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Hayashi T, Sano K, Okada M, Ura T, Konishi I. Hereditary Gastric Cancer Is Linked With Hereditary Breast and Ovarian Cancer. World J Oncol 2024; 15:722-730. [PMID: 38993249 PMCID: PMC11236378 DOI: 10.14740/wjon1871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 05/17/2024] [Indexed: 07/13/2024] Open
Abstract
Background Helicobacter pylori (H. pylori), a bacterium which chronically infects the stomach of approximately half the world's population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby H. pylori infection induces GC development remains unclear. Intermittent injection of the H. pylori cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between H. pylori infection, BRCA1/2 pathogenic variants (PVs), GC and higher GC incidence in HBOC families. Methods We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine. Results We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of BRCA1/2 (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of H. pylori-infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had gBRCA2 PVs. Furthermore, expressing wild-type BRCA1/2 in Gan mice (a mouse model of human GC) inhibited GC development. Thus, gBRAC1/2 PVs and H. pylori infection synergistically increase the risk of GC development. Conclusion Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs.
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Affiliation(s)
- Takuma Hayashi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Kenji Sano
- Pathological Division, Shinshu University Hospital, Matsumoto, , Nagano 390-0877, Japan
| | - Mako Okada
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Takashi Ura
- Medical Oncology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Ikuo Konishi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
- Kyoto University School of Medicine, Kyoto 606-8507, Japan
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Wu L, Xue Q, Xia X. High expression of TRIP13 is associated with tumor progression in H. pylori infection induced gastric cancer. Mutat Res 2024; 828:111854. [PMID: 38492425 DOI: 10.1016/j.mrfmmm.2024.111854] [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: 10/09/2023] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND/OBJECTIVE H. pylori is a recognized bacterial carcinogen in the world to cause gastric cancer (GC). However, the molecular mechanism of H. pylori infection-induced GC is not completely clear. Thus, there is an urgent need to reveal the precise mechanisms regulating cancer development due to H. pylori infection. METHODS GEO microarray databases and TCGA databases were extracted for the analysis of different expression genes (DEGs). Then, Kaplan-Meier Plotter was used for prognostic analysis. Functional enrichment analysis of TRIP13 was performed by metascape database and TIMER database. Specific role of TRIP13 in GC with H. pylori infection was confirmed by CCK8, cell cycle analysis and WB. RESULTS A total 10 DEGs were substantially elevated in GC and H. pylori+ tissues and might be associated with H. pylori infection in GC and only the highly expressed TRIP13 was statistically associated with poor prognosis in GC patients. Meanwhile, TRIP13 were upregulated in both CagA-transfected epithelial cells and GC cells. And TRIP13 deficiency inhibited cell proliferation and arrested the cell cycle at the G1 phase. CONCLUSION Our study suggested that high expression of TRIP13 can promote the proliferation, cell cycle in GC cells, which could be used as a biomarker for H. pylori infection GC.
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Affiliation(s)
- Longxiang Wu
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu 226361, China
| | - Qiu Xue
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu 226361, China
| | - Xiaochun Xia
- Department of Radiation Oncology, Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu 226361, China.
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Bootsma S, Bijlsma MF, Vermeulen L. The molecular biology of peritoneal metastatic disease. EMBO Mol Med 2023; 15:e15914. [PMID: 36700339 PMCID: PMC9994485 DOI: 10.15252/emmm.202215914] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 01/27/2023] Open
Abstract
Peritoneal metastases are a common form of tumor cell dissemination in gastrointestinal malignancies. Peritoneal metastatic disease (PMD) is associated with severe morbidity and resistance to currently employed therapies. Given the distinct route of dissemination compared with distant organ metastases, and the unique microenvironment of the peritoneal cavity, specific tumor cell characteristics are needed for the development of PMD. In this review, we provide an overview of the known histopathological, genomic, and transcriptomic features of PMD. We find that cancers representing the mesenchymal subtype are strongly associated with PMD in various malignancies. Furthermore, we discuss the peritoneal niche in which the metastatic cancer cells reside, including the critical role of the peritoneal immune system. Altogether, we show that PMD should be regarded as a distinct disease entity, that requires tailored treatment strategies.
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Affiliation(s)
- Sanne Bootsma
- Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular MedicineAmsterdam UMC, Location University of AmsterdamAmsterdamThe Netherlands
- Cancer Center Amsterdam, Cancer BiologyAmsterdamThe Netherlands
- Amsterdam Gastroenterology Endocrinology MetabolismAmsterdamThe Netherlands
- Oncode InstituteAmsterdamThe Netherlands
| | - Maarten F Bijlsma
- Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular MedicineAmsterdam UMC, Location University of AmsterdamAmsterdamThe Netherlands
- Cancer Center Amsterdam, Cancer BiologyAmsterdamThe Netherlands
- Amsterdam Gastroenterology Endocrinology MetabolismAmsterdamThe Netherlands
- Oncode InstituteAmsterdamThe Netherlands
| | - Louis Vermeulen
- Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular MedicineAmsterdam UMC, Location University of AmsterdamAmsterdamThe Netherlands
- Cancer Center Amsterdam, Cancer BiologyAmsterdamThe Netherlands
- Amsterdam Gastroenterology Endocrinology MetabolismAmsterdamThe Netherlands
- Oncode InstituteAmsterdamThe Netherlands
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Chen Y, Chen Y, Wen L, Tou L, Wang H, Teng L. PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study. Front Surg 2022; 9:986696. [PMID: 36439539 PMCID: PMC9684711 DOI: 10.3389/fsurg.2022.986696] [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] [Received: 07/05/2022] [Accepted: 10/24/2022] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. METHODS Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. RESULTS Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. CONCLUSIONS Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.
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Affiliation(s)
- Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Liping Wen
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Laizhen Tou
- Department of Gastrointestinal Surgery, Lishui Hospital, College of Medicine, Zhejiang University, Lishui, China
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Xiang L, Jin S, Zheng P, Maswikiti EP, Yu Y, Gao L, Zhang J, Zhang Y, Chen H. Risk Assessment and Preventive Treatment for Peritoneal Recurrence Following Radical Resection for Gastric Cancer. Front Oncol 2022; 11:778152. [PMID: 35047394 PMCID: PMC8763009 DOI: 10.3389/fonc.2021.778152] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 11/29/2021] [Indexed: 02/03/2023] Open
Abstract
As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of patients to a very large extent. Peritoneal status and risk of peritoneal recurrence can be evaluated by peritoneal lavage cytology, photodynamic diagnosis, imaging examination, and pathologic analysis. Presently, there is no standard approach for preventing peritoneal recurrence after radical surgery; furthermore, controversies exist regarding the effects of some preventive methods. Among the preventive methods, there are high expectations about the potential of preoperative therapy, surgical skill improvement, hyperthermic intraperitoneal chemotherapy, and postoperative treatment to reduce the incidence of peritoneal recurrence after radical gastrectomy. This study aimed to analyze the results of previous studies on the risk assessment and preventive methods of peritoneal recurrence after radical gastrectomy in recent years. We hope to provide references for better approach to clinical diagnosis and treatment strategies for peritoneal recurrence after radical gastrectomy.
