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Xu G, Feng F, Chen W, Xiao Y, Fu Y, Zhou S, Duan S, Li M. Development and External Validation of a CT-Based Radiomics Nomogram to Predict Perineural Invasion and Survival in Gastric Cancer: A Multi-institutional Study. Acad Radiol 2025; 32:120-131. [PMID: 39127522 DOI: 10.1016/j.acra.2024.07.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 07/20/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024]
Abstract
RATIONALE AND OBJECTIVES To develop and validate a radiomics nomogram utilizing CT data for predicting perineural invasion (PNI) and survival in gastric cancer (GC) patients. MATERIALS AND METHODS A retrospective analysis of 408 GC patients from two institutions: 288 patients from Institution I were divided 7:3 into a training set (n = 203) and a testing set (n = 85); 120 patients from Institution II served as an external validation set. Radiomics features were extracted and screened from CT images. Independent radiomics, clinical, and combined models were constructed to predict PNI. Model discrimination, calibration, clinical utility, and prognostic significance were evaluated using area under the curve (AUC), calibration curves, decision curves analysis, and Kaplan-Meier curves, respectively. RESULTS 15 radiomics features and three clinical factors were included in the final analysis. The AUCs of the radiomics model in the training, testing, and external validation sets were 0.843 (95% CI: 0.788-0.897), 0.831 (95% CI: 0.741-0.920), and 0.802 (95% CI: 0.722-0.882), respectively. A nomogram was developed by integrating significant clinical factors with radiomics features. The AUCs of the nomogram in the training, testing, and external validation sets were 0.872 (95% CI: 0.823-0.921), 0.862 (95% CI: 0.780-0.944), and 0.837 (95% CI: 0.767-0.908), respectively. Survival analysis revealed that the nomogram could effectively stratify patients for recurrence-free survival (Hazard Ratio: 4.329; 95% CI: 3.159-5.934; P < 0.001). CONCLUSION The radiomics-derived nomogram presented a promising tool for predicting PNI in GC and held significant prognostic implications. IMPORTANT FINDINGS The nomogram functioned as a non-invasive biomarker for determining the PNI status. The predictive performance of the nomogram surpassed that of the clinical model (P < 0.05). Furthermore, patients in the high-risk group stratified by the nomogram had a significantly shorter RFS (P < 0.05).
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Affiliation(s)
- Guodong Xu
- Department of Radiology, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224006, Jiangsu Province, China
| | - Feng Feng
- Department of Radiology, Affiliated Tumor Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wang Chen
- Department of Radiology, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224006, Jiangsu Province, China
| | - Yong Xiao
- Department of Radiology, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224006, Jiangsu Province, China
| | - Yigang Fu
- Department of Radiology, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224006, Jiangsu Province, China
| | - Siyu Zhou
- Department of Radiology, Affiliated Tumor Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | | | - Manman Li
- Department of Radiology, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224006, Jiangsu Province, China.
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Cong R, Xu R, Ming J, Zhu Z. Construction of a preoperative nomogram model for predicting perineural invasion in advanced gastric cancer. Front Med (Lausanne) 2024; 11:1344982. [PMID: 38912337 PMCID: PMC11190154 DOI: 10.3389/fmed.2024.1344982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 05/24/2024] [Indexed: 06/25/2024] Open
Abstract
Objective This study aimed to develop and validate a clinical and imaging-based nomogram for preoperatively predicting perineural invasion (PNI) in advanced gastric cancer. Methods A retrospective cohort of 351 patients with advanced gastric cancer who underwent surgical resection was included. Multivariable logistic regression analysis was conducted to identify independent risk factors for PNI and to construct the nomogram. The performance of the nomogram was assessed using calibration curves, the concordance index (C-index), the area under the curve (AUC), and decision curve analysis (DCA). The disparity in disease-free survival (DFS) between the nomogram-predicted PNI-positive group and the nomogram-predicted PNI-negative group was evaluated using the Log-Rank test and Kaplan-Meier analysis. Results Extramural vascular invasion (EMVI), Borrmann classification, tumor thickness, and the systemic inflammation response index (SIRI) emerged as independent risk factors for PNI. The nomogram model demonstrated a commendable AUC value of 0.838. Calibration curves exhibited excellent concordance, with a C-index of 0.814. DCA indicated that the model provided good clinical net benefit. The DFS of the nomogram-predicted PNI-positive group was significantly lower than that of the nomogram-predicted PNI-negative group (p < 0.001). Conclusion This study successfully developed a preoperative nomogram model that not only effectively predicted PNI in gastric cancer but also facilitated postoperative risk stratification.
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Affiliation(s)
- Ruochen Cong
- Department of Radiology, Nantong No. 1 People’s Hospital, Nantong, China
| | - Ruonan Xu
- Department of Radiology, Nantong No. 6 People’s Hospital, Nantong, China
| | - Jialei Ming
- Department of Radiology, Nantong No. 1 People’s Hospital, Nantong, China
| | - Zhengqi Zhu
- Department of Radiology, Nantong City Cancer Hospital, Nantong, China
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Li J, Wang Y, Zhang HK, Xu SN, Chen XJ, Qu JR. The value of intravoxel incoherent motion diffusion-weighted imaging in predicting perineural invasion for resectable gastric cancer: a prospective study. Clin Radiol 2024; 79:e65-e72. [PMID: 37833144 DOI: 10.1016/j.crad.2023.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 10/15/2023]
Abstract
AIM To investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted imaging to predict perineural invasion (PNI) preoperatively in resectable gastric cancer (GC). MATERIALS AND METHODS This study prospectively recruited 85 surgically resected GC patients (58 men, 27 women) aged 60.87 ± 10.17 (39-81) years, who underwent IVIM sequence within 1 week before surgery. According to histopathological PNI diagnoses, patients were divided into PNI positive and negative groups. Conventional apparent diffusion coefficient (ADC) and the IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D∗), and pseudodiffusion fraction (f), were compared between the two groups. Morphological MRI features were also analysed. Multivariate logistic regression was used to screen independent predictors of PNI. Receiver-operating characteristic curve analyses were preformed to evaluate the efficacy. Spearman's correlation test was performed to analyse the relationship between MRI parameters and PNI. RESULTS Tumour thickness and f in PNI-positive group were higher, whereas the ADC, D were lower than those in PNI-negative group (p<0.05). These four parameters correlated with PNI (p<0.05). The D, f, and tumour thickness were independent predictors of PNI. The area under the curve of ADC, D, f, thickness, and the combined parameter (D + f + thickness) were 0.648, 0.745, 0.698, 0.725, and 0.869, respectively. The combined parameter demonstrated higher efficacy than any other parameters (p<0.05). CONCLUSION The ADC, D, and f can effectively distinguish PNI status in GC. The D, f, and thickness were independent predictors of PNI.
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Affiliation(s)
- J Li
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127, Dongming Road, Zhengzhou 450008, Henan, China.
| | - Y Wang
- Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127, Dongming Road, Zhengzhou 450008, Henan, China
| | - H-K Zhang
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127, Dongming Road, Zhengzhou 450008, Henan, China
| | - S-N Xu
- Department of Digestive Oncology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127, Dongming Road, Zhengzhou 450008, Henan, China
| | - X-J Chen
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127, Dongming Road, Zhengzhou 450008, Henan, China
| | - J-R Qu
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127, Dongming Road, Zhengzhou 450008, Henan, China.
