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Wu LW, Jang SJ, Shapiro C, Fazlollahi L, Wang TC, Ryeom SW, Moy RH. Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics. Target Oncol 2024; 19:845-865. [PMID: 39271577 PMCID: PMC11557641 DOI: 10.1007/s11523-024-01097-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2024] [Indexed: 09/15/2024]
Abstract
Diffuse-type gastric cancer (DGC) accounts for approximately one-third of gastric cancer diagnoses but is a more clinically aggressive disease with peritoneal metastases and inferior survival compared with intestinal-type gastric cancer (IGC). The understanding of the pathogenesis of DGC has been relatively limited until recently. Multiomic studies, particularly by The Cancer Genome Atlas, have better characterized gastric adenocarcinoma into molecular subtypes. DGC has unique molecular features, including alterations in CDH1, RHOA, and CLDN18-ARHGAP26 fusions. Preclinical models of DGC characterized by these molecular alterations have generated insight into mechanisms of pathogenesis and signaling pathway abnormalities. The currently approved therapies for treatment of gastric cancer generally provide less clinical benefit in patients with DGC. Based on recent phase II/III clinical trials, there is excitement surrounding Claudin 18.2-based and FGFR2b-directed therapies, which capitalize on unique biomarkers that are enriched in the DGC populations. There are numerous therapies targeting Claudin 18.2 and FGFR2b in various stages of preclinical and clinical development. Additionally, there have been preclinical advancements in exploiting unique therapeutic vulnerabilities in several models of DGC through targeting of the focal adhesion kinase (FAK) and Hippo pathways. These preclinical and clinical advancements represent a promising future for the treatment of DGC.
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Affiliation(s)
- Lawrence W Wu
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, 161 Fort Washington Avenue, Room 956, New York, NY, 10032, USA
| | - Sung Joo Jang
- Division of Surgical Sciences, Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA
| | - Cameron Shapiro
- Division of Surgical Sciences, Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA
| | - Ladan Fazlollahi
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Timothy C Wang
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Sandra W Ryeom
- Division of Surgical Sciences, Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA
| | - Ryan H Moy
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, 161 Fort Washington Avenue, Room 956, New York, NY, 10032, USA.
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2
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Lee D, Ham IH, Oh HJ, Lee DM, Yoon JH, Son SY, Kim TM, Kim JY, Han SU, Hur H. Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1. J Transl Med 2024; 22:154. [PMID: 38355577 PMCID: PMC10868052 DOI: 10.1186/s12967-024-04963-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 02/07/2024] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. METHODS We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). RESULTS CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. CONCLUSIONS These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.
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Affiliation(s)
- Dagyeong Lee
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
- Cancer Biology Graduate Program, Ajou University School of Medicine Suwon, Suwon, Republic of Korea
- AI-Super Convergence KIURI Translational Research Center, Ajou University School of Medicine, Suwon, Republic of Korea
| | - In-Hye Ham
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
- Inflamm-Aging Translational Research Center, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hye Jeong Oh
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Dong Min Lee
- Inflamm-Aging Translational Research Center, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jung Hwan Yoon
- Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Functional RNomics Research Center, College of Medicine, The Catholic University of Korea Seoul, Seoul, Republic of Korea
| | - Sang-Yong Son
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Tae-Min Kim
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Biomedicine and Health Science, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae-Young Kim
- Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Republic of Korea
| | - Sang-Uk Han
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hoon Hur
- Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea.
- Cancer Biology Graduate Program, Ajou University School of Medicine Suwon, Suwon, Republic of Korea.
- Inflamm-Aging Translational Research Center, Ajou University School of Medicine, Suwon, Republic of Korea.
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3
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Bolliet M, Green M, Damadi A. Gastric adenocarcinoma metastasis to the rectum causing complete obstruction, a case report. J Surg Case Rep 2023; 2023:rjad560. [PMID: 37873050 PMCID: PMC10590633 DOI: 10.1093/jscr/rjad560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/21/2023] [Indexed: 10/25/2023] Open
Abstract
Gastric adenocarcinoma is a leading cause of mortality worldwide. The most common sites of metastases are the liver, peritoneum, lungs, and bones. Cases have been described in the colon and rectum, but are very rare. This case report describes a patient in remission from diffuse signet ring cell type gastric adenocarcinoma with resection and chemoradiation close to 10 years prior to presenting with a near-obstructing rectal mass that was consistent with metastatic gastric adenocarcinoma. Gastric cancer spreads via hematogenous, lymphatic, peritoneal seeding, or local recurrence pathways. Given the length of time between initial presentation and eventual metastasis, the theory of dormancy is discussed and proposed as a possible cause in the delay of metastasis to the rectum. This highlights the importance of maintaining a high index of suspicion for recurrence and metastasis in a patient with a history of gastric cancer, who presents with a new obstructing rectal mass.
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Affiliation(s)
- Marine Bolliet
- Department of Surgery, Ascension Providence Hospital-Michigan State University College of Human Medicine, Soutfield Campus, 16001 West Nine Mile Road, Southfield, MI 48075, United States
| | - Mary Green
- Michigan State University College of Osteopathic Medicine, East Lansing, MI, United States
| | - Amir Damadi
- Department of Surgery, Ascension Providence Hospital-Michigan State University College of Human Medicine, Soutfield Campus, 16001 West Nine Mile Road, Southfield, MI 48075, United States
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4
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Li H, Fu X, Zhao J, Li C, Li L, Xia P, Guo J, Wei W, Zeng R, Wu J, Sun Y, Huang L, Wang X. EXOC4 Promotes Diffuse-Type Gastric Cancer Metastasis via Activating FAK Signal. Mol Cancer Res 2022; 20:1021-1034. [PMID: 35471457 PMCID: PMC9381130 DOI: 10.1158/1541-7786.mcr-21-0441] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 12/01/2021] [Accepted: 03/17/2022] [Indexed: 01/07/2023]
Abstract
In comparison with intestinal-type gastric cancer, diffuse-type gastric cancer (DGC) is more likely to recur, metastasize, and exhibit worse clinical outcomes; however, the underlying mechanism of DGC recurrence remains elusive. By employing an LC/MS-MS proteomic approach, we identified that exocyst complex component 4 (EXOC4) was significantly upregulated in DGC with recurrence, compared to those with nonrecurrence. High expression of EXOC4 was correlated with tumor metastasis and poor prognosis in patients with DGC. Moreover, EXOC4 promoted cell migration and invasion as well as the tumor metastasis of DGC cells. Mechanistically, EXOC4 regulated the phosphorylation of focal adhesion kinase (FAK) at Y397 sites by stimulating the secretion of integrin α5/β1/EGF and enhancing the interaction of FAK and integrin or EGFR. The FAK inhibitor VS-4718 reversed the metastasis mediated by EXOC4 overexpression and suppressed the tumor growth of patient-derived xenografts derived from DGC with high EXOC4 expression. The EXOC4-FAK axis could be a potential therapeutic target for patients with DGC with high expression of EXOC4. IMPLICATIONS The EXOC4-FAK axis promoted DGC metastasis and could be a potential therapeutic target for patients with DGC.
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Affiliation(s)
- Haojie Li
- Department of General Surgery, Zhongshan Hospital, General Surgery Research Institute, Fudan University, Shanghai, China
| | - Xuhong Fu
- Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Junjie Zhao
- Department of General Surgery, Zhongshan Hospital, General Surgery Research Institute, Fudan University, Shanghai, China
| | - Chen Li
- Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.,Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lingmeng Li
- Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Peiyan Xia
- University of Michigan-Shanghai Jiaotong University Joint Institute, Shanghai Jiao Tong University, Shanghai, China
| | - Jianping Guo
- Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenyi Wei
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Rong Zeng
- Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Jiarui Wu
- Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.,Corresponding Authors: Xuefei Wang, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7224; E-mail: ; Jiarui Wu, Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Phone: 212-030-5000; Fax: 212-032-5034; E-mail: ; Yihong Sun, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7269; E-mail: ; and Liyu Huang, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Phone: 213-420-7042; E-mail:
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, General Surgery Research Institute, Fudan University, Shanghai, China.,Corresponding Authors: Xuefei Wang, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7224; E-mail: ; Jiarui Wu, Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Phone: 212-030-5000; Fax: 212-032-5034; E-mail: ; Yihong Sun, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7269; E-mail: ; and Liyu Huang, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Phone: 213-420-7042; E-mail:
| | - Liyu Huang
- Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.,Corresponding Authors: Xuefei Wang, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7224; E-mail: ; Jiarui Wu, Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Phone: 212-030-5000; Fax: 212-032-5034; E-mail: ; Yihong Sun, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7269; E-mail: ; and Liyu Huang, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Phone: 213-420-7042; E-mail:
| | - Xuefei Wang
- Department of General Surgery, Zhongshan Hospital, General Surgery Research Institute, Fudan University, Shanghai, China.,Corresponding Authors: Xuefei Wang, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7224; E-mail: ; Jiarui Wu, Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Phone: 212-030-5000; Fax: 212-032-5034; E-mail: ; Yihong Sun, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Phone: 216-404-1990; Fax: 216-403-7269; E-mail: ; and Liyu Huang, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Phone: 213-420-7042; E-mail:
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5
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Agnes A, Biondi A, Persiani R, Laurino A, Reddavid R, De Giuli M, Sicoli F, Cananzi F, De Pascale S, Fumagalli U, Galli F, Rausei S, Lorenzon L, D'Ugo D. Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer. Gastric Cancer 2022; 25:629-639. [PMID: 34811622 DOI: 10.1007/s10120-021-01268-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 11/13/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). METHODS Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). RESULTS The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . CONCLUSIONS We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.
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Affiliation(s)
- Annamaria Agnes
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Alberto Biondi
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy.
