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Zhao XY, Liu X, Li WH, Qiu LX, Huang MZ, Wang CC, Chen ZY, Zhang W, Feng WJ, Guo WJ, Zhu X. Randomized phase II study of TX followed by XELOX versus the reverse sequence for chemo-naive patients with metastatic gastric cancer. Front Oncol 2022; 12:911160. [PMID: 36387112 PMCID: PMC9643736 DOI: 10.3389/fonc.2022.911160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 09/07/2022] [Indexed: 10/19/2024] Open
Abstract
UNLABELLED This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients. BACKGROUND Docetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients. METHODS In this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment. RESULTS Total 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%). CONCLUSION TX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.
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Affiliation(s)
- Xiao-Yin Zhao
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xin Liu
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen-Hua Li
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Li-Xin Qiu
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ming-Zhu Huang
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chen-Chen Wang
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhi-Yu Chen
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen Zhang
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wan-Jing Feng
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei-Jian Guo
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaodong Zhu
- Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P, Farjah F, Gerdes H, Gibson MK, Hochwald S, Hofstetter WL, Ilson DH, Keswani RN, Kim S, Kleinberg LR, Klempner SJ, Lacy J, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Outlaw D, Park H, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian N, Pluchino LA. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022; 20:167-192. [PMID: 35130500 DOI: 10.6004/jnccn.2022.0008] [Citation(s) in RCA: 909] [Impact Index Per Article: 303.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.
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Affiliation(s)
| | | | - David J Bentrem
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Prajnan Das
- The University of Texas MD Anderson Cancer Center
| | - Peter C Enzinger
- Dana-Farber/Brigham and Women's Cancer Center
- Massachusetts General Hospital Cancer Center
| | | | | | - Farhood Farjah
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | | | | | - Rajesh N Keswani
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | - Samuel J Klempner
- Dana-Farber/Brigham and Women's Cancer Center
- Massachusetts General Hospital Cancer Center
| | - Jill Lacy
- Yale Cancer Center/Smilow Cancer Hospital
| | | | | | - Michael McNamara
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | - Mary F Mulcahy
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - Haeseong Park
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | - Kyle A Perry
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Scott Reznik
- UT Southwestern Simmons Comprehensive Cancer Center
| | - Robert E Roses
- Abramson Cancer Center at the University of Pennsylvania
| | | | | | | | | | | | - Danny Yakoub
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
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Farhat W, Chatelain F, Marret A, Faivre L, Arakelian L, Cattan P, Fuchs A. Trends in 3D bioprinting for esophageal tissue repair and reconstruction. Biomaterials 2020; 267:120465. [PMID: 33129189 DOI: 10.1016/j.biomaterials.2020.120465] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 10/15/2020] [Accepted: 10/18/2020] [Indexed: 02/08/2023]
Abstract
In esophageal pathologies, such as esophageal atresia, cancers, caustic burns, or post-operative stenosis, esophageal replacement is performed by using parts of the gastrointestinal tract to restore nutritional autonomy. However, this surgical procedure most often does not lead to complete functional recovery and is instead associated with many complications resulting in a decrease in the quality of life and survival rate. Esophageal tissue engineering (ETE) aims at repairing the defective esophagus and is considered as a promising therapeutic alternative. Noteworthy progress has recently been made in the ETE research area but strong challenges remain to replicate the structural and functional integrity of the esophagus with the approaches currently being developed. Within this context, 3D bioprinting is emerging as a new technology to facilitate the patterning of both cellular and acellular bioinks into well-organized 3D functional structures. Here, we present a comprehensive overview of the recent advances in tissue engineering for esophageal reconstruction with a specific focus on 3D bioprinting approaches in ETE. Current biofabrication techniques and bioink features are highlighted, and these are discussed in view of the complexity of the native esophagus that the designed substitute needs to replace. Finally, perspectives on recent strategies for fabricating other tubular organ substitutes via 3D bioprinting are discussed briefly for their potential in ETE applications.
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Affiliation(s)
- Wissam Farhat
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; AP-HP, Hôpital Saint-Louis, 1 avenue Vellefaux, F-75010, Paris, France; CEA, IRIG, F-38000, Grenoble, France
| | - François Chatelain
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; AP-HP, Hôpital Saint-Louis, 1 avenue Vellefaux, F-75010, Paris, France; CEA, IRIG, F-38000, Grenoble, France
| | - Auriane Marret
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; AP-HP, Hôpital Saint-Louis, 1 avenue Vellefaux, F-75010, Paris, France; CEA, IRIG, F-38000, Grenoble, France
| | - Lionel Faivre
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; Assistance Publique - Hôpitaux de Paris, Unité de Thérapie Cellulaire, Hôpital Saint-Louis, Paris, France
| | - Lousineh Arakelian
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; Assistance Publique - Hôpitaux de Paris, Unité de Thérapie Cellulaire, Hôpital Saint-Louis, Paris, France
| | - Pierre Cattan
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; Assistance Publique - Hôpitaux de Paris, Service de Chirurgie Digestive, Hôpital Saint-Louis, Paris, France
| | - Alexandra Fuchs
- Université de Paris, Inserm, U976 HIPI, F-75006, Paris, France; AP-HP, Hôpital Saint-Louis, 1 avenue Vellefaux, F-75010, Paris, France; CEA, IRIG, F-38000, Grenoble, France.
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Chronic High-Fat Diet Induces Early Barrett's Esophagus in Mice through Lipidome Remodeling. Biomolecules 2020; 10:biom10050776. [PMID: 32429496 PMCID: PMC7277507 DOI: 10.3390/biom10050776] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 05/07/2020] [Accepted: 05/12/2020] [Indexed: 12/15/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) incidence has been rapidly increasing, potentially associated with the prevalence of the risk factors gastroesophageal reflux disease (GERD), obesity, high-fat diet (HFD), and the precursor condition Barrett’s esophagus (BE). EAC development occurs over several years, with stepwise changes of the squamous esophageal epithelium, through cardiac metaplasia, to BE, and then EAC. To establish the roles of GERD and HFD in initiating BE, we developed a dietary intervention model in C57/BL6 mice using experimental HFD and GERD (0.2% deoxycholic acid, DCA, in drinking water), and then analyzed the gastroesophageal junction tissue lipidome and microbiome to reveal potential mechanisms. Chronic (9 months) HFD alone induced esophageal inflammation and metaplasia, the first steps in BE/EAC pathogenesis. While 0.2% deoxycholic acid (DCA) alone had no effect on esophageal morphology, it synergized with HFD to increase inflammation severity and metaplasia length, potentially via increased microbiome diversity. Furthermore, we identify a tissue lipid signature for inflammation and metaplasia, which is characterized by elevated very-long-chain ceramides and reduced lysophospholipids. In summary, we report a non-transgenic mouse model, and a tissue lipid signature for early BE. Validation of the lipid signature in human patient cohorts could pave the way for specific dietary strategies to reduce the risk of BE in high-risk individuals.
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A Comparative Study of Spatial Distribution of Gastrointestinal Cancers in Poverty and Affluent Strata (Kermanshah Metropolis, Iran). J Gastrointest Cancer 2020; 50:838-847. [PMID: 30136201 DOI: 10.1007/s12029-018-0163-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
INTRODUCTION The trend of cancers has witnessed a twofold rise in the last three decades, which is expected to be fivefold by 2030. On the other hand, gastrointestinal cancers have turned into one of the health issues in many societies. Given the presence of gastrointestinal cancer hot spots and evidence of health inequalities across Kermanshah Metropolis and the results of studies signaling the association between gastrointestinal cancers and socioeconomic status of individuals as well as evidence of unequal socioeconomic opportunities in this metropolis, the present study aimed to investigate the spatial distribution of gastrointestinal cancers in the poverty and affluent strata of Kermanshah Metropolis, Iran. MATERIALS AND METHODS In this descriptive-analytical study, the recorded data of patients, suffering from gastrointestinal cancers, in Kermanshah-based Pathology Centers and Vice Chancellery of Kermanshah University of Medical Sciences (2007-2012) were used. Moreover, to examine the status of gastrointestinal cancers in socioeconomic classes based on the census data collected during 2007-2012, 33 social, cultural, and structural indexes were extracted from the statistical blocks. Additionally, for data analysis and factor analysis, Kruskal-Wallis Test in the environment of SPSS and kernel density estimation (KDE) and Moran's I tests in the GIS environment were employed. FINDINGS The results of the present study revealed that the distribution of poverty (Z score = 48.916518, p value = 0.000000) and affluent strata (Z score = 14.345028, p value = 0.000000) followed clustered patterns (p < 0.01). Additionally, the results indicated that the spatial distribution pattern of the upper gastrointestinal cancer was clustered (Z score = 1.896996, p value = 0.007828), whereas the spatial distribution pattern of the lower gastrointestinal cancer was inclined to a randomized clustered pattern (Z score = 1.338121, p value = 0.000857) (p < 0.01). Finally, seven main hot spots were identified from the poverty stratum in Kermanshah, which perfectly overlapped the hot spots of upper gastrointestinal cancer. Similarly, four main hot spots were identified from the affluent stratum in Kermanshah, which overlapped the hot spots of lower gastrointestinal cancer. The results of the Kruskal-Wallis Test demonstrated that the poverty and affluent strata were significantly different from each other in terms of gastrointestinal cancer: upper gastrointestinal cancer (p < 0.05 and X2=10.064) and lower gastrointestinal cancer (p < 0.05 and X2=10.253). CONCLUSION The results of the present study showed that the ratio of patients with lower gastrointestinal cancers was higher than the incidence of upper gastrointestinal cancers over the 5-year period under study. Moreover, in Kermanshah Metropolis, there was a significant difference between the upper gastrointestinal cancer in the poverty stratum and the lower gastrointestinal cancer in the affluent stratum. Hence, it is suggested that GIS be applied as a tool for identifying the patterns of effective factors of this type of cancer in each social class, and it is recommended that some effective policies be presented and adopted by health managers according to the role and importance of socioeconomic, environmental, and nutritional factors in the poverty and affluent strata of society, and people at risk be equipped with preventive training programs in this respect.