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Wang L, Xia Y, Jiang T, Li Y, Shen Y, Lin J, Li F, Wang W, Zhang D, Xu H, Yang L, Xu Z. Neural Invasion is an Independent Prognostic Factor in Young and Lymph Node Negative Gastric Cancer Patients Underwent Curative Gastrectomy. J INVEST SURG 2023; 36:2257785. [PMID: 37731247 DOI: 10.1080/08941939.2023.2257785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 09/06/2023] [Indexed: 09/22/2023]
Abstract
BACKGROUND The prognostic significance of neural invasion (NI) in gastric cancer (GC) has not been established. This study is to investigate the characteristic and prognostic value of NI in GC. METHODS 592 patients who had undergone gastrectomy for GC were retrospectively analyzed. NI was defined when cancer cells infiltrated into the perineurium or neural fascicles by hematoxylin and eosin staining of surgical specimens. NI and the other clinical factors were analyzed. RESULTS NI was detected in 270 of the 592 patients. NI was associated with tumor size, site, depth of invasion, lymph node metastasis, TNM stage, D dissection, tumor differentiation, Lauren classification, and blood vessel invasion. NI was associated with the overall survival. Multivariate analysis indicated that NI was not an independent prognostic factor for total patients, while NI independently predicted prognosis for age < 60 and lymph node metastasis negative patients by subgroup analysis. Concomitant existence of NI with tumor size ≥3cm, TNM stage III, or diffused Lauren classification independently predicted prognosis. CONCLUSIONS The frequency of NI is high in GC patients and increases with disease progression. NI is related to poor survival in GC patients who underwent curative gastrectomy and provides independent prognostic value for young and lymph node metastasis negative patients.
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Affiliation(s)
- Linjun Wang
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yiwen Xia
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tianlu Jiang
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ying Li
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yikai Shen
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jie Lin
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fengyuan Li
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weizhi Wang
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Diancai Zhang
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Xu
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Li Yang
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zekuan Xu
- Division of Gastric Surgery, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Muduly DK, Kar M, Sultania M, Shahin M, Patra S, Singh V, Imaduddin M, Mohakud S, Nayak HK, Panigraphi MK, Das Majumdar SK, Parida DK. Inclusion of Perineural Invasion with AJCC-TNM Staging: Outcomes from a South Asian Cohort of Curatively Treated Gastric Cancer Patients. J Gastrointest Cancer 2023; 54:606-613. [PMID: 35749055 DOI: 10.1007/s12029-022-00838-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND The incidence of perineural invasion (PNI) in patients with gastric cancer (GC) is high, and patients with PNI positive disease have a poor prognosis compared to PNI-negative disease. The present study aims to study the incidence and evaluate the impact of PNI on the survival outcome of a cohort of South Asian GC patients. MATERIAL AND METHODS All consecutive patients undergoing curative gastrectomy were included in the study. The incidence of PNI and correlation with different clinico-pathological features and overall survival was performed. RESULTS A total of 59.54% had PNI-positive disease and the median OS of PNI + ve patients was 29.3 months, while it was not reached in PNI-ve patients. The PNI positivity was a significant prognostic factor for overall survival both on univariate and multivariate analysis. On TNM-PNI staging, those with TNM stage I/II patients with PNI + ve disease had similar OS to all stage III patients (p = 0.835) and were worse than that of PNI-ve patients (p < 0.05). CONCLUSION The incidence of PNI in gastric cancer is high. The inclusion of PNI with AJCC-TNM staging may better stratify prognostic staging in curatively treated gastric cancer patients.
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Affiliation(s)
- Dillip Kumar Muduly
- Department of Surgical Oncology, All India Institute of Medical Sciences, Bhubaneswar, India.
| | - Madhabananda Kar
- Department of Surgical Oncology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Mahesh Sultania
- Department of Surgical Oncology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Mohammed Shahin
- Department of Pathology & Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Susama Patra
- Department of Pathology & Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Vishwajeet Singh
- Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Mohammed Imaduddin
- Department of Surgical Oncology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Sudipta Mohakud
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Hemant Kumar Nayak
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Manas Kumar Panigraphi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, India
| | | | - Dilip Kumar Parida
- Department of Radiotherapy, All India Institute of Medical Sciences, Bhubaneswar, India
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Li J, Xu S, Wang Y, Fang M, Ma F, Xu C, Hailiang L. Spectral CT-based nomogram for preoperative prediction of perineural invasion in locally advanced gastric cancer: a prospective study. Eur Radiol 2023:10.1007/s00330-023-09464-9. [PMID: 36826503 DOI: 10.1007/s00330-023-09464-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/15/2022] [Accepted: 01/22/2023] [Indexed: 02/25/2023]
Abstract
OBJECTIVES This work focused on developing and validating the spectral CT-based nomogram to preoperatively predict perineural invasion (PNI) for locally advanced gastric cancer (LAGC). METHODS This work prospectively included 196 surgically resected LAGC patients (139 males, 57 females, 59.55 ± 11.97 years) undergoing triple enhanced spectral CT scans. Patients were labeled as perineural invasion (PNI) positive and negative according to pathologic reports, then further split into primary (n = 130) and validation cohort (n = 66). We extracted clinicopathological information, follow-up data, iodine concentration (IC), and normalized IC values against to aorta (nICs) at arterial/venous/delayed phases (AP/VP/DP). Clinicopathological features and IC values between PNI positive and negative groups were compared. Multivariable logistic regression was performed to screen independent risk factors of PNI. Then, a nomogram was established, and its capability was determined by ROC curves. Its clinical use was evaluated by decision curve analysis. The correlations of PNI and the nomogram with patients' survival were explored by log-rank survival analysis. RESULTS Borrmann classification, tumor thickness, and nICDP were independent predictors of PNI and used to build the nomogram. The nomogram yielded higher AUCs of 0.853 (0.744-0.928) and 0.782 (0.701-0.850) in primary and validation cohorts than any other parameters (p < 0.05). Both PNI and the nomogram were related to post-surgical treatment planning. Only PNI was associated with disease-free survival in the primary cohort (p < 0.05). CONCLUSION This work prospectively established a spectral CT-based nomogram, which can effectively predict PNI preoperatively and potentially guide post-surgical treatment strategy in LAGC. KEY POINTS • The present prospective study established a spectral CT-based nomogram for preoperative prediction of perineural invasion in LAGC. • The proposed nomogram, including morphological features and the quantitative iodine concentration values from spectral CT, had the potential to predict PNI for LAGC before surgery, along with guide post-surgical treatment planning. • Normalized iodine concentration at the delayed phase was the most valuable quantitative parameter, suggesting the importance of delayed enhancement in gastric CT.
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Affiliation(s)
- Jing Li
- Department of Radiology, the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127 Dongming Road, Zhengzhou, 450008, Henan, China
| | - Shuning Xu
- Department of Gastrointestinal Oncology, the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, Henan, China
| | - Yi Wang
- Department of Pathology, the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, Henan, China
| | - Mengjie Fang
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Fei Ma
- Department of Gastrointestinal Surgery, the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, Henan, China
| | - Chunmiao Xu
- Department of Radiology, the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127 Dongming Road, Zhengzhou, 450008, Henan, China
| | - Li Hailiang
- Department of Radiology, the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), No. 127 Dongming Road, Zhengzhou, 450008, Henan, China.
