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Allehdan S, Hammad SS, Alatrash RM, Al-Jaberi T, Hushki A, Yacoub S, Dahoud M, Elobeid T, Tayyem RT. Protective effect of dietary micronutrients on gastric cancer risk among Jordanians. NUTR HOSP 2024; 41:163-174. [PMID: 37705441 DOI: 10.20960/nh.04547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Abstract
Introduction Objective: several dietary and non-dietary factors and genetic predisposition may play an important role in gastric carcinogenesis. The findings about associations between micronutrients and gastric cancer (GC) is still inconsistent. This study aimed to investigate the effect of dietary micronutrients on gastric cancer risk. Methods: a case-control study comprised of 173 GC (107 males: 66 females) patients and 313 (190 males: 123 females) population-based controls matched for age, occupation, and marital status. Demographics, medical history, physical activity, and nutrient intake information were collected using reliable interview-based questionnaires. Information on dietary micronutrient intake was collected from the participants using a validated food frequency questionnaire (FFQ). Multinomial logistic regression was used to calculate Odds ratios (ORs) and their corresponding 95 % confidence intervals (CIs) and evaluate associations between dietary micronutrients and GC risk. Results: GC was inversely associated with the consumption of vitamin A, beta-carotene, vitamins D, E, K, B2, B3, B6, B12, and C, folate, chromium, iodine, and selenium. Additionally, a protective effect was observed for consumption of calcium, copper, iron, magnesium, phosphate, sodium, and zinc. In almost all the micronutrients, the second tertile showed a more pronounced reduction in GC risk as compared to the first tertile. Conclusions: our data support favorable effects of dietary consumption of some vitamins and minerals against GC risk.
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Affiliation(s)
- Sabika Allehdan
- Department of Biology. College of Science. University of Bahrain
| | - Shatha S Hammad
- Department of Nutrition and Food Technology. Faculty of Agriculture. University of Jordan
| | | | - Tareq Al-Jaberi
- Department of General and Pediatric Surgery. Faculty of Medicine. Jordan University of Science and Technology
| | - Ahmad Hushki
- Gastroenterology Division. King Hussein Cancer Center
| | | | | | - Tahra Elobeid
- Department of Human Nutrition. College of Health Sciences. Qatar University
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Agarwal S, Bell MG, Dhaliwal L, Codipilly DC, Dierkhising RA, Lansing R, Gibbons EE, Leggett CL, Kisiel JB, Iyer PG. Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma. Dig Dis Sci 2024; 69:246-253. [PMID: 37914889 PMCID: PMC10926253 DOI: 10.1007/s10620-023-08126-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 07/02/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance. AIMS We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort. METHODS EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival. RESULTS We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976-2019 was 1.40 (CI 1.1-1.74) and 0.83 (CI 0.61-1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995-1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality. CONCLUSION The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection.
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Affiliation(s)
- Siddharth Agarwal
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - Matthew G Bell
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Lovekirat Dhaliwal
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - D Chamil Codipilly
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - Ross A Dierkhising
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA
| | - Ramona Lansing
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - Erin E Gibbons
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - Cadman L Leggett
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - John B Kisiel
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA
| | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Barrett's Esophagus Unit, Mayo Clinic, Rochester, MN, USA.
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Matz M, Valkov M, Šekerija M, Luttman S, Caldarella A, Coleman MP, Allemani C, the CONCORD Working Group. Worldwide trends in esophageal cancer survival, by sub-site, morphology, and sex: an analysis of 696,974 adults diagnosed in 60 countries during 2000-2014 (CONCORD-3). Cancer Commun (Lond) 2023; 43:963-980. [PMID: 37488785 PMCID: PMC10508138 DOI: 10.1002/cac2.12457] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 05/04/2023] [Accepted: 06/11/2023] [Indexed: 07/26/2023] Open
Abstract
BACKGROUND Esophageal cancer survival is poor worldwide, though there is some variation. Differences in the distribution of anatomical sub-site and morphological sub-type may help explain international differences in survival for all esophageal cancers combined. We estimated survival by anatomic sub-site and morphological sub-type to understand further the impact of topography and morphology on international comparisons of esophageal cancer survival. METHODS We estimated age-standardized one-year and five-year net survival among adults (15-99 years) diagnosed with esophageal cancer in each of 60 participating countries to monitor survival trends by calendar period of diagnosis (2000-2004, 2005-2009, 2010-2014), sub-site, morphology, and sex. RESULTS For adults diagnosed during 2010-2014, tumors in the lower third of the esophagus were the most common, followed by tumors of overlapping sub-site and sub-site not otherwise specified. The proportion of squamous cell carcinomas diagnosed during 2010-2014 was generally higher in Asian countries (50%-90%), while adenocarcinomas were more common in Europe, North America and Oceania (50%-60%). From 2000-2004 to 2010-2014, the proportion of squamous cell carcinoma generally decreased, and the proportion of adenocarcinoma increased. Over time, there were few improvements in age-standardized five-year survival for each sub-site. Age-standardized one-year survival was highest in Japan for both squamous cell carcinoma (67.7%) and adenocarcinoma (69.0%), ranging between 20%-60% in most other countries. Age-standardized five-year survival from squamous cell carcinoma and adenocarcinoma was similar for most countries included, around 15%-20% for adults diagnosed during 2010-2014, though international variation was wider for squamous cell carcinoma. In most countries, survival for both squamous cell carcinoma and adenocarcinoma increased by less than 5% between 2000-2004 and 2010-2014. CONCLUSIONS Esophageal cancer survival remains poor in many countries. The distributions of sub-site and morphological sub-type vary between countries, but these differences do not fully explain international variation in esophageal cancer survival.