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy.
| | - Roberto Persiani
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Antonio Laurino
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Rossella Reddavid
- Department of Oncology, Surgical Oncology and Digestive Surgery Unit, San Luigi University Hospital, University of Turin, Orbassano, Turin, Italy
| | - Maurizio De Giuli
- Department of Oncology, Surgical Oncology and Digestive Surgery Unit, San Luigi University Hospital, University of Turin, Orbassano, Turin, Italy
| | - Federico Sicoli
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Italy
| | - Ferdinando Cananzi
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Italy
| | - Stefano De Pascale
- Digestive Surgery, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy
| | - Uberto Fumagalli
- Digestive Surgery, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy
| | - Federica Galli
- ASST Sette Laghi, Presidio Ospedaliero Gallarate, Corso Leonardo da Vinci, 1, 21013, Gallarate, Italy
| | - Stefano Rausei
- ASST Sette Laghi, Presidio Ospedaliero Gallarate, Corso Leonardo da Vinci, 1, 21013, Gallarate, Italy
| | - Laura Lorenzon
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Domenico D'Ugo
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
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6
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Ooki A, Yamaguchi K. The dawn of precision medicine in diffuse-type gastric cancer. Ther Adv Med Oncol 2022; 14:17588359221083049. [PMID: 35281349 PMCID: PMC8908406 DOI: 10.1177/17588359221083049] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/31/2022] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide. The histology- and morphology-based Lauren classification of GC has been widely used for over 50 years in clinical practice. The Lauren classification divides GC into intestinal and diffuse types, which have distinct etiology, molecular profiles, and clinicopathological features. Diffuse-type GC (DGC) accounts for approximately 30% of GCs. Tumor cells lack adhesion and infiltrate the stroma as single cells or small subgroups, leading to easy dissemination in the abdominal cavity. Clinically, DGC has aggressive traits with a high risk of recurrence and metastasis, which results in unfavorable prognosis. Although systemic chemotherapy is the main therapeutic approach for recurrent or metastatic GC patients, clinical benefits are limited for patients with DGC. Therefore, it is urgent to develop effective therapeutic strategies for DGC patients. Considerable research studies have characterized the molecular and genomic landscape of DGC, of which tight junction protein claudin-18 isoform 2 (CLDN18.2) and fibroblast growing factors receptor-2 isoform IIIb (FGFR2-IIIb) are the most attractive targets because of their close association with DGC. Recently, the impressive results of two phase II FAST and FIGHT trials demonstrate proof-of-concept, suggesting that anti-CLDN18.2 antibody (zolbetuximab) and FGFR2-IIIb antibody (bemarituzumab) are promising approaches for patients with CLDN18.2-positive and FGFR2-IIIb-positive GC, respectively. In this review, we summarize the clinicopathological features and molecular profiles of DGC and highlight a potential therapeutic target based on the findings of pivotal clinical trials.
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Affiliation(s)
- Akira Ooki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
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7
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Tonello AS, Capelli G, Bao QR, Marchet A, Farinati F, Pawlik TM, Gregori D, Pucciarelli S, Spolverato G. A nomogram to predict overall survival and disease-free survival after curative-intent gastrectomy for gastric cancer. Updates Surg 2021; 73:1879-1890. [PMID: 34125428 PMCID: PMC8500903 DOI: 10.1007/s13304-021-01083-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 05/04/2021] [Indexed: 02/07/2023]
Abstract
An individual prediction of DFS and OS may be useful after surgery for gastric cancer to inform patients and to guide the clinical management. Patients who underwent curative-intent resection for gastric cancer between January 2010 and May 2020 at a single Italian institution were identified. Variables associated with OS and DFS were recorded and analysed according to univariable and multivariable Cox models. Nomograms predicting OS and DFS were built according to variables resulting from multivariable Cox models. Discrimination ability was calculated using the Harrell's Concordance Index. Overall, 168 patients underwent curative-intent resection. Nomograms to predict OS were developed including age, tumor size, tumor location, T stage, N stage, M stage and post-operative complications, while nomogram to predict DFS includes Lauren classification, and lymph node ratio (LNR). On internal validation, both nomograms demonstrated a good discrimination with a Harrell's C-index of 0.77 for OS and 0.71 for DFS. The proposed nomogram to predict DFS and OS after curative-intent surgery for gastric cancer showed a good discrimination on internal validation, and may be useful to guide clinician decision-making, as well help identify patients with high-risk of recurrence or with a poor estimated survival.
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Affiliation(s)
- Alice Sabrina Tonello
- First Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Giulia Capelli
- First Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Quoc Riccardo Bao
- First Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Alberto Marchet
- First Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Timothy M Pawlik
- Department of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Dario Gregori
- Unit of Biostatistics, Epidemiology, and Public Health, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy
| | - Salvatore Pucciarelli
- First Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy.
| | - Gaya Spolverato
- First Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
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8
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Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients With Malignant Ascites Secondary to Unresectable Gastric Cancer. Surg Laparosc Endosc Percutan Tech 2020; 30:55-61. [PMID: 32004214 DOI: 10.1097/sle.0000000000000380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND To compare the efficacy of 3 chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS From January 2010 to December 2013, 38 GC patients were randomly divided into 3 groups and treated by laparoscopic HIPPC with 1 of the 3 following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin (L-OHP), Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the 3 groups. RESULTS The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months and the median survival was 7.5 months for all patients. Patients in the Ra/L-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/L-OHP group and Ra/MMC group is significantly longer than Ra/DDP group (P<0.05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky performance scale, and incidence rate of port-site metastases among the 3 groups. CONCLUSIONS Laparoscopy-assisted HIPPC provide modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutical combination of Ra/L-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.
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9
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Iyer P, Moslim M, Farma JM, Denlinger CS. Diffuse gastric cancer: histologic, molecular, and genetic basis of disease. Transl Gastroenterol Hepatol 2020; 5:52. [PMID: 33073047 DOI: 10.21037/tgh.2020.01.02] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 01/15/2020] [Indexed: 12/24/2022] Open
Abstract
Diffuse gastric cancer (DGC) is a distinct histopathologic and molecular disease, characterized by mutations in CDH1, RHOA, and others. In addition, DGC is associated with familial syndromes, including hereditary DGC and germline mutation in CDH1. Clinically, this subtype of gastric adenocarcinoma is associated with a poor prognosis and possible resistance to available systemic therapies. An understanding of the genetic and molecular underpinnings of DGC may help inform of its clinical behavior and aid in screening, diagnosis, and response to treatment. In this review, we will review the current histologic, molecular, and genetic landscape of DGC and its relevance to clinical practice.
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Affiliation(s)
- Pritish Iyer
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Maitham Moslim
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Jeffrey M Farma
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Crystal S Denlinger
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
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10
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Agnes A, Biondi A, Laurino A, Strippoli A, Ricci R, Pozzo C, Persiani R, D'Ugo D. A detailed analysis of the recurrence timing and pattern after curative surgery in patients undergoing neoadjuvant therapy or upfront surgery for gastric cancer. J Surg Oncol 2020; 122:293-305. [PMID: 32350878 DOI: 10.1002/jso.25959] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 04/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES The aim of this study was to determine whether the administration of neoadjuvant therapy (NAD) affects the incidence, timing, and pattern of recurrence in patients treated by curative gastrectomy. METHODS Sixty-nine patients undergoing NAD and R0 gastrectomy were compared with 198 patients undergoing upfront surgery using the propensity score matching (PSM) method. Disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) analyses were conducted with a log-rank test and Cox regression. Risk factors for recurrence were assessed by logistic regression. RESULTS Among 69 patients with NAD, 28 (40.6%) experienced recurrence, and signet-ring cell (SRC) carcinoma was the only factor independently associated with recurrence. In the whole sample, NAD did not influence DFS, DSS, rate of recurrence, or PFS. After PSM, the variables associated with DFS were cN1, type of gastrectomy, the presence of SRCs, and the presence of lymphovascular invasion. Variables independently associated with recurrence were cN1, type of gastrectomy, and the presence of SRCs. CONCLUSIONS NAD had no impact on DFS, DSS, or the pattern of recurrence in any patients with gastric cancer. To define a better treatment strategy, future studies should focus on subtypes that do not respond to the current neoadjuvant regimens.
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Affiliation(s)
- Annamaria Agnes
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Alberto Biondi
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Laurino
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Antonia Strippoli
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Riccardo Ricci
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carmelo Pozzo
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Persiani
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Domenico D'Ugo
- Dipartimento Scienze Mediche e Chirurgiche, UOC di Chirurgia Generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
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11
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Zhou W, Zhang Y, He F, Lv S, Zhang X, Fei C. Abundance of CD163-Positive Tumor-Associated Macrophages in the Early Gastric Cancer Predicts the Recurrence after Curative Resection. Dig Dis 2020; 38:458-465. [PMID: 32721976 DOI: 10.1159/000506122] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 01/23/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND We aimed to investigate the prognostic value of M2 macrophages to predict the recurrence of early gastric cancer (EGC). METHODS A retrospective analysis was carried out among EGC patients (95 non-recurrence and 78 recurrence) who underwent surgery at Luhe People's Hospital of Nanjing. A 5-year recurrence status was utilized to classify the patients into the recurrence group and non-recurrence group. CD163 and proliferating cell nuclear antigen were utilized as markers to detect M2 macrophages and proliferation. Cumulative tumor recurrence curve was adopted to analyze the association between the number of tumor-associated macrophages (TAMs) and the recurrence of EGC. Colony formation and invasion abilities of MKN45 (JCRB0254, human gastric epithelial cell line) with or without M2 macrophage coculture were detected in vitro, and the xenograft model was utilized to detect in vivo effect of M2 macrophages on tumor growth. RESULTS The number of CD163+ macrophages and expression of transforming growth factor-β1, matrix metallopeptidase 9, and vascular endothelial growth factor A were significantly different between the EGC recurrence and non-recurrence group. The cumulative tumor recurrence rate was found to be dependent on the infiltration number of TAMs. M2 macrophages promoted the proliferation and invasion of human MKN45 cells in vitro, as well as tumor growth in the xenograft model. CONCLUSION The abundance of CD163+-positive TAMs in EGC predicts the recurrence after curative resection.
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Affiliation(s)
- Wenxing Zhou
- Department of General Surgery, Luhe People's Hospital of Nanjing, Nanjing, China
| | - Yiyang Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Fei He
- Department of Gastroenterology, Luhe People's Hospital of Nanjing, Nanjing, China
| | - Shaohua Lv
- Department of Gastroenterology, Luhe People's Hospital of Nanjing, Nanjing, China
| | - Xiaodong Zhang
- Department of Gastroenterology, Luhe People's Hospital of Nanjing, Nanjing, China
| | - Chunming Fei
- Department of Gastroenterology, Luhe People's Hospital of Nanjing, Nanjing, China,
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12
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Jiang Y, Huang W, Xie J, Han Z, Chen C, Xi S, Sun Z, Hu Y, Zhao L, Yu J, Li T, Zhou Z, Cai S, Li G. Young age increases risk for lymph node positivity in gastric cancer: A Chinese multi-institutional database and US SEER database study. J Cancer 2020; 11:678-685. [PMID: 31942191 PMCID: PMC6959045 DOI: 10.7150/jca.37531] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 10/26/2019] [Indexed: 12/15/2022] Open
Abstract
Object: The risk of lymph node positivity (LN+) in gastric cancer (GC) impacts therapeutic recommendations. The aim of this study was to quantify the effect of younger age on LN+. Methods: Data from a Chinese multi-institutional database and the US SEER database on stage I to III resected GC were analyzed for the relationship between age and LN+ status. The association of age and LN+ status was examined with logistic regression separately for each T stage, adjusting for multiple covariates. Poisson regression was used to evaluate age and number of LN+. Results: 4,905 and 14,877 patients were identified in the China and SEER datasets respectively. 479 (9.8%) patients were under age 40 years, with 768 (15.7%) between age 40 and 49 years in China dataset, and 416 (2.8%) patients were under age 40 years, with 1176 (7.9%) between age 40 and 49 years in SEER dataset. Both datasets exhibited significantly proportional decreases of N3a and N3b LN+ with age increasing. Patients younger than age 40 years were more likely to show LN+ compared with the reference age 60 to 69 years. The youngest patients had the highest ORs of N1, N2, N3a, and N3b vs N0 LN+ within T4 stage of China dataset and T3 stage of SEER dataset, the values of ORs decreased with increasing age. Young age was a predictor of an increased number of LNs positive for each T stage. Conclusion: In the two large datasets, young age at diagnosis is associated with an increased risk of LN+.
