最新刊期

    32 9 2022

      Specialists' Commentary

    • Updates on medical treatment for neuroendocrine neoplasm

      Yun LIANG, Shunrong JI, Xianjun YU, Jie CHEN
      Vol. 32, Issue 9, Pages: 757-764(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.001
      摘要:Neuroendocrine neoplasm (NEN) is a group of heterogeneous malignancies arising from neuroendocrine cells and peptidergic neurons. According to its cell differentiation, NEN can be divided into two distinct groups as well-differentiated neuroendocrine tumor (NET) and poorly-differentiated neuroendocrine carcinoma (NEC). For advanced NEN, medication is the preferred treatment. In this article, we reviewed current clinical trials in medical treatment for NEN and aimed to provide treatment reference in clinical practice.  
      关键词:Neuroendocrine neoplasms;Medicine;Clinical trial   
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    • Xianze WANG, Wenming WU
      Vol. 32, Issue 9, Pages: 765-771(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.002
      摘要:Pancreatic neuroendocrine neoplasm (pNEN) is highly heterogeneous. Surgery is an important part of the comprehensive treatment for pNEN, however, the low incidence and strong heterogeneity of the disease retard the progress of surgical treatment. In terms of treatment concepts, the therapeutic strategy of surgery may transform from condition-orientated to prognosis-orientated treatment, and the evaluation of tumor characteristics relies more on morphology combined with molecular pathology. In addition, pNEN surgical treatment is becoming individualized, minimally invasive and delicate, and the timing of surgical intervention has extended to the entire disease period. Based on the research progresses in related fields, we analyzed the issues and challenges and discussed the evolution in the surgical treatment concepts of pNEN.  
      关键词:Pancreatic neuroendocrine neoplasm;Surgical treatment;Treatment concept   
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    • Heli GAO, Jin XU, Xianjun YU
      Vol. 32, Issue 9, Pages: 772-778(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.003
      摘要:Pancreatic neuroendocrine neoplasm (PanNEN) has a low incidence and strong heterogeneity. Research on molecular mechanism of PanNEN is gradually increasing. At the same time, the updates on clinical diagnosis, treatment and prognosis prediction of PanNEN patients are increasing. In addition to surgery and systemic treatment such as somatostatin analogs and tyrosine kinase inhibitors, there are unsolved problems and questions in the management of PanNEN patients, which emphasizes individualized treatment and multidisciplinary treatment. This article summarized the basic and clinical research progress of PanNEN in 2021.  
      关键词:Pancreatic neuroendocrine tumor;Molecular marker;Diagnosis;Prognosis;Treatment   
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    • Lingjun CUI, Chao TIAN, Zixuan CHENG, Jiabin ZHENG, Fei SU, Huangying TAN
      Vol. 32, Issue 9, Pages: 779-785(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.004
      摘要:Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is a rare, heterogeneous tumor that can be divided into neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) due to its degree of differentiation. With the gradual deepening of the exploration of its pathogenesis and treatment methods, the importance of preclinical models has become increasingly prominent. Here we reviewed the published preclinical models such as cell lines, organoid models, patient-derived xenograft models and genetically engineered mouse models. We also discussed the current practical applications of these models and their strengths and weaknesses, to provide threads and directions for future research.  