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Affiliation(s)
- Melissa Matz
- Cancer Survival GroupDepartment of Non‐Communicable Disease EpidemiologyLondon School of Hygiene and Tropical MedicineLondon WC1E 7HTGreater LondonUnited Kingdom
| | - Mikhail Valkov
- Department of RadiologyRadiotherapy and OncologyNorthern State Medical University, ArkhangelskArkhangelsk OblastRussia
| | - Mario Šekerija
- Croatian National Cancer RegistryCroatian Institute of Public Health, ZagrebZagreb CountyCroatia
| | | | - Adele Caldarella
- Tuscany Cancer RegistryIstituto per lo studio e la prevenzione oncologicaFlorenceTuscanyItaly
| | - Michel P Coleman
- Cancer Survival GroupDepartment of Non‐Communicable Disease EpidemiologyLondon School of Hygiene and Tropical MedicineLondon WC1E 7HTGreater LondonUnited Kingdom
- Cancer DivisionUniversity College London Hospitals NHS Foundation Trust, London NW1 2BUGreater LondonUnited Kingdom
| | - Claudia Allemani
- Cancer Survival GroupDepartment of Non‐Communicable Disease EpidemiologyLondon School of Hygiene and Tropical MedicineLondon WC1E 7HTGreater LondonUnited Kingdom
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Gao Y, Xin L, Lin H, Yao B, Zhang T, Zhou AJ, Huang S, Wang JH, Feng YD, Yao SH, Guo Y, Dang T, Meng XM, Yang ZZ, Jia WQ, Pang HF, Tian XJ, Deng B, Wang JP, Fan WC, Wang J, Shi LH, Yang GY, Sun C, Wang W, Zang JC, Li SY, Shi RH, Li ZS, Wang LW. Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study. Lancet Gastroenterol Hepatol 2023; 8:432-445. [PMID: 36931287 DOI: 10.1016/s2468-1253(23)00004-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/10/2023] [Accepted: 01/11/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING Science and Technology Commission of Shanghai Municipality.
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Affiliation(s)
- Ye Gao
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China
| | - Lei Xin
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China
| | - Han Lin
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China
| | - Bin Yao
- School of Computer Science and Engineering, Southeast University, Nanjing, Jiangsu Province, China
| | - Tao Zhang
- Department of Gastroenterology, Nanchong Central Hospital, Nanchong, Sichuan Province, China
| | - Ai-Jun Zhou
- Department of Gastroenterology, Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu Province, China
| | - Shu Huang
- Department of Gastroenterology, Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu Province, China
| | - Jian-Hua Wang
- Department of Gastroenterology, The First People's Hospital of Yancheng, Yancheng, Jiangsu Province, China
| | - Ya-Dong Feng
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China
| | - Sheng-Hua Yao
- Department of Gastroenterology, Yangzhong People's Hospital, Zhenjiang, Jiangsu Province, China
| | - Yan Guo
- Department of Gastroenterology, Yangzhong People's Hospital, Zhenjiang, Jiangsu Province, China
| | - Tong Dang
- Department of Digestive Diseases, Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
| | - Xian-Mei Meng
- Department of Digestive Diseases, Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
| | - Zeng-Zhou Yang
- Digestive Endoscopy Unit, Linzhou People's Hospital, Anyang, Henan Province, China
| | - Wan-Qi Jia
- Gastrointestinal Endoscopy Center, Nanyang Second People's Hospital, Nanyang, Henan Province, China
| | - Hui-Fang Pang
- Department of Gastroenterology, Digestive Endoscopy Unit, Tongliao City Hospital, Tongliao, Inner Mongolia, China
| | - Xiao-Juan Tian
- Department of Gastroenterology, Xixia County People's Hospital, Nanyang, Henan Province, China
| | - Bin Deng
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Jun-Ping Wang
- Department of Gastroenterology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi Province, China
| | - Wen-Chuan Fan
- Department of Gastroenterology, Digestive Endoscopy Center, The People's Hospital of Yanting City, Mianyang, Sichuan Province, China
| | - Jun Wang
- Department of Gastroenterology, Jinhu County People's Hospital, Huaian, Jiangsu Province, China
| | - Li-Hong Shi
- Department of Gastroenterology, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Guan-Yu Yang
- School of Computer Science and Engineering, Southeast University, Nanjing, Jiangsu Province, China
| | - Chang Sun
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China
| | - Wei Wang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China
| | - Jun-Cai Zang
- Harbor Scientific Instrument, Xiangtan, Hunan, China
| | - Song-Yang Li
- Harbor Scientific Instrument, Xiangtan, Hunan, China
| | - Rui-Hua Shi
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China
| | - Luo-Wei Wang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; National Clinical Research Center for Digestive Diseases (Shanghai), Shanghai, China.