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Affiliation(s)
- Lin Xiang
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Pathology, Lanzhou University Second Hospital, Lanzhou, China
| | - Shuai Jin
- Department of Technology, Beijing Weitai’an Pharmaceutical Ltd, Beijing, China
| | - Peng Zheng
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | | | - Yang Yu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Lei Gao
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Jing Zhang
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Ying Zhang
- Department of Laboratory Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Hao Chen
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, China
- The Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China
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Huang J, Chen Y, Zhang Y, Xie J, Liang Y, Yuan W, Zhou T, Gao R, Wen R, Xia Y, Long L. Comparison of clinical-computed tomography model with 2D and 3D radiomics models to predict occult peritoneal metastases in advanced gastric cancer. Abdom Radiol (NY) 2022; 47:66-75. [PMID: 34636930 DOI: 10.1007/s00261-021-03287-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/10/2021] [Accepted: 09/11/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE To compare the ability of a clinical-computed tomography (CT) model vs. 2D and 3D radiomics models for predicting occult peritoneal metastasis (PM) in patients with advanced gastric cancer (AGC). METHODS In this retrospective study, we included 49 patients with occult PM and 49 control patients (without PM) who underwent preoperative CT and subsequent surgery between January 2016 and December 2018. Clinical information and CT semantic features were collected, and CT radiomics features were extracted. A predictive clinical-CT model was created using multivariate logistic regression. The least absolute shrinkage and selection operator algorithm and logistic regression were used for constructing 2D and 3D radiomics models. These models were validated with an external cohort (n = 30). Receiver operating characteristics curve with area under the curve (AUC), sensitivity, and specificity were used to evaluate predictive performance. RESULTS Tumor size, mild ascites, and serum CA125 were independent factors predictive of occult PM. The clinical-CT model of these independent factors showed better diagnostic performance than 2D and 3D radiomics models. In the external validation cohort, the AUCs of different models were as follows-clinical-CT model: 0.853 (sensitivity, 66.7%; specificity, 93.3%); 2D radiomics model: 0.622 (sensitivity, 80.0%; specificity, 46.7%); and 3D radiomics model: 0.676 (sensitivity, 60.0%; specificity, 86.0%). The clinical-CT model nomogram showed good clinical predictive efficiency to assess occult PM. CONCLUSION The clinical-CT model was better than the radiomics models in predicting occult PM in AGC.
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Affiliation(s)
- Jiang Huang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Yidi Chen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuying Zhang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Jinhuan Xie
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Yiqiong Liang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Wenzhao Yuan
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Ting Zhou
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Ruizhi Gao
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Rong Wen
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Yuwei Xia
- Huiying Medical Technology Co. Ltd, Beijing, 100192, China
| | - Liling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China.
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Zhu M, Zhang N, Ma J, He S. Integration of exosomal miR-106a and mesothelial cells facilitates gastric cancer peritoneal dissemination. Cell Signal 2021; 91:110230. [DOI: 10.1016/j.cellsig.2021.110230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 12/24/2022]
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Pachaury A, Chaudhari V, Batra S, Ramaswamy A, Ostwal V, Engineer R, Bal M, Shrikhande SV, Bhandare MS. Pathological N3 Stage (pN3/ypN3) Gastric Cancer: Outcomes, Prognostic Factors and Pattern of Recurrences After Curative Treatment. Ann Surg Oncol 2021; 29:229-239. [PMID: 34283313 DOI: 10.1245/s10434-021-10405-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 06/21/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND pN3 or ypN3 stage gastric cancers (GCs) are known to have aggressive clinical behaviour. This study aimed to investigate factors affecting survival and pattern of recurrences of N3 stage GCs, treated with curative intent. METHODS A total of 196 GC patients, operated on at the Tata Memorial Centre from 2003 to 2017 and reported as pN3 or ypN3 status on histopathology after D2 gastrectomy were included in this retrospective analysis. RESULTS On multivariate analysis, use of NACT (neoadjuvant chemotherapy) and LN ratio (≤ 0.5/> 0.5) emerged as significant predictors for long-term survival. Patients who received NACT but were still harbouring N3 nodes (ypN3; n = 102) had a worse prognosis than those operated on upfront (pN3; n = 94), with a median survival of 19 months versus 24 months respectively (p = 0.003). The 5-year overall survival of the entire cohort was 16.3% (95% CI 12.8-19.8%), while 5-year disease-free survival (DFS) was 14.6% (95% CI 12.6-20%). Adjuvant chemoradiotherapy, though offered in a small number of patients (n = 38) resulted in improvement in DFS. Median DFS of adjuvant CT versus adjuvant CRT was 13 months versus 23 months (p = 0.020). The commonest site of relapse was the peritoneum (49.18%) and incidence of isolated loco-regional failure was 10.7%. CONCLUSION In GCs with N3 stage determined after radical D2 gastrectomy, LN ratio of > 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.
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Affiliation(s)
- Anadi Pachaury
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikram Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Swati Batra
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Munita Bal
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
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Kohli P, Penumadu P, Srinivas BH, M S, Dubashi B, Kate V, Kumar H, R K, Balasubramanian A. Clinicopathological profile and its association with peritoneal disease among gastric cancer patients. Surg Oncol 2021; 38:101595. [PMID: 33991942 DOI: 10.1016/j.suronc.2021.101595] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 03/30/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND There are no clinicopathological criteria or test to predict peritoneal metastasis either in primary or recurrent gastric cancer. The early prediction will help in altering or adding other adjuvant potential therapy modalities like HIPEC and maintenance chemotherapy. METHODS Paraffin based blocks of 110 gastric tumor specimens were subjected to IHC staining to assess VEGF, Her 2 neu, E cadherin, bcl 2 and p 53 expression and its association with peritoneal disease evaluated. RESULTS Her 2 neu uptake was present in 17.3%, bcl-2 expression in 19.1%, P53 expression in 40.9%, VEGF in 41.8% and E cadherin expression in 49.1% patients. On univariate analysis, a younger age(p = .029), female sex(p = .026), positive VEGF expression (p = .001) and p53 expression(p = .015) were significantly associated with peritoneal disease. A binomial logistic regression was performed to ascertain the effects of independent variables evaluated on univariate analysis. Of the 10 predictors variables, only three were statistically significant: tumor type, P53, and VEGF. Positive VEGF expression had 48.7, E cadherin 2.6 and Her2neu 1.5 times higher odds of exhibiting peritoneal disease. CONCLUSION A younger age, female sex, distal 2/3rd, diffuse variant, VEGF staining in >10% cells and decrease p53 expression were associated with peritoneal disease.
