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Wang HN, An JH, Zong L. Estimating prognosis of gastric neuroendocrine neoplasms using machine learning: A step towards precision medicine. World J Gastrointest Oncol 2024; 16:4548-4552. [PMID: 39678793 PMCID: PMC11577357 DOI: 10.4251/wjgo.v16.i12.4548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/05/2024] [Accepted: 08/12/2024] [Indexed: 11/12/2024] Open
Abstract
Survival rates following radical surgery for gastric neuroendocrine neoplasms (g-NENs) are low, with high recurrence rates. This fact impacts patient prognosis and complicates postoperative management. Traditional prognostic models, including the Cox proportional hazards (CoxPH) model, have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients. Machine learning methods offer a unique opportunity to analyze complex relationships within datasets, providing tools and methodologies to assess large volumes of high-dimensional, multimodal data generated by biological sciences. These methods show promise in predicting outcomes across various medical disciplines. In the context of g-NENs, utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies. This editorial reviews a study exploring the advantages and effectiveness of the random survival forest (RSF) model, using the lymph node ratio (LNR), in predicting disease-specific survival (DSS) in postoperative g-NEN patients stratified into low-risk and high-risk groups. The findings demonstrate that the RSF model, incorporating LNR, outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.
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Affiliation(s)
- Hong-Niu Wang
- Graduate School of Medicine, Changzhi Medical College, Changzhi 046000, Shanxi Province, China
| | - Jia-Hao An
- Graduate School of Medicine, Changzhi Medical College, Changzhi 046000, Shanxi Province, China
| | - Liang Zong
- Department of Gastrointestinal Surgery, Changzhi People’s Hospital, Changzhi 046000, Shanxi Province, China
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Liu W, Wu HY, Lin JX, Qu ST, Gu YJ, Zhu JZ, Xu CF. Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients. World J Gastrointest Oncol 2024; 16:3507-3520. [PMID: 39171165 PMCID: PMC11334026 DOI: 10.4251/wjgo.v16.i8.3507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/14/2024] [Accepted: 06/12/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Lymph node ratio (LNR) was demonstrated to play a crucial role in the prognosis of many tumors. However, research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm (NEN) patients was limited. AIM To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models. METHODS A total of 286 patients from the Surveillance, Epidemiology, and End Results database were divided into the training set and validation set at a ratio of 8:2. 92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set. Cox regression analysis was used to explore the relationship between LNR and disease-specific survival (DSS) of gastric NEN patients. Random survival forest (RSF) algorithm and Cox proportional hazards (CoxPH) analysis were applied to develop models to predict DSS respectively, and compared with the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging. RESULTS Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death. The RSF model exhibited the best performance in predicting DSS, with the C-index in the test set being 0.769 [95% confidence interval (CI): 0.691-0.846] outperforming the CoxPH model (0.744, 95%CI: 0.665-0.822) and the 8th edition AJCC TNM staging (0.723, 95%CI: 0.613-0.833). The calibration curves and decision curve analysis (DCA) demonstrated the RSF model had good calibration and clinical benefits. Furthermore, the RSF model could perform risk stratification and individual prognosis prediction effectively. CONCLUSION A higher LNR indicated a lower DSS in postoperative gastric NEN patients. The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set, showing potential in clinical practice.
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Affiliation(s)
- Wen Liu
- Department of Gastroenterology, Changzhou Hospital of Traditional Chinese Medicine, Changzhou 213000, Jiangsu Province, China
| | - Hong-Yu Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Jia-Xi Lin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Shu-Ting Qu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Yi-Jie Gu
- Department of Gastroenterology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou 215200, Jiangsu Province, China
| | - Jin-Zhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Chun-Fang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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Zi M, Ma Y, Chen J, Pang C, Li X, Yuan L, Liu Z, Yu P. Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis. Cancer Med 2024; 13:e7011. [PMID: 38457192 PMCID: PMC10922030 DOI: 10.1002/cam4.7011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/29/2023] [Accepted: 01/31/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVE This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.