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Li M, Park JY, Sheikh M, Kayamba V, Rumgay H, Jenab M, Narh CT, Abedi-Ardekani B, Morgan E, de Martel C, McCormack V, Arnold M. Population-based investigation of common and deviating patterns of gastric cancer and oesophageal cancer incidence across populations and time. Gut 2023; 72:846-854. [PMID: 36241389 DOI: 10.1136/gutjnl-2022-328233] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 09/28/2022] [Indexed: 12/08/2022]
Abstract
BACKGROUND The subtypes of gastric cancer (GC) and oesophageal cancer (EC) manifest distinct epidemiological profiles. Here, we aim to examine correlations in their incidence rates and to compare their temporal changes globally, both overall and by subtype. METHODS Long-term incidence data were obtained from population-based registries available from the Cancer Incidence in Five Continents series. Variation in the occurrence of EC and GC (overall and by subtype) was assessed using the GC:EC ratio of sex-specific age-standardised rates (ASR) in 2008-2012. Average annual per cent changes were estimated to assess temporal trends during 1998-2012. RESULTS ASRs for GC and EC varied remarkably across and within world regions. In the countries evaluated, the GC:EC ratio in men exceeded 10 in several South American countries, Algeria and Republic of Korea, while EC dominated in most sub-Saharan African countries. High rates of both cardia gastric cancer and oesophageal squamous cell carcinoma (ESCC) were observed in several Asian populations. Non-cardia gastric cancer rates correlated positively with ESCC rates (r=0.60) and negatively with EAC (r=-0.79). For the time trends, while GC incidence has been uniformly decreasing by on average 2%-3% annually over 1998-2012 in most countries, trends for EC depend strongly on histology, with several but not all countries experiencing increases in EAC and decreases in ESCC. CONCLUSIONS Correlations between GC and EC incidence rates across populations are positive or inverse depending on the GC subsite and EC subtype. Multisite studies that include a combination of populations whose incidence rates follow and deviate from these patterns may be aetiologically informative.
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Affiliation(s)
- Mengmeng Li
- Department of Cancer Prevention, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jin Young Park
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Mahdi Sheikh
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Violet Kayamba
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
- Department of Medicine, University of Zambia School of Medicine, Lusaka, Zambia
| | - Harriet Rumgay
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Mazda Jenab
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Clement Tetteh Narh
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
- Department of Epidemiology and Biostatistics, University of Health and Allied Sciences, Ho, Ghana
| | - Behnoush Abedi-Ardekani
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Eileen Morgan
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Catherine de Martel
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Valerie McCormack
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
| | - Melina Arnold
- Branches of Environment and Lifestyle Epidemiology, Cancer Surveillance and Genomics, International Agency for Research on Cancer, Lyon, France
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Bordin DS, Livzan MA, Osipenko MF, Mozgovoy SI, Andreyev DN, Maev IV. The key statements of the Maastricht VI consensus. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:5-21. [DOI: 10.31146/1682-8658-ecg-205-9-5-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
An analysis of the most important changes and provisions of the Maastricht VI consensus published in August 2022 is presented. 41 experts from 29 countries took part in the creation of the consensus. Recommendations have been developed in five areas: (1) indications for treatment and clinical associations of Helicobacter pylori (H. pylori) infection, (2) diagnosis, (3) treatment, (4) prevention of gastric cancer, (5) H. pylori and gastric microbiota -intestinal tract (GIT), taking into account the level of evidence and the strength of recommendations. Emphasis is placed on molecular testing, which is becoming an increasingly accessible research method in the world to identify both H. pylori itself and its sensitivity to antibiotics. The growing resistance of H. pylori strains to previously effective antibacterial agents requires a treatment strategy that implies the ability to determine the sensitivity of H. pylori to antibacterial agents both in the population and in a particular individual. The use of modern diagnostic tests expands the possibilities of individualization of therapy, since it allows determining not only the presence of H. pylori in the gastric mucosa, but also the sensitivity of the infection to antibacterial drugs. Along with individual approaches to treatment, the most effective empirical therapy regimens are given in case of impossibility to determine individual resistance to antibiotics. New data on the effectiveness and results of the use of primary and secondary preventive strategies for gastric cancer are presented. Given the important role of the entire microbiome of the gastrointestinal tract in the functioning of the body, the question of the interaction of H. pylori with other microorganisms is discussed. The critical issues of the near future are related to the global prevention of gastric cancer; the need to control antibiotic resistance, and the development of new methods of therapy and prevention of Helicobacter pylori infection.
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Affiliation(s)
- D. S. Bordin
- State Budgetary Institution of Healthcare of the city of Moscow “A. S. Loginov Moscow Clinical Scientific and Practical Center of the Department of Healthcare of the City of Moscow”; Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation; Federal State Educational Establishment of Higher Education Tver State Medical University
| | - M. A. Livzan
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - M. F. Osipenko
- Federal State Educational Establishment of Higher Education Novosibirsk State Medical University of the Ministry of Health of the Russian Federation
| | - S. I. Mozgovoy
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - D. N. Andreyev
- Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
| | - I. V. Maev
- Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
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7
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Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022; 71:gutjnl-2022-327745. [PMID: 35944925 DOI: 10.1136/gutjnl-2022-327745] [Citation(s) in RCA: 598] [Impact Index Per Article: 199.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/21/2022] [Indexed: 01/06/2023]
Abstract
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department 2, LMU, Munchen, Germany
- Department of Radiology, LMU, Munchen, Germany
| | - Francis Megraud
- INSERM U853 UMR BaRITOn, University of Bordeaux, Bordeaux, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
- Medical School, European University, Nicosia, Cyprus
| | - Javier P Gisbert
- Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jyh-Ming Liou
- Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Christian Schulz
- Medical Department 2, LMU, Munchen, Germany
- Partner Site Munich, DZIF, Braunschweig, Germany
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
| | - Richard H Hunt
- Medicine, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
- Veneto Tumor Registry (RTV), Padova, Italy
| | - Sebastian Suerbaum
- Partner Site Munich, DZIF, Braunschweig, Germany
- Max von Pettenkofer Institute, LMU, Munchen, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - Emad M El-Omar
- Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
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Arnold M, Morgan E, Bardot A, Rutherford MJ, Ferlay J, Little A, Møller B, Bucher O, De P, Woods RR, Saint-Jacques N, Gavin AT, Engholm G, Achiam MP, Porter G, Walsh PM, Vernon S, Kozie S, Ramanakumar AV, Lynch C, Harrison S, Merrett N, O'Connell DL, Mala T, Elwood M, Zalcberg J, Huws DW, Ransom D, Bray F, Soerjomataram I. International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study). Gut 2022; 71:1532-1543. [PMID: 34824149 DOI: 10.1136/gutjnl-2021-325266] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 11/04/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. METHODS As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. RESULTS Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. CONCLUSION Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.
