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.

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

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

High-grade mixed neuroendocrine non-neuroendocrine neoplasm of the gastroesophageal junction: A rare case report and review of literature

Mixed neuroendocrine non-neuroendocrine neoplasm (MiNeN) is a recently described entity of the esophagus in the latest (fifth) edition of WHO Classification of Digestive System Tumors. It is often a difficult pathological diagnosis, especially in small preoperative biopsies. We herein report a case of high-grade MiNeN of gastroesophageal junction diagnosed as a squamous cell carcinoma in preoperative biopsy and subsequently as a high-grade MiNeN in esophagogastrectomy specimen comprising areas of mucoepidermoid carcinoma and large-cell neuroendocrine carcinoma (NEC). This report accentuates the importance of deeper multisite preoperative biopsies as the management is completely different in a MiNeN from esophageal squamous cell carcinoma.

Strategies of neoadjuvant and conversion therapy for gastroenteropancreatic neuroendocrine neoplasms / 中华消化外科杂志

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) refer to a group of relatively rare and heterogeneous tumors. The treatment and prognosis are distinct for GEP-NENs of different genetic phenotypes, differentiation degree, pathological categories, staging and grading, clinical characteristics. Neoadjuvant therapy is becoming increasingly accepted in the compre-hensive treatment of GEP-NENs. More and more researches show that neoadjuvant therapy contri-butes to improve R 0 resection rate and eliminate metastasis of malignancies. However, the value of neoadjuvant therapy and whether it improves overall survival of GEP-NENs patients remain contro-versial. The principle of neoadjuvant therapy is to bring survival benefits for selective patients treated by optimal therapy at appropriate time. It is important to master certain degrees for above event nodes. Whether the neoadjuvant /conversion therapy serve as castle in the air or Noah's ark for GEP-NENs requires prospective randomized controlled tests to answer. Combined with guidelines at home and abroad, the authors systematically review the evidence based medicines on neoadju-vant and conversion therapy for GEP-NENs, demonstrate relative research progress, carry an indepth discussion on hot and difficult subjects and controversial issues, aiming to provide references for individualized, precised and standardized comprehensive treatment of GEP-NENs.

Renewal and interpretation of concepts related to paragangliomas and pheochromocytomas according to WHO classification in 2022 / 中华泌尿外科杂志

WHO issued the fifth edition of classification of neuroendocrine neoplasms in 2022. The content of paragangliomas and pheochromocytomas (PPGL) was updated compared with the fourth edition in 2017. In the fifth edition of PPGL classification system, the author redefined the concepts that were vague and unclear in the past, and also put forward some new ideas. On this basis, this article introduces the relevant updates in combination with the current clinical situation in China. The content includes the concept evolution of paragangliomas and pheochromocytomas, accurate interpretation of the definitions of paraganglioid tumor, composite paraganglioma, adrenal medullary hyperplasia, and micro-pheochromocytoma. This article also help readers to understand molecular diagnostic and prognostic markers, the definition and clinical staging of benign and malignant PPGL. The domestic scholars can unify some concepts in PPGL to avoid confusion and facilitate academic exchanges through the discussion of these key concepts.

Clinical characteristics and prognostic analysis of renal primary neuroendocrine neoplasms / 中华泌尿外科杂志