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Zhang CD, Yamashita H, Seto Y. Gastric cancer surgery: historical background and perspective in Western countries versus Japan. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:493. [PMID: 31700929 PMCID: PMC6803217 DOI: 10.21037/atm.2019.08.48] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 08/08/2019] [Indexed: 12/12/2022]
Abstract
Gastrectomy plus D2 lymphadenectomy plays a decisive role in the management of resectable gastric cancer in Japan. Before recent advances in chemotherapy, Japanese surgeons considered that extensive surgery involving extended lymphadenectomy with combined resection of neighboring organ(s) was required to eliminate any possible lymphatic cancer spread and improve patient survival. This approach differs radically from that in Western countries, which aim to improve survival outcomes by multidisciplinary approaches including perioperative chemotherapy and/or radiotherapy with limited lymph node dissection. However, a randomized controlled trial conducted in Japan found that more extensive lymphadenectomy including the para-aortic lymph nodes provided no survival benefit over D2 lymphadenectomy. Splenic hilum dissection with splenectomy also failed to show superiority over the procedure without splenectomy in patients with proximal gastric cancer, except in cases with tumor invasion of the greater curvature. Furthermore, bursectomy recently demonstrated similar outcomes to omentectomy alone. Although "D2 lymphadenectomy" as carried out in Japan contributes to low local recurrence rates and good survival outcomes, the results of randomized controlled trials have led to a decreased extent of surgical resection, with no apparent adverse effects on survival outcome. Notably, gastrectomy with D2 dissection has tended to become acceptable for advanced gastric cancer in Western countries, based on the latest results of the Dutch D1D2 trial. Differences in surgical practices between the West and Japan have thus lessened and procedures are becoming more standardized. Japanese D2 lymphadenectomy for advanced gastric cancer is evolving toward more minimally invasive approaches, while consistently striving to achieve the optimal surgical extent, thereby promoting consensus with Western counterparts.
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Affiliation(s)
- Chun-Dong Zhang
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Blaser MJ, Chen Y. A New Gastric Cancer Among Us. J Natl Cancer Inst 2019; 110:549-550. [PMID: 29361121 DOI: 10.1093/jnci/djx279] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 12/01/2017] [Indexed: 12/19/2022] Open
Affiliation(s)
- Martin J Blaser
- Department of Medicine, Department of Microbiology, NYU Perlmutter Cancer Center, New York University School of Medicine, New York, NY
| | - Yu Chen
- Department of Medicine, Department of Microbiology, NYU Perlmutter Cancer Center, New York University School of Medicine, New York, NY.,Department of Population Health, New York University School of Medicine, New York, NY
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Choe JW, Kim YC, Joo MK, Kim HJ, Lee BJ, Kim JH, Yeon JE, Park JJ, Kim JS, Byun KS, Bak YT. Application of the Prague C and M criteria for endoscopic description of columnar-lined esophagus in South Korea. World J Gastrointest Endosc 2016; 8:357-361. [PMID: 27114749 PMCID: PMC4835663 DOI: 10.4253/wjge.v8.i8.357] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 09/16/2015] [Accepted: 12/02/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To ascertain whether the Prague circumferential (C) length and maximal (M) length criteria for grading the extent of Barrett’s esophagus can be applied prior to its widespread application in South Korea.
METHODS: Two hundred and thirteen consecutive cases with endoscopic columnar-lined esophagus (CLE) were included and classified according to the Prague C and M criteria.
RESULTS: Of 213 cases with CLE, the distribution of maximum CLE lengths was: 0.5-0.9 cm in 99 cases (46.5%); 1.0-1.4 cm in 63 cases (29.6%); 1.5-1.9 cm in 15 cases (7.0%); 2.0-2.4 cm in 14 cases (6.6%); 2.5-2.9 cm in 1 case (0.5%); and 7.0 cm in 1 case (0.5%). Twenty cases (9.4%) had columnar islands alone. Two hundred and eight cases (97.7%) lacked the circumferential CLE component (C0Mx). Columnar islands were found in 70 cases (32.9%), of which 20 cases (9.4%) had columnar islands alone.
CONCLUSION: In regions where most CLE patients display short or ultrashort tongue-like appearance, more detailed descriptions of CLE’s in < 1.0 cm lengths and columnar islands, as well as avoidance of repeating the prefix “C0” need to be considered in parallel with the widespread application of the Prague system in South Korea.
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The early diagnostic value of C-reactive protein for anastomotic leakage post radical gastrectomy for esophagogastric junction carcinoma: A retrospective study of 97 patients. Int J Surg 2016; 27:182-186. [DOI: 10.1016/j.ijsu.2016.02.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 02/03/2016] [Indexed: 01/27/2023]
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Gharahkhani P, Tung J, Hinds D, Mishra A, Vaughan TL, Whiteman DC, MacGregor S. Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus. Hum Mol Genet 2015; 25:828-35. [PMID: 26704365 PMCID: PMC4743691 DOI: 10.1093/hmg/ddv512] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 12/10/2015] [Indexed: 12/19/2022] Open
Abstract
Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3–11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA.
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Affiliation(s)
| | | | | | - Aniket Mishra
- Statistical Genetics Laboratory, Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, The Netherlands and
| | | | - Thomas L Vaughan
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
| | - David C Whiteman
- Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia
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Qu X, Biagi J, Banashkevich A, Mercer C, Tremblay L, Mahmud A. Management and outcomes of localized esophageal and gastroesophageal junction cancer in older patients. Curr Oncol 2015; 22:e435-42. [PMID: 26715880 PMCID: PMC4687668 DOI: 10.3747/co.22.2661] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Older patients are commonly excluded from clinical trials in esophageal and gastroesophageal junction (gej) cancer. High-level evidence to guide management in this group is lacking. In the present study, we compared outcomes and described tolerance for curative- and noncurative-intent treatments among patients 70 years of age and older. METHODS We retrospectively reviewed all patients 70 years of age and older diagnosed with localized esophageal and gej cancer at our centre between 2005 and 2012. RESULTS The 74 patients identified had a median age of 77 years. Of those patients, 62% received curative-intent treatment, consisting mostly of concomitant chemoradiation therapy (n = 43, 93%). Median overall survival for patients receiving curative-intent treatment was 18.6 months [95% confidence interval (ci): 13.0 to 28.0 months], with 23% being long-term survivors (95% ci: 11.3% to 36.7%). In contrast, patients receiving noncurative-intent treatment had a median overall survival of 8.8 months (95% ci: 6.7 to 11.9 months), with none being long-term survivors (p < 0.0001). Improvement of dysphagia was seen after curative (81%) or palliative radiotherapy (78%) in symptomatic patients, and toxicities were manageable. The odds of not receiving curative treatment was higher by a factor of 8.5 among patients 80 years of age or older compared with those 70-79 years of age (95% ci: 2.5 to 28.7). CONCLUSIONS In managing older patients with esophageal and gej cancer, curative-intent treatment (compared with noncurative-intent treatment) leads to a significant survival benefit with a reasonable toxicity profile. Informed counselling of patients and their families about a curative treatment approach and efforts to increase awareness among oncology care providers are suggested.