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Affiliation(s)
- Melina Arnold
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Eileen Morgan
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Aude Bardot
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Mark J Rutherford
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Jacques Ferlay
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Alana Little
- Cancer Institute New South Wales, Alexandria, New South Wales, Australia
| | | | | | - Prithwish De
- Surveillance and Cancer Registry, Cancer Care Ontario, Toronto, Ontario, Canada
| | | | - Nathalie Saint-Jacques
- Registry & Analytics, Nova Scotia Health Authority Cancer Care Program, Halifax, Nova Scotia, Canada
| | - Anna T Gavin
- Northern Ireland Cancer Registry, Queen's University Belfast, Belfast, UK
| | - Gerda Engholm
- Cancer Prevention & Documentation, Danish Cancer Society, Copenhagen, Denmark
| | - Michael P Achiam
- Danish EsophagoGastric Cancer group, Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen, Denmark
| | - Geoff Porter
- Canadian Partnership Against Cancer, Toronto, Ontario, Canada
| | | | | | - Serena Kozie
- Saskatchewan Cancer Agency, Regina, Saskatchewan, Canada
| | | | - Charlotte Lynch
- International Cancer Benchmarking Partnership (ICBP), Policy & Information, Cancer Research UK, London, UK
| | - Samantha Harrison
- International Cancer Benchmarking Partnership (ICBP), Policy & Information, Cancer Research UK, London, UK
| | - Neil Merrett
- Department of Upper Gastrointestinal Surgery, Bankstown-Lidcombe Hospital and School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Dianne L O'Connell
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia
| | - Tom Mala
- Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway
| | - Mark Elwood
- School of Population Health, The University of Auckland, Auckland, New Zealand
| | - John Zalcberg
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Dyfed W Huws
- Swansea University, Swansea, Wales, UK
- Welsh Cancer Intelligence and Surveillance Unit, Public Health Wales, Cardiff, Wales, UK
| | - David Ransom
- WA Cancer and Palliative Care Network Policy Unit, Health Networks Branch, Department of Health, Perth, WA, Australia
| | - Freddie Bray
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
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9
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Zhang CD, Takeshima H, Sekine S, Yamashita S, Liu YY, Hattori N, Abe H, Yamashita H, Fukuda M, Imamura Y, Ushiku T, Katai H, Makino H, Watanabe M, Seto Y, Ushijima T. Prediction of tissue origin of adenocarcinomas in the esophagogastric junction by DNA methylation. Gastric Cancer 2022; 25:336-345. [PMID: 34557982 DOI: 10.1007/s10120-021-01252-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 09/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Prediction of tissue origin of esophagogastric junction (EGJ) adenocarcinomas can be important for therapeutic decision, but no molecular marker is available. Here, we aimed to develop such a marker taking advantage of tissue-specific profiles of DNA methylation. METHODS DNA methylation profiles of gastric adenocarcinomas (GACs) were obtained by an Infinium HumanMethylation450 BeadChip array, and those of esophageal adenocarcinoma (EACs) were obtained from the TCGA database. DNA from formalin-fixed paraffin-embedded (FFPE) samples was analyzed by bisulfite pyrosequencing. RESULTS In the screening set, 51 of 145,841 CpG sites in CpG islands were methylated at significantly higher levels in 30 GACs compared to those in 30 EACs. Among them, SLC46A3 and cg09177106 were unmethylated in all the 30 EACs. Predictive powers of these two markers were successfully confirmed in an independent validation set (18 GACs and 18 EACs) (SLC46A3, sensitivity = 77.8%, specificity = 100%; cg09177106, sensitivity = 83.3%, specificity = 94.4%), and could be applied to FFPE samples (37 GACs and 18 EACs) (SLC46A3, P = 0.0001; cg09177106, P = 0.0028). On the other hand, EAC-specific markers informative in the FFPE samples could not be isolated. Using these GAC-specific markers, nine of 46 (19.6%) TCGA EGJ adenocarcinomas were predicted to be GACs. CONCLUSIONS Two GAC-specific markers, SLC46A3 and cg09177106, had a high specificity for identifying the tissue origin of EGJ adenocarcinoma.
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Affiliation(s)
- Chun-Dong Zhang
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.,Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Hideyuki Takeshima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shigeki Sekine
- Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Satoshi Yamashita
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yu-Yu Liu
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Naoko Hattori
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Hiroyuki Abe
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Masahide Fukuda
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Hitoshi Katai
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Hiroshi Makino
- Department of Surgery, Tama-Nagayama Hospital, Nippon Medical School, Tokyo, 206-8512, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Toshikazu Ushijima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
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10
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Optimal surgery for esophagogastric junctional cancer. Langenbecks Arch Surg 2021; 407:1399-1407. [PMID: 34786603 DOI: 10.1007/s00423-021-02375-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 10/30/2021] [Indexed: 10/19/2022]
Abstract
Esophagogastric junctional cancer is classified into three categories according to the Siewert classification, which reflects the epidemiological and biological characteristics. Therapeutic strategies have been evaluated according to the three Siewert types. There is a consensus that types I and III should be treated as esophageal cancer and gastric cancer, respectively. On the other hand, type II is often described as true cardiac cancer, which has different clinicopathological features from the other types. Thus, there is no consensus on the surgical management of type II esophagogastric junctional cancer. The optimal surgical management should focus on the principles of cancer surgery, which take into consideration oncological curability, including an appropriate resection margin, adequate lymphadenectomy, and minimization of postoperative complications. In this review, we evaluate the current relevant literature and evidence, on the surgical treatment of esophagogastric junctional cancer, focusing on type II. Esophagectomy with a thoracic approach has the advantage of ensuring a sufficient proximal resection margin and adequate mediastinal lymphadenectomy. However, the oncological benefit is offset by a high incidence of postoperative complications. Minimally invasive esophagectomy could be a possible solution to reduce complications and improve long-term outcomes. Further development of surgical treatments for Siewert type II is required to improve the outcomes. Furthermore, the surgical team should have expertise in both gastric cancer and esophageal cancer treatment, or patients should be managed with close collaboration between thoracic surgeons and gastric cancer surgeons.