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Nerves in gastrointestinal cancer: from mechanism to modulations. Nat Rev Gastroenterol Hepatol 2022; 19:768-784. [PMID: 36056202 DOI: 10.1038/s41575-022-00669-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/20/2022] [Indexed: 12/08/2022]
Abstract
Maintenance of gastrointestinal health is challenging as it requires balancing multifaceted processes within the highly complex and dynamic ecosystem of the gastrointestinal tract. Disturbances within this vibrant environment can have detrimental consequences, including the onset of gastrointestinal cancers. Globally, gastrointestinal cancers account for ~19% of all cancer cases and ~22.5% of all cancer-related deaths. Developing new ways to more readily detect and more efficiently target these malignancies are urgently needed. Whereas members of the tumour microenvironment, such as immune cells and fibroblasts, have already been in the spotlight as key players of cancer initiation and progression, the importance of the nervous system in gastrointestinal cancers has only been highlighted in the past few years. Although extrinsic innervations modulate gastrointestinal cancers, cells and signals from the gut's intrinsic innervation also have the ability to do so. Here, we shed light on this thriving field and discuss neural influences during gastrointestinal carcinogenesis. We focus on the interactions between neurons and components of the gastrointestinal tract and tumour microenvironment, on the neural signalling pathways involved, and how these factors affect the cancer hallmarks, and discuss the neural signatures in gastrointestinal cancers. Finally, we highlight neural-related therapies that have potential for the management of gastrointestinal cancers.
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Li C, Wang M, Cheng X, Jiang Y, Xiao H. Nerve invasion as an independent predictor of poor prognosis in gastric cancer after curative resection. Medicine (Baltimore) 2022; 101:e30084. [PMID: 35984131 PMCID: PMC9387962 DOI: 10.1097/md.0000000000030084] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The study aims to reveal the clinical significance of perineural invasion (PNI) for gastric cancer prognosis and determine the risk factors of PNI in gastric cancer. This study retrospectively analyzed 350 patients who were diagnosed with GC and underwent curative surgical resection. Variables used to analyze survival included gender, age, degree of differentiation, T classification, lymph node metastasis, lymphovascular invasion, nerve invasion, mucinous adenocarcinoma component, and signet ring cell carcinoma component. The tumors of all patients were surgically resected. All resected specimens were stained with hematoxylin-eosin and immunohistochemical. The data for the patient's lymphovascular invasion and PNI came from the collected pathological reports. The results of the survival analysis showed that T staging (P < .001), lymph node metastasis (P < .001), lymphovascular invasion (P = .013), PNI (P = .001), and signet ring cell carcinoma components (P = .046) affect the survival time and have a statistically significant difference. Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .014). T staging (P = .006) and lymph node metastasis (P = .013) were independent prognostic parameters too. Using the Spearman correlation analysis, the following clinicopathological indicators were associated with PNI positivity, such as tumor differentiation, T staging, lymph node metastasis, vascular invasion, and signet ring cell carcinoma components (P < .05). PNI is an independent marker of poor prognosis in patients with gastric cancer.
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Affiliation(s)
- Chunsheng Li
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Avenue, Changchun, China
| | - Mingchuan Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Avenue, Changchun, China
| | - Xianbin Cheng
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Avenue, Changchun, China
| | - Yang Jiang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Avenue, Changchun, China
| | - Huijie Xiao
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Avenue, Changchun, China
- *Correspondence: Huijie Xiao, Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China (e-mail: )
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Tumour invasion and dissemination. Biochem Soc Trans 2022; 50:1245-1257. [PMID: 35713387 PMCID: PMC9246329 DOI: 10.1042/bst20220452] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/16/2022] [Accepted: 05/30/2022] [Indexed: 11/17/2022]
Abstract
Activating invasion and metastasis are one of the primary hallmarks of cancer, the latter representing the leading cause of death in cancer patients. Whilst many advances in this area have been made in recent years, the process of cancer dissemination and the underlying mechanisms governing invasion are still poorly understood. Cancer cells exhibit multiple invasion strategies, including switching between modes of invasion and plasticity in response to therapies, surgical interventions and environmental stimuli. The ability of cancer cells to switch migratory modes and their inherent plasticity highlights the critical challenge preventing the successful design of cancer and anti-metastatic therapies. This mini-review presents current knowledge on the critical models of tumour invasion and dissemination. We also discuss the current issues surrounding current treatments and arising therapeutic opportunities. We propose that the establishment of novel approaches to study the key biological mechanisms underlying the metastatic cascade is critical in finding novel targets that could ultimately lead to complete inhibition of cancer cell invasion and dissemination.
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Shi C, Badgwell BD, Grabsch HI, Gibson MK, Hong SM, Kumarasinghe P, Lam AK, Lauwers G, O'Donovan M, van der Post RS, Tang L, Ushiku T, Vieth M, Selinger CI, Webster F, Nagtegaal ID. Data Set for Reporting Carcinoma of the Stomach in Gastrectomy. Arch Pathol Lab Med 2021; 146:1072-1083. [DOI: 10.5858/arpa.2021-0225-oa] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2021] [Indexed: 11/06/2022]
Abstract
Context.—
A standardized detailed surgical pathology report is the cornerstone of gastric cancer management.
Objective.—
To guide management and prognostication for patients with gastric carcinomas globally, the International Collaboration on Cancer Reporting aimed to produce an evidence-based international pathology reporting data set with a panel of globally recognized expert pathologists and clinicians.
Design.—
Based on published guidelines/data sets for gastric carcinomas, a working draft was developed by the chair of the expert panel of pathologists and clinicians. The draft was then circulated to the panel and discussed in a series of teleconferences and email communications until consensus was achieved. The draft data set was uploaded on the International Collaboration on Cancer Reporting Web site for public comment. The data set was reviewed in consideration of the feedback, and a final version was approved by the panel.
Results.—
This data set was developed for gastrectomy specimens for primary gastric carcinomas, including neuroendocrine carcinomas and mixed neuroendocrine-nonneuroendocrine neoplasms. Well-differentiated neuroendocrine tumors, nonepithelial malignancies, and secondary tumors were excluded from this data set. The final data set contains 15 core (required) elements and 8 noncore (recommended) elements. A commentary is provided for each element.
Conclusions.—
The International Collaboration on Cancer Reporting has published freely available, evidence-based data sets for gastric cancer reporting. Standardized reporting has been shown to improve patient care and facilitates data exchange and analysis for quality assurance, cancer epidemiology, and clinical and basic research.
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Affiliation(s)
- Chanjuan Shi
- From the Department of Pathology, Duke University School of Medicine, Durham, North Carolina (Shi)
| | - Brian D. Badgwell
- The Division of Surgery, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston (Badgwell)
| | - Heike I. Grabsch
- The Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands (Grabsch)
- The Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom (Grabsch)
| | - Michael K. Gibson
- The Division of Hematology and Oncology, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee (Gibson)
| | - Seung-Mo Hong
- The Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (Hong)
| | - Priyanthi Kumarasinghe
- PathWest Laboratory Medicine, PathWest QEII Medical Center, Perth, Australia (Kumarasinghe)
| | - Alfred K. Lam
- Pathology, School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, Australia (Lam)
- Pathology Queensland, Gold Coast University Hospital, Southport, Australia (Lam)
- Faculty of Medicine, The University of Queensland, Herston, Australia (Lam)
| | - Gregory Lauwers
- The Department of Pathology, Moffitt Cancer Center, Tampa, Florida (Lauwers)
| | - Maria O'Donovan
- The Histopathology Department, Cambridge University Hospitals NHS Foundation Trust Addenbrookes Hospital, Cambridge, United Kingdom (O'Donovan)
| | - Rachel S. van der Post
- The Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (van der Post and Nagtegaal)
| | - Laura Tang
- The Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York, (Tang)
| | - Tetsuo Ushiku
- The Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (Ushiku)
| | - Michael Vieth
- The Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Germany (Vieth)
| | | | - Fleur Webster
- The International Collaboration on Cancer Reporting, Sydney, Australia (Webster)
| | - Iris D. Nagtegaal
- The Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (van der Post and Nagtegaal)
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Wang H, Zheng Q, Lu Z, Wang L, Ding L, Xia L, Zhang H, Wang M, Chen Y, Li G. Role of the nervous system in cancers: a review. Cell Death Discov 2021; 7:76. [PMID: 33846291 PMCID: PMC8041826 DOI: 10.1038/s41420-021-00450-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/08/2021] [Accepted: 03/08/2021] [Indexed: 02/02/2023] Open
Abstract
Nerves are important pathological elements of the microenvironment of tumors, including those in pancreatic, colon and rectal, prostate, head and neck, and breast cancers. Recent studies have associated perineural invasion with tumor progression and poor outcomes. In turn, tumors drive the reprogramming of neurons to recruit new nerve fibers. Therefore, the crosstalk between nerves and tumors is the hot topic and trend in current cancer investigations. Herein, we reviewed recent studies presenting direct supporting evidences for a better understanding of nerve-tumor interactions.