Objective:To investigate the clinicopathological characteristics, treatment methods and prognosis of renal primary neuroendocrine neoplasms.Methods:The clinical data of 42 patients with renal neuroendocrine neoplasms admitted to the First Affiliated Hospital of Zhengzhou University from October 2011 to June 2021 were retrospectively analyzed.There were 17 males and 25 females. The median age was 60.0 (50.0, 67.0) years old.The CT enhancement scan lesion was slightly intensified with less intensification than normal renal parenchyma.The clinic manifestation included lumbar abdominal pain in 7 cases, hematuria in 3 cases, abdominal distension in 1 cases, and asymptomatic in 8 cases. The average diameter of tumor was 8.0 (4.0, 10.0) cm. The tumor of 13 cases was in the left, and 6 cases was in the right. 6 cases were in T 1 stage, 11 cases were in T 2, 11 cases were in T 3, and 14 cases were in T 4.17 cases had lymph node metastasis, 11 cases had distant metastasis.The surgical method was radical nephrectomy in 27 cases, nephrectomy in 5 cases and interventional embolization in 4 case, and no operation in 6 cases, including 5 with chemotherapy alone and 1 with supportive care.Patients were classified by WHO Classification of renal tumors of the urinary system and the male reproductive organs (2016) into high-differentiated renal neuroendocrine tumors (NET, including carcinoid and atypical carcinoids) and high-grade renal neuroendocrine carcinoma (NEC, including small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma). The clinicopathological characteristics and prognosis of the 2 groups were compared, and the Cox proportional regression risk model was used to analyze the clinical factors affecting the prognosis. Results:In the NET group, 12 cases were carcinoids and 7 cases were atypical carcinoids. In the NEC group, 23 cases were small cell carcinomas.The mean Ki-67 index of 42 cases was 35% (4.5%, 62.5%). The proportion of positive expression of the neuroendocrine markers CD56, chromogranin A (CgA), and synapsin (Syn) were (37/42), (15/42), and (38/42), respectively. A total of 42 patients were followed up, and the median follow-up time was 60 (35, 99) months, and the median survival time was 25 (15, 60) months. The 3-year and 5-year overall survival rates were 40.0% and 21.2%. The 3-year and 5-year overall survival rates in the NET group were 72.6% and 42.3%.The 3-year and 5-year overall survival rates in the NEC groups were 6.3% and 0, respectively. The mean Ki-67 index was 3% (2%, 10%) in the NET group, 2 patients received postoperative chemotherapy and 3 patients had early progression after initial treatment.The mean Ki-67 index in the NEC group was 60% (40%, 80%), 15 patients received postoperative chemotherapy, and 13 patients had early progression of initial treatment.There were statistically differences in treatment method, postoperative chemotherapy, Ki-67 index, and early disease progression (all P <0.05) between the two groups.The results of univariate analysis showed that sex, age, early progression, treatment method, tumor differentiation, and Ki-67 index were all factors influencing patient prognosis (all P <0.05). Cox multivariate analysis showed that poorly differentiated NEC ( HR=13.964, P=0.003) and early progression ( HR=3.626, P=0.018) were independent risk factors for patient survival, and renal radical surgery ( HR=0.197, P=0.033) was independent protective factors for patient survival. Further subgroup analysis showed that the median survival time of the NEC patients with adjuvant chemotherapy after surgery was significantly longer compared with the patients without adjuvant chemotherapy (21 and 9 months, P=0.012). Conclusions:Primary renal neuroendocrine tumors are clinically rare, often manifested as lumbar and abdominal pain, and radical renal surgical treatment is preferred.The NET has a better prognosis and NEC prognosis is extremely poor, but NEC patients can have survival benefit from chemotherapy. NEC and early progression of the disease are independent prognostic risk factors, and radical renal surgical treatment is an independent protective factor for prognosis.

Reflections on hot issues of pancreatic neuroendocrine neoplasms / 中华消化外科杂志

Pancreatic neuroendocrine neoplasms (pNENs) is one of the gastrointestinal malignancies of significantly heterogeneous, pathologically classified into well differentiated pancreatic neuro-endocrine tumors (pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas. The prognosis and treatment response of pNETs are primely determined by tumor-intrinsic biolo-gical behavior. Accordingly, surgeons need to operate debulking surgery for low-risk patients, as well as implement adjuvant therapies for those at high-risk of relapse and metastasis after curative resection. Notably, as to two distinct subtypes of patients who suffer primary tumor with diameter less than 2 cm and functional pNETs, oncological benefits and functionally symptomatic control should be considered when formulating surgical strategies. In recent years, advances in next-generation sequencing and organoid technologies have provided practical tools for revealing the gene mutations and tumor microenvironment of pNETs. The four signalling pathways, including mTOR signalling, histone modification, altered telomere length and DNA damage repair pathways, are related to the occurrence and development of pNETs and can be used for the personalization precision therapy of pNETs and guiding the development of new drugs. Empirical therapy and clinical trial studies of pNETs are a continuum of contradictions. Therefore, clinicians need to summarize the rules in treatment and develop disciplines in the summary. Based on relevant literatures, the authors explore the hot issues related to pNENs in recent years, in order to provide reference for the diagnosis and treatment of this disease.

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

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

Chinese expert consensus on lung and thymus neuroendocrine neoplasms / 中华肿瘤杂志

Lung and thymus neuroendocrine neoplasms (NENs) are rare tumors. According to the fifth edition of the World Health Organization classification of thoracic tumors published in 2021, lung and thymus NENs include typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinomas, and small cell carcinomas. Although the incidence of lung and thymus NENs has gradually increased in recent years, there is a lack of randomized controlled clinical study results to guide clinical practice. The treatment of early-stage lung and thymus NENs is complete surgical resection, and the treatment methods for unresectable advanced diseases include different medical treatments, peptide receptor radionuclide therapy, and local therapy. To improve the standardization of diagnosis and treatment of lung and thymus NENs in China, the Expert Committee of Neuroendocrine Neoplasms, Chinese Society of Clinical Oncology developed the expert consensus after multidisciplinary expert discussions based on existing clinical study evidences and guidelines from different neuroendocrine tumor societies. The contents of the consensus cover the epidemiology, diagnosis, pathological classification, staging, treatment and follow-up of lung and thymus NENs (except small cell lung cancer).