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11
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Morgan E, Soerjomataram I, Gavin AT, Rutherford MJ, Gatenby P, Bardot A, Ferlay J, Bucher O, De P, Engholm G, Jackson C, Kozie S, Little A, Møller B, Shack L, Tervonen H, Thursfield V, Vernon S, Walsh PM, Woods RR, Finley C, Merrett N, O'Connell DL, Reynolds JV, Bray F, Arnold M. International trends in oesophageal cancer survival by histological subtype between 1995 and 2014. Gut 2021; 70:234-242. [PMID: 32554620 DOI: 10.1136/gutjnl-2020-321089] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/24/2020] [Accepted: 05/12/2020] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Survival from oesophageal cancer remains poor, even across high-income countries. Ongoing changes in the epidemiology of the disease highlight the need for survival assessments by its two main histological subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS The ICBP SURVMARK-2 project, a platform for international comparisons of cancer survival, collected cases of oesophageal cancer diagnosed 1995 to 2014, followed until 31st December 2015, from cancer registries covering seven participating countries with similar access to healthcare (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK). 1-year and 3-year age-standardised net survival alongside incidence rates were calculated by country, subtype, sex, age group and period of diagnosis. RESULTS 111 894 cases of AC and 73 408 cases of SCC were included in the analysis. Marked improvements in survival were observed over the 20-year period in each country, particularly for AC, younger age groups and 1 year after diagnosis. Survival was consistently higher for both subtypes in Australia and Ireland followed by Norway, Denmark, New Zealand, the UK and Canada. During 2010 to 2014, survival was higher for AC compared with SCC, with 1-year survival ranging from 46.9% (Canada) to 54.4% (Ireland) for AC and 39.6% (Denmark) to 53.1% (Australia) for SCC. CONCLUSION Marked improvements in both oesophageal AC and SCC survival suggest advances in treatment. Less marked improvements 3 years after diagnosis, among older age groups and patients with SCC, highlight the need for further advances in early detection and treatment of oesophageal cancer alongside primary prevention to reduce the overall burden from the disease.
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Affiliation(s)
- Eileen Morgan
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
- Northern Ireland Cancer Registry, Queen's University Belfast, Belfast, UK
| | - Isabelle Soerjomataram
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Anna T Gavin
- Northern Ireland Cancer Registry, Queen's University Belfast, Belfast, UK
| | - Mark J Rutherford
- Biostatistics Research Group, Department of Health Sciences, University of Leicester, Leicester, UK
| | - Piers Gatenby
- Department of Clinical and Experimental Medicine, University of Surrey, Guildford, Surrey, UK
| | - Aude Bardot
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Jacques Ferlay
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Oliver Bucher
- Department of Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, Manitoba, Canada
| | - Prithwish De
- Surveillance and Cancer Registry, Ontario Health (Cancer Care Ontario), Toronto, Ontario, Canada
| | - Gerda Engholm
- Cancer Surveillance and Pharmacoepidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Christopher Jackson
- Cancer Society of New Zealand, Wellington, New Zealand
- Department of Medicine, Otago Medical School, Dunedin, New Zealand
| | - Serena Kozie
- Saskatchewan Cancer Agency, Regina, Saskatchewan, Canada
| | - Alana Little
- Cancer Information and Analysis, Cancer Institute NSW, Alexandria, New South Wales, Australia
| | - Bjorn Møller
- Department of Registration, Cancer Registry of Norway, Oslo, Norway
| | - Lorraine Shack
- Cancer Control Alberta, Alberta Health Services, Edmonton, Alberta, Canada
| | - Hanna Tervonen
- Cancer Information and Analysis, Cancer Institute NSW, Alexandria, New South Wales, Australia
| | - Vicky Thursfield
- Victorian Cancer Registry, Cancer Council Victoria, Melbourne, Victoria, Australia
| | - Sally Vernon
- National Cancer Registration and Analysis Service, Public Health England, Cambridge, UK
| | | | - Ryan R Woods
- BC Cancer Agency, Vancouver, British Columbia, Canada
| | - Christian Finley
- Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Neil Merrett
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Dianne L O'Connell
- Cancer Research Division, Cancer Council NSW, Sydney, New South Wales, Australia
| | - John V Reynolds
- National Centre for Oesophageal Cancer, St James's Hospital and Trinity College Dublin, Dublin, Ireland
| | - Freddie Bray
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Melina Arnold
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
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12
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Global Burden, Risk Factors, and Trends of Esophageal Cancer: An Analysis of Cancer Registries from 48 Countries. Cancers (Basel) 2021; 13:cancers13010141. [PMID: 33466239 PMCID: PMC7795486 DOI: 10.3390/cancers13010141] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/22/2020] [Accepted: 12/28/2020] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Esophageal cancer is the seventh most common cancer globally. Preventive measures and clinical management differ based on histologic subtype. However, information has been lacking on its most recent patterns according to histological subtype, associated risk factors, and epidemiological trends on a global scale. This study is a global analysis of the incidence/mortality trends of esophageal cancer in more than 48 countries/regions based on high quality population-based registries. We conclude that adenocarcinoma has already surpassed squamous cell carcinoma as the most frequent type of esophageal cancer in some western countries and is expected to increase in other countries. It is important to closely monitor and slow down the growing rates of obesity and metabolic syndrome, which are the important risk factors for adenocarcinoma. With the development of more advanced and less invasive technology, population-based targeted screening endoscopy would be recommended for high-risk individuals. Abstract This study aimed to examine the global burden, risk factors, and trends of esophageal cancer based on age, sex, and histological subtype. The data were retrieved from cancer registries database from 48 countries in the period 1980–2017. Temporal patterns of incidence and mortality were evaluated by average annual percent change (AAPC) using joinpoint regression. Associations with risk