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Affiliation(s)
- X. Qu
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - J. Biagi
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - A. Banashkevich
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - C.D. Mercer
- Department of Surgery, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - L. Tremblay
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - A. Mahmud
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
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Old O, Moayyedi P, Love S, Roberts C, Hapeshi J, Foy C, Stokes C, Briggs A, Jankowski J, Barr H. Barrett's Oesophagus Surveillance versus endoscopy at need Study (BOSS): protocol and analysis plan for a multicentre randomized controlled trial. J Med Screen 2015; 22:158-64. [PMID: 25767103 DOI: 10.1177/0969141315575052] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 02/06/2015] [Indexed: 08/30/2023]
Abstract
OBJECTIVES The absolute annual risk of patients with Barrett's oesophagus (BO) developing oesophageal adenocarcinoma (OAC) is ≤ 0.5%. Screening BO patients for malignant progression using endoscopic surveillance is widely practised. To assess the efficacy and cost-effectiveness of this, we developed a protocol for a randomized controlled trial of surveillance versus 'at need' endoscopy. METHODS In a multicentre trial, 3400 BO patients randomized to either 2-yearly endoscopic surveillance or 'at need' endoscopy will be followed up for 10 years. Urgent endoscopy will be offered to all patients who develop symptoms of dysphagia, unexplained weight loss > 7lb (3.2 kg), iron deficiency anaemia, recurrent vomiting, or worsening upper gastrointestinal symptoms. Participants must have endoscopically and histologically confirmed BO, with circumferential BO ≥ 1 cm or maximal tongue/island length ≥ 2 cm. Candidates with existing oesophageal high-grade dysplasia or cancer, or previous upper gastrointestinal cancer will be excluded. Primary outcome will be overall survival. Secondary outcomes will be cost effectiveness (cost per life year saved and quality adjusted life years); cancer-specific survival; time to OAC diagnosis and stage at diagnosis; morbidity and mortality related to any interventions; and frequency of endoscopy. CONCLUSIONS This randomized trial will provide data to evaluate the efficacy and cost-effectiveness of screening BO patients for OAC.
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Affiliation(s)
- Oliver Old
- Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN
| | - Paul Moayyedi
- Division of Gastroenterology, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
| | - Sharon Love
- Centre for Statistics in Medicine, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD
| | - Corran Roberts
- Centre for Statistics in Medicine, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD
| | - Julie Hapeshi
- Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN
| | - Chris Foy
- Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN
| | - Clive Stokes
- Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN
| | - Andrew Briggs
- University of Glasgow, Health Economics and Health Technology Assessment, Institute of Health & Wellbeing, 1 Lilybank Gardens, Glasgow G12 8RZ
| | - Janusz Jankowski
- University Hospitals Coventry and Warwickshire, University of Warwick, Warwickshire, CV2 2DX
| | - Hugh Barr
- Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN
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Shrivastava MS, Hussain Z, Giricz O, Shenoy N, Polineni R, Maitra A, Verma A. Targeting chemokine pathways in esophageal adenocarcinoma. Cell Cycle 2015; 13:3320-7. [PMID: 25485576 DOI: 10.4161/15384101.2014.968426] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets.
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14
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Sugimoto H, Kawai T, Naito S, Yanagizawa K, Yamagishi T, Fukuzawa M, Yagi K, Matsubayashi J, Nagao T, Tomiyama H, Hoshino S, Tsuchida A, Moriyasu F. Surveillance of short-segment Barrett's esophagus using ultrathin transnasal endoscopy. J Gastroenterol Hepatol 2015; 30 Suppl 1:41-5. [PMID: 25827803 DOI: 10.1111/jgh.12879] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. METHODS AND RESULTS Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. CONCLUSION We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.
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Affiliation(s)
- Hiroko Sugimoto
- Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan
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15
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Esophageal Adenocarcinoma and Its Rare Association with Barrett's Esophagus in Henan, China. PLoS One 2014; 9:e110348. [PMID: 25333822 PMCID: PMC4198241 DOI: 10.1371/journal.pone.0110348] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 09/11/2014] [Indexed: 12/19/2022] Open
Abstract
Incidence of esophageal adenocarcinoma (EAC) has increased sharply in Western Europe and United States over the past three decades. Nearly all cases of EAC in the west are thought to be associated with Barrett's esophagus (BE) at the time of diagnosis. Regions in the Henan province of China have one of world's highest incidences of esophageal cancer, yet recent temporal trends in the relative rates of EAC with respect to esophageal squamous-cell carcinoma (ESCC), as well as its association with Barrett's esophagus (BE), have not been reported. In this report, we present large-scale longitudinal clinical and histological data on 5401 esophageal cancers (EC) patients diagnosed during the recent 10-year period (2002-2011) at Henan Cancer Hospital, China. All 217 esophageal adenocarcinoma (EAC) patients from these 5401 EC patients were examined to better understand the relationship between Barrett's esophagus (BE) and EAC. We found that EAC was relatively rare and accounted for approximately 5% of all esophageal cancers each year during 2002-2011. There is no evidence of significant temporal trends in the rate of EAC relative to ESCC. Only 10 out of 217 (4.6%) EAC cases were detected to have any evidence of Barrett's esophagus. This result raises the possibility of a different etiological basis for EAC in China motivating more detailed epidemiological, clinical and molecular characterization of EAC in China in order to better understand the neoplastic development of EAC.
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16
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Clavier JB, Antoni D, Atlani D, Ben Abdelghani M, Schumacher C, Dufour P, Kurtz JE, Noel G. Baseline nutritional status is prognostic factor after definitive radiochemotherapy for esophageal cancer. Dis Esophagus 2014; 27:560-7. [PMID: 23106980 DOI: 10.1111/j.1442-2050.2012.01441.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Identify prognostic factors for survival and patterns of treatment failure after definitive radiochemotherapy for esophageal cancer. Between 2003 and 2006, 143 patients with squamous cell carcinoma and adenocarcinoma of the esophagus were retrospectively reviewed. Median age was 65 years (42-81). Median radiation dose was 62.5 Gy (38-72) with 1.8-2 Gy fraction. Median follow-up was 20.8 months (2.8-92.4). Three and 5-year local recurrence-free survival rates were 58.3% and 50.9%. In univariate analysis, traversable esophageal stricture was a prognostic factor. Three, 5-year locoregional recurrence-free survival rates were 42.4% and 34.9%. In multivariate analysis, traversable esophageal stricture and stage < IIB were independent prognostic factors. Three and 5-year disease-free survival rates were 30.5% and 25.9%. In multivariate analysis, Nutritional Risk Index (NRI) ≥ 97.5 and performance status (PS) = 0 were independent prognostic factors. Median, 3, and 5-year overall survival rates were 22.1 months, 34.4%, and 19.8%. In multivariate analysis, independent prognostic factors were NRI ≥ 97.5 and PS = 0. Median survival times for the NRI classes (no denutrition, moderate and severe denutrition) were 29.5, 19.7, and 12 months (P = 0.0004), respectively. A major impact of baseline NRI was found in terms of survival; it should be included in future prospective trials.
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Affiliation(s)
- J-B Clavier
- Department of Radiation Oncology, Paul Strauss Cancer Center, Strasbourg, France
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17
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E-cadherin expression in Barrett’s esophagus and esophageal carcinoma. Esophagus 2014. [DOI: 10.1007/s10388-014-0424-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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18
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Alexandre L, Clark AB, Bhutta HY, Holt S, Lewis MPN, Hart AR. Statin use is associated with reduced risk of histologic subtypes of esophageal cancer: a nested case-control analysis. Gastroenterology 2014; 146:661-8. [PMID: 24315828 DOI: 10.1053/j.gastro.2013.11.046] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2012] [Revised: 11/21/2013] [Accepted: 11/26/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. METHODS We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. RESULTS In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). CONCLUSIONS In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups.
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Affiliation(s)
- Leo Alexandre
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom.
| | - Allan B Clark
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom
| | - Hina Y Bhutta
- Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom
| | - Sean Holt
- Roundwell Medical Centre, Norwich, United Kingdom
| | - Michael P N Lewis
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom
| | - Andrew R Hart
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom
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Mine S, Sano T, Hiki N, Yamada K, Kosuga T, Nunobe S, Shigaki H, Yamaguchi T. Thoracic lymph node involvement in adenocarcinoma of the esophagogastric junction and lower esophageal squamous cell carcinoma relative to the location of the proximal end of the tumor. Ann Surg Oncol 2014; 21:1596-601. [PMID: 24531703 DOI: 10.1245/s10434-014-3548-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Indexed: 12/27/2022]
Abstract
BACKGROUND It is difficult to determine preoperatively whether upper/middle thoracic lymphadenectomy is necessary in patients with adenocarcinoma of the esophagogastric junction (AEG) or lower esophageal squamous cell carcinoma (ESCC). Here, we investigated whether stratification based on the location of the proximal end of the tumor, as assessed using preoperative computed tomography (CT) images, would be useful for predicting upper/middle thoracic lymph node involvement for AEG and lower ESCC. METHODS A total of 142 patients with AEG and lower ESCC treated by R0-1 surgical resection via a thoracotomy was retrospectively investigated. The location of the proximal end of the tumor in comparison with the vena cava foramen (VCF) was decided by inspecting preoperative CT images and then correlated with upper/middle thoracic lymph node involvement. RESULTS The incidence of upper/middle thoracic lymph node involvement was low in AEG and ESCC tumors having proximal ends below the VCF (0 %, 0 of 13, and 5.9 %, 1 of 17, for AEG and ESCC, respectively). In contrast, when the tumors' proximal ends were above the VCF, patients had higher frequencies of upper/middle thoracic lymph node involvement (36.4 %, 8 of 22, and 37.8 %, 34 of 90, for AEG and ESCC, respectively). Multivariate analysis showed that the location of the proximal end of the tumor is an independent risk factor related to upper/middle thoracic lymph node involvement (odds ratio 14.3, 95 % confidence interval 1.76-111, p = 0.013), whereas other clinical factors (cT, cN, tumor length, and histologic types) are not. CONCLUSIONS This manner of stratification using preoperative CT images could be useful in deciding the extent of thoracic lymphadenectomy in both AEG and ESCC.