      关键词:Gastroenteropancreatic neuroendocrine neoplasm;Cell line;Organoid model;Patient-derived xenograft model;Genetically engineered mouse model   
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      Specialists' Article

    • Wensheng LIU, Shunrong JI, Qifeng ZHUO, Heli GAO, Yihua SHI, Wenyan XU, Mengqi LIU, Zheng LI, Xianjun YU, Jie CHEN, Xiaowu XU
      Vol. 32, Issue 9, Pages: 786-793(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.005
      摘要:Background and purpose: Pancreatic neuroendocrine tumor (pNET) is a rare tumor. At present, there is still a lack of large-scale clinical research data to summarize the clinical effect of minimally invasive technology in the treatment of pNET. This study analyzed the clinical data of pNET patients undergoing surgical treatment, in order to provide reference for the surgical treatment of pNET. Methods: The clinical data of 118 patients with well-differentiated pNET undergoing minimally invasive surgery admitted by the Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center from September 2018 to July 2022 were retrospectively analyzed. The patients were divided into robot group (n=17) and laparoscopic group (n=101) according to the minimally invasive operation mode. According to the surgical resection mode, they were divided into regular resection group (n=86) and local resection group (n=32). The clinical data of operation and postoperation were collected and analyzed. Results: Of the 118 patients who underwent minimally invasive surgery on pNET included in this study, 17 were in the robot group, and 101 were in the laparoscopic group. There were 32 cases in local resection group and 86 cases in regular resection group. There was no significant difference between robot group and laparoscopic group in operation time and intraoperative bleeding (P>0.05). The operation time of local resection group [(145.3&#x000b1;55.5) min] was significantly shorter compared with regular resection group [(247.4&#x000b1;94.7) min](P <0.05). At the same time, the bleeding volume [(71.8&#x000b1;23.2) mL] was significantly less in the local resection group than in the regular resection group [(147.5&#x000b1;59.9) mL](P<0.05). The recovery of gastrointestinal function in the robot group was earlier compared with laparoscopic group (P<0.05). There was no significant difference between the two groups in terms of postoperative ambulatory time, postoperative pancreatic fistula, delayed gastric emptying, postoperative effusion and postoperative hospitalization time (P>0.05). The incidence of postoperative b-pancreatic fistula was higher in the local resection group than in the regular resection group (P<0.05), and the postoperative hospital stay was significantly longer in the local resection group than in the regular resection group (P<0.05). Conclusion: Minimally invasive surgery is safe and feasible to treat well-differentiated pNET. There was no significant difference in minimally invasive effect between laparoscope and robot. The incidence of pancreatic fistula after local resection of tumor is higher, and the postoperative hospital stay is longer, however the long-term benefit is expected.  
      关键词:Pancreatic neuroendocrine tumor;Minimally invasive surgery;Robotic surgery;Local excision of tumor;Function-preserving operation   
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    • Hang YU, Wensheng LIU, Ning ZHANG, Haikuan LIU, Luohai CHEN, Wang YAO, Wenzhe FAN, Jiaping LI, Jie CHEN, Yu WANG
      Vol. 32, Issue 9, Pages: 794-799(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.006
      摘要:Background and Purpose: Liver metastases are common in neuroendocrine neoplasm (NEN). Cystic NEN liver metastases (cNENLM) are rare, and the efficacy of transarterial embolization (TAE) has not been reported. This study summarized and analyzed the efficacy and safety of TAE for cNENLM. Methods: From January 2016 to April 2022, 10 patients with cNENLM were enrolled in this study among 440 patients under TAE treatment at The First Affiliated Hospital, Sun Yat-sen University and Fudan University Shanghai Cancer center. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were analyzed as well. The common terminology criteria for adverse events (CTCAE) v5.0 was applied to evaluate the adverse effects. Results: With 80.0% ORR and 100.0% DCR according to RECIST 1.1, 3 cases achieved PFS. Among them, the longest one was 25.0 months. Disease progression was not observed in the remaining patients. The common complications were fever, hepatalgia and transient liver dysfunction, which could be alleviated by symptomatic treatment. No severe complication occurred. Conclusion: cNENLM are infrequent. TAE had significant curative effect on cNENLM, and complications were manageable.  