factors were examined by linear regression. The highest incidence of esophageal cancer was observed in Eastern Asia. The highest incidence of adenocarcinoma (AC) was found in the Netherlands, the United Kingdom, and Ireland. A higher AC/squamous cell carcinoma (SCC) incidence ratio was associated with a higher prevalence of obesity and elevated cholesterol. We observed an incidence increase (including AC and SCC) in some countries, with the Czech Republic (female: AAPC 4.66), Spain (female: 3.41), Norway (male: 3.10), Japan (female: 2.18), Thailand (male: 2.17), the Netherlands (male: 2.11; female: 1.88), and Canada (male: 1.51) showing the most significant increase. Countries with increasing mortality included Thailand (male: 5.24), Austria (female: 3.67), Latvia (male: 2.33), and Portugal (male: 1.12). Although the incidence of esophageal cancer showed an overall decreasing trend, an increasing trend was observed in some countries with high AC/SCC incidence ratios. More preventive measures are needed for these countries.
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13
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Seidlitz T, Koo BK, Stange DE. Gastric organoids-an in vitro model system for the study of gastric development and road to personalized medicine. Cell Death Differ 2021; 28:68-83. [PMID: 33223522 PMCID: PMC7852679 DOI: 10.1038/s41418-020-00662-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 10/24/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer ranks as the fifth most common human malignancy and the third leading cause of cancer related deaths. Depending on tumor stage, endoscopic or surgical resection supported by perioperative chemotherapy is the only curative option for patients. Due to late clinical manifestation and missing reliable biomarkers, early detection is challenging and overall survival remains poor. Organoids are cell aggregates cultured in three-dimensions that grow with similar characteristics as their tissue-of-origin. Due to their self-renewal and proliferative capacity, organoids can be maintained long term in culture and expanded in many cases in an unlimited fashion. Patient-derived organoid (PDO) libraries function as living biobanks, allowing the in depth analysis of tissue specific function, development and disease. The recent successful establishment of gastric cancer PDOs opens up new perspectives for multiple translational clinical applications. Here, we review different adult stem cell derived gastric organoid model systems and focus on their establishment, phenotypic and genotypic characterizations as well as their use in predicting therapy response.
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Affiliation(s)
- Therese Seidlitz
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Bon-Kyoung Koo
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter (VBC), Vienna, Austria
| | - Daniel E Stange
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
- National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
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14
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Alzeeb G, Metges JP, Corcos L, Le Jossic-Corcos C. Three-Dimensional Culture Systems in Gastric Cancer Research. Cancers (Basel) 2020; 12:E2800. [PMID: 33003476 PMCID: PMC7601358 DOI: 10.3390/cancers12102800] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/25/2020] [Accepted: 09/27/2020] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer (GC), which includes cancer of the esophagus, the oesophagogastric junction, and the stomach fundus, is highly deadly with strong regional influence, Asia being the most affected. GC is often detected at late stages, with 30% of metastatic cases at diagnosis. Many authors have devised models to both unravel the mechanisms of GC development and to evaluate candidate therapeutics. Among these models, 2D-cell cultures are progressively replaced by 3D-cell cultures that recapitulate, much more comprehensively, tumor cellular and genetic heterogeneity, as well as responsiveness to environmental changes, such as exposure to drugs or irradiation. With respect to the specifics of GC, there are high hopes from such model systems, especially with the aim of identifying prognostic markers and novel drug targets.
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Affiliation(s)
- George Alzeeb
- Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France; (G.A.); (L.C.)
| | - Jean-Philippe Metges
- CHU de Brest, Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France;
| | - Laurent Corcos
- Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France; (G.A.); (L.C.)
- CHU de Brest, Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France;
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15
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Arnold M, Ferlay J, van Berge Henegouwen MI, Soerjomataram I. Global burden of oesophageal and gastric cancer by histology and subsite in 2018. Gut 2020; 69:1564-1571. [PMID: 32606208 DOI: 10.1136/gutjnl-2020-321600] [Citation(s) in RCA: 343] [Impact Index Per Article: 68.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 05/25/2020] [Accepted: 05/25/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To provide updated estimates of the global burden of oesophageal and gastric cancer by subsite and type. METHODS Using data from population-based cancer registries, proportions of oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) out of all oesophageal as well as cardia gastric cancer (CGC) and non-CGC (NCGC) out of all gastric cancer cases were computed by country, sex and age group. Proportions were subsequently applied to the estimated numbers of oesophageal and gastric cancer cases from GLOBOCAN 2018. Age-standardised incidence rates (ASR) were calculated. RESULTS In 2018, there were an estimated 572 000 new cases of oesophageal cancer worldwide, 85 000 OACs (ASR 0.9 per 100 000, both sexes combined) and 482 000 OSCCs (ASR 5.3). Out of 1.03 million gastric cancers, there were an estimated 181 000 cases of CGC (ASR 2.0) and 853 000 cases of NCGC (ASR 9.2). While the highest incidence rates of OSCC, CGC and NCGC were observed in Eastern Asia (ASRs 11.1, 4.4 and 17.9, respectively), rates of OAC were highest in Northern Europe (ASR 3.5). While globally OSCC and NCGC remain the most common types of oesophageal and gastric cancer, respectively, rates of OAC exceed those of OSCC in an increasing number of high-income countries. CONCLUSIONS These updated estimates of the global burden of oesophageal and gastric cancer by subtype and site suggest an ongoing transition in epidemiological patterns. This work will serve as a cornerstone for policy-making and will aid in developing appropriate cancer control strategies.