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Affiliation(s)
- Shinji Mine
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan,
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20
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Cellini F, Morganti AG, Di Matteo FM, Mattiucci GC, Valentini V. Clinical management of gastroesophageal junction tumors: past and recent evidences for the role of radiotherapy in the multidisciplinary approach. Radiat Oncol 2014; 9:45. [PMID: 24499595 PMCID: PMC3942272 DOI: 10.1186/1748-717x-9-45] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 02/01/2014] [Indexed: 11/16/2022] Open
Abstract
Gastroesophageal cancers (such as esophageal, gastric and gastroesophageal-junction -GEJ- lesions) are worldwide a leading cause of death being relatively rare but highly aggressive. In the past years, a clear shift in the location of upper gastrointestinal tract tumors has been recorded, both affecting the scientific research and the modern clinical practice. The integration of pre- or peri-operative multimodal approaches, as radiotherapy and chemotherapy (often combined), seems promising to further improve clinical outcome for such presentations. In the past, the definition of GEJ led to controversies and confusion: GEJ tumors have been managed either grouped to gastric or esophageal lesions, following slightly different surgical, radiotherapeutic and systemic approaches. Recently, the American Joint Committee on Cancer (AJCC) changed the staging and classification system of GEJ to harmonize some staging issues for esophageal and gastric cancer. This review discusses the most relevant historical and recent evidences of neoadjuvant treatment involving Radiotherapy for GEJ tumors, and describes the efficacy of such treatment in the frame of multimodal integrated therapies, from the new point of view of the recent classification of such tumors.
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Affiliation(s)
- Francesco Cellini
- Radiation Oncology, Policlinico Universitario Campus Bio-Medico, Via Álvaro del Portillo, 200, 00144 Rome, Italy
| | - Alessio G Morganti
- Radiotherapy Department, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Largo Agostino Gemelli 1, 86100 Campobasso, Italy
- Radiation Oncology Department, Policlinico Universitario “A. Gemelli”, Universita` Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Rome, Italy
| | - Francesco M Di Matteo
- GI Endoscopy Unit, Policlinico Universitario Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128 Rome, Italy
| | - Gian Carlo Mattiucci
- Radiation Oncology Department, Policlinico Universitario “A. Gemelli”, Universita` Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Rome, Italy
| | - Vincenzo Valentini
- Radiation Oncology Department, Policlinico Universitario “A. Gemelli”, Universita` Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Rome, Italy
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Connor CA, Adriaens M, Pierini R, Johnson IT, Belshaw NJ. Procyanidin induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun. Nutr Cancer 2014; 66:335-41. [PMID: 24471892 DOI: 10.1080/01635581.2014.868914] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Procyanidins are polymeric flavanols found in fruits and vegetables and have shown anticarcinogenic/chemopreventive properties. We previously showed that oligomeric procyanidin extracted from apples induced cell cycle arrest and apoptosis in esophageal adenocarcinoma (OA) cells. To understand the mechanism of action, we determined transcriptomic changes induced by procyanidin in OA cells. Pathway analysis implicated mitogen-activated protein kinase signaling pathways in eliciting these responses. Procyanidin induced the activation of JNK and p38 and the phosphorylation and expression of c-Jun. Inhibition of JNK but not p38 kinase activity prevented the procyanidin-induced phosphorylation and expression of c-Jun. Knockdown of the expression of JNK1, JNK2, or JUN diminished procyanidin-induced effects on cell proliferation and apoptosis. c-Jun is a component of the transcription factor AP-1 and AP-1 binding sites are overrepresented in the promoters of procyanidin-induced genes. This indicates that JNK activation of c-Jun by procyanidin leads to the induction of apoptosis of OA cells and suggests a role for a c-Jun-mediated transcriptional program. These data provide a mechanistic understanding of how procyanidin specifically targets a distinct pathway involved in the induction of apoptosis in OA cells and will inform future studies investigating its use as a chemopreventive/therapeutic agent.
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22
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Ye LY, Liu DR, Li C, Li XW, Huang LN, Ye S, Zheng YX, Chen L. Systematic review of laparoscopy-assisted versus open gastrectomy for advanced gastric cancer. J Zhejiang Univ Sci B 2014; 14:468-78. [PMID: 23733423 DOI: 10.1631/jzus.b1200197] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The study compared laparoscopy-assisted gastrectomy (LAG) with open gastrectomy (OG) in the management of advanced gastric cancer (AGC). METHODS Literature search was performed in the Medline, Embase, and Cochrane Library databases to identify control studies that compared LAG and OG for AGC. A meta-analysis was conducted to examine the surgical safety and oncologic adequacy, using the random-effect model. RESULTS Seven eligible studies including 815 patients were analyzed. LAG was associated with less blood loss, less use of analgesics, shorter time of flatus and periods of hospital stay, but longer time of operation. The incidence of most complications was similar between the two groups. However, LAG was associated with a lower rate of pulmonary infection (odds ratio (OR) 0.19; 95% confidence interval (CI) 0.05 to 0.68; P<0.05). No significant differences were noted in terms of the number of harvested lymph nodes (weighted mean difference (WMD) 1.165; 95% CI -2.000 to 4.311; P>0.05), overall mortality (OR 0.65; 95% CI 0.39 to 1.10; P>0.05), cancer-related mortality (OR 0.64; 95% CI 0.32 to 1.25; P>0.05), or recurrence (OR 0.62; 95% CI 0.33 to 1.16; P>0.05). CONCLUSIONS LAG could be performed safely for AGC with adequate lymphadenectomy and has several short-term advantages compared with conventional OG. No differences were found in long-term outcomes. However, these results should be validated in large randomized controlled studies (RCTs) with sufficient follow-up.
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Affiliation(s)
- Long-yun Ye
- Department of Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
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23
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Ek WE, Levine DM, D'Amato M, Pedersen NL, Magnusson PKE, Bresso F, Onstad LE, Schmidt PT, Törnblom H, Nordenstedt H, Romero Y, Chow WH, Murray LJ, Gammon MD, Liu G, Bernstein L, Casson AG, Risch HA, Shaheen NJ, Bird NC, Reid BJ, Corley DA, Hardie LJ, Ye W, Wu AH, Zucchelli M, Spector TD, Hysi P, Vaughan TL, Whiteman DC, MacGregor S. Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett's esophagus, and gastroesophageal reflux. J Natl Cancer Inst 2013; 105:1711-8. [PMID: 24168968 DOI: 10.1093/jnci/djt303] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. METHODS We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h(2)g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were two-sided, except in the case of variance-explained estimation where one-sided tests were used. RESULTS We estimated a statistically significant genetic variance explained for BE (h(2)g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10(-9)) and for EA (h(2)g = 25 %; SE = 5%; one-sided P = 2 × 10(-7)). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10(-6)), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. CONCLUSIONS We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases.
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Affiliation(s)
- Weronica E Ek
- Affiliations of authors: Statistical Genetics (WEE, SM) and Cancer Control Group (DCW), QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (WEE, SM); Department of Biostatistics, University of Washington, Seattle, WA (DML); Department of Biosciences and Nutrition (MD, FB, MZ) Department of Medical Epidemiology and Biostatistics (NLP, PKEM), Unit of Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery (HN) , and Department of Medical Epidemiology and Biostatistics (WY) , Karolinska Institutet, Stockholm, Sweden; Gastrocentrum Medicin, Karolinska University Hospital, Stockholm, Sweden (FB, PTS); Division of Public Health Sciences (LEO, TLV) and Division of Human Biology (BJR), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (HT); Division of Gastroenterology & Hepatology (YR), Department of Otolaryngology (YR), and GI Outcomes Unit (YR), Mayo Clinic, Rochester, MN; Department of Epidemiology, MD Anderson Cancer Center, Houston, TX (W-HC); Centre for Public Health, Queen's University, Belfast, Ireland (LJM); Department of Epidemiology, School of Public Health (MDG) and Division of Gastroenterology and Hepatology, UNC School of Medicine (NJS) , University of North Carolina, Chapel Hill, NC (MDG); Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, ON, Canada (GL); Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA (LB); Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada (AGC); Yale School of Public Health, New Haven, CT (HAR); Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK (NCB); Division of Research and Oakland Medical Center, Kaiser Permanente, Oakland, CA (DAC); Division of Epidemiology, University of Leeds, Leeds, UK (LJH); Department of Preventive Medicine
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Saira Chowdhury, Orla Hynes. Nutrition in Upper Gastrointestinal Cancer. Nutr Cancer 2013. [DOI: 10.1002/9781118788707.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Shen Q, Shi P, Gao M, Yu X, Liu Y, Luo L, Zhu Y. Progress on materials and scaffold fabrications applied to esophageal tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2013; 33:1860-6. [DOI: 10.1016/j.msec.2013.01.064] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Revised: 01/01/2013] [Accepted: 01/26/2013] [Indexed: 12/29/2022]
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Löfdahl HE, Lu Y, Lagergren P, Lagergren J. Risk factors for esophageal adenocarcinoma after antireflux surgery. Ann Surg 2013; 257:579-582. [PMID: 23426349 DOI: 10.1097/sla.0b013e3182888384] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Gastroesophageal reflux is the main risk factor for esophageal adenocarcinoma, but there is no strong support for any cancer-protective effect after antireflux surgery. We hypothesized that recurrent reflux or high exposure to other established risk factors, that is, obesity and tobacco smoking, are overrepresented among patients who despite antireflux surgery develop esophageal adenocarcinoma. DESIGN A population-based case-control study was nested within an antireflux surgery cohort from the Swedish Patient Register between 1965 and 2006. Cases were patients who developed esophageal adenocarcinoma more than 5 years after antireflux surgery, whereas randomly selected controls were matched to the cases regarding age, sex, and calendar year of the antireflux surgery. Study exposures among cases and controls were collected through review of medical records. Data on cancer were assessed through the Swedish Cancer Register. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariable conditional logistic regression, adjusted for recurrent reflux, body mass index (BMI), tobacco smoking, and type of antireflux surgery. RESULTS From 14,102 patients in the total antireflux surgery cohort, 55 cases and 240 controls were included. Patients who developed esophageal adenocarcinoma were 3 times more likely to have recurrent reflux after their antireflux surgery, compared with those who had not (OR: 3.1, 95% CI: 1.5-6.3). There were no statistically significant differences in risk when comparing BMI of 30 kg/m or more with BMI of less than 25 kg/m (OR: 1.6, CI: 0.8-3.5), ever smokers with never smokers (OR: 1.4, 95% CI: 0.7-2.8), or total fundoplication with partial fundoplication (OR: 0.6, 95% CI: 0.3-1.3). CONCLUSIONS Recurrence of reflux might explain the lack of protective effect of antireflux surgery regarding risk of developing esophageal adenocarcinoma.