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Affiliation(s)
- Pavneet Kohli
- Department of Surgical Oncology, JIPMER, Puducherry, 6050006, India
| | - Prasanth Penumadu
- Department of Surgical Oncology, JIPMER, Puducherry, 6050006, India.
| | - B H Srinivas
- Department of Pathology, JIPMER, Puducherry, 605006, India
| | - Sivasanker M
- HPB Unit, Department of Surgery, Royal Liverpool University Hospitals NHS Trust, Merseyside, UK
| | - Biswajit Dubashi
- Department of Medical Oncology, JIPMER, Puducherry, 605006, India
| | - Vikram Kate
- Department of General Surgery, JIPMER, Puducherry, 605006, India
| | | | - Kalayarasan R
- Department of Surgical Gastroenterology, JIPMER, Puducherry, 605006, India
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A Nomogram Based on Clinicopathologic Features and Preoperative Hematology Parameters to Predict Occult Peritoneal Metastasis of Gastric Cancer: A Single-Center Retrospective Study. DISEASE MARKERS 2020; 2020:1418978. [PMID: 33376558 PMCID: PMC7746455 DOI: 10.1155/2020/1418978] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/22/2020] [Accepted: 11/22/2020] [Indexed: 01/19/2023]
Abstract
Background In patients with gastric cancer (GC), peritoneal metastasis is an indication of the end stage and often indicates a poor outcome. The diagnosis of peritoneal metastasis, especially occult peritoneal metastasis (OPM), remains a challenge for surgeons. This study was designed to explore the relationship between OPM and clinicopathological characteristics and preoperative hematological parameters in patients with GC and to develop a nomogram to predict the probability of OPM before surgery. Methods A total of 672 patients with GC from our center were included, including 583 OPM-negative and 89 OPM-positive patients. These patients were divided into training and validation groups based on when they received treatment. OPM was diagnosed during surgery in patients without any signs of metastasis through imaging examination. Predictive factors were screened by least absolute shrinkage and selection operator logistic regression of all 18 characteristics. The nomogram of OPM was constructed based on these filtered variables. The discriminative and calibration performance of the model were simultaneously evaluated. Results A total of six variables, including tumor size, degree of differentiation, depth of invasion, Glasgow prognosis score, and plasma levels of CA125 and fibrinogen, were selected for integration into the final predictive nomogram. The area under curve (AUC) of the nomogram with six factors was 0.906 (95% confidence interval (CI): 0.872-0.941) and 0.889 (95% CI: 0.795-0.984) in the training and validation groups, respectively. Calibration plots of the nomogram in the two sets revealed a good consistency between predicted and actual probabilities. Decision curve analysis showed that the nomogram had a positive net benefit among all threshold probabilities between 0% and 82%. This nomogram was superior to models incorporating only clinicopathologic or hematologic features. Conclusion Both clinicopathological and preoperative hematological parameters are significantly associated with OPM. The nomogram constructed with six factors could be used to calculate the probability of OPM and identify the high-risk population in GC. This may be helpful for early detection of OPM in patients with GC.
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Alavi S, Haeri A, Mahlooji I, Dadashzadeh S. Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy. Pharm Res 2020; 37:119. [DOI: 10.1007/s11095-020-02818-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 04/06/2020] [Indexed: 12/12/2022]
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Chen X, Chen S, Wang X, Nie R, Chen D, Xiang J, Lin Y, Chen Y, Peng J. Analysis and external validation of a nomogram to predict peritoneal dissemination in gastric cancer. Chin J Cancer Res 2020; 32:197-207. [PMID: 32410797 PMCID: PMC7219103 DOI: 10.21147/j.issn.1000-9604.2020.02.07] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 04/08/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE Peritoneal dissemination is difficult to diagnose by conventional imaging technologies. We aimed to construct a nomogram to predict peritoneal dissemination in gastric cancer (GC) patients. METHODS We retrospectively analyzed 1,112 GC patients in Sun Yat-sen University Cancer Center between 2001 and 2010 as the development set and 474 patients from The Sixth Affiliated Hospital, Sun Yat-sen University between 2010 and 2016 as the validation set. The clinicopathological variables associated with gastric cancer with peritoneal dissemination (GCPD) were analyzed. We used logistic regression analysis to identify independent risk factors for peritoneal dissemination. Then, we constructed a nomogram for the prediction of GCPD and defined its predictive value with a receiver operating characteristic (ROC) curve. External validation was performed to validate the applicability of the nomogram. RESULTS In total, 250 patients were histologically identified as having peritoneal dissemination. Logistic regression analysis demonstrated that age, sex, tumor location, tumor size, signet-ring cell carcinoma (SRCC), T stage, N stage and Borrmann classification IV (Borrmann IV) were independent risk factors for peritoneal dissemination. We constructed a nomogram consisting of these eight factors to predict GCPD and found an optimistic predictive capability, with a C-index of 0.791, an area under the curve (AUC) of 0.791, and a 95% confidence interval (95% CI) of 0.762-0.820. The results found in the external validation set were also promising. CONCLUSIONS We constructed a highly sensitive nomogram that can assist clinicians in the early diagnosis of GCPD and serve as a reference for optimizing clinical management strategies.
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Affiliation(s)
- Xijie Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Shi Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Xinyou Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Runcong Nie
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Dongwen Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Jun Xiang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Yijia Lin
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Yingbo Chen
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Junsheng Peng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
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13
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Dong D, Tang L, Li ZY, Fang MJ, Gao JB, Shan XH, Ying XJ, Sun YS, Fu J, Wang XX, Li LM, Li ZH, Zhang DF, Zhang Y, Li ZM, Shan F, Bu ZD, Tian J, Ji JF. Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer. Ann Oncol 2020; 30:431-438. [PMID: 30689702 PMCID: PMC6442651 DOI: 10.1093/annonc/mdz001] [Citation(s) in RCA: 283] [Impact Index Per Article: 56.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. Patients and methods A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients’ PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. Results RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923–0.993], 0.941 (95% CI 0.904–0.977), 0.928 (95% CI 0.886–0.971), and 0.920 (95% CI 0.862–0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. Conclusion CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.
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Affiliation(s)
- D Dong
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Radiology Department, , Peking University Cancer Hospital & Institute, Beijing; University of Chinese Academy of Sciences, Beijing
| | - L Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Radiology Department, , Peking University Cancer Hospital & Institute, Beijing
| | - Z-Y Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing
| | - M-J Fang
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing; University of Chinese Academy of Sciences, Beijing
| | - J-B Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou
| | - X-H Shan
- Department of Radiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang
| | - X-J Ying
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing
| | - Y-S Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Radiology Department, , Peking University Cancer Hospital & Institute, Beijing
| | - J Fu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Radiology Department, , Peking University Cancer Hospital & Institute, Beijing
| | - X-X Wang
- Department of Radiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang
| | - L-M Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou
| | - Z-H Li
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming
| | - D-F Zhang
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming
| | - Y Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing
| | - Z-M Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing
| | - F Shan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing
| | - Z-D Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing
| | - J Tian
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing; University of Chinese Academy of Sciences, Beijing; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, China.
| | - J-F Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing.
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14
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Zhao B, Huang X, Zhang J, Luo R, Lu H, Xu H, Huang B. Clinicopathologic factors associated with recurrence and long-term survival in node-negative advanced gastric cancer patients. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 111:111-120. [PMID: 30404528 DOI: 10.17235/reed.2018.5829/2018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND despite a better prognosis in node-negative advanced gastric cancer (GC), a proportion of patients have a tumor recurrence within five years and eventually die due to cancer-related causes. The present study aimed to evaluate the predictive factors of tumor recurrence and long-term survival in node-negative advanced GC. METHODS a total of 646 node-negative advanced GC patients who underwent a curative gastrectomy in our institution were included in the study. The impact of different clinicopathologic factors on tumor recurrence and overall survival were analyzed. RESULTS tumor recurrences were observed in 181 patients and the cumulative recurrence rate at two-years and five-years were 50.8% and 86.2%, respectively. Lymphovascular invasion, advanced T stage (T3-T4) and an inadequate number of retrieved lymph nodes (LNs) were independent predictive factors of tumor recurrence in node-negative advanced GC. Older age, an upper 1/3 tumor, lymphovascular invasion, infiltration growth pattern (INFγ) and the depth of tumor invasion (T4 stage) were independently associated with long-term survival. With regard to node-negative patients with ≥ 15 retrieved LNs, infiltration growth pattern (INFγ) and advanced T stage (T3-T4) were independent risk factors for both tumor recurrence and long-term survival. CONCLUSION in addition to lymphovascular invasion, inadequate RLNs and advanced T stage, the prognostic significance of infiltration growth pattern in node-negative advanced GC was especially emphasized. These risk factors should be considered when selecting candidates for adjuvant chemotherapy and postoperative surveillance.