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Affiliation(s)
- Mengli Zi
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Yubo Ma
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Jinxia Chen
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Chuhong Pang
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Xiao Li
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Li Yuan
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Zhuo Liu
- Department of Colorectum surgeryZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
| | - Pengfei Yu
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
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Abstract
Purpose of Review Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach cancer. The three main subtypes have different pathogeneses, biological behaviours and clinical characteristics, so they require different management strategies. This article will provide an overview of g-NENs and highlight recent advances in the field. Recent Findings Molecular profiling has revealed differences between indolent and aggressive g-NENs, as well as a new somatic mutation responsible for some familial type I g-NENs. Novel biomarkers have been developed which will hopefully improve diagnosis, treatment, risk stratification and follow-up. Patient treatment is also changing, as evidence supports the use of less aggressive options (e.g. endoscopic surveillance or resection) in some patients with more indolent tumours. Summary g-NEN heterogeneity poses challenges in understanding and managing this rare disease. More basic science research is needed to investigate molecular pathogenesis, and future larger clinical studies will hopefully also further improve treatment and patient outcomes.
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Li X, Shao L, Lu X, Yang Z, Ai S, Sun F, Wang M, Guan W, Liu S. Risk factors for lymph node metastasis in gastric neuroendocrine tumor: a retrospective study. BMC Surg 2021; 21:174. [PMID: 33789664 PMCID: PMC8011070 DOI: 10.1186/s12893-021-01174-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 03/23/2021] [Indexed: 12/15/2022] Open
Abstract
Background Lymph node metastasis (LNM) plays a vital role in the determination of clinical outcomes in patients with gastric neuroendocrine tumor (G-NET). Preoperative identification of LNM is helpful for intraoperative lymphadenectomy. This study aims to investigate risk factors for LNM in patients with G-NET. Methods We performed a retrospective study involving 37 patients in non-LNM group and 82 patients in LNM group. Data of demographics, preoperative lab results, clinical–pathological results, surgical management, and postoperative situation were compared between groups. Significant parameters were subsequently entered into logistic regression for further analysis. Results Patients in LNM group exhibited older age (p = 0.011), lower preoperative albumin (ALB) (p = 0.003), higher carcinoembryonic antigen (CEA) (p = 0.020), higher International normalized ratio (p = 0.034), longer thrombin time (p = 0.018), different tumor location (p = 0.005), higher chromogranin A positive rate (p = 0.045), and higher Ki-67 expression level (p = 0.002). Logistic regression revealed ALB (p = 0.043), CEA (p = 0.032), tumor location (p = 0.013) and Ki-67 (p = 0.041) were independent risk factors for LNM in G-NET patients. Conclusions ALB, CEA, tumor location, and Ki-67 expression level correlate with the risk of LNM in patients with G-NET.
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Affiliation(s)
- Xianghui Li
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Lihua Shao
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Xiaofeng Lu
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Zhengyang Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Shichao Ai
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Feng Sun
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Meng Wang
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China.
| | - Wenxian Guan
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China.
| | - Song Liu
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China.