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Affiliation(s)
- Hedvig E Löfdahl
- Unite of Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
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Esophageal cancer in Canada: trends according to morphology and anatomical location. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2013; 26:723-7. [PMID: 23061066 DOI: 10.1155/2012/649108] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Esophageal adenocarcinoma has one of the fastest rising incidence rates and one of the lowest survival rates of any cancer type in the Western world. However, in many countries, trends in esophageal cancer differ according to tumour morphology and anatomical location. In Canada, incidence and survival trends for esophageal cancer subtypes are poorly known. METHODS Cancer incidence and mortality rates were obtained from the Canadian Cancer Registry, the National Cancer Incidence Reporting System and the Canadian Vital Statistics Death databases for the period from 1986 to 2006. Observed trends (annual per cent change) and five-year relative survival ratios were estimated separately for esophageal adenocarcinoma and squamous cell carcinoma, and according to location (upper, middle, or lower one-third of the esophagus). Incidence rates were projected up to the year 2026. RESULTS Annual age-standardized incidence rates for esophageal cancer in 2004 to 2006 were 6.1 and 1.7 per 100,000 for males and females, respectively. Esophageal adenocarcinoma incidence rose by 3.9% (males) and 3.6% (females) per year for the period 1986 to 2006, with the steepest increase in the lower one-third of the esophagus (4.8% and 5.0% per year among males and females, respectively). In contrast, squamous cell carcinoma incidence declined by 3.3% (males) and 3.2% (females) per year since the early 1990s. The five-year relative survival ratio for esophageal cancer was 13% between 2004 and 2006, approximately a 3% increase since the period from 1992 to 1994. Projected incidence rates showed increases of 40% to 50% for esophageal adenocarcinoma and decreases of 30% for squamous cell carcinoma by 2026. DISCUSSION Although esophageal cancer is rare in Canada, the incidence of esophageal adenocarcinoma has doubled in the past 20 years, which may reflect the increasing prevalence of obesity and gastroesophageal reflux disease. Declines in squamous cell carcinoma may be the result of the decreases in the prevalence of smoking in Canada. Given the low survival rates and the potential for further increases in incidence, esophageal adenocarcinoma warrants close attention.
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Abstract
BACKGROUND AND AIM Negative association has been reported between presence of Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its complications. The aim of this study was to determine whether H. pylori (HP) can be protective against GERD in an African American (AA) population. METHODS From 2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both esophagitis and gastritis (363) and a normal control group (41). We collected their pathology and endoscopy unit reports. HP status was determined based on staining of gastric biopsy. RESULTS HP data was available for 79 % (1,611) of the cases. The frequency of HP positivity in gastritis patients was 40 % (506), in esophagitis patients 4 % and in normal controls 34 % (11), while HP was positive in 34 % of the patients with both esophagitis and gastritis. After adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01-0.59; P value = 0.01) for the esophagitis group versus the normal group. CONCLUSIONS Our results show H. pylori has a significant negative association with esophagitis in AAs which may point to a protective role of H. pylori in the pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low GERD complications in AAs.
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p16 gene mutations in Barrett's esophagus in gastric metaplasia - intestinal metaplasia - dysplasia - adenocarcinoma sequence. Adv Med Sci 2012; 57:71-6. [PMID: 22440936 DOI: 10.2478/v10039-012-0003-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE Barrett's associated esophageal adenocarcinoma (ADC) is one of the malignancies of most rapidly increasing incidence. The aim of the study was to assess p16 tumor suppressor gene alterations in the ADC premalignant conditions. MATERIAL & METHODS In the present study two p16 gene mutations (A148T and I49S) analysis with PCR- RFLP method have been performed in oesophageal biopsy specimen in 33 patients with Barrett's gastric metaplasia (GM), 27 - with Barrett's intestinal metaplasia (IM), 8 - with dysplasia and 11 - with ADC. RESULTS We have detected the I49S mutation in 12% (4/33) patients with GM, 18% (5/27) with IM, 50% - with dysplasia (4/8) and in 27% (3/11) - with ADC. The A148T mutation were found in 3% (1/33) patients with GM, 22% (6/27) - IM, 25% (2/8) - dysplasia and 27% patients with ADC (3/11). The frequency of the A148S mutation was rising in GM - IM - dysplasia - ADC sequence and was significantly lower in GM compared to all other grades taken together (p=0.0256). The frequency of the I49S mutation was rising in GM - IM - dysplasia sequence, to drop in ADC cases. There were no significant differences in frequency of the I49S mutation between studied groups. CONCLUSIONS These findings are consistent with the hypothesis on the role of the p16 mutations in early phase of Barrett's epithelium progression to ADC. The presence of p16 mutations in esophageal metaplastic columnar epithelium without goblet cells suggest that this pathology may have malignancy potential.
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Yang H, Sukocheva OA, Hussey DJ, Watson DI. Estrogen, male dominance and esophageal adenocarcinoma: is there a link? World J Gastroenterol 2012; 18:393-400. [PMID: 22346245 PMCID: PMC3270506 DOI: 10.3748/wjg.v18.i5.393] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2011] [Revised: 08/11/2011] [Accepted: 08/15/2011] [Indexed: 02/06/2023] Open
Abstract
Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.
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Ma Y, Tang L, Wang HX, Xu YC, Ma Y, Zhang FC. Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity. J Clin Pharm Ther 2011; 37:266-75. [PMID: 21950464 DOI: 10.1111/j.1365-2710.2011.01289.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Capecitabine- and 5-fluorouracil (5-FU)-based regimens are widely used for the treatment for advanced gastric cancer (AGC). We aimed to compare the efficacy of the two regimens for both Caucasian and Asian subjects, through a meta-analysis of the available trial evidence. METHODS We searched PubMed, ASO, ECCO, ESMO, Wanfang database (Chinese), CNKI (Chinese), Weipu database (Chinese) and J-STAGE (Japanese) using combinations of keywords, including 'capecitabine', '5-fluorouracil', 'chemotherapy', 'stomach neoplasms' and 'gastric cancer'. We identified relevant trial evidence and pooled the results on both efficacy and adverse events. RESULTS AND DISCUSSION Capecitabine-based chemotherapy for AGC prolonged the overall survival (OS; 10·7 months vs. 9·5 months, P = 0·03) and enhanced the response rate (RR; OR = 1·32; 95% CI, 1·11-1·57; P = 0·002) over 5-FU-based chemotherapy. Similar trends were observed in both Caucasian and Asian patients. Capecitabine-based regimens were associated with reduced incidence rates of grade 3 or grade 4 leukopenia (OR = 0·42; P = 0·005), stomatitis (OR = 0·43; P = 0·004) and nausea and vomiting (OR = 0·60; P = 0·002) compared with 5-FU-based treatment. Incidence of haematological toxicity such as anaemia (OR = 0·88; P = 0·53), thrombocytopenia (OR = 0·58; P = 0·06), neutropenia (OR = 1·03; P = 0·78) and treatment-related mortality was similar between capecitabine- and 5-FU-based treatments. Higher frequency of grade 3 or grade 4 hand-foot syndrome (HFS; OR 2·45; P = 0·0007) was observed in capecitabine-based combination therapies. Asian patients with AGC receiving capecitabine-based combination therapies showed less frequent occurrence of grade 3 or grade 4 gastrointestinal toxicity including nausea and vomiting (OR = 0·24; P = 0·0002) and stomatitis (OR = 0·33; P = 0·02) than those receiving 5-FU-based regimens. These differences in GI toxicity between treatment regimens were not significant in Caucasian subjects. No significant difference was found for the occurrence of anaemia (Caucasian subgroup: OR = 0·97, P = 0·88; Asian subgroup: OR = 0·63, P = 0·29), neutropenia (Caucasian subgroup: OR = 1·16, P = 0·27; Asian subgroup: OR = 0·75, P = 0·21) or thrombocytopenia (Caucasian subgroup: OR = 0·62, P = 0·18; Asian subgroup: OR = 0·51, P = 0·17) between the two ethnic subgroups. WHAT IS NEW AND CONCLUSION Capecitabine-based chemotherapy strategies show prolonged OS and enhanced ORR compared with traditional 5-FU-based treatments and therefore should be considered as one of the first choices for treatment for AGC. Asian patients also showed less grade 3 or grade 4 gastrointestinal toxicity with the capecitabine-based regimens.