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Affiliation(s)
- Bochao Zhao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, China
| | - Xinyu Huang
- Department of Clinical Medicine of year 2013, Liaoning University of Traditional Chinese Medicine
| | - Jiale Zhang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, China
| | - Rui Luo
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, China
| | - Huiwen Lu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, China
| | - Huimian Xu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, China
| | - Baojun Huang
- Department of Surgical Oncology, Affiliated Hospital of China Medical University, China
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Genomewide Expression Profiling Identifies a Novel miRNA-Based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer. Ann Surg 2019; 274:e425-e434. [PMID: 31663973 DOI: 10.1097/sla.0000000000003647] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.
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16
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Molecular Profiles and Metastasis Markers in Chinese Patients with Gastric Carcinoma. Sci Rep 2019; 9:13995. [PMID: 31570735 PMCID: PMC6769015 DOI: 10.1038/s41598-019-50171-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 09/06/2019] [Indexed: 02/08/2023] Open
Abstract
The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. PTPRT is significantly associated with metastasis of GC, suggesting its predictive role in metastasis of GC. Patients carrying BRCA2 mutations tend not to metastasize, which may be related to their sensitivity to chemotherapy. Mutations in MACF1, CDC27, HMCN1, CDH1 and PDZD2 were moderately enriched in peritoneal metastasis (PM) samples. Furthermore, we found two genomic regions (1p36.21 and Xq26.3) were associated with PM of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (P = 0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies.
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Hølmebakk T, Bjerkehagen B, Lobmaier IVK, Hompland I, Stoldt S, Boye K. Is Peritoneal Tumor Penetration of Prognostic Importance in Gastrointestinal Stromal Tumors? Ann Surg Oncol 2019; 26:4730-4736. [PMID: 31520212 DOI: 10.1245/s10434-019-07813-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Indexed: 11/18/2022]
Abstract
BACKGROUND Peritoneal tumor penetration (PP) strongly affects prognosis in gastrointestinal carcinomas. In gastrointestinal stromal tumor (GIST), its significance in the absence of tumor rupture has not been subjected to detailed analysis. METHODS Patients undergoing complete resection for non-metastatic GIST from 2000 to 2017 were identified in the regional sarcoma database at Oslo University Hospital. Patients with extraperitoneal tumors (esophagus, rectum) or ruptured tumors were excluded from the study. Rupture was defined according to the Oslo criteria, and PP was assessed via routine histopathologic examination by sarcoma pathologists. RESULTS The study enrolled 341 patients. The median follow-up period was 51 months (range 0-175) months. In 82 (24%) of the 341 patients, PP was recorded. There were 32 recurrences, 9 in patients with PP and 23 in patients without PP. Despite statistically significant associations between PP and established risk factors (size, mitotic index, non-gastric location), the 5-year recurrence-free survival rate did not differ between the patients with PP (86%) and those without PP (90%) (hazard ratio 1.25; 95% confidence interval 0.58-2.70; P = 0.577). Adjuvant imatinib was administered to 53 of 97 patients in the high-risk category. The recurrence rates did not differ between the PP-positive and PP-negative patients in either group. CONCLUSIONS In GIST, PP without tumor rupture appears not to influence prognosis. This lack of prognostic significance may reflect unexplored differences between epithelial and mesenchymal malignancies.
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Affiliation(s)
- T Hølmebakk
- Department of Abdominal and Pediatric Surgery, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
| | - B Bjerkehagen
- Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.,Institute of Clinical Medicine and Institute of Oral Biology, University of Oslo, Oslo, Norway
| | - I V K Lobmaier
- Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - I Hompland
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - S Stoldt
- Department of Abdominal and Pediatric Surgery, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - K Boye
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
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18
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Lin S, Zhang Y, Hu Y, Yang B, Cui J, Huang J, Wang JM, Xing R, Lu Y. Epigenetic downregulation of MUC17 by H. pylori infection facilitates NF-κB-mediated expression of CEACAM1-3S in human gastric cancer. Gastric Cancer 2019; 22:941-954. [PMID: 30778796 PMCID: PMC8320707 DOI: 10.1007/s10120-019-00932-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Helicobacter pylori invades the mucosal barrier and infects the mucins of gastric epithelial cells. However, whether gastric carcinogenesis caused by H. pylori infection involves the membrane-bound mucins is unclear. This study explored the role of mucin 17 (MUC17) in gastric cancer (GC) associated with H. pylori infection. METHODS The expression of MUC17 and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was examined in human GC cells and tissues with H. pylori infection. Gain- and loss-of-function assays were performed to assess the role of MUC17 in regulating CEACAM1 in H. pylori-infected GC cells. RESULTS MUC17 was downregulated in H. pylori-infected GC cells and tissues in association with poor survival of GC patients. Downregulation of MUC17 was attributable to MUC17 promoter methylation mediated by DNA methyltransferase 1 (DNMT1) H. pylori-enhanced GC cell proliferation and colony formation associated with MUC17 downregulation. Gain- and loss-of-function assays showed that MUC17 inhibited the H. pylori-enhanced GC cell growth by preventing the translocation of H. pylori CagA into GC cells. Moreover, MUC17 downregulated the expression of CEACAM1 variant 3S (CEACAM1-3S) in GC cells and tissues with H. pylori infection. Additionally, MUC17 downregulated CEACAM1 promoter activity via attenuation of NF-κB activation in GC cells. CONCLUSIONS MUC17 was epigenetically downregulated in GC with H. pylori infection. MUC17 inhibited H. pylori CagA translocation via attenuation of NF-κB-mediated expression of CEACAM1-3S in GC cells. Thus, MUC17 may serve as a valuable prognostic biomarker for H. pylori-associated GC.
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Affiliation(s)
- Shuye Lin
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
| | - Yaping Zhang
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
| | - Yingqi Hu
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
| | - Bing Yang
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
| | - Jiantao Cui
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
| | - Jiaqiang Huang
- College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuancun, Haidian District, Beijing 100044, People’s Republic of China,Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
| | - Ji Ming Wang
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
| | - Rui Xing
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
| | - Youyong Lu
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China
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19
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Zhao B, Zhang J, Mei D, Huang X, Zou S, Luo R, Xu H, Huang B. Prognostic significance of tumour infiltration growth pattern in patients with advanced gastric cancer. J Clin Pathol 2018; 72:165-171. [DOI: 10.1136/jclinpath-2018-205403] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 10/29/2018] [Accepted: 11/03/2018] [Indexed: 11/03/2022]
Abstract
AimsThe prognostic significance of infiltration growth pattern (INF) in patients with gastric cancer (GC) remains controversial. In the present study, we evaluated the impact of INF pattern on the prognosis of patients with advanced GC.MethodsA total of 1455 patients with advanced GC who underwent curative gastrectomy in our institution were retrospectively analysed. All patients were histopathologically classified as INFa/b and INFc pattern according to the Japanese Classification of Gastric Cancer. The prognostic difference between two patterns was compared and clinicopathological features were analysed.ResultsThe prognosis of the patients with INFc pattern was poorer than that of those with INFa/b pattern (5-year disease-free survival, INFa/b: 48.4% vs INFc: 33.5%, p < 0.001), even when they were stratified according to lymph node metastasis and the tumour, node, metastases stage. In addition, the subgroup analysis indicated that INFc pattern was significantly associated with poorer prognosis of T2–T3 stage patients (T2, INFa/b: 72.7% vs INFc: 55.4%; T3, INFa/b: 47.4% vs INFc: 33.5%; p<0.001). However, a similar result was not observed among T4a stage patients (INFa/b: 26.8% vs INFc: 24.8%, p>0.05). The prognosis of T2 stage patients with INFc pattern was similar to that of T3 stage patients with INFa/b pattern (p>0.05). Also, there was no significantly prognostic difference between T3 stage patients with INFc pattern and T4a stage patients (p>0.05). The multivariate analysis indicated that INF pattern was an independent prognostic factor for patients with advanced GC (HR 1.259, 95%CI 1.089 to 1.454).ConclusionIn view of its prognostic significance, histopathological evaluation of INF pattern in surgically resected specimens should be recommended in patients with advanced GC.