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Xiao C, Song B, Yi P, Xie Y, Li B, Lian P, Ding S, Lu Y. Deaths of colon neuroendocrine tumors are associated with increasing metastatic lymph nodes and lymph node ratio. J Gastrointest Oncol 2020; 11:1146-1154. [PMID: 33456989 PMCID: PMC7807263 DOI: 10.21037/jgo-20-444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 11/25/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Colon neuroendocrine tumors (NETs) are uncommon. Currently, the impact of the number of metastatic lymph nodes (LNs) and lymph node ratio (LNR) on survival has been well investigated in other colon malignancies, but both remain nebulous for patients with colon NETs. METHODS Surgically resected patients with histologically proven nonmetastatic colon NETs were queried from the Surveillance, Epidemiology, and End Results database between 1988 and 2011. Patients with lymph nodes involved were investigated and categorized into four LNs-based classifications (≤4, >4-10, >10-13, and >13) or three LNR-based subgroups (≤0.51, >0.51-0.71, and >0.71) according to the threshold, determined by Harrell's C statistic. Univariate and multivariate survival analyses were performed by log-rank test and Cox stepwise regression analysis, respectively. RESULTS Eight hundred fifty-one patients met the inclusion criteria. Among them, higher LNR and LNs classification are associated with a worse prognosis. The 10-year NETs-specific survival rate was 78.3% (74.2-82.6%), 61.3% (52.4-71.7%), 40.8% (20.7-80.7%) for patients in the ≤4, >4-10, and 10-13 LNs groups, respectively. When patients were classified with LNR, the observed 10-year NETs-specific survival rate was 79.9% (74.8-85.5%) for ≤0.51, 57.4% (43.8-75.2%) for >0.51-0.71, and 40.0% (31.0-51.5%) for >0.71. In stratified analysis, higher LNs and LNR groups have worse prognosis only in patients with advanced T stage (T3-T4). Regarding stage migration, the LNR-based system did not show superiority to LNs-based classification. CONCLUSIONS Current TNM staging classification could be improved by considering the count of metastatic nodes and LNR instead of a simple record of lymph node status (N1 or N0) for colon NETs.
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Affiliation(s)
- Changchun Xiao
- Department of General Surgery, Shanghai Electric Power Hospital, Shanghai, China
| | - Baorong Song
- Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Peipei Yi
- Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, China
| | - Yangyang Xie
- Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Biqing Li
- Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Peng Lian
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shaoqing Ding
- Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Yuanming Lu
- Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, China
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Zhao YJ, Zhuang LP, Liu YY, Chen RC, Zhang J, Zhu HX, Wang YC, You H, Zhang MW, He XY. Comparative study of laparoscopic versus open radical gastrectomy in advanced gastric neuroendocrine carcinoma: Analysis from a high-volume institution. Asian J Surg 2020; 43:488-496. [DOI: 10.1016/j.asjsur.2019.07.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 06/26/2019] [Accepted: 07/19/2019] [Indexed: 12/23/2022] Open
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Lu J, Zhao YJ, Zhou Y, He Q, Tian Y, Hao H, Qiu X, Jiang L, Zhao G, Huang CM. Modified staging system for gastric neuroendocrine carcinoma based on American Joint Committee on Cancer and European Neuroendocrine Tumor Society systems. Br J Surg 2020; 107:248-257. [PMID: 31971627 DOI: 10.1002/bjs.11408] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/04/2019] [Accepted: 10/01/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognostic values of the AJCC staging system for gastric cancer (GC-AJCC), the AJCC staging system for gastric neuroendocrine tumours (NET-AJCC) and the European Neuroendocrine Tumor Society (ENETS) system for gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma (MA)NEC remain controversial. METHODS Data on patients with (MA)NEC from 21 centres in China were analysed. Different staging systems were evaluated by performing Kaplan-Meier survival analysis and calculating the concordance index (C-index) and Akaike information criterion (AIC). Based on three existing systems, a modified staging system (mTNM) was developed. RESULTS A total of 871 patients were included. In the GC-AJCC system, an overlap was noticed for pT2 and pT3 categories. Patients with stage IIIC disease had a similar prognosis to those with stage IV disease. The pT categories of the NET-AJCC system had a lower C-index and higher AIC than those of the other systems. In the ENETS system, there was a low proportion (0·2 per cent) of patients with stage IIIA and a high proportion (67·6 per cent) of stage IIIB disease. The mTNM system adopted the NET-AJCC pT and GC-AJCC pN and pM definitions, and was developed based on the ENETS stage definitions. The proportion of patients in each stage was better distributed and the mTNM system showed improved prognostic performance in predicting overall and disease-free survival. CONCLUSION The mTNM system offers more accurate prognostic value for gastric (MA)NEC than the AJCC or ENETS staging systems.