      关键词:Transaterial embolization;Neuroendocrine neoplasm;Liver metastasis;Cystic;Efficacy;Safety   
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    • Xiuli ZHENG, Zhiyuan YAO, Mingli WU, Limian ER, Shengmian LI
      Vol. 32, Issue 9, Pages: 800-806(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.007
      摘要:Background and purpose: In recent years, the incidence of rectal neuroendocrine neoplasm (R-NEN) has been on the rise. However, its treatment remains controversial, especially for tumors of 10-20 mm in diameter. In this study, the clinicopathological characteristics of R-NEN were analyzed, the risk factors for lymph node metastasis were discussed, and the effects of different endoscopic resection were compared, so as to ascertain the indications and methods of endoscopic treatment of R-NEN. Methods: Clinical data of patients with R-NEN treated in the Fourth Hospital of Hebei Medical University from February 2007 to December 2020 were collected and retrospectively analyzed. The risk factors of lymph node metastasis were analyzed, and the safety and effectiveness of different endoscopic resection methods were compared. Results: The clinicopathological features of 190 patients with R-NEN were analyzed, suggesting that tumor size &#x02265;12.5 mm (OR = 69.081, 95% CI: 11.385-419.155, P<0.001) and lymphovascular invasion (OR = 11.732, 95% CI: 1.028-84.567, P = 0.015) were independent risk factors for lymph node metastasis. The clinical data of 114 patients with R-NEN treated with endoscopic mucosal resection with cap (EMR-c) and endoscopic submucosal dissection (ESD) respectively were compared. The results showed that the duration of operation was significantly shorter in EMR-c group than in ESD group [(10.23&#x000b1;1.99) min vs (24.78&#x000b1;8.09) min, P<0.001]. There was no significant difference in rate of endoscopic en bloc resection, pathological complete resection rate and complication rate between the two groups (P>0.05). Conclusion: Tumor size &#x02265;12.5 mm in diameter and presence of lymphovascular invasion are independent risk factors for lymph node metastasis in patients with R-NEN. Both EMR-c and ESD are safe and effective treatments for R-NEN of <12.5 mm in diameter and without lymph node metastasis.  
      关键词:Rectal neuroendocrine neoplasms;Lymph node metastasis;Endoscopic resection   
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    • Rihong ZHANG, Yu GUO, Yun LIANG, Luohai CHEN, Jie CHEN, Wei WANG
      Vol. 32, Issue 9, Pages: 807-817(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.008
      摘要:Background and purpose: Gastric neuroendocrine neoplasm (NEN) is a rare type of gastric malignant tumors. According to the 2019 World Health Organization (WHO) classification criteria for gastrointestinal NEN, gastric NEN can be divided into well-differentiated neuroendocrine tumor (NET) and poorly-differentiated neuroendocrine carcinoma (NEC). At present, there is a lack of research on the prognosis of adjuvant chemotherapy for gastric NEC (GNEC). The aim of the research was to investigate whether adjuvant chemotherapy can benefit patients with GNEC and provide a basis for clinical decision-making. Methods: A retrospective analysis was performed on the clinical data of about 184 patients with GNEC from July 2008 to June 2019 in Sun Yat-sen University Cancer Center, The First Affiliated Hospital of Sun Yat-sen University and Fudan University Shanghai Cancer Center. The follow-up deadline was May 31, 2022. Kaplan-Meier method was used to draw the survival curve, and prognostic relevant factors affecting the survival of patients with GNEC and the independent prognostic factors were screened out according to univariate and multivariate COX regression analyses. Finally, the effects of chemotherapy and surgery on the prognosis of patients were further analyzed. The test level was &#x003b1; = 0.05, and SPSS 25.0 was used for all statistical analyses. Results: By univariate COX regression analysis, it was found that surgery, chemotherapy, treatment method, N stage, M stage and TNM stage were the variables affecting the prognosis of patients with GNEC (P<0.05). Multivariable COX regression analysis results showed that surgery, chemotherapy and M stage were independent prognostic factors for survival in patients with GNEC (P<0.001). The 3-year cumulative survival rates of TNM stage &#x02160;, &#x02161;, &#x02162; and &#x02163; were 51.9%, 55.8%, 40.7% and 23.6%, respectively. In the radical resection group, adjuvant chemotherapy could improve the prognosis of patients with GNEC (P=0.008). The 3-year cumulative survival rates of adjuvant chemotherapy group and non-adjuvant chemotherapy group were 58.8% and 33.3%, respectively. Stratified analysis showed that adjuvant chemotherapy could benefit the prognosis of patients with TNM stage &#x02161; (P = 0.018) and TNM stage &#x02162; (P = 0.023). In addition, there was no significant difference in prognosis between the first-line chemotherapy regimen [etoposide plus cisplatin (EP), irinotecan plus cisplatin (IP)] and the gastric adenocarcinoma regimen [oxaliplatin plus capecitabine (XELOX), oxaliplatin plus tegafur (SOX), oxaliplatin plus 5-fluorouracil (FOLFOX)] (P = 0.668). Conclusion: Adjuvant chemotherapy can significantly improve the prognosis of patients with GNEC, providing a reference for clinical decision-making.  