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Affiliation(s)
- Yuming Jiang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Weicai Huang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Jingjing Xie
- Center for Drug and Clinical Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhen Han
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Chuanli Chen
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, 510515 Guangzhou, China
| | - Sujuan Xi
- Guangdong Key Laboratory of Liver Disease Research, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Zepang Sun
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Yanfeng Hu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Liying Zhao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Tuanjie Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, P. R. China, 510060
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China, 510060
| | - Shirong Cai
- Department of Gastrointestinal Surgery of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510700, Guangdong, China
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China
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13
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Rawicz-Pruszyński K, Mielko J, Pudło K, Lisiecki R, Skoczylas T, Murawa D, Polkowski WP. Yield of staging laparoscopy in gastric cancer is influenced by Laurén histologic subtype. J Surg Oncol 2019; 120:1148-1153. [PMID: 31544969 DOI: 10.1002/jso.25711] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 09/10/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Staging laparoscopy (SL) with cytologic lavage is a useful staging procedure that allows tailoring the treatment of advanced gastric cancer (GC). The current study aimed to evaluate the total yield of SL in patients with various Laurén histo-types of GC, before planned neoadjuvant chemotherapy and gastrectomy. METHODS After exclusion of distant metastatic disease on imaging modalities, 173 patients with primary advanced gastric adenocarcinoma who underwent SL between August 2016 and September 2018, were eligible for the analysis. Patients sex, age, Lauren histo-type, tumor location, grade, cT, and cN were assessed in bivariate analysis. Multivariable logistic regression analysis was used to identify independent factors associated with peritoneal metastases. RESULTS Peritoneal metastases, ascites, and positive cytology were found in 39 (22.5%), 17 (9.8%) and 38 (22%) patients, respectively. The total yield of the SL in the current study was 36.4%. Multivariable logistic regression analysis revealed that serosal involvement (cT4) and diffuse histo-type were independent predictors of peritoneal metastases (OR, 15; 95% CI, 1.9-119, P = .02 and OR, 2.4; 95% CI, 1.2-4.6, P = .01, respectively). CONCLUSIONS Although cT4 and diffuse tumors show the highest association with peritoneal metastases, SL is a valuable diagnostic procedure in all advanced GC patients.
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Affiliation(s)
| | - Jerzy Mielko
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Kamil Pudło
- Department of General, Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University of Lublin, Lublin, Poland
| | - Radosław Lisiecki
- Department of General Surgery and Oncological Surgery, Pleszewskie Medical Center, Pleszew, Poland
| | - Tomasz Skoczylas
- Department of General, Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University of Lublin, Lublin, Poland
| | - Dawid Murawa
- Department of Surgery and Oncology, University of Medical Science, Zielona Góra, Poland
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Shen J, Cao B, Wang Y, Xiao A, Qin J, Wu J, Yan Q, Hu Y, Yang C, Cao Z, Hu J, Yin P, Xie D, Gong J. Prospective randomized controlled trial to compare laparoscopic distal gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision, D2 + CME) with conventional D2 lymphadenectomy for locally advanced gastric adenocarcinoma: study protocol for a randomized controlled trial. Trials 2018; 19:432. [PMID: 30092843 PMCID: PMC6085680 DOI: 10.1186/s13063-018-2790-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 07/05/2018] [Indexed: 12/13/2022] Open
Abstract
Background Although radical gastrectomy with D2 lymph node dissection has become the standard surgical approach for locally advanced gastric cancer, patients still have a poor prognosis after operation. Previously, we proposed laparoscopic distal gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision [D2 + CME]) as an optimized surgical procedure for locally advanced gastric cancer. By dissection along the boundary of the mesogastrium, D2 + CME resected proximal segments of the dorsal mesogastrium completely with less blood loss, and it improved the short-term surgical outcome. However, the oncologic therapeutic effect of D2 + CME has not yet been confirmed. Methods/design A single-center, prospective, parallel-group, randomized controlled trial of laparoscopic distal gastrectomy with D2 + CME versus conventional D2 was conducted for patients with locally advanced gastric cancer at Tongji Hospital, Wuhan, China. In total, 336 patients who met the following eligibly criteria were included and were randomized to receive either the D2 + CME or D2 procedure: (1) pathologically proven adenocarcinoma; (2) 18 to 75 years old; cT2–4, N0–3, M0 at preoperative evaluation; (3) expected curative resection via laparoscopic distal gastrectomy; (4) no history of other cancer, chemotherapy, or radiotherapy; (5) no history of upper abdominal operation; and (6) perioperative American Society of Anesthesiologists class I, II, or III. The primary endpoint is 3 years of disease-free survival. The secondary endpoints are overall survival, recurrence pattern, mortality, morbidity, postoperative recovery course, and other parameters. Discussion Previous studies have demonstrated the safety and feasibility of D2 + CME for locally advanced gastric cancer; however, there is still a lack of evidence to support its therapeutic effect. Thus, we performed this randomized trial to investigate whether D2 + CME can improve oncologic outcomes of patients with locally advanced gastric cancer. The findings from this trial may potentially optimize the surgical procedure and may improve the prognosis of patients with locally advanced gastric cancer. Trial registration ClinicalTrials.gov, NCT01978444. Registered on October 31, 2013. Electronic supplementary material The online version of this article (10.1186/s13063-018-2790-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jie Shen
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Beibei Cao
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Yatao Wang
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Aitang Xiao
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Jichao Qin
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Jianhong Wu
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Qun Yan
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Yuanlong Hu
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Chuanyong Yang
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Zhixin Cao
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Junbo Hu
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China
| | - Ping Yin
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Daxing Xie
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China.
| | - Jianping Gong
- Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China.
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15
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Qiu MZ, Shi SM, Chen ZH, Yu HE, Sheng H, Jin Y, Wang DS, Wang FH, Li YH, Xie D, Zhou ZW, Yang DJ, Xu RH. Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: A SEER-based study. Cancer Med 2018; 7:3662-3672. [PMID: 29984918 PMCID: PMC6089142 DOI: 10.1002/cam4.1661] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 06/05/2018] [Accepted: 06/15/2018] [Indexed: 12/18/2022] Open
Abstract
The hematogenous metastatic pattern of gastric cancer (GC) was not fully explored. Here we analyzed the frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from GC patients. Data queried for this analysis included GC patients from the Surveillance, Epidemiology, and End Results Program database from 2010 to 2014. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). All statistical tests were two‐sided. Totally, there were 19 022 eligible patients for analysis. At the time of diagnosis, there were 7792 patients at stage IV, including 3218 (41.30%) patients with liver metastasis, 1126 (14.45%) with lung metastasis, 966 (12.40%) with bone metastasis and 151 (1.94%) with brain metastasis. GC patients with lung or liver metastasis have a higher risk of bone and brain metastasis than those without lung nor liver metastasis. Intestinal subtype had significantly higher rate of liver and lung metastasis, while diffuse type was more likely to have bone metastasis. Proximal stomach had significantly higher risk to develop metastasis than distal stomach. African‐Americans had the highest risk of liver metastasis and Caucasian had the highest prone to develop lung and brain metastasis. The median survival for patients with liver, lung, bone, and brain metastasis was 4 months, 3 months, 4 months and 3 months, respectively. It is important to evaluate the status of bone and brain metastasis in GC patients with lung or liver metastasis. Knowledge of metastatic patterns is helpful for clinicians to design personalized pretreatment imaging evaluation for GC patients.
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Affiliation(s)
- Miao-Zhen Qiu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Si-Mei Shi
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Nursing, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhan-Hong Chen
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Hong-En Yu
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Hui Sheng
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Ying Jin
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - De-Shen Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Feng-Hua Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yu-Hong Li
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Dan Xie
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhi-Wei Zhou
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Da-Jun Yang
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Rui-Hua Xu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
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16
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Marrelli D, Polom K, Neri A, Roviello F. Clinical impact of molecular classifications in gastric cancer. Updates Surg 2018; 70:225-232. [PMID: 29796937 DOI: 10.1007/s13304-018-0546-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 05/15/2018] [Indexed: 02/08/2023]
Abstract
Treatment options to gastric cancer (GC) have been changing in recent years from a standard to a tailored approach. Different individualized procedures can range from endoscopic resection, D2 with open or minimally invasive approach, to neo-adjuvant therapy followed by extended surgery. In more advanced stages, a combined approach with the inclusion of intraperitoneal chemo-hyperthermia (HIPEC) may represent a new advanced option. The inclusion of histological type according to Laurén classification in the flowchart of treatment could increase both accuracy and effectiveness of such tailored approach. New molecular classifications of GC have been introduced recently and translational clinical studies are ongoing. These classifications are expected to be included in multidisciplinary treatment of GC. In particular, in the group with microsatellite instability a less extended lymphadenectomy may be proposed. Also tailored neo-adjuvant treatment may be proposed according to molecular classifications. The group of patients with epithelial-to-mesenchymal transition shows very high propensity to peritoneal dissemination, as well as N-metastases, and may benefit from prophylactic HIPEC and extended lymphadenectomy when confirmed in prospective trials.