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Affiliation(s)
- J Lu
- Departments of Gastric Surgery
- General Surgery, Fujian Medical University Union Hospital
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer
- Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University
| | - Y J Zhao
- Department of Gastrointestinal Surgery, West District of the First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei
| | - Y Zhou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao
| | - Q He
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou
| | - Y Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
| | - H Hao
- Department of General Surgery, Huashan Hospital, Fudan University
| | - X Qiu
- Department of Gastrointestinal Surgery and Gastrointestinal Surgery Research Institute, Affiliated Hospital of Putian University, Putian
| | - L Jiang
- Department of Gastrointestinal Surgery, Yan Tai Yu Huang Ding Hospital, Yantai, China
| | - G Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiaotong University, Shanghai
| | - C-M Huang
- Departments of Gastric Surgery
- General Surgery, Fujian Medical University Union Hospital
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer
- Fujian Key Laboratory of Tumour Microbiology, Fujian Medical University
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Yan S, Liu T, Li Y, Zhu Y, Jiang J, Jiang L, Zhao H. Value of computed tomography evaluation in pathologic classification and prognosis prediction of gastric neuroendocrine tumors. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:545. [PMID: 31807527 DOI: 10.21037/atm.2019.09.114] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background The study aims to investigate the correlation of CT characteristics with pathological classifications and the prognostic value of CT features in patients with gastric neuroendocrine neoplasms (g-NENs). Methods Ninety-one cases of pathologically diagnosed g-NENs, including 15 cases of well-differentiated neuroendocrine tumors (NETs) (G1 and G2) and 76 cases of poor-differentiated neuroendocrine carcinomas (NECs) (G3 and MANEC) were retrospectively studied. All cases were included in correlation analysis of CT characteristics with pathologic grades. Among them, 76 patients who had fulfilled follow-up data were included for overall survival (OS) and disease-free survival (DFS) analysis. Results CT characteristics that favor poor differentiation include tumor location (fundus and cardia), larger tumor size (>3.0 cm), infiltrative growth, unclear tumor margin, serosa involvement, ulceration and lymph node metastasis (P<0.05). Most variables had sensitivities >80% and specificities >60% to distinguish NECs from NETs. Through log-rank analysis, it was revealed that serosa involvement, cystic degeneration, necrosis, heterogeneous enhancement and lymph node metastasis led to worse DFS and OS for patients with g-NENs (P<0.05). COX regression analysis showed that serosa involvement and lymph node metastasis were independent risk factor for DFS and OS, respectively, despite of grading, staging and therapeutic choices (P<0.05). Moreover, high Ki-67 index (>55%) in G3 g-NENs is in correlation with serosa involvement and lymph node metastasis; accordingly, patients with higher Ki-67 index had worse 1-year DFS (61.7% vs. 92.3%; P<0.05). Conclusions CT characteristics can be useful discriminators and prognostic factors for g-NENs and may help identify G3 g-NEC from G3 g-NEN by revealing its poor differentiation and high invasive potential.
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Affiliation(s)
- Shida Yan
- Department of Hepatobiliary Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Tongtong Liu
- Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Ying Li
- Department of Radiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yongjian Zhu
- Department of Radiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jun Jiang
- Department of Radiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Liming Jiang
- Department of Radiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Chen L, Qian K, Guo K, Zheng X, Sun W, Sun T, Wang Y, Li D, Wu Y, Ji Q, Wang Z. A Novel N Staging System for Predicting Survival in Patients with Medullary Thyroid Cancer. Ann Surg Oncol 2019; 26:4430-4438. [DOI: 10.1245/s10434-019-07871-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Indexed: 12/13/2022]
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Felder S, Jann H, Arsenic R, Denecke T, Prasad V, Knappe-Drzikova B, Maasberg S, Wiedenmann B, Pavel M, Pascher A, Pape UF. Gastric neuroendocrine neoplasias: manifestations and comparative outcomes. Endocr Relat Cancer 2019; 26:751-763. [PMID: 31272081 PMCID: PMC6686747 DOI: 10.1530/erc-18-0582] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 07/04/2019] [Indexed: 12/15/2022]
Abstract
Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analysed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification was gNEN-1 (n = 86/60.6%), gNEN-2 (n = 7/4.9%), gNEN-3 (n = 24/16.9%) and gNEN-4 (n = 25/17.6%), while hypergastrinemia-associated gNEN-1 and -2 were all low-grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification, OS differed for early and advanced stages, while WHO grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs -4).