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Affiliation(s)
- Y Ma
- Department of Oncology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Berg D, Wolff C, Langer R, Schuster T, Feith M, Slotta-Huspenina J, Malinowsky K, Becker KF. Discovery of new molecular subtypes in oesophageal adenocarcinoma. PLoS One 2011; 6:e23985. [PMID: 21966358 PMCID: PMC3179464 DOI: 10.1371/journal.pone.0023985] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2011] [Accepted: 07/28/2011] [Indexed: 12/22/2022] Open
Abstract
A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.
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Affiliation(s)
- Daniela Berg
- Institute of Pathology, Technische Universität München, Munich, Germany
| | - Claudia Wolff
- Institute of Pathology, Technische Universität München, Munich, Germany
| | - Rupert Langer
- Institute of Pathology, Technische Universität München, Munich, Germany
| | - Tibor Schuster
- Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany
| | - Marcus Feith
- Department of Surgery, Technische Universität München, Munich, Germany
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Chemoprevention in Barrett's oesophagus. Best Pract Res Clin Gastroenterol 2011; 25:569-79. [PMID: 22122772 DOI: 10.1016/j.bpg.2011.10.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2011] [Revised: 10/12/2011] [Accepted: 10/27/2011] [Indexed: 02/07/2023]
Abstract
Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus.
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Doherty GA, Cheriyan DG, Leyden JE, O'Dowd JF, Murray FE, Patchett SE. Inter-endoscopist agreement in diagnosis of Barrett's oesophagus. Frontline Gastroenterol 2011; 2:162-167. [PMID: 28839603 PMCID: PMC5536829 DOI: 10.1136/fg.2010.001529] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/13/2010] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE To assess how interpretation of abnormalities at the oesophago-gastric junction (OGJ) when making a diagnosis of Barrett's oesophagus (BO) varies between endoscopists and to examine the impact of the endoscopy experience on these decisions. DESIGN/SETTING Members of the Irish Society of Gastroenterology who regularly perform gastroscopy were invited to participate in a web based image assessment study. INTERVENTIONS Questions were posed to ascertain level of endoscopy experience, and participants were asked to indicate the presence or absence of BO in 12 endoscopic images of the OGJ. OUTCOME MEASURES Primary outcome was overall level of agreement in responses and relationship to endoscopy experience. RESULTS The responses of 65 clinicians regularly performing gastroscopy were analysed. In 3/12 images, showing typical long segment BO, there was a strong consensus on the endoscopic diagnosis (>95% agreement). However, agreement was fair to poor (κ for multiple raters, 0.31) on the presence or absence of short BO segments at endoscopy. Minimal differences were observed between experienced endoscopists (individuals with >10 years' endoscopy experience) and less experienced counterparts in the threshold for BO diagnosis. Inter-endoscopist agreement overall was not significantly better within the more experienced group. CONCLUSION The study demonstrates low interobserver agreement in endoscopic diagnosis of (short segment) BO, even among experienced endoscopists. Given the costs associated with endoscopic surveillance of BO, prompt efforts to promote consensus diagnosis and improve agreement are required as an important quality improvement measure in this area.
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Affiliation(s)
- Glen A Doherty
- Department of Gastroenterology, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Danny G Cheriyan
- Department of Gastroenterology, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Jan E Leyden
- Department of Gastroenterology, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland
| | - John F O'Dowd
- Department of Pathology, Bon Secours Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Frank E Murray
- Department of Gastroenterology, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Stephen E Patchett
- Department of Gastroenterology, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland
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Gillies RS, Simpkin A, Sgromo B, Marshall REK, Maynard ND. Left thoracoabdominal esophagectomy: results from a single specialist center. Dis Esophagus 2011; 24:138-44. [PMID: 20819097 DOI: 10.1111/j.1442-2050.2010.01107.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The left thoracoabdominal approach to esophagectomy is not widely performed, despite offering excellent exposure to tumors of the esophagogastric junction. Criticisms of the approach have focused on historically high rates of mortality, complications, and positive resection margins. Our aim was to determine whether left thoracoabdominal esophagectomy could combine a radical oncological resection with acceptably low mortality and morbidity. A retrospective cohort study of all left thoracoabdominal esophagectomies was performed at a single specialist center over an 11-year period. Primary outcomes were in-hospital mortality, complications, resection margin involvement, and lymph node yield; secondary outcomes were 1-year and 5-year survival. Two hundred eleven esophagectomies were performed. In-hospital mortality was 5.7% (12/211). One hundred one subjects (47.9%) had an uncomplicated recovery; 110 subjects (52.1%) developed at least one complication. There were 15 clinically significant anastomotic leaks (7.1%). Twenty-four subjects (11.4%) required emergency reoperation, the most common indication being anastomotic leakage. Complete tumor excision (R0 resection) was achieved in 151 of 211 cases (71.6%); median lymph node yield was 24. One-year and 5-year survival rates were 70% (147/211) and 21% (24/116), respectively. Left thoracoabdominal esophagectomy can combine a radical oncological resection with acceptably low mortality and morbidity.
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Affiliation(s)
- R S Gillies
- Department of Esophagogastric Surgery, Oxford Cancer and Hematology Centre, Churchill Hospital, Oxford, UK.
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Epidemiology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third. Recent Results Cancer Res 2010; 182:1-17. [PMID: 20676867 DOI: 10.1007/978-3-540-70579-6_1] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The incidence of adenocarcinoma of the esophagus and esophagogastric junction (gastric cardia) has risen rapidly over the past three decades in the United States and northern Europe. This increase had been most dramatic among White males. The majority of these cancers arise from Barrett's esophagus. However, less than 10% of the patients with esophageal adenocarcinoma were known to have Barrett's esophagus before. Current evidence indicates that gastroesophageal reflux and obesity are major risk factors for adenocarcinoma of the esophagus. Abdominal obesity, more prevalent in males, and independent of body mass index, seems to be associated with an increased risk of esophageal adenocarcinoma but not of cardia adenocarcinoma. This observation may explain the high male:female ratio observed in esophageal adenocarcinoma. Tobacco use has also been found as a possible risk factor for adenocarcinoma of the esophagus and gastric cardia. Infection with Helicobacter pylori and the use of nonsteroidal anti-inflammatory drugs might reduce the risk. On the other hand, low intake of fruits, vegetables, and cereal fibers seem to increase the risk of esophageal adenocarcinoma. Currently, there is no evidence that strongly supports any specific strategy to screen a subgroup of the population at risk for adenocarcinoma of the esophagus or esophagogastric junction. Future strategies to decrease obesity and tobacco use might help to reduce the burden of esophageal adenocarcinoma at least partially.
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Pultrum BB, Honing J, Smit JK, van Dullemen HM, van Dam GM, Groen H, Hollema H, Plukker JTM. A critical appraisal of circumferential resection margins in esophageal carcinoma. Ann Surg Oncol 2010; 17:812-20. [PMID: 19924487 PMCID: PMC2820690 DOI: 10.1245/s10434-009-0827-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2009] [Indexed: 11/18/2022]
Abstract
Background In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM. Methods To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1). Results A cutoff point of CRM at ≤1.0 mm and >1.0 mm appeared to be an adequate marker for survival and prognosis (both P < 0.001). The outcome in patients with CRMs ≤1.0 and >0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P < 0.001). Survival of patients with positive CRMs (≤1 mm) did not significantly differ from patients with an R1 resection (P = 0.12). Conclusion Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is ≤1 mm and for a free CRM is >1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.