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Affiliation(s)
- Huan Wang
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Qiming Zheng
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Zeyi Lu
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Liya Wang
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Lifeng Ding
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Liqun Xia
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Hao Zhang
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Mingchao Wang
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China
| | - Yicheng Chen
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
| | - Gonghui Li
- Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
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12
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Long-term Outcomes of Gastric Cancer in a Small Institute: a Single Surgeon Experience. Indian J Surg 2021. [DOI: 10.1007/s12262-020-02659-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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13
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Uzun O, Gülmez S, Senger AS, Ömeroğlu S, Polat E, Duman M. Prognostic effect of perineural invasion in successive years in patients with locally advanced gastric cancer. INDIAN J PATHOL MICR 2021; 64:479-483. [PMID: 34341257 DOI: 10.4103/ijpm.ijpm_612_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aim The present study evaluates the prognostic significance of perineural invasion (PNI) on 2-year, 5-year, and overall survival in patients undergoing gastrectomy and D2 lymphadenectomy due to locally advanced gastric cancer. Materials and Methods Included in the study were 231 patients who underwent surgery between November 2006 and October 2018 due to stage 1B and over locally advanced gastric cancer, whose records were reviewed retrospectively. Statistical Analysis The variables in the presence or absence of PNI were compared between the two groups with a Chi-square test, a Fisher's exact test, a likelihood ratio, and a Mann-Whitney U test. Overall survival data were evaluated with a Kaplan-Meier test. Prognostic factors were evaluated with a stepwise Cox regression analysis. Results PNI was identified in 167 (72.3%) of the patients. The 2-year, 5-year, and overall survival rates at the end of the follow-up period were 85.9%, 70.3%, and 64.1% in those without PNI, and 52.7%, 38.3%, and 36.5% in those with PNI, respectively. In a multivariate analysis, PNI appeared to be a significant prognostic factor for 2-year survival (P = 0.04) but had no effect on 5-year and overall survival. Conclusions Survival was shorter in patients with PNI than in patients without PNI, and PNI had no effect on overall survival, although it was found to be of prognostic significance for 2-year survival.
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Affiliation(s)
- Orhan Uzun
- Kartal Koşuyolu High Specialty Training and Research Hospital, Istanbul, Turkey
| | - Selçuk Gülmez
- Kartal Koşuyolu High Specialty Training and Research Hospital, Istanbul, Turkey
| | - Aziz Serkan Senger
- Kartal Koşuyolu High Specialty Training and Research Hospital, Istanbul, Turkey
| | - Sinan Ömeroğlu
- Kartal Koşuyolu High Specialty Training and Research Hospital, Istanbul, Turkey
| | - Erdal Polat
- Kartal Koşuyolu High Specialty Training and Research Hospital, Istanbul, Turkey
| | - Mustafa Duman
- Kartal Koşuyolu High Specialty Training and Research Hospital, Istanbul, Turkey
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14
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Zhao B, Lv W, Mei D, Luo R, Bao S, Huang B, Lin J. Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis. J Clin Pathol 2020; 73:544-551. [PMID: 31980559 DOI: 10.1136/jclinpath-2019-206372] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 12/22/2019] [Accepted: 12/23/2019] [Indexed: 12/24/2022]
Abstract
AIMS The prognostic significance of perineural invasion (PNI) for gastric cancer (GC) patients was under debate. This study aimed to review relevant studies and evaluate the impact of PNI on the survival outcome of GC patients. METHODS Systematic literature search was performed using PubMed and Embase databases. The relevant data were extracted, and the association between PNI and clinicopathological characteristics or survival outcome in GC patients were evaluated using a fixed-effect model or random-effect model. RESULTS A total 13 studies involving 7004 GC patients were included in this meta-analysis. The positive rate of PNI was 35.9% (2512/7004) in GC patients, ranging from 6.9% to 75.6%. There were significant relationships between PNI and a series of unfavourable clinicopathological factors including undifferentiated histology type (OR: 1.78, 95% CI 1.37 to 2.33, p<0.001; I2=75.3%), diffuse type (OR: 1.96, 95% CI 1.07 to 3.60, p=0.029; I2=79.5%), lymphatic invasion (OR: 7.00, 95% CI 3.76 to 13.03, p<0.001; I2=83.6%), vascular invasion (OR: 5.79, 95% CI 1.59 to 21.13, p=0.008; I2=95.8%), deeper tumour invasion (OR: 4.79, 95% CI 3.65 to 6.28, p<0.001; I2=65.0%) and lymph node metastasis (OR: 3.60, 95% CI 2.37 to 5.47, p<0.001; I2=89.6%). In addition, PNI was significantly associated with worse survival outcome in GC patients (HR: 1.69, 95% CI 1.38 to 2.06, p<0.001; I2=71.0%). CONCLUSION PNI was frequently detected in surgically resected specimens of GC patients, and it was a predictive factor for survival outcomes in these patients.
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Affiliation(s)
- Bochao Zhao
- Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.,Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Wu Lv
- Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Di Mei
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Rui Luo
- Department of Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Shiyang Bao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Baojun Huang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jie Lin
- Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
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15
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Wang K, Zhao XH, Liu J, Zhang R, Li JP. Nervous system and gastric cancer. Biochim Biophys Acta Rev Cancer 2019; 1873:188313. [PMID: 31647986 DOI: 10.1016/j.bbcan.2019.188313] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 09/04/2019] [Accepted: 09/05/2019] [Indexed: 02/07/2023]
Abstract
The nervous system has been recently shown to exert impact on gastric cancer directly and indirectly. Gastric cancer cells invade nerve fibers to induce outgrowth and branching of neural cells, and nerve fibers in turn infiltrate into tumor microenvironment to promote progression of gastric cancer. Additionally, the neuro-immune interaction also plays an important role in gastric cancer development. The interplay of nerves and gastric cancer is mediated by many nervous system-associated factors, which can not only be synthesized and released by both cancer cells and nerve terminals, but also participate in regulation of many aspects of gastric cancer such as cell proliferation, angiogenesis, metastasis and recurrence. Furthermore, clinical researches indicate that some of these factors are significant diagnosis and prognosis biomarkers for gastric cancer. Herein, we reviewed recent advances and future prospects of the interaction between nervous system and gastric cancer.