      关键词:Gastric neuroendocrine carcinoma;Adjuvant chemotherapy;Prognosis   
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      Article

    • Jingchen ZHANG, Xin LI, Jiangtao LI, Haiping LI, Yanli CHEN, Bing NIU, Chuanchuan QI, Beibei YE
      Vol. 32, Issue 9, Pages: 818-826(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.009
      摘要:Background and purpose: Long non-coding RNA (lncRNA) has been found to be dysregulated in breast cancer and is closely related to the malignant behavior of tumors. This study aimed to explore the effects of LINC02163 targeting miR-338-3p on the proliferation, invasion and migration of breast cancer cells. Methods: Breast cancer tissue samples and the adjacent tissue samples (2 cm to cancer tissue) were collected from 9 female breast cancer patients admitted to People&#x02019;s Hospital of Zhengzhou from January 2020 to September 2021. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of LINC02163 in tissue samples, human normal breast epithelial cell line (MCF-10A) and breast cancer cell lines (MCF-7, BT-20, MDA-MB-231, T47D). MDA-MB-231 was divided into control group, sh-NC group, sh-LINC02163 group, sh-LINC02163+inhibitor-NC group and sh-LINC02163+miR-338-3p inhibitor group. MTT method, transwell test and scratch test were used to detect the MDA-MB-231 cell viability, invasion and migration ability. Western blot was used to detect the protein expression of c-Myc, matrix metalloproteinase (MMP) 2, MMP9, E-cadherin and N-cadherin in MDA-MB-231 cells. Dual luciferase reporter gene was used to detect the targeting relationship between LINC02163 and miR-338-3p. In vivo tumor formation experiment was used to detect tumor volume and weight in nude mice. Immunohistochemical method was used to detect the Ki-67 proliferation index in tumor tissues of BALB/c nude mice. Results: Compared with adjacent tissues, the expression of LINC02163 in breast cancer tissues was significantly higher (P<0.05). Compared with MCF-10A cells, the expression of LINC02163 in MCF-7, BT-20, MDA-MB-231 and T47D cells was significantly higher, and it increased most significantly in MDA-MB-231 cells (P<0.05). Compared with the control group, the LINC02163 expression, cell survival rate, number of invasive cells, migration rate, expressions of c-Myc, MMP2, MMP9 and N-cadherin, tumor volume and weight, and Ki-67 proliferation index were significantly reduced in the sh-LINC02163 group, while the expressions of miR-338-3p and E-cadherin were significantly increased (P<0.05). Compared with the sh-LINC02163 group, the expression of LINC02163 in the sh-LINC02163+miR-338-3p inhibitor group did not change significantly (P>0.05), the cell survival rate, number of invasive cells, migration rate, expressions of c-Myc, MMP2, MMP9 and N-cadherin, tumor volume and weight, and Ki-67 proliferation index were significantly increased, while the expressions of miR-338-3p and E-cadherin were significantly reduced (P<0.05). LINC02163 had a potential targeting relationship with miR-338-3p in breast cancer. Conclusion: Silencing the expression of LINC02163 can inhibit the proliferation, invasion and migration of breast cancer cells by promoting the expression of miR-338-3p.  