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Nakagawa N, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y. Pathological tumor infiltrative pattern and sites of initial recurrence in stage II/III gastric cancer: Propensity score matching analysis of a multi-institutional dataset. Cancer Med 2018; 7:6020-6029. [PMID: 30411544 PMCID: PMC6308072 DOI: 10.1002/cam4.1868] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 09/27/2018] [Accepted: 10/22/2018] [Indexed: 12/23/2022] Open
Abstract
Background Advanced gastric cancer frequently recurs even after radical resection followed by adjuvant chemotherapy. The aim of this study was to evaluate the relationship between pathological infiltrative pattern (INF) and initial recurrence patterns in patients with stage II/III gastric cancer using a large multicenter database. Methods We retrospectively analyzed 1098 eligible patients who underwent curative gastrectomy for stage II/III gastric cancer at nine institutions between 2010 and 2014. Patients were categorized into the INF‐a/b and INF‐c groups and adjusted using propensity score matching. Results After propensity score matching, 686 patients (343 for each) were classified in the INF‐a/b and INF‐c groups. There were no significant differences in overall and disease‐free survival between the two groups. In the INF‐a/b group, frequencies of recurrence at the peritoneum, lymph node, and liver were equivalent. In contrast, the peritoneum was the most frequent site and accounted for 60% of the total recurrences in the INF‐c group. The cumulative peritoneal recurrence rate was significantly higher in the INF‐c group than in the INF‐a/b group (hazard ratio 2.47). INF‐c was a significant risk factor for peritoneal recurrences in most subgroups including age, sex, macroscopic type, tumor differentiation, and disease stage, and whether the postoperative treatment was given. Multivariate analysis identified INF‐c as an independent risk factor for peritoneal recurrences. The cumulative liver recurrence rate was significantly higher in the INF‐a/b group than in the INF‐c group (hazard ratio 3.44). Conclusions INF may represent an important predictor of recurrence patterns after curative resection of stage II/III gastric cancer.
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Affiliation(s)
- Nobuhiko Nakagawa
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | | | - Hitoshi Teramoto
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan
| | | | - Toshifumi Murai
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Takahiro Asada
- Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | | | | | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Murotani
- Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Li F, Shi J, Xu Z, Yao X, Mou T, Yu J, Liu H, Li G. S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition. J Cancer 2018; 9:3839-3849. [PMID: 30410586 PMCID: PMC6218764 DOI: 10.7150/jca.25469] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 07/17/2018] [Indexed: 12/16/2022] Open
Abstract
Driver genes conducing to peritoneal metastasis in advanced gastric cancer remain to be clarified. S100A4 is suggested to evolve in metastasis of gastrointestinal cancer, we aim to explore the role of S100A4 plays in metastasis of advanced gastric cancer and the potential mechanism. Transfection of siRNA or cDNA was applied to alter the expression of protein S100A4 and MYH9, investigation of the expression of epithelial and mesenchymal transition (EMT) associated markers was followed. Cell migration assay was used to screen the alteration of migration ability regulated by S100A4 and MYH9. IHC analysis for tissue sample microarray was performed to reveal their relationship with clinical pathological parameters and potential capacity of predicting survival. Consistent overexpression of S100A4 and MYH9 were found in peritoneal metastasis and primary site compared with adjacent normal tissue. Low expression of S100A4 led to increased epithelial markers as wells as decline of mesenchymal makers, while overexpression of S100A4 led to inverse impact. S100A4 expression was closely correlated with increased migration ability and EMT process induced by TGF-β stimulation. Interference of S100A4 led to downregulation of MYH9 and inactivation of Smad pathway through participating in EMT process, which could be reversed by overexpression of MYH9. Moreover, co-expression of S100A4 and MYH9 was identified in tissue microarray and confirmed by immunofluorescence assay. In conclusion, overexpression of S100A4 and downstream molecular MYH9 in advanced gastric cancer predicted poor prognosis; oncogene S100A4 facilitate EMT process induced by TGF-β stimulation, suggesting a potential target in management of peritoneal metastasis of gastric cancer.
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Affiliation(s)
- Fengping Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Jiaolong Shi
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Zhijun Xu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Xingxing Yao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Tingyu Mou
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Hao Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China
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Hydrogen Sulfide Demonstrates Promising Antitumor Efficacy in Gastric Carcinoma by Targeting MGAT5. Transl Oncol 2018; 11:900-910. [PMID: 29800930 PMCID: PMC6041565 DOI: 10.1016/j.tranon.2018.04.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/16/2018] [Accepted: 04/16/2018] [Indexed: 12/29/2022] Open
Abstract
Mannosyl (alpha-1,6-)-Glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase (MGAT5) is exclusively expressed in gastric carcinoma, and plays an essential role in cancer progression, but no targeted drug is available so far. The potential anti-cancer effect of Hydrogen Sulfide (H2S), has not been widely recognized. It intrigued broad interest to explore the clinical benefits of cancer therapy, with the current understanding of molecular mechanisms of H2S which remains very limited. In this study, we identify that H2S is an effective inhibitor of MGAT5, leading to reduce the expression of exclusively abnormal glycoprotein processes in gastric carcinoma. H2S specifically dissociation of karyopherin subunit alpha-2 (KPNA2) with Jun proto-oncogene (c-Jun) interaction, and blocking c-Jun nuclear translocation, and downregulation of MGAT5 expression at the level of gene and protein. Consequently, H2S impairs growth and metastasis in gastric carcinoma by targeting inhibits MGAT5 activity. In an animal tumor model study, H2S is well tolerated, inhibits gastric carcinoma growth and metastasis. Our preclinical work therefore supports that H2S acts as a novel inhibitor of MGAT5 that block tumorigenesis in gastric carcinoma. SIGNIFICANCE: This study shows that H2S can effective targeting inhibits MGAT5 activity, and demonstrates promising antitumor efficacy. These findings gain mechanistic insights into the anti-cancer capacity of H2S and may provide useful information for the clinical explorations of H2S in cancer treatment.