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Affiliation(s)
- Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy.
| | - Karol Polom
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy
| | - Alessandro Neri
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy
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17
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Clinical Assessment and Prognostic Evaluation of Tumor Markers in Patients with Gastric Cancer. Int J Biol Markers 2018; 28:192-200. [PMID: 23787496 DOI: 10.5301/jbm.5000023] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/11/2013] [Indexed: 12/27/2022]
Abstract
Aim To investigate the relationship between the serum levels of CEA, CA19-9, CA24-2, CA72-4, and AFP in patients with gastric cancer (GC) and their clinicopathological characteristics; to analyze the efficacy of these tumor markers in evaluating the prognosis of GC. Methods Overall, 389 patients with GC either located in the gastric cardia (132), the pyloric antrum (112) or the body of the stomach (145) were included in the study. Serum levels of CEA, CA19-9, CA72-4, and AFP were detected with the ECLIA method, while CA24-2 was measured with ELISA. Results First, the serum level of CEA in GC patients with a cardia-located cancer was significantly higher than in patients with pyloric antrum-located cancer (p=0.050). CA72-4 level in patients with GC located in the gastric body was significantly higher than in patients with cardia and pyloric antrum-located cancers (p=0.042 and p=0.039, respectively). Secondly, serum CA19-9 and CA24-2 levels in females with cardia-located GC were significantly higher than those in males with the same type of tumor (p=0.037 and p=0.033, respectively). Additionally, for females with gastric body-located GC the levels of CEA and CA72-4 were significantly higher than those in male patients with the same type of tumor (p=0.047 and p=0.048, respectively). Conversely, in female GC patients with pyloric antrum-located cancer the serum levels of CA19-9 and CA24-2 were significantly lower than those in male patients with the same type of cancer (p=0.013 and p=0.007, respectively). Moreover, CEA, CA19-9, CA24-2, and CA72-4 levels were strongly related to TNM grade and histological anatomy stage, whereas CEA and CA72-4 levels were strongly related to lymph node stage (p=0.000 and p=0.042, respectively). Patients with vascular embolism had higher serum levels of CEA, CA19-9, CA24-2, and CA72-4 compared with patients without vascular embolism (p=0.005, p=0.031, p=0.007, and p=0.014, respectively). In patients with distant metastases and ascites the levels of CEA, CA19-9, and CA24-2 were higher than in patients without these conditions (p=0.003, p=0.001, p=0.001, p=0.016, p= 0.011, and p=0.030, respectively). Serum CEA, CA19-9, and CA24-2 levels showed correlations with tumor invasive depth and growth types (p=0.001, p=0.040, and p=0.035, respectively). Patients with lump and catheter tumor growth types had significantly higher AFP levels than patients with invasion and anabrosis growth types (p=0.034 and p=0.005, respectively). Tumor size was correlated with the preoperative serum levels of CEA, AFP, and CA72-4 (p=0.007, p=0.020, and p=0.008, respectively). Additionally multiple linear regression analysis showed that preoperative levels of CEA and CA72-4 were correlated to TNM stages, CA19-9 and CA24-2 levels were correlated to both gender and distant metastasis, and AFP was correlated only to ascites. During follow-up there were 115 deaths. Median survival time for GC patients with negative preoperative CEA was 18.07 months, and was 10.97 months for patients with preoperative CEA positive levels (p=0.0005). Similarly, the median survival time for GC patients with negative preoperative CA72-4 was 33.60, and was 16.03 months for patients with preoperative CA72-4 positive levels (p=0.0041). Conclusions The preoperative levels of CEA, CA19-9, CA24-2, CA72-4, and AFP were closely related to TNM grade, gender, distant metastasis and ascites. These makers seem to play important roles in predicting recurrence and metastasis, and in evaluating prognosis.
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Yarema R. Gastric cancer with high risk of intraperitoneal progression: clinical course and current treatments. CURRENT ISSUES IN PHARMACY AND MEDICAL SCIENCES 2017; 30:190-194. [DOI: 10.1515/cipms-2017-0036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2023] Open
Abstract
Abstract
Locally advanced gastric cancer with a high risk of intraperitoneal progression is characterized by poor prognosis. After radical surgery, most patients die during the first two years post-operation as a result of disease progression. The prevailing type of progression and the leading cause of death in patients with gastric cancer is implantation metastasis.
The main risk factors for peritoneal carcinomatosis in such patients include: gastric tumor invasion into serosa, the presence of tumor cells in peritoneal washings, the largeness of the tumor as accompanied by extensive serous lesions, infiltrative type of tumor growth, histological variants of gastric cancer prone to implantation metastasis and metastatic lesions in regional lymph nodes. Systemic chemotherapy does not provide effective eradication of subclinical peritoneal carcinomatosis in patients with locally advanced gastric cancer.
The vast majority of patients who suffer from locally advanced gastric cancer and run a high risk of implantation metastasis are characterized by subclinical peritoneal dissemination at primary diagnosis, which means a rapidly fatal prognosis for such patients. In recent years, however, the paradigm of treatment of locally advanced gastric cancer has changed: a combination of surgery and adjuvant hyperthermic intraperitoneal chemotherapy is used increasingly, and presents an alternative to the previously accepted surgery only approach. It is also likely to increase the survival rate.
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Affiliation(s)
- Roman Yarema
- Department of Oncology and Medical Radiology , Danylo Halytsky Lviv National Medical University , Pekarska 69, 79010 , Lviv , Ukraine
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Polom K, Marrelli D, Roviello G, Voglino C, Vindigni C, Generali D, Roviello F. Single Center Experience on Anatomy-and Histopathology-Based Gastric Cancer Molecular Classification. Cancer Invest 2017; 35:325-332. [PMID: 28350490 DOI: 10.1080/07357907.2017.1292519] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 01/25/2017] [Indexed: 02/07/2023]
Abstract
We analyzed the clinical utility of molecular classification based on anatomical and histological background. The study was conducted on 457 patients treated for gastric cancer with additional information about microsatellite instability status. We divided the patients in three groups of molecular classification based on anatomical and histological background: proximal non-diffused, diffused, and distal non-diffused groups. These groups varied in terms of clinical and pathological factors as well as survival rates. The molecular classification based on anatomical and histological data seems to be a useful tool in a simple classification of gastric cancer.
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Affiliation(s)
- Karol Polom
- a General Surgery and Surgical Oncology Department , University of Siena , Siena , Italy
| | - Daniele Marrelli
- a General Surgery and Surgical Oncology Department , University of Siena , Siena , Italy
| | - Giandomenico Roviello
- b Department of Oncology, Medical Oncology Unit , San Donato Hospital , Arezzo , Italy
- c Department of Medical, Surgery and Health Sciences , University of Trieste , Piazza Ospitale, Trieste , Italy
| | - Costantino Voglino
- a General Surgery and Surgical Oncology Department , University of Siena , Siena , Italy
| | - Carla Vindigni
- d Department of Pathology , Azienda Ospedaliera Universitaria Senese , Siena , Italy
| | - Daniele Generali
- c Department of Medical, Surgery and Health Sciences , University of Trieste , Piazza Ospitale, Trieste , Italy
| | - Franco Roviello
- a General Surgery and Surgical Oncology Department , University of Siena , Siena , Italy
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van der Kaaij RT, Snaebjornsson P, Voncken FE, van Dieren JM, Jansen EP, Sikorska K, Cats A, van Sandick JW. The prognostic and potentially predictive value of the Laurén classification in oesophageal adenocarcinoma. Eur J Cancer 2017; 76:27-35. [DOI: 10.1016/j.ejca.2017.01.031] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 01/11/2017] [Accepted: 01/29/2017] [Indexed: 12/25/2022]
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Petrelli F, Berenato R, Turati L, Mennitto A, Steccanella F, Caporale M, Dallera P, de Braud F, Pezzica E, Di Bartolomeo M, Sgroi G, Mazzaferro V, Pietrantonio F, Barni S. Prognostic value of diffuse versus intestinal histotype in patients with gastric cancer: a systematic review and meta-analysis. J Gastrointest Oncol 2017; 8:148-163. [PMID: 28280619 DOI: 10.21037/jgo.2017.01.10] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND There are two distinct types of gastric carcinoma (GC), intestinal, more frequently sporadic and linked to environmental factors, and diffuse (undifferentiated) that is highly metastatic and characterized by rapid disease progression and a poor prognosis. However, there are many conflicting data in the literature concerning the association between histology and prognosis in GC. This meta-analysis was performed to provide demonstration if histology according to Lauren classification is associated with different prognosis in patients with GC. METHODS We searched PubMed, the Cochrane Library, SCOPUS, Web of Science, CINAHL, and EMBASE for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival (OS) were evaluated. RESULTS A total of 73 published studies including 61,468 patients with GC were included in this meta-analysis. Our analysis indicates that GC patients with diffuse-type histology have a worst prognosis than those with intestinal subgroup in all studies (HR 1.23; 95% CI, 1.17-1.29; P<0.0001), in both loco-regional confined (HR 1.21; 95% CI, 1.12-1.30; P<0.0001) and advanced disease (HR 1.25; 95% CI, 1.046-1.50; P=0.014), in Asiatic (HR 1.2; 95% CI, 1.14-1.27; P<0.0001) and Western patients (HR 1.3; 95% CI, 1.19-1.41; P<0.0001), and in those not exposed (HR 1.15; 95% CI, 1.07-1.24; P<0.0001) or exposed (HR 1.27; 95% CI, 1.17-1.37; P<0.0001) to (neo)adjuvant therapy. CONCLUSIONS Our results indicated that histology might be a useful prognostic marker for both early and advanced GC patients, with intestinal-type associated with a better outcome. This information could be used for stratification purpose in future clinical trials.
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Affiliation(s)
- Fausto Petrelli
- Medical Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Rosa Berenato
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luca Turati
- Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Alessia Mennitto
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Francesca Steccanella
- Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Marta Caporale
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Pierpaolo Dallera
- Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Filippo de Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ezio Pezzica
- Pathology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Maria Di Bartolomeo
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Sgroi
- Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Vincenzo Mazzaferro
- Hepatobiliopancreatic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Sandro Barni
- Medical Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy
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Choi HJ, Kim SM, An JY, Choi MG, Lee JH, Sohn TS, Bae JM, Kim S. Risk Factors and Tumor Recurrence in pT1N0M0 Gastric Cancer after Surgical Treatment. J Gastric Cancer 2017; 16:215-220. [PMID: 28053807 PMCID: PMC5206311 DOI: 10.5230/jgc.2016.16.4.215] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 10/04/2016] [Accepted: 10/06/2016] [Indexed: 01/21/2023] Open
Abstract
Purpose This study aimed to evaluate the rate, patterns, and risk factors associated with tumor recurrence in patients with T1N0 gastric cancer. Materials and Methods The medical records of 8,753 patients with pathological T1N0M0 gastric cancer who underwent gastrectomy between 1994 and 2014 at Sungkyunkwan University School of Medicine were examined. Results Among the 8,753 patients, 95 patients (1.1%) experienced tumor recurrence; this included 31 remnant, 27 hematogenous, 9 lymph nodal, 5 peritoneal, and 23 multiple-site recurrences. When patients were divided into two groups according to the presence of tumor recurrence, the following characteristics were higher in the recurrence group than in the non-recurrence group: older age (≥65 years), male gender, undifferentiated histology, submucosal invasion, and venous invasion. In multivariate analysis, older age, male gender, tumor depth (sm2 and sm3 invasion), and venous invasion were independent risk factors for tumor recurrence. The recurrence rates were 0.7% in patients with less than two risk factors, 1.7% in those with two risk factors, 3.0% in those with three risk factors, and 6.3% in those with four risk factors (P<0.001). Conclusions Although tumor recurrence is rare in pT1N0M0 gastric cancer, some patients with certain risk factors demonstrate an increased rate of tumor recurrence. Careful follow-up is required for patients with three or four risk factors.