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Affiliation(s)
- Melina Arnold
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Jacques Ferlay
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Mark I van Berge Henegouwen
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Noord-Holland, The Netherlands
| | - Isabelle Soerjomataram
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
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16
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Circumferential endoscopic submucosal dissection for the treatment of ultra-short-segment Barrett's adenocarcinoma with multifocal dysplasia. VideoGIE 2020; 5:649-651. [PMID: 33319131 PMCID: PMC7732717 DOI: 10.1016/j.vgie.2020.07.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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17
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Leers JM, Knepper L, van der Veen A, Schröder W, Fuchs H, Schiller P, Hellmich M, Zettelmeyer U, Brosens LAA, Quaas A, Ruurda JP, van Hillegersberg R, Bruns CJ. The CARDIA-trial protocol: a multinational, prospective, randomized, clinical trial comparing transthoracic esophagectomy with transhiatal extended gastrectomy in adenocarcinoma of the gastroesophageal junction (GEJ) type II. BMC Cancer 2020; 20:781. [PMID: 32819399 PMCID: PMC7439687 DOI: 10.1186/s12885-020-07152-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 07/08/2020] [Indexed: 12/18/2022] Open
Abstract
Background Adenocarcinoma of the gastroesophageal junction (GEJ) Siewert type II can be resected by transthoracic esophagectomy or transhiatal extended gastrectomy. Both allow for a complete tumor resection, yet there is an ongoing controversy about which surgical approach is superior with regards to quality of life, oncological outcomes and survival. While some studies suggest a better oncological outcome after transthoracic esophagectomy, others favor transhiatal extended gastrectomy for a better postoperative quality of life. To date, only retrospective studies are available, showing ambiguous results. Methods This study is a multinational, multicenter, randomized, clinical superiority trial. Patients (n = 262) with a GEJ type II tumor resectable by both transthoracic esophagectomy and transhiatal extended gastrectomy will be enrolled in the trial. Type II tumors are defined as tumors with their midpoint between ≤1 cm proximal and ≤ 2 cm distal of the top of gastric folds on preoperative endoscopy. Patients will be included in one of the participating European sites and are randomized to either transthoracic esophagectomy or transhiatal extended gastrectomy. The trial is powered to show superiority for esophagectomy with regards to the primary efficacy endpoint overall survival. Key secondary endpoints are complete resection (R0), number and localization of tumor infiltrated lymph nodes at dissection, post-operative complications, disease-free survival, quality of life and cost-effectiveness. Postoperative survival and quality of life will be followed-up for 24 months after discharge. Further survival follow-up will be conducted as quarterly phone calls up to 60 months. Discussion To date, as level 1 evidence is lacking, there is no consensus on which surgery is superior and both surgeries are used to treat GEJ type II carcinoma worldwide. The CARDIA trial is the first randomized trial to compare transthoracic esophagectomy versus transhiatal extended gastrectomy in patients with GEJ type II tumors. Several quality control measures were implemented in the protocol to ensure data reliability and increase the trial’s significance. It is hypothesized that esophagectomy allows for a higher rate of radical resections and a more complete mediastinal lymph node dissection, resulting in a longer overall survival, while still providing an acceptable quality of life and cost-effectiveness. Trial registration The trial was registered on August 2nd 2019 at the German Clinical Trials Register under the trial-ID DRKS00016923.
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Affiliation(s)
- Jessica M Leers
- Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Laura Knepper
- Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | - Arjen van der Veen
- Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Wolfgang Schröder
- Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Hans Fuchs
- Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Petra Schiller
- Institute of Medical Statistics and Computational Biology, University of Cologne, Robert-Koch-Str. 10, 50931, Cologne, Germany
| | - Martin Hellmich
- Institute of Medical Statistics and Computational Biology, University of Cologne, Robert-Koch-Str. 10, 50931, Cologne, Germany
| | - Ulrike Zettelmeyer
- Clinical Trials Centre Cologne, University of Cologne, Gleueler Str. 269, 50935, Cologne, Germany
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Alexander Quaas
- Institute for Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Jelle P Ruurda
- Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Richard van Hillegersberg
- Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Christiane J Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
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18
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Liu CT, Hong CQ, Huang XC, Li EM, Xu YW, Peng YH. Blood-based Markers in the Prognostic Prediction of Esophagogastric Junction Cancer. J Cancer 2020; 11:4332-4342. [PMID: 32489452 PMCID: PMC7255356 DOI: 10.7150/jca.44545] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/13/2020] [Indexed: 02/05/2023] Open
Abstract
Esophagogastric junction cancer poses a great threat to human beings both in western countries and East Asia, especially in China and Japan, and its incidence has increased during recent decades. The 5-year survival rate of esophagogastric junction cancer is quite poor compared with that of other gastric cancer sites. Until now, the traditional TNM staging system has been widely used in clinical practice for prognosis. However, the TNM system is based on pathology after surgical resection or radiology using CT and MRI, not on blood markers. Evidently, some research has been reported concentrated on the prognostic value of blood-based markers with the character of non-invasive and non-radioactive in EJA. Hematologic, biochemical and coagulation parameters could be obtained from clinical data and utilized to analyze their prognostic values. Tumor-associated antigens, microRNAs and circulating tumor cells have also been reported in EJC prognosis. In this article, we review research focused on blood-based markers to evaluate their prognostic value in esophagogastric junction cancer, especially its main subtype adenocarcinoma.