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Azarkhazin F, Tehrani GA. Detecting promoter methylation pattern of apoptotic genes Apaf1 and Caspase8 in gastric carcinoma patients undergoing chemotherapy. J Gastrointest Oncol 2018; 9:295-302. [PMID: 29755768 DOI: 10.21037/jgo.2017.12.05] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background DNA methylation patterns in cells dysregulation CpG island methylation of genes involved in cancer leads to increased levels of the cancer. Restoration of the apoptotic route in tumor cells of stomach in order for placing Casp8 and Apaf1 genes is a proper approach for new treatments of gastric cancer. The objective of the present study was to investigate the relationship between the pattern of methylation promoter in apoptotic genes of Casp8 and Apaf1 and gastric carcinoma in patients receiving chemotherapy. Methods Genomic DNA was extracted from 30 samples of FFPE tumor, normal tissues and blood samples. Hyper-methylation analysis of Casp8 and Apaf1 genes was conducted using MSP method; the results were analyzed through electrophoresis on agarose gel and software spss20. Results In this study, methylation rate of Apaf1 gene with (P>0.05) was not significant but methylation rate of Casp8 gene with (P<0.05) was significant. In addition, there was a significant relationship between Apaf1 gene methylation in blood with stage (P<0.05), Apaf1 gene methylation in tissue with stage (P<0.05) and grade (P<0.01) and between Casp8 gene methylation in blood with age (P<0.001) of patients but no significant relationship was seen for other factors. Conclusions Our results suggest that epigenetic mechanisms play an important role in the pathogenesis of gastric cancer and can be utilized as prognostic biomarkers for it. Also no significant difference between Casp8 and Apaf1 promoter hypermethylation in blood and tissue samples indicated that methylation status of blood sample can be early and non-invasive diagnostic marker in gastric cancer.
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Affiliation(s)
- Fatemeh Azarkhazin
- Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran
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Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study. Oncotarget 2018; 7:43894-43906. [PMID: 27270314 PMCID: PMC5190066 DOI: 10.18632/oncotarget.9707] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Accepted: 05/16/2016] [Indexed: 12/23/2022] Open
Abstract
Peritoneal metastasis occurs in more than half of patients with unresectable or recurrent gastric cancer and is associated with the worst prognosis. The associated genomic events and pathogenesis remain ambiguous. The aim of the present study was to characterize the mutation spectrum of gastric cancer with peritoneal metastasis and provide a basis for the identification of new biomarkers and treatment targets. Matched pairs of normal gastric mucosa and peritoneal tissue and matched pairs of primary tumor and peritoneal metastasis were collected from one patient for whole-exome sequencing (WES); Sanger sequencing was employed to confirm the somatic mutations. G>A and C>T mutations were the two most frequent transversions among the somatic mutations. We confirmed 48somatic mutations in the primary site and 49 in the peritoneal site. Additionally, 25 non-synonymous somatic variations (single-nucleotide variants, SNVs) and 2 somatic insertions/deletions (INDELs) were confirmed in the primary tumor, and 30 SNVs and 5 INDELs were verified in the peritoneal metastasis. Approximately 59% of the somatic mutations were shared between the primary and metastatic site. Five genes (TP53, BAI1, THSD1, ARID2, and KIAA2022) verified in our study were also mutated at a frequency greater than 5%in the COSMIC database. We also identified 9genes (ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16, and NCAM1) that were only mutated in metastasis and are expected to become treatment targets. In conclusion, we observed that the majority of the somatic mutations in the primary site persisted in metastasis, whereas several single-nucleotide polymorphisms occurred de novo at the second site.
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Agnes A, Biondi A, Ricci R, Gallotta V, D'Ugo D, Persiani R. Krukenberg tumors: Seed, route and soil. Surg Oncol 2017; 26:438-445. [PMID: 29113663 DOI: 10.1016/j.suronc.2017.09.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Revised: 08/28/2017] [Accepted: 09/09/2017] [Indexed: 01/10/2023]
Abstract
The aim of this narrative review was to summarize the current evidence on Krukenberg tumors (KTs), addressing what is known on their natural history and their impact on the clinical prognosis and which are the most appropriate management strategies to treat this condition. A literature search was conducted on Pubmed up to December 2016, selecting the most relevant studies on the basis of the scope of the review. KTs are ovarian metastases from primary signet-ring cell carcinomas., characterized by the presence of a sarcoma-like stroma. They have three possible routes of diffusion (lymphatic, peritoneal and hematogenous), but the preferential one is still unclear. Prognosis is dismal. When KTs are encountered in the clinical practice, it is reasonable to offer surgical resection to young, fit patients with limited disease. Palliative surgery should be considered for all patients with symptomatic disease. Further studies should clarify the clinicopathologic characteristics of KTs, their main routes of diffusion, and the possible role of prophylactic oophorectomy, lymphadenectomy and intraperitoneal chemotherapy. Molecular and transitional research should parallel the clinical one to help understanding the natural history of signet-ring cell carcinomas.
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Affiliation(s)
- Annamaria Agnes
- Polo Scienze Gastroenterologiche ed Endocrino-Metaboliche, Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario Agostino Gemelli Largo F. Vito, 1 00168 Rome, Italy
| | - Alberto Biondi
- Polo Scienze Gastroenterologiche ed Endocrino-Metaboliche, Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario Agostino Gemelli Largo F. Vito, 1 00168 Rome, Italy.
| | - Riccardo Ricci
- Polo Scienze Oncologiche ed Ematologiche, Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario Agostino Gemelli Largo F. Vito, 1 00168 Rome, Italy
| | - Valerio Gallotta
- Polo Scienze Della Salute Della Donna E Del Bambino, Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario Agostino Gemelli Largo F. Vito, 1 00168 Rome, Italy
| | - Domenico D'Ugo
- Polo Scienze Gastroenterologiche ed Endocrino-Metaboliche, Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario Agostino Gemelli Largo F. Vito, 1 00168 Rome, Italy
| | - Roberto Persiani
- Polo Scienze Gastroenterologiche ed Endocrino-Metaboliche, Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario Agostino Gemelli Largo F. Vito, 1 00168 Rome, Italy
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Liang H. Intraperitoneal chemotherapy for locally advanced gastric cancer to prevent and treat peritoneal carcinomatosis. Transl Gastroenterol Hepatol 2016; 1:62. [PMID: 28138628 DOI: 10.21037/tgh.2016.07.04] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 07/14/2016] [Indexed: 12/22/2022] Open
Abstract
Gastric cancer (GC) is one of the leading causes of cancer death in both sexes in the world. The overall survival (OS) of GC patients is still unsatisfactory. The peritoneal dissemination is the most common type of recurrence in advanced GC. The rationale for administering chemotherapeutic drugs directly into peritoneal cavity is supported by the relative transport barrier that is formed by the tissue surrounding the peritoneal space. Intraperitoneal (IP) chemotherapy with taxanes is safe and feasible. Further randomized phase III clinical trials are needed to validate IP chemotherapy with taxanes for peritoneal carcinomatosis (PC) from GC. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) used as prophylaxis against peritoneal recurrence in patients with high risk GC is safe, significantly improves the survival and reduces the risk of peritoneal recurrence. A drug delivery system with anticancer drugs seem to be have a pharmacokinetic advantage but further randomized clinical trials are needed to validate its effect.