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Affiliation(s)
- Ke Wang
- State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China
| | - Xin-Hui Zhao
- State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China
| | - Jun Liu
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China
| | - Rui Zhang
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China; State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, China.
| | - Ji-Peng Li
- State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China; Department of Experimental Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
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16
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Cao Y, Li R, Cheng L, Chen N, Li J, Yu D. p75 Nerve Growth Factor Receptor as a Specific Nerve Marker in the Diagnosis of Perineural Invasion of Squamous Cell Carcinoma. Am J Clin Pathol 2019; 151:574-583. [PMID: 30895287 DOI: 10.1093/ajcp/aqz011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 12/29/2018] [Accepted: 01/28/2019] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES Perineural invasion (PNI) is an important factor in tumor prognosis. We evaluated p75 nerve growth factor receptor (p75NGFR) as a neuromarker for perineural invasion of squamous cell carcinoma. METHODS A comparison of H&E, and S100 and p75NGFR immunohistochemical staining methods, using sequential sections from 29 samples, for identification nerve bundles and PNI diagnosis, was carried out. RESULTS p75NGFR and S100 correctly identified more nerve bundles than H&E. Accuracy of p75NGFR was higher than that of S100, but there was no significant difference from H&E. The accuracy of nerve bundle identification by p75NGFR and S100 showed no significant difference among different histopathologic grades of squamous cell carcinomas. p75NGFR gave mild staining of small vessels, while S100 gave strong staining of smooth muscle and glandular tissue. CONCLUSIONS p75NGFR specifically stains nerve tissue and is better than S100 and H&E in identifying nerve bundles. p75NGFR is expected to become a new neuromarker.
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Affiliation(s)
- Yong Cao
- College of Stomatology, Guangxi Medical University, Nanning, China
| | - Rouxi Li
- College of Stomatology, Guangxi Medical University, Nanning, China
| | - Li Cheng
- College of Stomatology, Guangxi Medical University, Nanning, China
| | - Nian Chen
- College of Stomatology, Guangxi Medical University, Nanning, China
| | - Jing Li
- Department of Stomatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Dahai Yu
- Department of Stomatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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17
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Lee D, Son SY, Kim YB, Han SU, Hur H. Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma. Ann Surg Oncol 2018; 25:1167-1175. [PMID: 29450754 DOI: 10.1245/s10434-018-6371-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients. METHODS This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed. RESULTS The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC. CONCLUSIONS This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.
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Affiliation(s)
- Dakeun Lee
- Department of Pathology, Ajou University School of Medicine, Suwon, Korea
| | - Sang-Yong Son
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Young-Bae Kim
- Department of Pathology, Ajou University School of Medicine, Suwon, Korea
| | - Sang-Uk Han
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hoon Hur
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea. .,Brain Korea 21 Plus Research Center for Biomedical Sciences, Ajou University, Suwon, Korea.
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18
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España-Ferrufino A, Lino-Silva LS, Salcedo-Hernández RA. Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas. J Pathol Transl Med 2017; 52:79-84. [PMID: 29121459 PMCID: PMC5859241 DOI: 10.4132/jptm.2017.11.01] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 10/20/2017] [Accepted: 11/01/2017] [Indexed: 12/13/2022] Open
Abstract
Background Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study. Methods Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group. Results Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023). Conclusions We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence.
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Affiliation(s)
- Alejandro España-Ferrufino
- Department of Gastrointestinal Pathology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | - Leonardo S Lino-Silva
- Department of Gastrointestinal Pathology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | - Rosa A Salcedo-Hernández
- Department of Surgical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
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19
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The role of enteric neurons in the development and progression of colorectal cancer. Biochim Biophys Acta Rev Cancer 2017; 1868:420-434. [PMID: 28847715 DOI: 10.1016/j.bbcan.2017.08.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 08/16/2017] [Accepted: 08/17/2017] [Indexed: 02/06/2023]
Abstract
The enteric nervous system (ENS) is the intrinsic neural network of the gastrointestinal tract, which is essential for regulating gut functions and intestinal homeostasis. The importance of the ENS is underscored by the existence of severe gastrointestinal diseases, such as Hirschsprung's disease and intestinal pseudo-obstruction, which arise when the ENS fails to develop normally or becomes dysregulated. Moreover, it is known that enteric neurons are involved in intestinal inflammation. However, the role of the ENS in colorectal cancer (CRC) carcinogenesis remains poorly understood, even though processes like perineural invasion and neoneurogenesis are important factors in CRC. Here we summarize how enteric neurons are affected during CRC and discuss the influence of enteric neurons, either direct or indirect, on the development and/or progression of CRC. Finally, we illustrate how the ENS could be targeted as a potential anti-cancer therapy, establishing the ENS as an integral part of the tumor microenvironment.
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20
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De Franco L, Marrelli D, Voglino C, Vindigni C, Ferrara F, Di Mare G, Iudici L, Marini M, Roviello F. Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype. Pathol Oncol Res 2017; 24:393-400. [PMID: 28555306 DOI: 10.1007/s12253-017-0257-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 05/23/2017] [Indexed: 12/11/2022]
Abstract
The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15-140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24-3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.
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Affiliation(s)
- Lorenzo De Franco
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy
| | - Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy.
| | - Costantino Voglino
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy
| | - Carla Vindigni
- Department of Medicine, Surgery and Neurosciences, Unit of Pathology, University of Siena, 53100, Siena, Italy
| | - Francesco Ferrara
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy
| | - Giulio Di Mare
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy
| | - Livio Iudici
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy
| | - Mario Marini
- Department of Oncology, Unit of gastroenterology and endoscopy, "Santa Maria alle Scotte" Hospital, 53100, Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, 53100, Siena, Italy
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Chen XZ, Chen HN, Liu K, Zhang WH, Guo DJ, Hu JK. Perineural Invasion Underlines the Necessity of Upper Lesser Curvature Skeletonization in Radical Distal Gastrectomy for Locally Advanced Gastric Cancer. Ann Surg 2017; 265:e67-e68. [PMID: 28394791 DOI: 10.1097/sla.0000000000001221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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22
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Sun R, Liu Z, Tong D, Yang Y, Guo B, Wang X, Zhao L, Huang C. miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer. Cell Death Dis 2017; 8:e2714. [PMID: 28358374 PMCID: PMC5386537 DOI: 10.1038/cddis.2017.134] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 02/23/2017] [Accepted: 02/28/2017] [Indexed: 02/07/2023]
Abstract
Accumulated evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse signaling pathways. However, the precise role of miRNAs in gastric cancer (GC) has not been elucidated. In this study, we describe the function and regulation network of miR-491-5p in GC. miR-491-5p is frequently downregulated in GC tissues compared with adjacent non-cancerous tissues. Forced expression of miR-491-5p significantly inhibits proliferation and colony formation, and promotes apoptosis in GC cells. Through bioinformatic analysis and luciferase assays, we confirm that miR-491-5p targets Wnt3a. Silencing Wnt3a inhibits cell proliferation and induces apoptosis. Similarly, restoration of Wnt3a counteracts the effects of miR-491-5p expression. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-491-5p is regulated by Foxi1, which binds to its promoter and activates miR-491-5p expression. In conclusion, to the best of our knowledge, our findings are the first to demonstrate that Foxi1 is a key player in the transcriptional control of miR-491-5p and that miR-491-5p acts as an anti-oncogene by targeting Wnt3a/β-catenin signaling in GC. Our study reveals that Foxi1/miR-491-5p/Wnt3a/β-catenin signaling is critical in the progression of GC. Targeting the pathway described in this study may open up new prospects to restrict the progression of GC.