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Affiliation(s)
- Hee Jun Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Su Mi Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Yeong An
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min-Gew Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Ho Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Sung Sohn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Moon Bae
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Lordick F, Janjigian YY. Clinical impact of tumour biology in the management of gastroesophageal cancer. Nat Rev Clin Oncol 2016; 13:348-60. [PMID: 26925958 PMCID: PMC5521012 DOI: 10.1038/nrclinonc.2016.15] [Citation(s) in RCA: 111] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The characterization of oesophageal and gastric cancer into subtypes based on genotype has evolved in the past decade. Insights into the molecular landscapes of gastroesophageal cancer provide a roadmap to assist the development of new drugs and their use in combinations, for patient stratification, and for trials of targeted therapies. Trastuzumab is the only approved treatment for gastroesophageal cancers that overexpress HER2. Acquired resistance usually limits the duration of response to this treatment, although a number of new agents directed against HER2 have the potential to overcome or prolong the time until resistance occurs. Beyond that, anti-VEGFR2 therapy with ramucirumab was the first biological treatment strategy to produce a survival benefit in an unselected population of patients with chemotherapy-refractory gastroesophageal cancer. Large initiatives are starting to address the role of biomarker-driven targeted therapy in the metastatic and in the perioperative setting for patients with this disease. Immunotherapy also holds promise, and our understanding of subsets of gastroesophageal cancer based on patterns of immune response continues to evolve. Efforts are underway to identify more relevant genomic subsets through genomic screening, functional studies, and molecular characterization. Herein, we provide an overview of the key developments in the treatment of gastroesophageal cancer, and discuss potential strategies to further optimize therapy by targeting disease subtypes.
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Affiliation(s)
- Florian Lordick
- University Cancer Center Leipzig, University Medicine Leipzig, Liebigstraße 20 D, 04103 Leipzig, Germany
| | - Yelena Y Janjigian
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 1275 York Avenue, New York, New York 10065, USA
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Degiuli M, De Manzoni G, Di Leo A, D’Ugo D, Galasso E, Marrelli D, Petrioli R, Polom K, Roviello F, Santullo F, Morino M. Gastric cancer: Current status of lymph node dissection. World J Gastroenterol 2016; 22:2875-2893. [PMID: 26973384 PMCID: PMC4779911 DOI: 10.3748/wjg.v22.i10.2875] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 10/09/2015] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
D2 procedure has been accepted in Far East as the standard treatment for both early (EGC) and advanced gastric cancer (AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials (RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council (MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recurrence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.
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Marrelli D, Polom K, Pascale V, Vindigni C, Piagnerelli R, De Franco L, Ferrara F, Roviello G, Garosi L, Petrioli R, Roviello F. Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer. Ann Surg Oncol 2016; 23:943-950. [PMID: 26530444 DOI: 10.1245/s10434-015-4931-3] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND The clinical role of microsatellite instability (MSI) in gastric cancer (GC) is controversial. A large series of patients submitted to respective surgery for primary GC with a long follow-up time was evaluated. METHODS 472 patients with prospectively collected frozen samples of normal mucosa and tumor tissue stored in a biological tissue bank were included. Microsatellite analysis was evaluated using 5 quasi monomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21, and NR-27). The presence of MSI in 2 or more loci was classified as MSI-H, whereas all other cases were included in the microsatellite-stable (MSS) group. RESULTS MSI-H phenotype was found in 111 of 472 patients (23.5%). MSI-H status was related significantly with older age, female gender, non-cardia location, WHO histotype, non-cardia Lauren intestinal type, and less advanced stages. Cancer-related 5-year survival was significantly higher in MSI-H versus MSS group (67.6% vs. 35%, p < 0.001). Stratified analysis revealed a significant impact of MSI on prognosis in non-cardia tumors of intestinal type or tubular/poorly differentiated histology, particularly in stages II and III; multivariate Cox regression analysis confirmed MSS status as a strong predictor of poor prognosis (hazard ratio 2.65, 95% CI 1.56-4.51, p < 0.001) in non-cardia intestinal type. No prognostic value of MSI in the diffuse-mixed type and signet-ring cell/mucinous histotypes was observed. CONCLUSIONS MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.
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Affiliation(s)
- Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
| | - Karol Polom
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
| | - Valeria Pascale
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
| | - Carla Vindigni
- Department of Pathology, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Riccardo Piagnerelli
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
| | - Lorenzo De Franco
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
| | - Francesco Ferrara
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
| | - Giandomenico Roviello
- Department of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Lorenzo Garosi
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
| | - Roberto Petrioli
- Department of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy
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Li X, Wu WKK, Xing R, Wong SH, Liu Y, Fang X, Zhang Y, Wang M, Wang J, Li L, Zhou Y, Tang S, Peng S, Qiu K, Chen L, Chen K, Yang H, Zhang W, Chan MTV, Lu Y, Sung JJY, Yu J. Distinct Subtypes of Gastric Cancer Defined by Molecular Characterization Include Novel Mutational Signatures with Prognostic Capability. Cancer Res 2016; 76:1724-32. [PMID: 26857262 DOI: 10.1158/0008-5472.can-15-2443] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 11/10/2015] [Indexed: 12/21/2022]
Abstract
Gastric cancer is not a single disease, and its subtype classification is still evolving. Next-generation sequencing studies have identified novel genetic drivers of gastric cancer, but their use as molecular classifiers or prognostic markers of disease outcome has yet to be established. In this study, we integrated somatic mutational profiles and clinicopathologic information from 544 gastric cancer patients from previous genomic studies to identify significantly mutated genes (SMG) with prognostic relevance. Gastric cancer patients were classified into regular (86.8%) and hypermutated (13.2%) subtypes based on mutation burden. Notably, TpCpW mutations occurred significantly more frequently in regular, but not hypermutated, gastric cancers, where they were associated with APOBEC expression. In the former group, six previously unreported (XIRP2, NBEA, COL14A1, CNBD1, ITGAV, and AKAP6) and 12 recurrent mutated genes exhibited high mutation prevalence (≥3.0%) and an unexpectedly higher incidence of nonsynonymous mutations. We also identified two molecular subtypes of regular-mutated gastric cancer that were associated with distinct prognostic outcomes, independently of disease staging, as confirmed in a distinct patient cohort by targeted capture sequencing. Finally, in diffuse-type gastric cancer, CDH1 mutation was found to be associated with shortened patient survival, independently of disease staging. Overall, our work identified previously unreported SMGs and a mutation signature predictive of patient survival in newly classified subtypes of gastric cancer, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping. Cancer Res; 76(7); 1724-32. ©2016 AACR.
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Affiliation(s)
- Xiangchun Li
- Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong. Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - William K K Wu
- Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong. Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
| | - Rui Xing
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Sunny H Wong
- Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Yuexin Liu
- Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China
| | - Xiaodong Fang
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Yanlin Zhang
- Department of Computer Science, City University of Hong Kong, Hong Kong, Hong Kong
| | - Mengyao Wang
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Jiaqian Wang
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Lin Li
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Yong Zhou
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Senwei Tang
- Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Shaoliang Peng
- School of Computer Science, National University of Defense Technology, Changsha, Hunan, P.R. China
| | - Kunlong Qiu
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Longyun Chen
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Kexin Chen
- Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China
| | - Huanming Yang
- Beijing Genomics Institute, Shenzhen, Guangdong, P.R. China
| | - Wei Zhang
- Department of Pathology, University of Texas MD Anderson Cancer Center Informatics Center, Houston, Texas
| | - Matthew T V Chan
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Youyong Lu
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Joseph J Y Sung
- Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
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27
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Ba MC, Long H, Zhang XL, Gong YF, Tang YQ, Wu YB, Yu FH, Cui SZ. Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer. J Laparoendosc Adv Surg Tech A 2016; 26:32-9. [PMID: 26779722 DOI: 10.1089/lap.2015.0266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Ming-chen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Hui Long
- Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, People's Republic of China
| | - Xiang-Liang Zhang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yuan-Feng Gong
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yun-Qiang Tang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yin-Bing Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Fei-Hong Yu
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Shu-Zhong Cui
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
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Polom K, Marano L, Roviello G, Petrioli R, Piagnerelli R, de Franco L, Marrelli D, Roviello F. Evolution and emerging future of cytoreducxtive surgery and hyperthermic intraperitoneal chemoperfusion in gastric cancer: From treating the incurable to preventing recurrence. Int J Hyperthermia 2015; 32:173-179. [PMID: 26670720 DOI: 10.3109/02656736.2015.1111432] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The number of new gastric cancer (GC) cases is decreasing, and these patients have longer survival thanks to new oncological treatments. In advanced GC a common evolution of this neoplasm is peritoneal metastases (PM). In the past this finding meant no chance for cure. However, today, using high quality operations and HIPEC, we are able to increase the number of patients treated with curative intention. New options in the diagnosis of PM, tumour susceptibility for different drugs, importance of quality of life, usage in ascites treatment, diagnostic tools in image-guided surgery, new targeted therapies and analysis of currently ongoing trials are presented together with today's knowledge of HIPEC efficacy in order to evaluate gastric PM. HIPEC is an effective tool in the treatment of selected patients with PM from GC. Together with new diagnostic options such as targeted therapies, HIPEC may improve the prognosis of these patients, not only by treating clinically manifest carcinomatosis, but also in the prophylactic setting, addressing occult peritoneal seeding.