Comparison of endoscopic mucosal resection with a cap and endoscopic submucosal dissection in the treatment of smaller gastric neuroendocrine neoplasms / 中华消化内镜杂志

Data of 55 cases of gastric neuroendocrine neoplasms (G-NENS) with diameter ≤12 mm in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to the methods of endoscopic resection, the patients were divided into two groups: the endoscopic mucosal resection with a cap (EMR-C) group (35 cases) and the endoscopic submucosal dissection (ESD) group (20 cases). The results showed that the success rates of operation, the whole resection rates and the complete resection rates were all 100.0% in the two groups. Compared with the ESD group, the EMR-C group had a shorter median operation time (12.00 min VS 28.35 min, P<0.001), less mean hospitalization costs (21 165.19 yuan VS 28 400.35 yuan, P=0.004), and a similar overall incidence of complications [2.86% (1/35) VS 0, P=1.000]. By March 2020, the recurrence rate of EMR-C group and ESD group were 28.6% (10/35) and 15.0% (3/20), respectively, without significant difference ( P=0.418). It is suggested that for G-NENS with diameter ≤12 mm, without muscular invasion, lymph node metastasis or distant metastasis, EMR-C and ESD are both safe and effective, but EMR-C has more advantages in terms of operation time and hospitalization costs.

Establishment and validation of a nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

Objective: To establish a novel nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms (g-NEN). Methods: A case control study was conducted. Clinicopathological and follow-up data of patients with g-NEN who were treated in two academic medical centers in Southern China between July 2008 and June 2018 were retrospectively collected, including 174 patients from Sun Yat-sen University Cancer Center and 102 patients from the First Affiliated Hospital of Sun Yat-sen University. Univariate survival analysis using Kaplan-Meier method and multivariate analysis using Cox regression were performed to identify prognostic factors. A nomogram was subsequently established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility. Results: A total of 276 patients were enrolled in the study, of whom 189 patients were male and 87 were female. The age at diagnosis was below 60 years old in 150 patients and 60 years or older in 126 patients. There were patients diagnosed with gastric neuroendocrine carcinoma (g-NEC) and 101 patients with gastric neuroendocrine tumor (g-NET). The number of patients with primary tumor locating at upper, middle and lower parts of stomach was 131, 98 and 47, respectively. As for TNM stage, 72 patients were categorized as stage I, 26 patients stage II, 93 patients stage III, and 85 patients stage IV. Univariate analysis indicated that age, pathological type, primary site, Ki-67 index, T stage, N stage, and M stage were associated with overall survival of g-NEN patients (all P<0.05). Multivariate regression analysis testified that high Ki-67 index, advanced T stage and advanced M stage were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.806 (95%CI: 0.769-0.863). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in g-NEN patients. The ROC curves and DCA showed that the nomogram had better differentiation and clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system (the area under the ROC curve was 0.862 vs. 0.792). Conclusion: The first nomogram to predict overall survival of patients with g-NEN is established and verified in this study, which provides individual prediction of 3-year overall survival rate and is applicable to both g-NET and g-NEC patients.

Advances in basic and translational research in neuroendocrine neoplasms / 中华胃肠外科杂志

With the development of diagnostic techniques and the improvement of people's living standards, the detection rate of neuroendocrine tumor has been increasing and people are paying more and more attention to it. With multiple treatment modalities, the clinical research progress of neuroendocrine tumor is remarkable. However, due to the tumor heterogeneity, metastasis and recurrence of neuroendocrine tumor remains a difficult problem for clinicians. The efficacy of neuroendocrine tumor still needs to be improved. Therefore, the biological behavior of neuroendocrine tumor needs to be further studied. In recent years, with the development of molecular biology, the basic and transformation research of neuroendocrine tumor has made some progress. In this paper, we focus on the hot topics of neuroendocrine tumor, such as multiomics (copy number variation, genomics, transcriptomics), tumor microenvironment (immune microenvironment, tumor microvasculature, tumor-associated fibroblasts, etc.), preclinical research model construction (cell lines, organoids, patient derived xenograft models, genetically engineered mice), etc. Specifically, the related clinical transformation significance will be elaborated.