      关键词:LINC02163;miR-338-3p;Breast cancer;Proliferation;Invasion;Migration   
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    • Ye LÜ, , Yexia YING, Wenjing YANG, Yujin HOU, Chunxiu YUAN, Xiangmei CAO
      Vol. 32, Issue 9, Pages: 827-835(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.010
      摘要:Background and purpose: Invasive breast carcinoma is the most prevalent malignancy in women worldwide and has a poor prognosis. Tumor xenobiotics change the tumor microenvironment and participate in the regulation of tumor occurrence, development and metastasis, which provide new ideas for the diagnosis and treatment of tumors. DZNep can target and regulate the degradation of H3K27me3 histone methyltransferase and specifically induce tumor cell apoptosis, thereby inhibiting cell proliferation and migration in a variety of tumors. In this study, we investigated the effect of DZNep on invasive breast carcinoma exosomes and observed its effect on epithelial-mesenchymal transition (EMT) of breast cancer cells by regulating intercellular junctions. Methods: EZH2 expression in invasive breast carcinoma was analyzed using the The Cancer Genome Atlas (TCGA) database and the online analysis software GEPIA2, and the Tumor Immunity Estimation Resources (TIMER) was used to analyze the relationship between EZH2 and the expressions of tumor microenvironment cytokines and EMT-related proteins. Intervention of invasive breast carcinoma MDA-MB-231 with DZNep and extraction of exosomes using differential ultracentrifugation were performed. Exosome membrane-bound protein expression was identified by detecting the expressions of CD9, CD63 and TSG101 using Western blot. The Brownian motion of exosomes was tracked and analyzed by nanoparticle tracking analysis (NTA) technique, and the hydrodynamic diameter and concentration of exosome particles were calculated in combination with the Stokes-Einstein equation. Transmission electron microscopy analysis of the size and shape of exosomes was carried out. The above methods were used to explore the changes of exogenous exosomes in breast cancer induced by DZNep. In addition, Western blot was used to detect the expressions of EZH2, intercellular junction proteins such as occludin, zonula occludens-1 (ZO-1), laminin, aquaporin 4 (AQP4), connexin 43, claudin5 and collagen &#x02165;, and EMT-related proteins such as E-cadherin and vimentin, respectively, to analyze the regulatory mechanism of DZNep on the tumor microenvironment.Results: EZH2 expression was higher in cancer tissues than in normal tissues. High EZH2 expression was positively correlated with the upregulation of both invasive breast carcinoma immune cells and stromal cells in Luminal A, positively correlated with E-cadherin, N-cadherin and vimentin expressions in invasive breast carcinoma, positively correlated with E-cadherin expression and negatively correlated with N-cadherin expression in BRCA-Luminal B, and positively correlated with N-cadherin and vimentin expressions in BRCA-Luminal A (P<0.05). The expressions of CD9, CD63 and TSG101 showed that the exosomes of MDA-MB-231 cells were successfully extracted. After DZNep intervention, the particle size of the exosomes was significantly reduced and the number was decreased. The expressions of intercellular junction proteins including occludin, ZO-1, laminin, AQP4 and connexin 43 were decreased, and the expressions of collagen &#x02165; and claudin 5 (CLDN5) were increased. The expression of EMT-related protein E-cadherin was increased, while the expressions of vimentin was decreased. Conclusion: DZNep reduces the generation of exosomes in BRCA by inhibiting EZH2, which further alters the tumor cell microenvironment and thus affects the EMT phenomenon.  
      关键词:DZNep;EZH2;Exosomes;Intercellular junction;Epithelial-mesenchymal transition   
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      Guideline and Consensus

    • Chinese Anti-Cancer Association Committee of Breast Cancer Society,, Chinese Medical Doctor Association Breast Surgeons Committee of Surgeons Branch,, Shanghai Anti-Cancer Association Committee of Breast Cancer Society,
      Vol. 32, Issue 9, Pages: 836-924(2022) DOI: 10.19401/j.cnki.1007-3639.2022.09.011
      摘要:With the new trend of oncoplastic surgery and breast reconstruction in China and the emergence of new evidence-based medical data, expert of Chinese Anti-Cancer Association, Committee of Breast Cancer Society convened domestic clinical experts in the field of breast cancer treatment, including breast surgeons, plastic surgeons, oncologist, radiologist and pathologist, who jointly discussed and formulated the &#x0201c;expert consensus on oncoplastic surgery of breast tumor and breast reconstruction (2022 edition)&#x0201d; on the basis of the 2018 edition. In the 2022 version, endoscopic breast reconstruction, prepectoral breast reconstruction and case management of breast reconstruction were added. Besides, the original nipple-sparing mastectomy chapter was replaced by conservative mastectomy. The consensus also elaborated the prepectoral breast reconstruction and deep inferior epigastric artery perforator flap (DIEP) surgery. It is believed that this update will help hospitals at all levels to improve the ability of oncoplastic surgery and breast reconstruction, improve the standardization of treatment, optimize the treatment outcome, and ultimately improve patient satisfaction.  
      关键词:Breast cancer;Oncoplastic surgery;Breast reconstruction;Expert consensus   
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