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Affiliation(s)
- Karol Polom
- a Department of Medicine , Surgery and Neurosciences, University of Siena
| | - Luigi Marano
- b General, Minimally Invasive and Robotic Surgery, Department of Surgery, 'San Matteo degli Infermi' Hospital , Spoleto , and
| | | | | | | | - Lorenzo de Franco
- a Department of Medicine , Surgery and Neurosciences, University of Siena
| | - Daniele Marrelli
- a Department of Medicine , Surgery and Neurosciences, University of Siena
| | - Franco Roviello
- a Department of Medicine , Surgery and Neurosciences, University of Siena
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Choi JK, Park YS, Jung DH, Son SY, Ahn SH, Park DJ, Kim HH. Clinical Relevance of the Tumor Location-Modified Lauren Classification System of Gastric Cancer. J Gastric Cancer 2015; 15:183-90. [PMID: 26468416 PMCID: PMC4604333 DOI: 10.5230/jgc.2015.15.3.183] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 09/11/2015] [Accepted: 09/13/2015] [Indexed: 12/14/2022] Open
Abstract
Purpose The Lauren classification system is a very commonly used pathological classification system of gastric adenocarcinoma. A recent study proposed that the Lauren classification should be modified to include the anatomical location of the tumor. The resulting three types were found to differ significantly in terms of genomic expression profiles. This retrospective cohort study aimed to evaluate the clinical significance of the modified Lauren classification (MLC). Materials and Methods A total of 677 consecutive patients who underwent curative gastrectomy from January 2005 to December 2007 for histologically confirmed gastric cancer were included. The patients were divided according to the MLC into proximal non-diffuse (PND), diffuse (D), and distal non-diffuse (DND) type. The groups were compared in terms of clinical features and overall survival. Multivariate analysis served to assess the association between MLC and prognosis. Results Of the 677 patients, 48, 358, and 271 had PND, D, and DND, respectively. Their 5-year overall survival rates were 77.1%, 77.7%, and 90.4%. Compared to D and PND, DND was associated with significantly better overall survival (both P<0.01). Multivariate analysis showed that age, differentiation, lympho-vascular invasion, T and N stage, but not MLC, were independent prognostic factors for overall survival. Multivariate analysis of early gastric cancer patients showed that MLC was an independent prognostic factor for overall survival (odds ratio, 5.946; 95% confidence intervals, 1.524~23.197; P=0.010). Conclusions MLC is prognostic for survival in patients with gastric adenocarcinoma, in early gastric cancer. DND was associated with an improved prognosis compared to PND or D.
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Affiliation(s)
- Jang Kyu Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Do Hyun Jung
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sang Yong Son
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sang Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer. Tumour Biol 2015; 37:1183-8. [PMID: 26280398 DOI: 10.1007/s13277-015-3903-3] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 08/05/2015] [Indexed: 12/12/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.
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Marrelli D, Polom K, de Manzoni G, Morgagni P, Baiocchi GL, Roviello F. Multimodal treatment of gastric cancer in the west: Where are we going? World J Gastroenterol 2015; 21:7954-7969. [PMID: 26185368 PMCID: PMC4499339 DOI: 10.3748/wjg.v21.i26.7954] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/25/2015] [Accepted: 05/02/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence of gastric cancer (GC) is decreasing worldwide, especially for intestinal histotype of the distal third of the stomach. On the contrary, proximal location and diffuse Lauren histotype have been reported to be generally stable over time. In the west, no clear improvement in long-term results was observed in clinical and population-based studies. Results of treatment in these neoplasms are strictly dependent on tumor stage. Adequate surgery and extended lymphadenectomy are associated with good long-term outcome in early-stage cancer; however, results are still unsatisfactory for advanced stages (III and IV), for which additional treatments could provide a survival benefit. This implies a tailored approach to GC. The aim of this review was to summarize the main multimodal treatment options in advanced resectable GC. Perioperative or postoperative treatments, including chemotherapy, chemoradiotherapy, targeted therapies, and hyperthermic intraperitoneal chemotherapy have been reviewed, and the main ongoing and completed trials have been analyzed. An original tailored multimodal approach to non-cardia GC has been also proposed.
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Ishimoto T, Baba H, Izumi D, Sugihara H, Kurashige J, Iwatsuki M, Tan P. Current perspectives toward the identification of key players in gastric cancer microRNA dysregulation. Int J Cancer 2015; 138:1337-49. [DOI: 10.1002/ijc.29627] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 05/27/2015] [Indexed: 12/21/2022]
Affiliation(s)
- Takatsugu Ishimoto
- Cancer and Stem Cell Biology; Duke-NUS Graduate Medical School Singapore; Singapore Singapore
- Department of Gastroenterological Surgery, Graduate School of Medical Science; Kumamoto University; Kumamoto Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science; Kumamoto University; Kumamoto Japan
| | - Daisuke Izumi
- Department of Gastroenterological Surgery, Graduate School of Medical Science; Kumamoto University; Kumamoto Japan
| | - Hidetaka Sugihara
- Department of Gastroenterological Surgery, Graduate School of Medical Science; Kumamoto University; Kumamoto Japan
| | - Junji Kurashige
- Department of Gastroenterological Surgery, Graduate School of Medical Science; Kumamoto University; Kumamoto Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Science; Kumamoto University; Kumamoto Japan
| | - Patrick Tan
- Cancer and Stem Cell Biology; Duke-NUS Graduate Medical School Singapore; Singapore Singapore
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Diversity of clinical implication of B-cell translocation gene 1 expression by histopathologic and anatomic subtypes of gastric cancer. Dig Dis Sci 2015; 60:1256-64. [PMID: 25487193 DOI: 10.1007/s10620-014-3477-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 11/28/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Genetic signatures may differ by histopathologic and anatomic subtypes of gastric cancer (GC). B-cell translocation gene 1 (BTG1) was identified as one of genes downregulated in GC tissues from our microarray data. AIMS To evaluate the clinical implications of BTG1 expression in GC and the genetic diversity among GC subtypes. METHODS BTG1 mRNA expression was analyzed in GC cell lines and 233 pairs of surgical specimens. The mutational and methylation status of BTG1 in GC cell lines was analyzed, and immunohistochemistry was conducted to determine the distribution of BTG1. The pattern and prognostic significance of BTG1 expression were correlated with the three proposed GC subtypes. RESULTS BTG1 mRNA was downregulated in 82 % of GC cell lines and in 88 % of clinical GC tissues. Promoter hypermethylation events or sequence mutations were not detected in GC cell lines. The pattern of BTG1 expression as observed by immunohistochemistry was consistent with that of its mRNA. Downregulation of BTG1 mRNA in GCs was significantly associated with shorter disease-specific and recurrence-free survival. Multivariate analysis of disease-specific survival identified downregulation of BTG1 transcription as an independent prognostic factor. BTG1 mRNA expression was more strongly suppressed in proximal nondiffuse and diffuse GC compared with distal nondiffuse GC, and subgroup analysis revealed that BTG1 downregulation led to adverse prognosis, specifically in patients with proximal nondiffuse and diffuse GC. CONCLUSIONS Altered expression of BTG1 is a potential biomarker for carcinogenesis and progression of GC, particularly for proximal nondiffuse and diffuse GC.
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Prognostic significance of the recurrence pattern and risk factors for recurrence in patients with proximal gastric cancer who underwent curative gastrectomy. Tumour Biol 2015; 36:6191-9. [PMID: 25761877 DOI: 10.1007/s13277-015-3304-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 03/02/2015] [Indexed: 02/07/2023] Open
Abstract
Proximal gastric cancer has a high propensity of early recurrence after curative resection due to high incidence of lymph node involvement. In the present study, we aimed to investigate the pattern and time of recurrence and to evaluate the risk factors for recurrence of patients with proximal gastric cancer. Between 2005 and 2013, 99 patients with recurrent proximal gastric cancer who underwent radical gastrectomy were retrospectively analyzed. The prognostic significance of the pattern and the time of recurrence and the relationship between the pattern of recurrence and the other clinicopathological factors were evaluated. The median time to recurrence was 24 months; 45.5 % of patients relapsed within 2 years. Forty-three (43.4 %) patients indicated hematogenous recurrence and 41 (41.4 %) patients revealed peritoneal recurrence with the most predominant patterns. The median progression-free survival (PFS) time for patients with locoregional recurrence was significantly better than that of patients with peritoneal recurrences, hematogenous recurrences, and distant lymph nodes (32.2 vs. 18.9 vs. 18.2 vs. 9.7 months, p = 0.005, respectively). Moreover, the median overall survival (OS) interval for patients with distant lymph nodes recurrence was significantly worse than that of patients with locoregional, peritoneal, and hematogenous recurrences (13.5 vs. 48.5 vs. 31.4 vs. 29.9 months, p = 0.006, respectively). The presence of lymph node metastasis (p = 0.004) and surgery type (p = 0.04) for PFS and the time of recurrence (p = 0.033), lymph node metastasis (p = 0.03), and surgery type (p = 0.04) for OS were found to be independent prognostic factors by multivariate analysis. Logistic regression analysis indicated that the presence of lymph node metastasis and surgery type were independent risk factors for predicting the occurrence of early recurrence (p = 0.001, OR 0.48 and p = 0.028, OR 0.41, respectively). The median OS time of early recurrence patients was significantly shorter than that of patients with late recurrence (16.6 vs. 55.2 months, p < 0.001). Furthermore, proximal gastrectomy, poorly differentiated histology, advanced pT stage, and lymph node metastasis were significantly associated with early recurrence. Our results showed that lymph node metastasis and surgery type were independent risk factors for prediction of early recurrence in proximal gastric cancer. Thus, total gastrectomy with regional lymph node dissection may be a suitable treatment option for proximal gastric cancer patients with tumors that have high risk features for recurrence.
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de Manzoni G, Verlato G, Bencivenga M, Marrelli D, Di Leo A, Giacopuzzi S, Cipollari C, Roviello F. Impact of super-extended lymphadenectomy on relapse in advanced gastric cancer. Eur J Surg Oncol 2015; 41:534-40. [PMID: 25707350 DOI: 10.1016/j.ejso.2015.01.023] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Revised: 01/14/2015] [Accepted: 01/15/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND In gastric cancer the incidence of loco-regional recurrences decreases when lymphadenectomy is expanded from D1 to D2. The present study aimed at evaluating whether the pattern of recurrence in advanced gastric cancer (AGC) is further modified when lymphadenectomy is expanded from D2 to D3. METHODS 568 patients undergoing curative gastrectomy for AGC (274 D2 and 294 D3) were considered; none of them received preoperative chemotherapy. MantelHaenszel test of homogeneity was used to verify whether the relation between extension of lymphadenectomy and recurrence varied as a function of each risk factor considered. The impact of D2 and D3 on relapse was further investigated by multivariable logistic regression model. RESULTS Cumulative incidence of recurrence did not significantly differ after D2 and after D3 in the whole series (45.3% vs 46.3%; p = 0.866). However, the association between recurrence and extension of lymphadenectomy was significantly affected by histology (Mantel-Haenszel test of homogeneity: p = 0.007). The risk of recurrence was higher after D3 than after D2 (45.1% vs 35.3%) in the intestinal histotype while the pattern was reversed in the mixed/diffuse histotype (48.3% vs 61.5%). This pattern was confirmed in multivariable logistic regression: the interaction between histology and extension of lymphadenectomy was highly significant (p = 0.004). In particular, cumulative incidence of locoregional recurrences was higher in the diffuse histotype after D2, while being higher in the intestinal histotype after D3. CONCLUSIONS D3 reverses the negative impact of diffuse histotype on relapses, especially on locoregional recurrences. Therefore D3 could be considered a valid therapeutic option in histotype-oriented tailored treatment of AGC.