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Affiliation(s)
- Han Liang
- Department of Gastric Cancer, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Treatment, Cancer Hospital, Tianjin Medical University, Tianjin 300060, China
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Yoshida M, Sugino T, Kusafuka K, Nakajima T, Makuuchi R, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M, Kawata N, Tanaka M, Kakushima N, Takizawa K, Ono H. Peritoneal dissemination in early gastric cancer: importance of the lymphatic route. Virchows Arch 2016; 469:155-61. [DOI: 10.1007/s00428-016-1960-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 04/03/2016] [Accepted: 05/12/2016] [Indexed: 12/12/2022]
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Pan Y, Lin S, Xing R, Zhu M, Lin B, Cui J, Li W, Gao J, Shen L, Zhao Y, Guo M, Wang JM, Huang J, Lu Y. Epigenetic Upregulation of Metallothionein 2A by Diallyl Trisulfide Enhances Chemosensitivity of Human Gastric Cancer Cells to Docetaxel Through Attenuating NF-κB Activation. Antioxid Redox Signal 2016; 24:839-54. [PMID: 26801633 PMCID: PMC4876530 DOI: 10.1089/ars.2014.6128] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS Metallothionein 2A (MT2A) and nuclear factor-kappaB (NF-κB) are both involved in carcinogenesis and cancer chemosensitivity. We previously showed decreased expression of MT2A and IκB-α in human gastric cancer (GC) associated with poor prognosis of GC patients. The present study investigated the effect of diallyl trisulfide (DATS), a garlic-derived compound, and docetaxel (DOC) on regulation of MT2A in relation to NF-κB in GC cells. RESULTS DATS attenuated NF-κB signaling in GC cells, resulting in G2/M cell cycle arrest and apoptosis, culminating in the inhibition of cell proliferation and tumorigenesis in nude mice. The anti-GC effect of DATS was attributable to its capacity to epigenetically upregulate MT2A, which in turn enhanced transcription of IκB-α to suppress NF-κB activation in GC cells. The combination of DATS with DOC exhibited a synergistic anti-GC activity accompanied by MT2A upregulation and NF-κB inactivation. Histopathologic analysis of GC specimens from patients showed a significant increase in MT2A expression following DOC treatment. GC patients with high MT2A expression in tumor specimens showed significantly improved response to chemotherapy and prolonged survival compared with those with low MT2A expression in tumors. INNOVATION AND CONCLUSION We conclude that DATS exerts its anti-GC activity and enhances chemosensitivity of GC to DOC by epigenetic upregulation of MT2A to attenuate NF-κB signaling. Our findings delineate a mechanistic basis of MT2A/NF-κB signaling for DATS- and DOC-mediated anti-GC effects, suggesting that MT2A may be a chemosensitivity indicator in GC patients receiving DOC-based treatment and a promising target for more effective treatment of GC by combination of DATS and DOC. Antioxid. Redox Signal. 24, 839-854.
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Affiliation(s)
- Yuanming Pan
- 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China
| | - Shuye Lin
- 2 College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuancun, Haidian District, Beijing, P.R. China .,3 Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland
| | - Rui Xing
- 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China
| | - Min Zhu
- 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China
| | - Bonan Lin
- 2 College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuancun, Haidian District, Beijing, P.R. China
| | - Jiantao Cui
- 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China
| | - Wenmei Li
- 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China
| | - Jing Gao
- 4 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University School of Oncology , Peking Cancer Hospital, Beijing, P.R. China
| | - Lin Shen
- 4 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University School of Oncology , Peking Cancer Hospital, Beijing, P.R. China
| | - Yuanyuan Zhao
- 5 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing, P.R. China
| | - Mingzhou Guo
- 6 Department of Gastroenterology and Hepatology, Chinese PLA General Hospital , Beijing, P.R. China
| | - Ji Ming Wang
- 3 Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland
| | - Jiaqiang Huang
- 2 College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuancun, Haidian District, Beijing, P.R. China .,3 Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland
| | - Youyong Lu
- 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China
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Hu YF, Deng ZW, Liu H, Mou TY, Chen T, Lu X, Wang D, Yu J, Li GX. Staging laparoscopy improves treatment decision-making for advanced gastric cancer. World J Gastroenterol 2016; 22:1859-1868. [PMID: 26855545 PMCID: PMC4724617 DOI: 10.3748/wjg.v22.i5.1859] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 10/19/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC).
METHODS: Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ2 test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics.
RESULTS: Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed.
CONCLUSION: Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy.
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Kanda M, Mizuno A, Fujii T, Shimoyama Y, Yamada S, Tanaka C, Kobayashi D, Koike M, Iwata N, Niwa Y, Hayashi M, Takami H, Nakayama G, Sugimoto H, Fujiwara M, Kodera Y. Tumor Infiltrative Pattern Predicts Sites of Recurrence After Curative Gastrectomy for Stages 2 and 3 Gastric Cancer. Ann Surg Oncol 2016; 23:1934-40. [PMID: 26847679 DOI: 10.1245/s10434-016-5102-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND In East Asia, the tumor infiltrative pattern (INF) has been routinely evaluated by hematoxylin and eosin-stained sections as a pathologic characteristic of surgically resected specimens. METHODS The infiltrative pattern of gastric cancer (GC) has been histopathologically classified as INFa (expansive growth), INFb (intermediate type) and INFc (infiltrative growth) according to the Japanese Classification of Gastric Carcinoma. The prognostic value and characteristics of the disease recurrence pattern for each INF type were assessed in 785 patients with various stages of GC and also in 243 patients with stages 2 and 3 GC. RESULTS Comparison of the overall survival experienced by patients independently of stage showed that INF was significantly associated with prognosis. Specifically, peritoneal metastasis was present in 91 % of stage 4 patients in the INFc group, whereas hepatic metastasis was present in 39 % of stage 4 patients in the INFa and INFb group. After curative gastrectomy of patients with stages 2 or 3 GC, INF was not significantly associated with survival. The prevalence of peritoneal recurrence was significantly higher in the INFc group than in the INFa and INFb group, whereas the prevalence of hepatic recurrence was significantly higher in the INFa and INFb group than in the INFc group. Multivariate analysis identified INFc as an independent risk factor for peritoneal recurrence after curative gastrectomy. The association of the INF type with the incidence of peritoneal recurrence was observed with all disease stages regardless whether the patient was given adjuvant chemotherapy or not. CONCLUSIONS Evaluation of the INF type shows promise for its role as a predictor of postoperative recurrence sites in patients with GC.
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Affiliation(s)
- Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Akira Mizuno
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsutomu Fujii
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshie Shimoyama
- Department of Pathology, Nagoya University Hospital, Nagoya, Japan
| | - Suguru Yamada
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masahiko Koike
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Naoki Iwata
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukiko Niwa
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideki Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Goro Nakayama
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroyuki Sugimoto
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Yuan H, Zheng B, Tu S. Clinical research of intraperitoneal implantation of sustained-release 5-fluorouracil in advanced colorectal cancer. World J Surg Oncol 2015; 13:320. [PMID: 26596801 PMCID: PMC4657249 DOI: 10.1186/s12957-015-0737-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 11/16/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The objective of this study was to investigate the safety and long-term clinical effect of intraperitoneal implantation of sustained-release 5-fluorouracil in patients with advanced colorectal cancer during radical resection. METHODS A total of 202 patients with advanced colorectal cancer undergoing radical operations were randomly divided into an experimental group (98 cases, intraoperative intraperitoneal implantation of sustained-release 5-fluorouracil 600 mg as local chemotherapy) and a control group (104 cases, without local chemotherapy). The clinical data of the two groups was compared including toxicity, complications, local recurrence rate, distant metastasis, disease-free survival, and 1-, 3-, and 5-year survival rates. RESULTS Both groups of patients were followed up for more than 5 years, the longest follow-up time was 7.5 years. Bone marrow suppression, hepato-renal function, postoperative anastomotic leakage, pelvic effusion, incision infection, the incidence of intestinal obstruction, venting time, and hospital stay after operation (days) between two groups had no statistical significant difference. Locoregional recurrence and liver metastasis rate were decreased significantly in experimental group (P = 0.04 and 0.04). Extensive peritoneal metastasis and other organ metastasis rates had no significant difference between two groups. In the experimental group, 1-, 3-, and 5-year survival rates were higher than in the control group (95.92 vs 87.50 %, 77.55 vs 64.42 %, and 56.12 vs 40.38 %), which had significant difference. Disease-free survival (DFS) of the experimental group was higher than that of the control group (χ (2) = 5.00, P = 0.025). CONCLUSIONS Intraperitoneal implantation of sustained-release 5-fluorouracil is safe for advanced colorectal cancer during radical resection, which can reduce locoregional recurrence rate and liver metastasis rate. The long-term efficacy was reliable, and long-term survival and disease-free survival rate can be improved.