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Affiliation(s)
- Ruifang Sun
- Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Zhigang Liu
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Department of Thoracic Surgery, Shaanxi Provincial Tumor Hospital, Xi'an Jiaotong University, 309 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Dongdong Tong
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Yang Yang
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- School of Public Health, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Bo Guo
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Xiaofei Wang
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Lingyu Zhao
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
| | - Chen Huang
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China
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Predictive factors for recurrence in T2N0 and T3N0 gastric cancer patients. Langenbecks Arch Surg 2016; 401:823-8. [PMID: 27460840 DOI: 10.1007/s00423-016-1480-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 07/12/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE Adjuvant chemotherapy is an indispensable component of treatment for preventing recurrence in advanced gastric cancer patients after macroscopically complete tumor resection (R0). However, the efficacy of this treatment for patients with T2N0 and T3N0 gastric cancer is not well characterized. METHODS This study examined 1019 T1, 126 T2N0, and 67 T3N0 gastric adenocarcinoma patients who underwent gastrectomies at our institution between 1975 and 2005 to determine the predictive factors for recurrence in T2N0 and T3N0 gastric cancer patients. RESULTS Among 193 T2N0 and T3N0 patients, 14 patients (7.3 %) have recurred. The prevalence of ly2/3 and v2/3 was significantly higher in patients with recurrence compared with those without recurrence. The prognosis for either T2N0 or T3N0 gastric cancer patients was significantly worse than that for T1 gastric cancer patients. Multivariate analysis indicated that lymphatic and blood vessel invasion were independent prognostic indicators in T2N0 and T3N0 gastric cancer patients. Ten-year survival rates for T2N0 and T3N0 gastric cancer patients with both ly2/3 and v2/3, with either ly2/3 or v2/3, and without ly2/3 and v2/3 were 42.9, 86.1, and 96.7 %, respectively. T2N0 and T3N0 gastric cancer patients with both ly2/3 and v2/3 had a significantly worse prognosis than that of patients with either ly2/3 or v2/3 and those without ly2/3 and v2/3. CONCLUSIONS Our data indicate that T2N0 and T3N0 patients with both ly2/3 and v2/3 have a high risk of recurrence. Therefore, adjuvant chemotherapy should be administered to these patients.
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Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer. Surg Today 2014; 45:1493-500. [DOI: 10.1007/s00595-014-1096-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 11/17/2014] [Indexed: 12/28/2022]
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Jiang N, Deng JY, Liu Y, Ke B, Liu HG, Liang H. Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor–node–metastasis staging system. Tumour Biol 2014; 35:9429-36. [PMID: 24972970 DOI: 10.1007/s13277-014-2258-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Accepted: 06/18/2014] [Indexed: 12/16/2022] Open
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Lv CY, Zhou T, Chen W, Yin XD, Yao JH, Zhang YF. Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion. World J Gastroenterol 2014; 20:4428-4432. [PMID: 24764683 PMCID: PMC3989981 DOI: 10.3748/wjg.v20.i15.4428] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2013] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the relationship between the CX3CL1 chemokine, its receptor CX3CR1, and gastric carcinoma/gastric carcinoma perineural invasion (PNI).
METHODS: Thirty cases of gastric carcinoma were surgically resected (radical resection or palliative resection) between February 2012 and July 2012. Tumour and tumour-adjacent tissues were evaluated for the presence of CX3CL1 (ELISA) and CX3CR1 (immunohistochemistry and Western blotting) in an effort to analyse the relationship between CX3CL1/CX3CR1 and gastric carcinoma/gastric carcinoma PNI.
RESULTS: Of these 30 cases, 14 were PNI-positive (46.7%). No significant differences in CX3CL and CX3CR1 expression in tumour-adjacent tissues were found between the PNI positive and negative groups. Expression levels of CX3CL and CX3CR1 in tumour tissues were significantly higher than those in adjacent tissues (P < 0.01), and were significantly higher in tumour tissues from the PNI-positive group compared to the PNI-negative group (P < 0.01).
CONCLUSION: CX3CL1/CX3CR1 expression may be associated with the occurrence and development of gastric carcinoma as well as gastric carcinoma PNI.
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Zhou ZH, Xu GF, Zhang WJ, Zhao HB, Wu YY. Reevaluating significance of perineural invasion in gastric cancer based on double immunohistochemical staining. Arch Pathol Lab Med 2014; 138:229-34. [PMID: 24476520 DOI: 10.5858/arpa.2012-0669-oa] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT In gastric cancer, the significance of perineural invasion remains controversial. Detecting perineural invasion with hematoxylin-eosin staining often leads to misdiagnosis. Labeling nerves by immunohistochemistry greatly assists perineural invasion detection, but it might also be misdiagnosed, because scattered cancer cells are difficult to recognize. OBJECTIVE To reevaluate the significance of perineural invasion in gastric cancer by double immunohistochemical staining that labels both nerves and cancer cells, and to examine agreements on perineural invasion detection between double immunohistochemical staining and single immunochemical staining (to label nerves) or hematoxylin-eosin staining. DESIGN We evaluated perineural invasion in 160 cases of gastric cancer with double immunohistochemical staining, single immunochemical staining, and hematoxylin-eosin staining, respectively; then we investigated the prognostic significance of perineural invasion. RESULTS Perineural invasion was detected in 65.0% (104 of 160), 38.1% (61 of 160), and 56.9% (91 of 160) of cases with double immunohistochemical staining, hematoxylin-eosin staining, and single immunohistochemical staining, respectively. Agreement was low between double staining and hematoxylin-eosin staining (κ = .34), and most false reports occurred in diffuse gastric cancer. Agreement between single immunochemical staining and double staining was good (κ = .67), but it declined in diffuse gastric cancer (κ = .28). Perineural invasion was closely associated with other clinicopathologic variables. Although perineural invasion-positive patients had a worse outcome than perineural invasion-negative patients, it was not an independent prognostic factor (P = .11; hazard ratio, 0.637; 95% confidence interval, 0.366-1.110). CONCLUSIONS Double immunohistochemical staining could improve accuracy of perineural invasion detection in gastric cancer, particularly in the diffuse type. Moreover, perineural invasion predicts a poor outcome in gastric cancer, but it cannot provide more information than traditional clinicopathologic variables.
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Affiliation(s)
- Zhi-Hua Zhou
- From the Department of Pathology, 101 Hospital of People's Liberation Army and the Teaching Hospital of Jiangsu University, Wuxi, China (Drs Zhou, Zhao, and Wu); and the Departments of Gastroenterology (Dr Xu) and Emergency (Dr Zhang), The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Deng J, You Q, Gao Y, Yu Q, Zhao P, Zheng Y, Fang W, Xu N, Teng L. Prognostic value of perineural invasion in gastric cancer: a systematic review and meta-analysis. PLoS One 2014; 9:e88907. [PMID: 24586437 PMCID: PMC3931634 DOI: 10.1371/journal.pone.0088907] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2013] [Accepted: 01/13/2014] [Indexed: 12/14/2022] Open
Abstract
Background The prognostic role of perineural invasion in gastric cancer is controversial. Here, we present a systemic review and meta-analysis of the association between perineural invasion and survival in resectable gastric cancer patients. Methods A comprehensive literature search for relevant reports published up to April 2013 was performed using PubMed, Embase, Web of Science and Wanfang Data. Studies that investigated the role of perineural invasion with a sample size greater than 100 were included and analyzed. Results A total of 30,590 gastric cancer patients who had undergone curative gastrectomy from twenty-four studies were included. The median rate of perineural invasion positive was 40.9% (6.8%–75.6%). Fourteen studies investigated overall survival unadjusted for other variables in 23,233 gastric cancer patients. The relative hazard estimates ranged from 0.568–7.901 with a combined random effects estimate of 2.261 (95% CI = 1.841–2.777, P = 0.000). The effect of perineural invasion on overall survival adjusted for other prognostic factors was reported in 17 studies incorporating 8,551 cases. The hazard estimates ranged from 0.420–8.110 with a pooled random effects estimates of 1.484 (95% CI = 1.237–1.781, P = 0.000). There was heterogeneity between the studies (Q = 49.22, I-squared = 67.5%, P = 0.000). Disease-free survival was investigated adjusted in four studies incorporating 9,083 cases and the pooled fixed hazard ratio estimate was 1.371(95% CI = 1.230–1.527, P = 0.000). Conclusion Perineural invasion is an independent prognostic factor affecting overall survival and disease-free survival of gastric cancer patients who had undergone the curative resection. This effect is independent of lymph node status, tumor size and the depth of invasion as well as a range of other biological variables on multivariate analysis. Large prospective studies are now needed to establish perineural invasion as an independent prognostic marker for gastric cancer.