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Affiliation(s)
- G de Manzoni
- Dept. of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy.
| | - G Verlato
- Unit of Epidemiology and Medical Statistics, University of Verona, Verona, Italy
| | - M Bencivenga
- Dept. of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy
| | - D Marrelli
- Dept. of Human Pathology and Oncology, Section of General Surgery and Surgical Oncology, Translational Research Laboratory, University of Siena, Siena, Italy
| | - A Di Leo
- Unit of General Surgery, Rovereto Hospital, APSS of Trento, Trento, Italy
| | - S Giacopuzzi
- Dept. of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy
| | - C Cipollari
- Dept. of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy
| | - F Roviello
- Dept. of Human Pathology and Oncology, Section of General Surgery and Surgical Oncology, Translational Research Laboratory, University of Siena, Siena, Italy
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Goodman KA. Refining the Role for Adjuvant Radiotherapy in Gastric Cancer: Risk Stratification Is Key. J Clin Oncol 2015; 33:3082-4. [PMID: 25559799 DOI: 10.1200/jco.2014.59.1941] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Moorcraft SY, Smyth EC, Cunningham D. Adjuvant or neoadjuvant therapy for operable esophagogastric cancer? Gastric Cancer 2015; 18:1-10. [PMID: 24638977 DOI: 10.1007/s10120-014-0356-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Accepted: 02/08/2014] [Indexed: 02/07/2023]
Abstract
Esophagogastric cancer encompasses proximal squamous cell carcinoma of the esophagus, distal esophageal/junctional adenocarcinoma of the esophagus and gastric adenocarcinoma. These diseases have different etiologies, geographic incidences and biologies. This review mainly focuses on the treatment of operable esophagogastric adenocarcinoma. In Asia, adjuvant chemotherapy is commonly used for patients with gastric cancer following the landmark ACTS-GC trial. In contrast, perioperative chemotherapy is a standard of care in many Western countries based on the results of the MAGIC trial. Neoadjuvant chemotherapy is better tolerated than adjuvant therapy, and therefore dose intensity is likely to be maintained in a greater proportion of patients. In addition, neoadjuvant treatment can lead to tumor downstaging, increasing the likelihood of achieving a complete surgical resection. This may be particularly important in Western populations, as these patients often present with more advanced tumors than Asian patients. Adjuvant chemoradiotherapy is a standard treatment option in the USA for adenocarcinoma of the stomach or gastroesophageal junction as a result of the INT-0116 trial, but the benefit of this approach after a D2 resection has not been confirmed. Neoadjuvant chemoradiotherapy may reduce the risk of local recurrence and may be particularly beneficial for patients with squamous cell carcinoma as these tumors are more radiosensitive. However, patients with esophagogastric adenocarcinoma are more likely to relapse with distant disease, and therefore a systemic disease approach with chemotherapy is likely to be more beneficial than a purely localized treatment strategy for these patients.
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Affiliation(s)
- Sing Yu Moorcraft
- Gastrointestinal Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, UK,
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Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma. Case Rep Med 2014; 2014:268919. [PMID: 25349615 PMCID: PMC4198811 DOI: 10.1155/2014/268919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Accepted: 09/23/2014] [Indexed: 12/24/2022] Open
Abstract
A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma.
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Rosa F, Alfieri S, Tortorelli AP, Fiorillo C, Costamagna G, Doglietto GB. Trends in clinical features, postoperative outcomes, and long-term survival for gastric cancer: a Western experience with 1,278 patients over 30 years. World J Surg Oncol 2014; 12:217. [PMID: 25030691 PMCID: PMC4114092 DOI: 10.1186/1477-7819-12-217] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 07/04/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of the present study was to identify temporal trends in long-term survival and postoperative outcomes and to analyze prognostic factors influencing the prognosis of patients with gastric cancer (GC) treated in a 30-year interval in a tertiary referral Western institution. METHODS Between January 1980 and December 2010, 1,278 patients who were diagnosed with GC at the Digestive Surgery Department, Catholic University of Rome, Italy, were identified. Among them, 936 patients underwent surgical resection and were included in the analysis. RESULTS Over time there was a significant improvement in postoperative outcomes. Morbidity and mortality rates decreased to 19.4% and 1.6%, respectively, in the last decade. By contrast, the multivisceral resection rate steadily increased from 12.7% to 29.6%. The overall five-year survival rate steadily increased over time, reaching 51% in the last decade, and 64.5% for R0 resections. Multivariate analysis showed a higher probability of overall survival for early stages (I and II), extended lymphadenectomy, and R0 resections. CONCLUSIONS Over three decades there was a significant improvement in perioperative and postoperative care and a steady increase in overall survival.
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Affiliation(s)
- Fausto Rosa
- Department of Digestive Surgery, Catholic University, "A, Gemelli" Hospital, Largo A, Gemelli, 8, Rome 00168, Italy.
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Stessin AM, Sison C, Schwartz A, Ng J, Chao CK, Li B. Does adjuvant radiotherapy benefit patients with diffuse-type gastric cancer? Results from the Surveillance, Epidemiology, and End Results database. Cancer 2014; 120:3562-8. [DOI: 10.1002/cncr.28913] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Revised: 05/24/2014] [Accepted: 06/02/2014] [Indexed: 12/14/2022]
Affiliation(s)
- Alexander M. Stessin
- Department of Radiation Oncology; Weill Cornell Medical College; New York New York
| | - Cristina Sison
- Department of Biostatistics; The Feinstein Institute for Medical Research; Manhasset New York
| | - Allie Schwartz
- Department of Economics; Harvard University; Cambridge Massachusetts
| | - John Ng
- Department of Radiation Oncology; Weill Cornell Medical College; New York New York
| | - Clifford K.S. Chao
- Department of Radiation Oncology; Weill Cornell Medical College; New York New York
| | - Baoqing Li
- Department of Radiation Oncology; Weill Cornell Medical College; New York New York
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Jung JJ, Cho JH, Shin S, Shim YM. Surgical treatment of anastomotic recurrence after gastrectomy for gastric cancer. THE KOREAN JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2014; 47:269-74. [PMID: 25207225 PMCID: PMC4157478 DOI: 10.5090/kjtcs.2014.47.3.269] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 11/14/2013] [Accepted: 11/21/2013] [Indexed: 01/27/2023]
Abstract
Background The purpose of this study was to evaluate the outcome of reoperation with curative intent for the treatment of anastomotic recurrent gastric cancer. Methods Ten patients with anastomotic recurrence of gastric cancer who underwent reoperation from November 1995 to February 2011 were analyzed retrospectively. The time interval between the first operation and reoperation, recurrence pattern, type of surgery, survival, and postoperative outcome were analyzed. Results The average time to recurrence after initial surgery was 48.8 months (median, 23.5 months). Of the ten patients, eight (80.0%) had recurrence at the esophagojejunostomy, one (10.0 %) at the esophagogastrostomy, and two (20.0%) at the esophagus. Among these patients, five had combined metastasis or invasion to major organs in addition to anastomotic recurrence. Complete resection was achieved in five patients (50.0%), and incomplete resection or bypass surgery was performed in the remaining five patients (50.0%). The overall median survival time was 7.0 months (range, 2.2 to 105.5 months). The median survival time following complete resection and palliative surgery (incomplete resection or bypass surgery) was 28.1 months (range, 4.2 to 105.5 months) and 5.5 months (range, 2.2 to 7.5 months), respectively. Conclusion Surgical resection of anastomotic recurrent gastric cancer should be implemented only in selected patients in whom complete resection is possible.
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Affiliation(s)
- Jae Jun Jung
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
| | - Jong Ho Cho
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
| | - Sumin Shin
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
| | - Young Mog Shim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
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Baiocchi GL, Marrelli D, Verlato G, Morgagni P, Giacopuzzi S, Coniglio A, Marchet A, Rosa F, Capponi MG, Di Leo A, Saragoni L, Ansaloni L, Pacelli F, Nitti D, D'Ugo D, Roviello F, Tiberio GAM, Giulini SM, De Manzoni G. Follow-up after gastrectomy for cancer: an appraisal of the Italian research group for gastric cancer. Ann Surg Oncol 2014; 21:2005-2011. [PMID: 24526547 DOI: 10.1245/s10434-014-3534-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The Italian Research Group for Gastric Cancer supports the practice of follow-up after radical surgery for gastric cancer. METHODS This multicenter, retrospective study (1998-2009) included patients with T1-4N0-3M0 gastric cancer who had undergone D2 gastrectomy and lymphadenectomy, with at least 15 lymph nodes examined, and who had developed recurrent disease. Timing and site of recurrence were correlated to the actual scheduled follow-up timing and modalities. RESULTS From eight centers, 814 patients with recurrent cancer and over 1,754 (46.4 %) patients undergoing gastrectomy were investigated (median follow-up 31 months). The most frequent sites of recurrence were local/regional lymph nodes (35.4 %), liver (24.3 %), peritoneum (30.3 %), lung (10.4 %) and intraluminal (7.5 %). Ninety-four percent of the recurrences were diagnosed within 2 years and 98 % within 3 years. Thoracoabdominal computed tomography (CT) scan and (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET) detected more than 90 % of recurrences, abdominal ultrasound detected 70 % and tumor markers detected 40 %, while <10 % were identified by physical examination, chest X-ray, and upper gastrointestinal endoscopy. Twenty-six percent of patients with recurrence were treated, but only 3.2 % were treated with potentially radical intent. CONCLUSION Oncological follow-up after radical surgery for gastric cancer should be focused in the first 3 years, and based mainly on thoracoabdominal CT scan and 18-FDG-PET.
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Affiliation(s)
- Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, Surgical Clinic, Brescia University, Brescia, Italy,
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The PAS positive material in gastric cancer cells of signet ring type is not mucin. Exp Mol Pathol 2014; 96:274-8. [PMID: 24589859 DOI: 10.1016/j.yexmp.2014.02.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 02/21/2014] [Indexed: 01/17/2023]
Abstract
PURPOSE The purpose of this study is to assess the exocrine and neuroendocrine properties of tumour cells in diffuse gastric cancer with signet ring cell differentiation. MATERIAL AND METHODS Mucin mRNA and protein expressions (MUC1, 2, 3, 4, 5AC, 6 and MUC13) were assessed by immunohistochemistry and in situ hybridization. The neuroendocrine properties were evaluated by protein and mRNA expression of the general neuroendocrine markers chromogranin A and synaptophysin. RESULTS No MUC expression was observed in signet ring tumour cells including the amorphous substance in any of the nine cases. All cases showed immunoreactivity to synaptophysin, and seven out of nine cases immunoreactivity to chromogranin A in signet ring and non-signet ring tumour cells. Chromogranin A mRNA expression was observed in tumour cells in all samples with retained mRNA. CONCLUSIONS The lack of MUC protein and mRNA in signet ring tumour cells suggests the amorphous substance is not mucin. The lack of MUC mRNA expression in non-signet ring tumour cells questions exocrine differentiation in this tumour group. The abundant protein expression of the general neuroendocrine markers CgA and synaptophysin, and mRNA expression in tumour cells strengthens the hypothesis that this tumour group may be of neuroendocrine origin.