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Affiliation(s)
- S Felder
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - H Jann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - R Arsenic
- Institut für Pathologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - T Denecke
- Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - V Prasad
- Klinik für Nuklearmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Nuklearmedizin, Universitätklinikum Ulm, Ulm, Germany
| | - B Knappe-Drzikova
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - S Maasberg
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
| | - B Wiedenmann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - M Pavel
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum der Friedrich-Alexander Universität Erlangen, Erlangen, Germany
| | - A Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uinversitätsklinikum Münster, Münster, Germany
| | - U F Pape
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
- Correspondence should be addressed to U F Pape:
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Further Classification for Node-Positive Gastric Neuroendocrine Neoplasms. J Gastrointest Surg 2019; 23:720-729. [PMID: 29951901 DOI: 10.1007/s11605-018-3845-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 06/13/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND For gastric neuroendocrine neoplasms (GNEN), the current AJCC lymph node (N) stage classifies patients into N0/N1 disease (with/without locoregional nodal metastases); however, this does not account for the number of involved nodes. The objective of this study was to evaluate the prognostic significance of the number of involved locoregional nodes among resected GNEN. METHODS The National Cancer Database (2004-2014) was queried for GNEN patients who had undergone partial/total gastrectomy with known nodal status. Nearest-neighborhood grouping was used to identify survival clusters by number of metastatic nodes and to use these groupings to construct a new N classification (pN). External validation was performed using the SEER database. Kaplan-Meier analysis and Cox regression models were used to assess the prognostic strength of the pN classification. RESULTS One thousand two hundred seventy-five patients met study inclusion criteria. Patients with 1-6 positive nodes (pN1) demonstrated a distinct survival pattern from patients with > 6 positive nodes (pN2) as well as those with no positive nodes (N0) {5-year OS N0: 80% (95% CI 77-83%) vs. 65% (95% CI 61-69%) vs. 43% (95% CI 33-53%), p < 0.001}. On external validation, the pN classification demonstrated strong discriminatory ability for survival {5-year OS N0: 70% (95% CI 65-75%) vs. pN1:53% (95% CI 46-59%) vs. pN2:18% (95% CI 9-29%), p < 0.001}. On multivariable analysis, the pN classification remained an independent predictor of OS. CONCLUSIONS The number of metastatic lymph nodes is an independent prognostic factor in GNEN. Current AJCC N1 disease contains two groups of patients with distinctive prognoses, hence needs to be subclassified into pN1 (1-6 positive lymph nodes) and pN2 (> 6 positive nodes).