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Affiliation(s)
- Jing Deng
- Department of Medical Oncology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
| | - Qihan You
- Department of Pathology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
| | - Yang Gao
- Medical School of Zhejiang University, Hangzhou, China
| | - Qing Yu
- Medical School of Zhejiang University, Hangzhou, China
| | - Peng Zhao
- Department of Medical Oncology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
| | - Yulong Zheng
- Department of Medical Oncology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
| | - Weijia Fang
- Department of Medical Oncology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
| | - Nong Xu
- Department of Medical Oncology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
- * E-mail:
| | - Lisong Teng
- Department of Surgical Oncology, The First Hospital Affiliated to Medical School of Zhejiang University, Hangzhou, China
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Correlations between vascular invasion, neural structures invasion and microvessel density with clinicopathological parameters in gastric cancer. REV ROMANA MED LAB 2014. [DOI: 10.2478/rrlm-2014-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Kim DH, Kim SM, Hyun JK, Choi MG, Noh JH, Sohn TS, Bae JM, Kim S. Changes in postoperative recurrence and prognostic risk factors for patients with gastric cancer who underwent curative gastric resection during different time periods. Ann Surg Oncol 2013; 20:2317-27. [PMID: 23677605 DOI: 10.1245/s10434-012-2700-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Current rates of survival for gastric cancer patients are much improved compared with those of the past. The purpose of our study was to analyze the survival of gastric cancer patients according to time period and to examine how different prognostic factors are related to changing survival rates. METHODS We analyzed data from 7,757 patients who underwent curative gastrectomy after diagnoses of gastric cancer at Samsung Medical Center from 1994 to 2006. Clinicopathologic characteristics and prognostic factors were analyzed retrospectively, with patients divided into period I, from 1994 to 2001, and period II, from 2002 to 2006. RESULTS The 5-year, disease-free survival rate of patients with gastric cancer increased significantly from 76.7 % during period I to 85.9 % during period II (p < 0.001). The prognosis of the patient who underwent surgery during period I was worse than that of the patient in period II. When multivariate analyses were performed for each time period, independent prognostic factors for period I included patient age >60 years, tumor located in the whole stomach, tumor size, stage, vascular invasion, perineural invasion, and adjuvant chemotherapy. For period II, tumor size, vascular, and adjuvant chemotherapy were no longer independent prognostic risk factors. CONCLUSIONS The disease-free survival of gastric cancer improved and prognostic factors changed over time. Active, concurrent chemoradiotherapy together with radical gastric resection performed by an expert surgeon seemed to contribute to the improvement in the survival rates of gastric cancer.
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Affiliation(s)
- Dae Hoon Kim
- Department of Surgery, Chungbuk National University Hospital, Cheongju, Korea.
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Selcukbiricik F, Tural D, Buyukunal E, Serdengecti S. Perineural Invasion Independent Prognostic Factors in Patients with Gastric Cancer Undergoing Curative Resection. Asian Pac J Cancer Prev 2012; 13:3149-3152. [DOI: 10.7314/apjcp.2012.13.7.3149] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Bai Y, Li ZS. Endoscopic, clinicopathological features and prognosis of very young patients with gastric cancer. J Gastroenterol Hepatol 2011; 26:1626-9. [PMID: 21557767 DOI: 10.1111/j.1440-1746.2011.06759.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The number of clinical reports of very young (<35 years) patients with gastric cancer are limited. We aimed to investigate the endoscopic and clinicopathological features and long-term prognosis of this unique group of patients. METHODS A prospective endoscopy database review of all consecutive very young patients with gastric cancer was performed. The gender, age, clinical features, endoscopic and pathologic findings, and long-term survival of these very young patients were analyzed and compared with those of elderly patients. RESULTS A total of 210 patients were included with a median age of 31 year, 60.0% was female, and 34.3% presented with alarm features, 19.0% reported family history of gastric cancer. 58.1% of these cancers were located in gastric body, 33.8% were located in the antrum. 63.8% of these cancers were found to be diffuse type; 18.1% of patients underwent curative surgical treatment, and the 5-year survival rate was 42.1%. CONCLUSIONS The study describes that very young patients with gastric cancer were mainly females, who were less likely to present with alarm features, but had a high frequency of family history of gastric cancer; and the majority of these cancers were located in gastric body, and they had similar long-term prognosis compared with elderly counterparts if curative surgical resection was performed.
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Affiliation(s)
- Yu Bai
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Shanghai, China
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Du C, Zhou Y, Cai H, Zhao G, Fu H, Shi YQ. Poor prognostic factors in patients with stage I gastric cancer according to the seventh edition TNM classification: a comparative analysis of three subgroups. J Surg Oncol 2011; 105:323-8. [PMID: 22271501 DOI: 10.1002/jso.22082] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2011] [Accepted: 08/05/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVES The purpose of this study was to investigate the prognosis of stage I gastric cancer and to compare clinicopathologic characteristics by subgroup. METHODS Between January 2000 and December 2006, 384 patients with gastric cancer were reclassified as stage I according to the seventh edition classification. A comparative analysis was performed between three subgroups. Univariate and multivariate analyses were conducted. RESULTS The 5-year overall survival rates in T1N0, T1N1, and T2N0 were 98.8%, 94.1%, 91.1%, respectively (P = 0.009). In patients with T2N0 gastric cancer, tumors in the upper third and larger tumors were more common than in patients with T1N0 and T1N1 gastric cancer (P < 0.001). In patients with T1N1 and T2N0 gastric cancer, the presence of lymphatic and/or blood vessel invasion (LBVI) and perineural invasion (PNI) were more common than in patients with T1N0 gastric cancer (P < 0.001). Univariate analysis showed tumor stage, depth of invasion, LBVI, and PNI were significant prognostic factors. However, multivariate analysis demonstrated that only tumor stage, LBVI, and PNI were significant variables. CONCLUSIONS Survival data support the accuracy of new TNM classification for stage I gastric cancer. Tumor stage, the presence of LBVI and PNI are important independent prognostic factors in stage I gastric cancer.