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Bittoni A, Scartozzi M, Giampieri R, Faloppi L, Bianconi M, Mandolesi A, Prete MD, Pistelli M, Cecchini L, Bearzi I, Cascinu S. Clinical evidence for three distinct gastric cancer subtypes: time for a new approach. PLoS One 2013; 8:e78544. [PMID: 24265697 PMCID: PMC3827058 DOI: 10.1371/journal.pone.0078544] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 09/19/2013] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Recently, a new classification for gastric cancer (GC) has been proposed, based on Lauren's histology and on anatomic tumour location, identifying three subtypes of disease: type 1 (proximal non diffuse GC), type 2 (diffuse GC) and type 3 (distal non diffuse GC). Aim of our analysis was to compare clinical outcome according to different GC subtypes (1,2,3) in metastatic GC patients receiving first-line chemotherapy. PATIENTS AND METHODS Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2 and type 3) as previously defined. RESULTS A total of 248 advanced GC pts were included: 45.2% belonged to type 2, 43.6% to type 3 and 11.2% to type 1. Patients received a fluoropyrimidine-based chemotherapy doublet or three drugs regimens including a platinum derivate and a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C. RR was higher in type 1 pts (RR = 46.1%) and type 3 (34,3%) compared to type 2 (20,4%), (p = 0.015). Type 2 presented a shorter PFS, median PFS = 4.2 months, compared to type 1, mPFS = 7.2 months, and type 3, mPFS = 5.9 months (p = 0.011) and also a shorter OS (p = 0.022). CONCLUSIONS Our analysis suggests that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients.
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Affiliation(s)
- Alessandro Bittoni
- Clinica di Oncologia Medica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Mario Scartozzi
- Clinica di Oncologia Medica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
- * E-mail:
| | - Riccardo Giampieri
- Clinica di Oncologia Medica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Luca Faloppi
- Scuola di Specializzazione in Oncologia Medica, Università Politecnica delle Marche, Ancona, Italy
| | - Maristella Bianconi
- Scuola di Specializzazione in Oncologia Medica, Università Politecnica delle Marche, Ancona, Italy
| | - Alessandra Mandolesi
- Anatomia Patologica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Michela Del Prete
- Scuola di Specializzazione in Oncologia Medica, Università Politecnica delle Marche, Ancona, Italy
| | - Mirco Pistelli
- Clinica di Oncologia Medica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Luca Cecchini
- Clinica di Oncologia Medica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Italo Bearzi
- Anatomia Patologica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
| | - Stefano Cascinu
- Clinica di Oncologia Medica, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
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Simpson GS, Mahapatra SR, Evans J. Incidental complete excision of appendiceal gastric cancer metastasis. J Surg Case Rep 2013; 2013:rjt080. [PMID: 24964324 PMCID: PMC3854853 DOI: 10.1093/jscr/rjt080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer is a common malignancy with high recurrence rates following surgical resection. A common site of disease recurrence is the peritoneum. We report the case of a 73-year-old female who had previously undergone a total gastrectomy for gastric cancer who presented acutely with features classical of acute appendicitis and underwent open appendectomy. Histological analysis showed metastasis of gastric cancer with clear resection margins. The patient recovered fully and has remained disease-free for 14 months following presentation. Peritoneal metastasis is associated with difficulty in treatment and poor prognosis. The unplanned excision of this patient’s peritoneal metastasis has yielded a favourable clinical outcome in a difficult clinical situation.
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Affiliation(s)
- Gregory S Simpson
- Department of General Surgery, Countess of Chester Hospital, Chester, UK
| | | | - James Evans
- Department of General Surgery, Countess of Chester Hospital, Chester, UK
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Iravani O, Tay BWR, Chua PJ, Yip GWC, Bay BH. Claudins and gastric carcinogenesis. Exp Biol Med (Maywood) 2013; 238:344-9. [PMID: 23759999 DOI: 10.1177/1535370213477981] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Gastric carcinoma arises from aberrant growth of normal gastric mucosa. There is increasing evidence that claudins (CLDNs) may play a critical role in the significant steps of gastric tumorigenesis, from metaplasia to metastasis. The CLDN family which consists of at least 27 member proteins is known to mediate selective permeability in cellular tight junctions. It is now established that CLDNs are differentially altered in gastric cancer and CLDN proteins are believed to play different roles in the growth and progression of gastric cancer.
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Affiliation(s)
- Omid Iravani
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
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Nakanishi Y, Ohara M, Domen H, Shichinohe T, Hirano S, Ishizaka M. Differences in risk factors between patterns of recurrence in patients after curative resection for advanced gastric carcinoma. World J Surg Oncol 2013; 11:98. [PMID: 23683476 PMCID: PMC3668996 DOI: 10.1186/1477-7819-11-98] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2012] [Accepted: 05/09/2013] [Indexed: 01/19/2023] Open
Abstract
Background Recurrence patterns in patients who have undergone curative gastrectomy for advanced gastric carcinoma can be classified as peritoneal, hematogenous, or lymphatic. The aim of this study was to clarify differences in risk factors between these different types of recurrence pattern. Methods Postoperative courses, including sites of recurrence and periods between surgery and recurrence, of patients who had undergone curative gastrectomy for advanced gastric carcinoma (more than pT2 invasion) were surveyed in detail. Clinicopathological factors were examined as potential independent risk factors for each recurrence pattern, based on recurrence-free survival, using multivariate analysis. Results Multivariate analysis identified depth of tumor invasion (pT4 vs. pT2/3; hazard ratio (HR), 7.05; P < 0.001), number of lymph node metastases (pN2/3 vs. pN0/1; HR, 4.02; P = 0.001), and histological differentiation (G3/4 vs. G1/2; HR, 2.22; P = 0.041) as independent risk factors for peritoneal metastasis. The number of lymph node metastases (HR, 26.21; P < 0.001) and venous vessel invasion (HR, 5.09; P = 0.001) were identified as independent risk factors for hematogenous metastasis. The number of lymph node metastases (HR, 6.00; P = 0.007) and depth of tumor invasion (HR, 4.70; P = 0.023) were identified as independent risk factors for lymphatic metastasis. Conclusions This study clarified differences in risk factors between various patterns of recurrence. Careful examination of risk factors could help prevent oversight of recurrences and improve detection of recurrences during follow-up. The number of lymph node metastases represents an independent risk factor for all three patterns of recurrence; thus, patients with multiple lymph node metastases warrant particular attention.
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Affiliation(s)
- Yoshitsugu Nakanishi
- Department of Surgery, National Hospital Organization, Hakodate Hospital, 18-16 Kawahara-cho, Hakodate, Japan.
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Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, Roviello F, Oliveira C. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol 2013; 31:868-75. [PMID: 23341533 DOI: 10.1200/jco.2012.44.4612] [Citation(s) in RCA: 132] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. PATIENTS AND METHODS A series of patients with sporadic and familial GC (diffuse and intestinal; n = 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. RESULTS CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. CONCLUSION CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease.
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Mabula JB, Mchembe MD, Koy M, Chalya PL, Massaga F, Rambau PF, Masalu N, Jaka H. Gastric cancer at a university teaching hospital in northwestern Tanzania: a retrospective review of 232 cases. World J Surg Oncol 2012; 10:257. [PMID: 23181624 PMCID: PMC3527214 DOI: 10.1186/1477-7819-10-257] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2012] [Accepted: 10/31/2012] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Despite marked decreases in its incidence, particularly in developed countries, gastric cancer is still the second most common tumor worldwide. There is a paucity of information regarding gastric cancer in northwestern Tanzania. This study was undertaken to describe our experience, in our local setting, on the management of gastric cancer, outlining the clinicopathological and treatment outcome of these patients and suggesting ways to improve the treatment outcome. METHODS This was a retrospective study of histologically confirmed cases of gastric cancer seen at Bugando Medical Centre between January 2007 and December 2011. Data were retrieved from patients' files and analyzed using SPSS computer software version 17.0. RESULTS A total of 232 gastric cancer patients were enrolled in the study, representing 4.5% of all malignancies. The male to female ratio was 2.9:1. The median age of patients was 52 years. The majority of the patients (92.1%) presented late with advanced gastric cancer (Stages III and IV). Lymph node and distant metastasis at the time of diagnosis was recorded in 31.9% and 29.3% of cases, respectively. The antrum was the most frequent anatomical site (56.5%) involved and gastric adenocarcinoma (95.1%) was the most common histopathological type. Out of 232 patients, 223 (96.1%) patients underwent surgical procedures for gastric cancer of which gastro-jejunostomy was the most frequent performed surgical procedure, accounting for 53.8% of cases. The use of chemotherapy and radiotherapy was documented in 56 (24.1%) and 12 (5.1%) patients, respectively. Postoperative complication and mortality rates were 37.1% and 18.1%, respectively. According to multivariate logistic regression analysis, preoperative co-morbidity, histological grade and stage of the tumor, presence of metastases at the time of diagnosis was the main predictors of death (P <0.001). At the end of five years, only 76 (32.8%) patients were available for follow-up and the overall five-year survival rate was 6.9%. Evidence of cancer recurrence was reported in 45 (19.4%) patients. Positive resection margins, stage of the tumor and presence of metastasis at the time of diagnosis were the main predictors of local recurrence (P <0.001). CONCLUSIONS Gastric cancer in this region shows a trend towards relative young age at diagnosis and the majority of patients present late with an advanced stage. Lack of awareness of the disease, poor accessibility to health care facilities and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment and proper follow-up to improve treatment outcome.
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Affiliation(s)
- Joseph B Mabula
- Department of Surgery, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania
| | - Mabula D Mchembe
- Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania
| | - Mheta Koy
- Department of Internal Medicine, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania
| | - Phillipo L Chalya
- Department of Surgery, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania
| | - Fabian Massaga
- Department of Surgery, University of Dodoma, Dodoma, Tanzania
| | - Peter F Rambau
- Department of Pathology, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania
| | - Nestory Masalu
- Department of Oncology, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania
| | - Hyasinta Jaka
- Department of Internal Medicine, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania
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Janjigian YY, Kelsen DP. Genomic Dysregulation in gastric tumors. J Surg Oncol 2012; 107:237-42. [DOI: 10.1002/jso.23263] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Accepted: 08/20/2012] [Indexed: 12/12/2022]
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