that clinical prediction model, radiomics prediction model and clinical-radiomics combined prediction model had good predictive ability. Results of decision curve show that the clinical-radiomics combined prediction model is superior to the clinical prediction model, radiomics prediction model in evaluating the prognosis of patients with GNEN. Conclusions:The predection model for predicting the prognosis of patients with GNEN is constructed based on 14 radiomics features after selecting. The prediction model can predict the prognosis of patients with GNEN well, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Research progress on the correlation between early life adversity and the puberty initiation / 中华实用儿科临床杂志

Earlier onset of puberty has become a worldwide trend.A large number of epidemiologic and animal experiment evidences have indicated that environmental changes in the early life may influence development plasticity and cause structural and functional changes, which are correlated with adult chronic diseases.The impact of fluctuations in environmental factors on the reproductive phenotype of offspring has been well concerned in recent years.This review summarizes the influences of nutritional state, endocrine disrupting chemicals, hormonal perturbation and stressful events during the prenatal and early childhood on the puberty initiation, especially neuroendocrine changes in puberty, thus providing a new idea for the prevention and control of pubertal disorders.

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.

Treatment and Outcome of Merkel Cell Carcinoma in A Single Center / 肿瘤防治研究

Objective To investigate the clinical features, treatment, and outcome characteristics of patients with Merkel cell carcinoma. Methods The clinical manifestations, laboratory tests, diagnosis and treatment, and follow-up data of six patients with Merkel cell carcinoma were retrospectively analyzed. Results Among the six patients with Merkel cell carcinoma, four were males and two were females, with a median age of 66 years old (57-76 years old). All six patients presented with skin swelling, and the clinical stages were as follows: stageⅠ in three patients, stage Ⅲ in one patient, and stage IV in two patients. Two patients were treated with surgery alone, three patients with surgery combined with radiotherapy and/or chemotherapy, and one patient with immunotherapy combined with chemotherapy. Until the follow-up time, four patients had no disease progression, one patient died because of disease progression, and one patient remained under treatment. Conclusion Limited-stage Merkel cell carcinoma is primarily treated with surgery and radiotherapy, meanwhile, metastatic Merkel cell carcinoma needs systemic therapy, and first-line immune checkpoint inhibitors targeting PD-1/ PD-L1 pathway can achieve better therapeutic results.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Poorly differentiated neuroendocrine carcinoma of the tongue base: a case report / 临床耳鼻咽喉头颈外科杂志

Neuroendocrine carcinoma(NEC) is a malignant tumor derived from neuroendocrine cells, with distinct clinical, morphological and immunohistochemical characteristics. Neuroendocrine carcinoma of the head and neck is very rare in clinic. Larynx is the most common affected site, and the root of the tongue is extremely rare. The clinical manifestations are mainly eating pain, cauliflower like mass in the mouth, and ulcerative lesions that have not healed for a long time. Maxillofacial MRI and contrastenhanced CT are the most commonly used examination tools for such diseases, which can detect the spaceoccupying lesions of tumors. Neuroendocrine granules found in the cytoplasm under pathological light microscope can be diagnosed as neuroendocrine carcinoma. However, for most cases, it is difficult to make a diagnosis only under light microscope, and it is often necessary to make a diagnosis by means of immunohistochemistry and other technical means. This paper reports a case of neuroendocrine carcinoma of the root of the tongue, introduces its characteristics, diagnosis and treatment, and reviews the relevant literature of this case.

Cancer-cell-intrinsic mechanisms shaping the immunosuppressive landscape of prostate cancer / 亚洲男科学杂志(英文版)

Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types, only a subset of patients shows meaningful clinical responses. In particular, advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy. This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer. Therefore, it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment. Here, we review recent findings that reveal the roles of the genetic alterations, androgen receptor signaling, cancer cell plasticity, and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance. Based on preclinical and clinical observations, a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.

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.

Taquipnea persistente como manifestación inicial de hiperplasia de células neuroendocrinas: reporte de un caso clínico / Persistent tachypnea as initial manifestation of hyperplasia of neuroendocrine cells: case report

Se realiza revisión de la literatura y presentación de un caso clínico de Hiperplasia de Células Neuroendocrinas en paciente lactante masculino que inicia su padecimiento a los 3 meses de vida con dificultad respiratoria caracterizada por retracciones subcostales y taquipnea persistente, posterior-mente a los 8 meses de edad se agrega hipoxemia respirando aire ambiente que requiere uso de oxígeno suplementario continuo. Tiene antecedente de tres hospitalizaciones, con diagnóstico de Bronquiolitis y Neumonía atípica, realizándose panel viral respiratorio con reporte negativo. El paciente persiste con sintomatología respiratoria a pesar de tratamientos médicos, por lo que se deriva a neumología pediátrica, unidad de enfermedad pulmonar intersticial del lactante, iniciando protocolo de estudio, se realiza tomografía tórax de alta resolución, que evidencia imágenes en vidrio despulido en lóbulo medio y región lingular, además de atrapamiento aéreo. Se concluye el diagnóstico de Hiperplasia de Células neuroendocrinas con base a la clínica y hallazgos tomográficos. La Hiperplasia de Células Neuroendocrinas es una patología pulmonar intersticial poco frecuente, cuyo diagnóstico es clínico y radiológico, en la minoría de los casos se requiere biopsia pulmonar para confirmación. Puede ser fácilmente confundida con otras enfermedades respiratorias comunes, por lo que es importante sospecharla para realizar un diagnóstico precoz. La mayor parte de los casos evolucionan con declinación de los síntomas, mejorando espontáneamente en los primeros años de vida.

A review of the literature and presentation of a clinical case of Neuroendocrine Cell Hyperplasia in a male infant patient who begins his condition at 3 months of age with respiratory distress characterized by subcostal retractions and persistent tachypnea is presented. After 8 months of age hypoxemia is added requiring continuous oxygen therapy. He has a history of three hospitalizations, with a diagnosis of bronchiolitis and atypical pneumonia, respiratory viral panel has a negative report. The patient persists with respiratory symptoms despite medical treatments, so it is referred to pediatric pulmonology, initiating study protocol for interstitial lung disease of the infant. A high resolution chest tomography is performed, which evidences images in polished glass in the middle lobe and lingular region, in addition to air entrapment. The diagnosis of neuroendocrine cell hyperplasia is concluded based on clinical and tomographic findings. Neuroendocrine Cell Hyperplasia is a rare interstitial pulmonary pathology, whose diagnosis is clinical and radiological. Lung biopsy is required only in the minority of cases for confirming diagnosis. It can be easily confused with other common respiratory diseases, so it is important to suspect it to make an early diagnosis. Most cases evolve with decline in symptoms, improving spontaneously in the first years of life.