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Affiliation(s)
- Bareld B Pultrum
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Goscinski MA, Larsen SG, Warloe T, Stoldt S, Nesland JM, Suo ZH, Giercksky KE. Adenocarcinomas on the rise--does it influence survival from oesophageal cancer? Scand J Surg 2010; 98:214-20. [PMID: 20218417 DOI: 10.1177/145749690909800404] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND AIMS A significant change in the occurrence of oesophageal squamous cell carcinomas (SCCs) in relation to adenocarcinomas (ACs) has been observed in the Norwegian population during the last 20 years (1988-2007). The AC incidence has increased from 5-10% to more than 50% nowadays, while the incidence of SCCs has decreased. Our goal was to evaluate if the change from SCC to AC and the increased effort to control reflux could be reflected in tumour stage, patient demographics and treatment results. MATERIAL AND METHODS We analysed clinical and pathological data from 347 patients with oesophageal AC (n = 189) and SCC (n = 158) treated at The Norwegian Radium Hospital during said period for patient- and tumour characteristics, treatment modalities and survival. RESULTS An oesophageal resection was performed in 169 of 347 patients. The median survival rate for all patients was 15 months, with a 5-year survival rate of 10%. The median survival time for operated and non-operated patients was 25 and 12 months respectively, with the corresponding 5-year survival rate of 13% and 2%. Patients with N0M0 disease operated with free resection margins presented a 5-year survival rate of 28%. CONCLUSIONS The change from SCC to AC and the ensuing considerable efforts made in surveillance and treatment of AC did not lead to improved long time survival for our patients.
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Affiliation(s)
- M A Goscinski
- Department of Surgical Oncology, The Norwegian Radium Hospital, Montebello, Oslo, Faculty of Medicine, University of Oslo, Oslo, Norway.
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Aragonés N, Izarzugaza M, Ramos M, Chirlaque M, Almar E, Martínez C. Trends in oesophago-gastric cancer incidence in Spain: analysis by subsite and histology. Ann Oncol 2010; 21 Suppl 3:iii69-75. [DOI: 10.1093/annonc/mdq083] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Abdullah M, Karim AA, Goh KL. Late presentation of esophageal cancer: observations in a multiracial South-East Asian population. J Dig Dis 2010; 11:28-33. [PMID: 20132428 DOI: 10.1111/j.1751-2980.2009.00410.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Esophageal cancer (ECA) is an important cancer in Malaysia. The aim of the study is to review the demographic data and clinical presentation of patients with ECA seen at the University of Malaya Medical Centre, Kuala Lumpur. METHODS Patients with histologically proven ECA were recruited for the study. Patients' case notes, endoscopy and operating theater records were reviewed. All cases were histologically confirmed. RESULTS A total of 143 patients with ECA was diagnosed between 1998 and 2003. The mean age of the patients was 63.1 +/- 12.1 years with a male : female ratio of 1.8:1. Of these 50.3 percent were Indians, 32.9 percent, Chinese and 16.8 percent Malays. The overall hospital-based prevalence rates per 100 000 admissions according to races were: Malay; 23.5, Chinese; 57.4 and Indian; 134.1. The location of the tumors was: upper; 16 (11.2%) middle; 52 (36.4%) and lower; 75 (52.4%). The histological type of ECA were: squamous cell carcinomas; 113 (79.0%) and adenocarcinomas; 30 (21.0%). The ECA stage at diagnosis, was: II; 18 (12.6%), III; 23 (16.1%) and IV; 102 (71.3%). Only 24 (16.8%) patients underwent surgery and13 (9.1%) were considered curative. Overall 114 (79.7%) patients underwent palliative endoscopic stenting and six (4.2%) were given other palliative therapy including radiotherapy. CONCLUSIONS Squamous cell cancer was the predominant type. ECA presents late in our patients and only a minority of patients underwent curative surgery.
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Affiliation(s)
- Muhammad Abdullah
- Department of Surgery, Faculty of Medicine, University of Malaya, Malaysia
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Akiyama T, Inamori M, Iida H, Endo H, Hosono K, Sakamoto Y, Fujita K, Yoneda M, Takahashi H, Koide T, Tokoro C, Goto A, Abe Y, Shimamura T, Kobayashi N, Kubota K, Saito S, Nakajima A. Shape of Barrett’s epithelium is associated with prevalence of erosive esophagitis. World J Gastroenterol 2010; 16:484-9. [PMID: 20101776 PMCID: PMC2811803 DOI: 10.3748/wjg.v16.i4.484] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To test the hypothesis that the shape and length of Barrett’s epithelium are associated with prevalence of erosive esophagitis.
METHODS: A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital. The presence and extent of Barrett’s epithelium were diagnosed based on the Prague C & M Criteria. We originally classified cases of Barrett’s epithelium into two types based on its shape, namely, flame-like and lotus-like Barrett’s epithelium, and into two groups based on its length, its C extent < 2 cm, and ≥ 2 cm. Correlation of shape and length of Barrett’s epithelium with erosive esophagitis was examined.
RESULTS: Barrett’s epithelium was diagnosed in 374 cases (43%). Most of these were diagnosed as short-segment Barrett’s epithelium. The prevalence of erosive esophagitis was significantly higher in subjects with flame-like than lotus-like Barrett’s epithelium, and in those with a C extent of ≥ 2 cm than < 2 cm.
CONCLUSION: Flame-like rather than lotus-like Barrett’s epithelium, and Barrett’s epithelium with a longer segment were more strongly associated with erosive esophagitis.
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42
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Gajperia C, Barbiere JM, Greenberg D, Wright K, Lyratzopoulos G. Recent incidence trends and sociodemographic features of oesophageal and gastric cancer types in an English region. Aliment Pharmacol Ther 2009; 30:873-80. [PMID: 19624549 DOI: 10.1111/j.1365-2036.2009.04100.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Oesophageal and gastric cancers comprise various common tumour types with possible different aetiology and historically different incidence trends. AIM To enhance and update evidence about the descriptive epidemiology of oesophageal and gastric cancers. METHODS Population-based information from the East of England was available on 16 319 (65% male) incident cases of oesophago-gastric cancer (ICD-10 C150-169) diagnosed during 1995-2006. Age-standardized incidence trends by gender and deprivation groups and sex ratios were compared for four different tumour types [oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), junctional/cardia adenocarcinoma (JCA), and non-cardia gastric adenocarcinoma (NCGA)]. RESULTS Between 1995-1997 and 2004-2006, the age-standardized incidence of OAC and JCA increased slightly (by 4% and 6% in men and 17% and 8% in women respectively), with a sex ratio >4 for both. Conversely, OSCC and NCGA incidence decreased (-20% and -32% in men and -15% and -26% in women respectively), with sex ratio of <2 for both. In men, OSCC and NCGA incidence was associated with increasing deprivation. CONCLUSIONS Within the study context, there was a modest rise in OAC and JCA incidence. OAC and JCA share common incidence trends and sociodemographic features (contrasting with those of OSCC and NCGA cancers).
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Affiliation(s)
- C Gajperia
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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Chandanos E, Lagergren J. The mystery of male dominance in oesophageal cancer and the potential protective role of oestrogen. Eur J Cancer 2009; 45:3149-55. [PMID: 19804965 DOI: 10.1016/j.ejca.2009.09.001] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2009] [Revised: 08/24/2009] [Accepted: 09/02/2009] [Indexed: 12/19/2022]
Abstract
Oesophageal cancer is the sixth most common form of cancer death globally with almost 400,000 deaths annually. More than 90% of all cases are either adenocarcinomas (OAC) or squamous-cell carcinomas (OSCC). There is a strong male predominance with up to 8 and 3 men for every woman affected with OAC and OSCC, respectively. It has been hypothesised that sex hormonal factors may play a role in the development of oesophageal cancer or more specifically that oestrogen prevents such development. This article reviews the available literature on this topic. Basic science studies suggest an inhibitory effect of oestrogen in the growth of oesophageal cancer cells, and a possible mechanism of any oestrogen protection might be mediated through oestrogen receptors. But from the few epidemiological studies in which the hypothesis of oestrogen protection has been tested, no firm conclusions can yet be drawn of the role of oestrogen in human oesophageal cancer aetiology. More evidence from valid and large human studies is needed before any conclusions can be drawn.
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Affiliation(s)
- Evangelos Chandanos
- Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
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44
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Balbuena L, Casson AG. Physical activity, obesity and risk for esophageal adenocarcinoma. Future Oncol 2009; 5:1051-63. [DOI: 10.2217/fon.09.65] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Over the past three decades, an increasing incidence of esophageal adenocarcinoma (EADC) has been reported throughout North America and Europe at a rate exceeding that of any other human solid tumor. Recent studies have clearly implicated chronic gastroesophageal reflux disease and several lifestyle risk factors, including tobacco consumption, diet and obesity, to be associated with increased risk of EADC. Although physical inactivity is now recognized as a risk factor for several chronic diseases including cancer, only a very limited number of studies have specifically evaluated the association between physical activity and esophageal malignancy. Furthermore, the precise biological mechanisms underlying the association between physical activity, obesity and cancer risk remain unclear. Since successful promotion of healthy body weight and exercise may substantially reduce the future incidence of cancer in the population, the purpose of this review is to explore current evidence linking physical activity, obesity and risk of malignancy – specifically EADC.