Endoscopic diagnosis and treatment of gastrointestinal neuroendocrine neoplasms / 中华胃肠外科杂志

The incidence of neuroendocrine neoplasms (NEN) is increasing globally, and gastrointestinal NEN (GI-NEN) is the most common type of NEN. Diagnosis and treatment of GI-NEN are quite different, according to tumor's location, size, background, cell origin, and pathogenesis. Digestive endoscopy has unique advantages in detecting of GI-NEN. However, endoscopist should not perform endoscopic resection arbitrarily, due to the high heterogeneity and complexity of GI-NEN. We need to establish the concept about comprehensive assessment for GI-NEN, including medical history and physical signs, serology, imaging, radionuclide and end·oscopic examination, to make an individualized treatment after rigorous multidisciplinary discussion.

Surgical treatment of gastric neuroendocrine neoplasms / 中华胃肠外科杂志

Neuroendocrine neoplasms (NEN) are rare neoplasms originating from all major systems, in which gastric neuroendocrine neoplasms (G-NEN) is rarely malignant neoplasm originated in stomach. In 2019, the 5th WHO classification of digestive system tumors updated the classification of G-NEN and solved several naming problems. Since the classification of G-NEN has become more specific and more scientific, the surgical treatment of G-NEN is becoming more individual and more precise. Generally, endoscopic resection is often recommended for the treatment of type I gastric neuroendocrine tumors (NET). Type II gastric NET is mostly secondary to gastrinoma originating from the duodenum or pancreas, and thus surgical treatment of primary gastrinoma deserves enough attention. The decision of operation for type III gastric NET needs comprehensive consideration of tumor size, invasive depth and lymph node metastasis. For gastric neuroendocrine carcinomas without distant metastasis, aggressive surgery should be performed, and the resection range of primary site and lymph nodes can refer to the standard of gastric adenocarcinoma. For locally advanced gastric NEC, it has not been reported whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy could reduce tumor stage and improve radical resection rate. In addition, for functional gastric NEN with distant metastasis, radical resection or palliative surgery can be performed to control hormone secretion and may improve the survival. In general, it is an important principle to thoroughly consider biological behavior, extent of primary and metastatic sites, resectability and function of tumor before surgery of gastric neuroendocrine neoplasm, and thus multi-disciplinary treatment (MDT) is recommended.

Interpretation of updated international guidelines for diagnosis and treatment of gastroenter-opancreatic neuroendocrine neoplasms / 中华胃肠外科杂志

The incidence of neuroendocrine neoplasms (NEN) is continuously increasing with gastrointestinal tract and pancreas being the most common primary sites. Currently, the guidelines proposed by European Neuroendocrine Tumor Society (ENETS), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and North American Neuroendocrine Tumor Society (NANETS) are being widely applied. Among these, ENETS and NANETS guidelines were proposed in 2017 while ESMO and NCCN recently updated their guidelines for gastroenteropancreatic NEN in 2020 and 2021, respectively. This article interprets the diagnosis and treatment of gastroenteropancreatic NEN based on the newly updated ESMO and NCCN guidelines. The diagnosis of gastroenteropancreatic NEN depends on histological assessment including morphological evaluation, grading and immunohistochemistry results. Combination of different imaging methods can help determine tumor staging and risk assessment. Decision-making of treatment and follow-up strategies is based on primary tumor site, tumor classification, tumor grade, tumor type, functional status etc.

Analysis of Factors Associated With Synchronous Liver Metastasis in Gastroenteropancreatic Neuroendocrine Neoplasm and Establishment of A Predictive Model / 胃肠病学