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Affiliation(s)
- Hang Yuan
- The Surgical Department of Coloproctology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China
| | - Bo'an Zheng
- The Surgical Department of Coloproctology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China
| | - Shiliang Tu
- The Surgical Department of Coloproctology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
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Kwee RM, Kwee TC. Modern imaging techniques for preoperative detection of distant metastases in gastric cancer. World J Gastroenterol 2015; 21:10502-10509. [PMID: 26457011 PMCID: PMC4588073 DOI: 10.3748/wjg.v21.i37.10502] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 04/20/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
A substantial portion of patients with newly diagnosed gastric cancer has distant metastases (M1 disease). These patients have a very poor prognosis and it is generally accepted that they should be treated with noncurative intent. Because it dramatically changes prognosis and treatment plans, it is very important to diagnose distant metastases. In this article, the definition, pathways, incidence and sites of distant metastases in gastric cancer are described. Subsequently, the current performance of imaging in detecting distant metastases in newly diagnosed gastric cancer is outlined and future prospects are discussed.
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Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma. Sci Rep 2015; 5:13750. [PMID: 26330360 PMCID: PMC4557136 DOI: 10.1038/srep13750] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 08/04/2015] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis.
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Lee JW, Jo K, Cho A, Noh SH, Lee JD, Yun M. Relationship Between 18F-FDG Uptake on PET and Recurrence Patterns After Curative Surgical Resection in Patients with Advanced Gastric Cancer. J Nucl Med 2015; 56:1494-500. [PMID: 26251414 DOI: 10.2967/jnumed.115.160580] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 07/30/2015] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED This study evaluated the predictive value of 18F-FDG PET for distant metastasis-free survival and peritoneal recurrence-free survival as well as recurrence-free survival and overall survival after curative surgical resection in patients with advanced gastric cancer (AGC). METHODS Two hundred seventy-nine patients with AGC who underwent preoperative 18F-FDG PET and subsequent curative surgical resection were included. The tumor-to-normal liver uptake ratio (TLR) of cancer lesions was measured, and the prognostic significance of TLR and tumor factors for distant metastasis-free survival, peritoneal recurrence-free survival, recurrence-free survival, and overall survival was assessed. RESULTS The 5-y recurrence-free survival, peritoneal recurrence-free survival, distant metastasis-free survival, and overall survival rates were 46.9%, 68.5%, 76.0%, and 58.1%, respectively. Depth of tumor invasion, lymph node metastasis, lymphovascular invasion, and TLR were independent prognostic factors for both recurrence-free survival and overall survival (P<0.05). For distant metastasis-free survival, lymphovascular invasion and TLR were independent risk factors (P<0.05). In patients with a TLR of 2.0 or less, the 5-y distant metastasis-free survival rate was 95.5%; in patients with a TLR greater than 2.0, the 5-y distant metastasis-free survival rate was 68.8%. For peritoneal recurrence-free survival, TLR showed no statistical significance (P=0.7) whereas pT stage, lymph node metastasis, Lauren classification, and Bormann type were independent prognostic factors (P<0.05). CONCLUSION 18F-FDG uptake of AGC is an independent prognostic factor for distant metastasis-free survival, recurrence-free survival, and overall survival. The possibility of distant metastasis during follow-up should be considered in patients with high 18F-FDG uptake.
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Affiliation(s)
- Jeong Won Lee
- Department of Nuclear Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Kwanhyeong Jo
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Arthur Cho
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Noh
- Departement of Surgery, Yonsei University College of Medicine, Seoul, Korea; and
| | - Jong Doo Lee
- Department of Radiology, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Mijin Yun
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
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Mei LJ, Wang LW, Huang CQ, Yang XJ, Li Y. Oral gastrografin radiography for the evaluation of the functional impact of peritoneal carcinomatosis: Correlation with clinicopathological findings. Mol Clin Oncol 2015; 3:979-986. [PMID: 26623037 DOI: 10.3892/mco.2015.573] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 04/15/2015] [Indexed: 02/06/2023] Open
Abstract
This study was conducted to evaluate the functional impact of peritoneal carcinomatosis (PC) on the gastrointestinal system by oral gastrografin radiography (OGR). OGR was performed on 105 patients with PC from abdominal malignancies. The OGR characteristics were analyzed and compared with intraoperative observations. OGR provided real-time dynamic information on the functional impacts of PC. The OGR findings were normal in 9 (8.6%) and abnormal in 96 (91.4%) cases. In terms of frequency, 33 cases (31.4%) exhibited mild intestinal aggregation and flattening of the intestinal mucosa; 29 cases (27.6%) exhibited limited intestinal invasion, marginally stenotic small bowel and mucosal deformities; 26 cases (24.8%) exhibited only mild mesenteric contracture and mild slowing of gastrointestinal peristalsis; 5 cases (4.8%) exhibited obvious mesenteric contracture, ball-like changes, fixed position and disappearance of the intestinal mucosa; 2 cases (1.9%) exhibited complete pyloric obstruction; and 1 case (0.9%) exhibited duodenal obstruction. Gastric PC was associated with a higher percentage of stomach filling defects and small intestinal aggregates compared with PC from other malignancies (P<0.01 for both). In 87 cases, the ORG findings were in accordance with the intraoperative findings (κ=0.726, P<0.001), whereas 17 cases (16.2%) were underestimated and 1 (0.9%) was overestimated by OGR. This study indicated that OGR may be a useful technique for the evaluation of the functional impacts of PC on the gastrointestinal system and may help optimize the selection of patients for treatment.
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Affiliation(s)
- Lie-Jun Mei
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Lin-Wei Wang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
| | - Chao-Qun Huang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
| | - Xiao-Jun Yang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
| | - Yan Li
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
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Tokumitsu Y, Yoshino S, Iida M, Yoshimura K, Ueno T, Hazama S, Oka M. Intraoperative dissemination during gastrectomy for gastric cancer associated with serosal invasion. Surg Today 2014; 45:746-51. [DOI: 10.1007/s00595-014-1005-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 07/11/2014] [Indexed: 12/13/2022]
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Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F. Treatment of gastric cancer. World J Gastroenterol 2014; 20:1635-1649. [PMID: 24587643 PMCID: PMC3930964 DOI: 10.3748/wjg.v20.i7.1635] [Citation(s) in RCA: 479] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/29/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status
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