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Affiliation(s)
- Lloyd Balbuena
- Department of Surgery, University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Suite 2646, Saskatoon SK, S7N 0W8, Canada
| | - Alan G Casson
- Professor and Head, Department of Surgery, University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Suite 2646, Saskatoon SK, S7N 0W8, Canada
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45
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Changing incidence of gastric and oesophageal cancer subtypes in central Switzerland between 1982 and 2007. Eur J Epidemiol 2009; 24:603-9. [DOI: 10.1007/s10654-009-9379-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2009] [Accepted: 07/22/2009] [Indexed: 12/21/2022]
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46
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Akiyama T, Inamori M, Akimoto K, Iida H, Mawatari H, Endo H, Ikeda T, Nozaki Y, Yoneda K, Sakamoto Y, Fujita K, Yoneda M, Takahashi H, Hirokawa S, Goto A, Abe Y, Kirikoshi H, Kobayashi N, Kubota K, Saito S, Nakajima A. Risk factors for the progression of endoscopic Barrett's epithelium in Japan: a multivariate analysis based on the Prague C & M Criteria. Dig Dis Sci 2009; 54:1702-7. [PMID: 19003532 DOI: 10.1007/s10620-008-0537-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2007] [Accepted: 09/11/2008] [Indexed: 01/10/2023]
Abstract
PURPOSE To determine the prevalence and progression of Barrett's epithelium and associated risk factors in Japan. METHODS The study population comprised 869 cases. Endoscopic Barrett's epithelium was diagnosed based on the Prague C & M Criteria. The correlations of clinical factors with the prevalence and progression of endoscopic Barrett's epithelium were examined. RESULTS Endoscopic Barrett's epithelium was diagnosed in 374 cases (43%), in the majority of which the diagnosis was short-segment Barrett's esophagus. The progression of Barrett's epithelium was identified in 47 cases. In univariate and multiple logistic regression analyses, aging, smoking habit, and erosive esophagitis were significantly associated with the prevalence of Barrett's epithelium, whereas aging and erosive esophagitis, especially severe erosive esophagitis, were significant contributing factors to the progression of Barrett's epithelium. CONCLUSIONS Forty-three percent of the total study population was diagnosed as having endoscopic Barrett's epithelium. During the follow-up period, 12.6% of the cases with Barrett's epithelium exhibited progression which was associated with aging and severe erosive esophagitis.
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Affiliation(s)
- T Akiyama
- Division of Gastroenterology, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
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Falk J, Carstens H, Lundell L, Albertsson M. Incidence of carcinoma of the oesophagus and gastric cardia. Changes over time and geographical differences. Acta Oncol 2009; 46:1070-4. [PMID: 17851842 DOI: 10.1080/02841860701403046] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND The incidence of adenocarcinoma of the oesophagus is rising in many western countries including Sweden. METHODS We have studied the latest data concerning this as well as trends in the incidence of squamous cell carcinoma and adenocarcinoma of gastric cardia. Data was extracted from the Swedish cancer registry and analyzed regarding gender, age, region, histology and location of tumour. RESULTS The results show an increasing incidence of adenocarcinoma in both oesophagus and gastric cardia. Squamous cell carcinomas show a more stable development with a slight decrease of incidence. Adenocarcinoma is now the most common histological type of cancer in the oesophageal/cardia region in Sweden. Results also suggest a possible drift in location of adenocarcinoma from gastric cardia towards oesophagus. Overall a higher incidence was found in the male population and no trends in patient age at onset could be found. Squamous cell carcinoma is still slightly more common in urban regions.
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Affiliation(s)
- Jens Falk
- Department of Clinical Oncology, Södersjukhuset, Karolinska University Hospital, Stockholm, Sweden.
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48
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Peters CJ, Hardwick RH, Vowler SL, Fitzgerald RC, Oesophageal Cancer Clinical and Molecular Stratification Study Group. Generation and validation of a revised classification for oesophageal and junctional adenocarcinoma. Br J Surg 2009; 96:724-33. [PMID: 19526624 DOI: 10.1002/bjs.6584] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Collaborators] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Oesophageal adenocarcinoma is the commonest oesophageal malignancy in the West, but is staged using a system designed for squamous cell carcinoma. The aim was to develop and validate a staging system for oesophageal and junctional adenocarcinoma. METHODS Patients with oesophageal adenocarcinoma (Siewert types I and II) undergoing oesophagectomy with curative intent were randomly assigned to generation (313 patients) and validation (131) data sets. Outcome in the generation data set was associated with histopathological features; a revised node (N) classification was derived using recursive partitioning and tested on the validation data set. RESULTS A revised N classification based on number of involved lymph nodes (N0, none; N1, one to five; N2, six or more) was prognostically significant (P < 0.001). Patients with involved nodes on both sides of the diaphragm, regardless of number, had the same outcome as the N2 group. When applied to the validation data set, the revised classification (including nodal number and location) provided greater discrimination between node-positive patients than the existing system (P < 0.001). CONCLUSION A revised N classification based on number and location of involved lymph nodes provides improved prognostic power and incorporates features that may be useful before surgery in clinical management decisions.
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Affiliation(s)
- C J Peters
- Medical Research Council (MRC) Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK
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Collaborators
J R E Rees, P M Safranek, N Carroll, S Dwerryhouse, V Save, R Berrisford, S A Wajed, P Sarsfield, I Chandler, J Going, M McKernan, R Stuart, J Blazeby, N Imrit, N Maynard, G W B Clark, H Barr, N Shepherd,
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Bafandeh Y, Farhang S. Subsite distribution of gastric cancer in an area of high prevalence--northwest Iran. J Epidemiol 2009; 19:202-5. [PMID: 19542688 PMCID: PMC3924110 DOI: 10.2188/jea.je20080044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2008] [Accepted: 03/25/2009] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The aim of the present study was to determine subsites of gastric cancer in East Azerbaijan, Iran-a high incidence region for gastric cancer and Helicobacter pylori infection. METHODS Data were collected from 2002 through 2007 from patients who sought treatment for gastrointestinal symptoms or signs at a university clinic and subsequently underwent upper gastrointestinal endoscopy. RESULTS Cancer was diagnosed and histologically confirmed in 362 patients (352 adenocarcinomas). The mean age of the patients was 64.57 +/- 11.32 (range, 16-94 years) and the male-to-female ratio was 2.8:1. The gastric cardia was involved in 40.3% of patients with gastric adenocarcinoma, while the gastric fundus was involved in 3.7%, the gastric body in 49.1%, and the gastric antrum in 24.1% of patients. Complete evaluation for metastasis was possible in 144 patients; 61 were free of metastasis, and most of these patients underwent surgical therapy. Cardia involvement was not associated with the sex or age of patients. CONCLUSIONS Noncardia gastric cancer is still more frequent in East Azerbaijan, which is likely due to the very high prevalence of infection with Helicobacter pylori. The low rate of cancer involving the fundus is a target for further research on the etiology of gastric cancer.
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Affiliation(s)
- Yousef Bafandeh
- Professor of Gastroenterology and Hepatology Liver and Gastrointestinal Diseases Research Center Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Farhang
- General practitioner, Liver and Gastrointestinal Diseases Research Center Tabriz University of Medical Sciences, Tabriz, Iran
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Cooper SC, Day R, Brooks C, Livings C, Thomson CS, Trudgill NJ. The influence of deprivation and ethnicity on the incidence of esophageal cancer in England. Cancer Causes Control 2009; 20:1459-67. [PMID: 19533393 DOI: 10.1007/s10552-009-9372-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2008] [Accepted: 05/26/2009] [Indexed: 10/20/2022]
Abstract
The incidence of esophageal cancer (EC), particularly esophageal adenocarcinoma (EAC), has been rising dramatically. In the USA, esophageal squamous cell carcinoma (ESCC) is associated with deprivation and black ethnicity, while EAC is more common among whites. The influence of social deprivation and ethnicity has not been studied in England. West Midlands Cancer Intelligence Unit data were used to study the incidence of ESCC and EAC, and the influence of age, sex, socioeconomic status (Townsend quintiles by postcode) and ethnicity (to individual patients from Hospital Episode Statistics). From 1977 to 2004, a total of 15,138 EC were identified. Five-year directly age standardized incidence rates per 100,000 (95% CI) for men increased from 8.6 (8.0-9.1) in 1977-1981 to 13.7 (13.1-14.3) in 2000-2004 and for women from 5.0 (4.7-5.4) to 6.3 (5.9-6.6). ESCC incidence did not alter, but EAC incidence rose rapidly in males [2.1 (1.9-2.4) to 8.5 (8.1-9.0)] and in females [0.5 (0.4-0.6) to 1.7 (1.5-1.9)]. ESCC was strongly associated with the most socially deprived quintile. EAC was not associated with differences in socioeconomic status. EAC was significantly more common in white men 7.3 (6.9-7.7) and women 1.5 (1.3-1.6) when compared with black and Asian populations. In England the incidence of EAC has rapidly risen, particularly in men over the last three decades. ESCC was strongly associated with social deprivation. EAC was more common in white populations, but no association with the socioeconomic status was found.
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Affiliation(s)
- Sheldon C Cooper
- Department of Gastroenterology, Sandwell General Hospital, Lyndon, West Bromwich, West Midlands, B71 4HJ, UK.
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