Background: Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is a rare heterogeneous tumor. Liver metastasis seriously affects the prognosis of GEP-NEN. However, few tools are existed to predict GEP-NEN complicated with synchronous liver metastasis. Aims: To analyze the risk factors of synchronous liver metastasis in patients with GEP-NEN and establish a nomogram to predict synchronous liver metastasis in patients with GEP-NEN. Methods: A total of 10 973 pathologically confirmed patients with GEP-NEN from Jan. 2010 to Dec. 2017 were collected from SEER database and divided randomly into training set (n=7 511) and test set (n=3 462). Both groups were divided into liver metastasis group and non-liver metastasis group according to the occurrence of liver metastasis. Multifactorical logistic regression analysis was used to identify the risk factors of liver metastasis in patients with GEP-NEN. R software was used to establish and verify the nomogram of liver metastasis in GEP-NEN patients. Results: Liver metastasis was associated with gender, age, race, primary tumor site, degree of differentiation, tumor diameter, T3/4 stage, and lymph node metastasis in patients with GEP-NEN. The results of multivariate logistic regression analysis showed that primary tumor site (small intestine and pancreas), differentiation degree (poorly differentiated and undifferentiated), diameter of tumor ≥ 5 cm, T3/4 stage and lymph node metastasis were independent risk factors affecting liver metastasis in patients with GEP-NEN (P< 0.001). The concordance index of internal validation for nomogram was 0.838 (95% CI: 0.826-0.849), and the concordance index of external validation was 0.847 (95% CI: 0.829-0.864). Conclusions: GEP-NEN patients with primary tumor site in small intestine or pancreas, poor differentiation and undifferentiation, diameter of tumor ≥5 cm, T3/4 stage and lymph node metastasis are more likely to develop liver metastasis which suggested that such patients need to be alert for the occurrence of liver metastasis and need more aggressive treatment. The calibration curves fits are good for both the training and test sets, and can help clinicians to make individualized prediction for whether the GEP-NEN patient has synchronous liver metastasis at the initial diagnosis.

Clinical characteristics of inflammatory bowel disease complicating neuroendocrine neoplasms / 中华消化内镜杂志

A case of inflammatory bowel disease (IBD) complicating neuroendocrine neoplasms (NENs) was reported and 69 cases in references were reviewed to analyze the clinical features of IBD complicating NENs and to explore the connection between IBD and NENs. Thirty-two cases of Crohn disease (CD) and 37 cases of ulcerative colitis (UC) were included in the study. The occurrence rate showed no significant difference between males and females ( P=0.151). NENs mostly occurred after the diagnosis of IBD. The median interval duration of NENs after CD was 4.5 years, which was significantly shorter than that of UC (17 years, P=0.002). Thirty-three cases discovered NENs occasionally with no special indications. Among those symptomatic patients, 11 of them suffered from intestinal obstruction. The location of NENs was similar to IBD, that was, ileum and appendix in CD (27 cases) while colon and rectal in UC (31 cases, P<0.001). Neuroendocrine tumors were more common in CD (26 cases) while neuroendocrine carcinomas were more common in UC (22 cases, P<0.001). There is possibility that IBD complicate with NENs with no specific clinical features. The etiology of this phenomenon is still not clear, which needs further exploration.

Status of liquid biopsy application in gastroenteropancreatic neuroendocrine neoplasms / 中国肿瘤临床

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are neoplasms that develop from neuroendocrine cells and exhibit neuroendocrine functions. The lack of specific clinical symptoms and biological behaviors for NENs cause early misdiagnosis and missed diagnosis in a majority of cases. However, the molecular biology of GEP-NENs vary greatly in different primary sites and grades, contributing to the high heterogeneity in such type of tumors. Currently, the diagnosis of GEP-NENs mainly depends on traditional methods such as imaging and tissue biopsy, leading to imperfect diagnostics by only reflecting genetic information about the location of the biopsy sample in the overall neoplasm. With the rapid development of genome sequencing technology in recent years, the exploration of circulating biomarkers and liquid biopsy technology have compensated for the limitations of tissue biopsy, thereby creating new opportunities to improve the diagnostic rate of GEP-NENs and the realization of precise treatment. This review summarizes and compares the status of liquid biopsy applications in investigating GEP-NENs.

The diagnostic value of endoscopic ultrasonography in gastrointestinal neuroendocrine neoplasms / 西安交通大学学报(医学版)

Objective: To evaluate the diagnostic value of endoscopic ultrasonography in gastrointestinal neuroendocrine neoplasms (GI-NENs). Methods: We studied the patients diagnosed with GI-NENs from January 2015 to February 2019 at The First Affiliated Hospital of Xi'an Jiaotong University, and recorded their pathology, endoscopic features and treatment. We analyzed the accuracy of diagnosis GI-NENs by endoscopic ultrasonography, endosonographic characteristics and the choice of surgical methods for different lesions. Results: A total of 33 patients had pathological findings and were treated at our hospital. With pathological diagnosis as the gold standard, the accuracy of endoscopic ultrasonography diagnosis was 90.9%. GI-NENs usually occurred in the rectum and the stomach. Endoscopically, they were spherical or hemispherical, yellow or white and hypoechoic bulging lesions with smooth surface and hard texture, which usually originated from the submucosa. Results: Endoscopic ultrasonography has a great diagnostic value in GI-NENs and it helps make decision on treatment.

Clinicopathologic features and prognostic analysis of 240 patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

Objective@#To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN).@*Methods@#Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test.@*Results@#In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012).@*Conclusions@#Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.