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Affiliation(s)
- Chunyan Du
- Cancer Center, Department of Gastric Cancer and Soft Tissue Surgery, Fudan University, Shanghai, People's Republic of China
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Mahar AL, Qureshi AP, Ottensmeyer CA, Pollett A, Wright FC, Coburn NG, Chetty R. A descriptive analysis of gastric cancer specimen processing techniques. J Surg Oncol 2011; 103:248-56. [PMID: 21337553 DOI: 10.1002/jso.21827] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Adherence to guidelines for adequate gastric cancer specimen assessment is poor in North America. Inadequate staging and poor prognosis were noted in some series when these guidelines are not met. Recent advances have been made in standardizing cancer pathology reports in Canada; however, the uptake of these reporting systems is unknown for gastric cancer. A survey of pathologists in Ontario was performed to outline the processing techniques and practices for assessing gastric cancer specimens. METHODS A survey was designed through a collaboration of surgical oncologists, general surgeons, pathologists, and research staff. Pathologists were identified using the College of Physicians and Surgeons of Ontario and MD Select databases. Participants were surveyed online or by mail-out. RESULTS The response rate was 40.2% (147/366). Vascular invasion, perineural invasion, and signet ring cells were all reported as being examined for by the majority of pathologists. Fat clearing solution and keratin immunohistochemical techniques were not reported as being consistently utilized. Less than 70% of pathologists indicated using a form of synoptic report. CONCLUSION Variations in practice and technique were observed. This may or may not reflect differences in quality of care or simply preferences for achieving equivalent results in the absence of standardized procedures. Education, evidence-based procedural guidelines and further research are required to provide infrastructure and support for pathologists and surgeons involved in the care of gastric cancer patients.
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Peng J, Sheng W, Huang D, Venook AP, Xu Y, Guan Z, Cai S. Perineural invasion in pT3N0 rectal cancer: the incidence and its prognostic effect. Cancer 2010; 117:1415-21. [PMID: 21425141 DOI: 10.1002/cncr.25620] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2010] [Revised: 07/07/2010] [Accepted: 08/02/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND The authors' purpose was to explore the incidence and prognostic significance of perineural invasion (PNI) in pT3N0 rectal cancer. METHODS Pathologic materials from resected specimens of 173 patients with pT3N0 rectal cancer were retrospectively collected. PNI-positivity was categorized into 2 groups: surrounding the nerve sheath (SS-PNI) and invading through the nerve sheath (TS-PNI). The rate of PNI-positivity was compared with PNI as initially recorded in the original reports. Patients' outcome was studied in groups with different PNI status, and multivariate analysis was performed to determine its prognostic value. RESULTS In this retrospective analysis, PNI-positivity was found in 24.3% of all cases, in which SS-PNI and TS-PNI were 11% and 13.3%, respectively, and was related to lymphovascular invasion. Only 7.5% of patients' specimens were reported as PNI-positive in the original reports. Detection of SS-PNI was likelier to be missed than TS-PNI. The rates of local recurrence, disease-free survival, and overall survival at 5 years were similar between the groups of SS-PNI and TS-PNI. The 5-year local recurrence rate was more than 2.5-fold higher in the PNI-positive group compared with the PNI-negative group (22.7% vs 7.9%, respectively; P = .017). Multivariate analysis proved that PNI-positivity was the only independent risk factor for predicting 5-year local recurrence rate, whereas only sampled lymph nodes was related to 5-year disease-free survival and overall survival. CONCLUSIONS PNI is a common pathologic feature in rectal cancer. The definition of PNI should include SS-PNI and TS-PNI. Rectal cancer patients who are PNI-positive are at higher risk of local recurrence and should be considered for more intensive treatment.
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Affiliation(s)
- Junjie Peng
- Department of Colorectal Surgery, Cancer Hospital of Fudan University, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
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Bilici A, Seker M, Ustaalioglu BBO, Kefeli U, Yildirim E, Yavuzer D, Aydin FM, Salepci T, Oncel M, Gumus M. Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection. Ann Surg Oncol 2010; 17:2037-44. [PMID: 20333555 DOI: 10.1245/s10434-010-1027-y] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2009] [Indexed: 12/12/2022]
Abstract
BACKGROUND The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated in a few studies, but had not reached a consensus. The aim of this study was to determine the prognostic value of PNI in patients with gastric cancer who underwent curative resection. MATERIALS AND METHODS We retrospectively analyzed 238 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. PNI and the other prognostic factors were evaluated by univariate and multivariate analysis. RESULTS PNI was detected as positive in 180 of the 238 patients (75.6%). pT stage, tumor size, lymph node metastasis, clinical stage, tumor differentiation, Borrmann classification, histological type, lymphatic vessel invasion, and blood vessel invasion were closely associated with the presence of PNI. The PNI-positive tumors had significantly larger size and more lymph node metastasis than the PNI-negative tumors (P = .001 and P < .001, respectively). The median survival of the PNI-positive patients was significantly worse than that of the PNI-negative patients (28.1 vs. 64.9 months, P = .001). Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .02, hazard ratio [HR]: 2.75; 95% confidence interval [95% CI]:1.12-3.13) as were classical clinicopathological features. CONCLUSION Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer.
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Affiliation(s)
- Ahmet Bilici
- Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.
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Marchesi F, Piemonti L, Mantovani A, Allavena P. Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis. Cytokine Growth Factor Rev 2010; 21:77-82. [PMID: 20060768 DOI: 10.1016/j.cytogfr.2009.11.001] [Citation(s) in RCA: 184] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Invasion and metastasis are key components of cancer progression. Inflammatory mediators, including cytokines and chemokines, can facilitate tumor dissemination. A distinct and largely forgotten path is perineural invasion (PNI), defined as the presence of cancer cells in the perinerium space. PNI is frequently used by many human carcinomas, in particular by pancreas and prostate cancer, and is associated with tumor recurrence and pain in advanced patients. Neurotrophic factors have been identified as molecular determinants of PNI. A role for chemokines in this process has been proposed; the chemokine CX3CL1/Fractalkine attracts receptor positive pancreatic tumor cells to disseminate along peripheral nerves. Better understanding of the neurotropism of malignant cells and of the clinical significance of PNI would help the design of innovative strategies for the control of tumor dissemination and pain in cancer patients.
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Affiliation(s)
- Federica Marchesi
- Dpt Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan, Italy
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Bilici A, Seker M, Ustaalioglu BBO, Yilmaz B, Doventas A, Salepci T, Gumus M. Determining of metastatic lymph node ratio in patients who underwent D2 dissection for gastric cancer. Med Oncol 2009; 27:975-84. [PMID: 19885750 DOI: 10.1007/s12032-009-9319-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2009] [Accepted: 09/18/2009] [Indexed: 12/11/2022]
Abstract
The purpose of this study was to determine outcome of the ratio of metastatic lymph nodes to the total number of dissected lymph nodes (MLR) in patients with gastric cancer. We retrospectively analyzed 111 patients who underwent D(2) lymph node dissection. The prognostic factors including UICC/AJCC TNM classification and MLR were evaluated by univariate and multivariate analysis. The MLR was significantly higher in patients with a larger tumor, lymphatic vessel invasion, blood vessel invasion and perineural invasion, and advanced stage. Moreover, the MLR was significantly associated with the depth of invasion and the number of lymph node metastasis. The univariate analysis revealed for overall survival (OS) that stage of disease, lymphatic vessel invasion, blood vessel invasion, perineural invasion, lymph node metastasis (UICC/AJCC pN stage) and MLR were relevant prognostic indicators. Furthermore, both UICC/AJCC pN stage and MLR were detected as prognostic factor by multivariate analysis, as was perineural invasion. Our results indicated that MLR and UICC/AJCC pN staging system were important prognostic factors for OS of patients with D(2) lymph node dissection in gastric cancer in a multivariate analysis. MLR may be useful for evaluating the status of lymph node metastasis in gastric cancer.
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Affiliation(s)
- Ahmet Bilici
- Department of Medical Oncology, Dr. Lütfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.
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