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Xie JW, Li P, Wang JB, Lin JX, Lu J, Chen QY, Yang YH, Kang DY, Zheng CH, Huang CM. Modified AJCC staging of gastric neuroendocrine carcinoma based on T staging can improve the capacity of prognosis assessment. J Cancer Res Clin Oncol 2018; 144:2391-2397. [PMID: 30209612 DOI: 10.1007/s00432-018-2750-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 09/08/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND OR PURPOSE This study was designed to determine the value of AJCC staging 7th edition and improved AJCC staging in assessing the prognosis of gastric neuroendocrine carcinoma (GNEC). METHODS In total, GNEC 475 patients in the Surveillance, Epidemiology, and End Results (SEER) database and 129 GNEC patients in our department undergoing resection were included. The former served as the test group, and the latter served as the validation group. Those with stage IIIb disease were allocated into four subgroups, and improved AJCC staging was established. The AIC and C indices were used to evaluate the capacities of different TNM staging. RESULTS Significant overlap between stages IIIb and IIIa in both the test and validation groups was found. In the test group, T staging and age at disease diagnosis were independent prognostic factors for patients with stage IIIb. Stage IIIb was divided into T1N1, T2N1, T3N1 and T4N1, and the improved AJCC staging-mTNM staging was created. In mTNM staging, the IIIb survival curve did not cross those of stages IIIa and IIb, which had a smaller AIC (2490 vs. 2507) value and larger C index (0.7624 vs. 0.7450, P = 0.228). Similar results were obtained for the validation group. CONCLUSION T stage was an independent factor influencing the prognosis of stage IIIb GNEC patients, and the improved AJCC staging proposed here has good prognostic value.
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Affiliation(s)
- Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ying-Hong Yang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China
| | - De-Yong Kang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
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Yamashita K, Hosoda K, Ema A, Watanabe M. Lymph node ratio as a novel and simple prognostic factor in advanced gastric cancer. Eur J Surg Oncol 2016; 42:1253-60. [PMID: 27017273 DOI: 10.1016/j.ejso.2016.03.001] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Revised: 01/02/2016] [Accepted: 03/01/2016] [Indexed: 12/14/2022] Open
Abstract
TNM staging is no doubt the most critical prognostic factors, representing tumor (T)/lymph node metastasis (N)/distant metastasis (M) in gastric cancer. Lymph node ratio-based N system (Nr) has been repeatedly reported to be of prognostic relevance in advanced gastric cancer independent of stage in the multivariate analysis world-wide, and proposed as more sophisticated than N with regard to predicting accurate prognosis. As a result, proposed TNrM system may predict survival more accurately than the present TNM staging system for patients undergoing limited lymph node analysis. It could adjust stage migration when the lymph node number was used as staging factor. Although correlation of the number of metastatic lymph nodes and lymph node ratio is obvious, biological characteristics other than that could also have been reflected on. It may indicate how successful the operation of lymph node dissection was, or it may be revealing the potential of the patient's lymph node immune-reaction. Recently, high lymph node ratio is closely associated with EGFR expression in advanced gastric cancer. When efficiency of applying lymph node ratio as a biomarker is verified and confirmed in an expansive research, and when cancer causing molecules are identified, as well as the competence as a treatment target is studied, the new biomarker, namely, lymph node ratio, could find itself in a limelight in gastric cancer treatment in the future.
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Affiliation(s)
- K Yamashita
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kangawa 252-0374, Japan.
| | - K Hosoda
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kangawa 252-0374, Japan
| | - A Ema
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kangawa 252-0374, Japan
| | - M Watanabe
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kangawa 252-0374, Japan
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Yu X, Yao L, Di Y, He H, Li X, Zhang C, Fu D, Jin C, Li J. Application of Deuteporfin in the Metastatic Lymph Node Mapping of Pancreatic Cancer: An in vivo Study. Photochem Photobiol 2016; 92:325-330. [PMID: 26833269 DOI: 10.1111/php.12574] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 01/14/2016] [Indexed: 12/15/2022]
Abstract
For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650-700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (P < 0.05). Our research confirmed this targeting property of deuteporfin using in vivo fluorescent imaging. Consistent with observations from in vivo imaging experiments, frozen sections of metastatic lymph nodes intuitively displayed significantly higher and wider distributions of deuteporfin than normal sections.
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Affiliation(s)
- Xinzhe Yu
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
| | - Lie Yao
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
| | - Yang Di
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
| | - Hang He
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaoxia Li
- Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai, China
| | - Chun Zhang
- Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai, China
| | - Deliang Fu
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
| | - Chen Jin
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
| | - Ji Li
- Pancreatic Surgery Department, Huashan Hospital, Fudan University, Shanghai, China
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