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Affiliation(s)
- Can-Tong Liu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, Guangdong, China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, the Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Xu-Chun Huang
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, Guangdong, China
| | - En-Min Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, Guangdong, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, Guangdong, China
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19
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Bornschein J, Quante M, Fassan M. Gastric Cancer; Epidemiology and Diagnosis. ENCYCLOPEDIA OF GASTROENTEROLOGY 2020:553-564. [DOI: 10.1016/b978-0-12-801238-3.65678-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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20
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Bornschein J, Wernisch L, Secrier M, Miremadi A, Perner J, MacRae S, O'Donovan M, Newton R, Menon S, Bower L, Eldridge MD, Devonshire G, Cheah C, Turkington R, Hardwick RH, Selgrad M, Venerito M, Malfertheiner P, Fitzgerald RC. Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction. Int J Cancer 2019; 145:3389-3401. [PMID: 31050820 PMCID: PMC6851674 DOI: 10.1002/ijc.32384] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 03/24/2019] [Accepted: 04/04/2019] [Indexed: 12/17/2022]
Abstract
Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment-naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina-HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune-response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed.
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Affiliation(s)
- Jan Bornschein
- MRC Cancer Unit, Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUnited Kingdom
- Department of Gastroenterology, Hepatology and Infectious DiseasesOtto‐von‐Guericke UniversityMagdeburgGermany
- Translational Gastroenterology UnitOxford University HospitalsOxfordUnited Kingdom
| | - Lorenz Wernisch
- MRC Biostatistics UnitUniversity of CambridgeCambridgeUnited Kingdom
| | - Maria Secrier
- Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUnited Kingdom
| | - Ahmad Miremadi
- Department of Histopathology, Addenbrooke's HospitalCambridge University HospitalsCambridgeUnited Kingdom
| | - Juliane Perner
- Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUnited Kingdom
| | - Shona MacRae
- MRC Cancer Unit, Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUnited Kingdom
| | - Maria O'Donovan
- Department of Histopathology, Addenbrooke's HospitalCambridge University HospitalsCambridgeUnited Kingdom
| | - Richard Newton
- MRC Biostatistics UnitUniversity of CambridgeCambridgeUnited Kingdom
| | - Suraj Menon
- Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUnited Kingdom
| | - Lawrence Bower
- Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUnited Kingdom
| | - Matthew D. Eldridge
- Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUnited Kingdom
| | - Ginny Devonshire
- Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUnited Kingdom
| | - Calvin Cheah
- MRC Cancer Unit, Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUnited Kingdom
| | | | - Richard H. Hardwick
- Department of Surgery, Addenbrooke's HospitalCambridge University HospitalsCambridgeUnited Kingdom
| | - Michael Selgrad
- Department of Gastroenterology, Hepatology and Infectious DiseasesOtto‐von‐Guericke UniversityMagdeburgGermany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious DiseasesOtto‐von‐Guericke UniversityMagdeburgGermany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious DiseasesOtto‐von‐Guericke UniversityMagdeburgGermany
| | - Rebecca C. Fitzgerald
- MRC Cancer Unit, Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUnited Kingdom
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21
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Seidlitz T, Chen YT, Uhlemann H, Schölch S, Kochall S, Merker SR, Klimova A, Hennig A, Schweitzer C, Pape K, Baretton GB, Welsch T, Aust DE, Weitz J, Koo BK, Stange DE. Mouse Models of Human Gastric Cancer Subtypes With Stomach-Specific CreERT2-Mediated Pathway Alterations. Gastroenterology 2019; 157:1599-1614.e2. [PMID: 31585123 PMCID: PMC6902245 DOI: 10.1053/j.gastro.2019.09.026] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 09/02/2019] [Accepted: 09/09/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patterns of genetic alterations characterize different molecular subtypes of human gastric cancer. We aimed to establish mouse models of these subtypes. METHODS We searched databases to identify genes with unique expression in the stomach epithelium, resulting in the identification of Anxa10. We generated mice with tamoxifen-inducible Cre recombinase (CreERT2) in the Anxa10 gene locus. We created 3 mouse models with alterations in pathways that characterize the chromosomal instability (CIN) and the genomically stable (GS) subtypes of human gastric cancer: Anxa10-CreERT2;KrasG12D/+;Tp53R172H/+;Smad4fl/f (CIN mice), Anxa10-CreERT2;Cdh1fl/fl;KrasG12D/+;Smad4fl/fl (GS-TGBF mice), and Anxa10-CreERT2;Cdh1fl/fl;KrasG12D/+;Apcfl/fl (GS-Wnt mice). We analyzed tumors that developed in these mice by histology for cell types and metastatic potential. We derived organoids from the tumors and tested their response to chemotherapeutic agents and the epithelial growth factor receptor signaling pathway inhibitor trametinib. RESULTS The gastric tumors from the CIN mice had an invasive phenotype and formed liver and lung metastases. The tumor cells had a glandular morphology, similar to human intestinal-type gastric cancer. The gastric tumors from the GS-TGFB mice were poorly differentiated with diffuse morphology and signet ring cells, resembling human diffuse-type gastric cancer. Cells from these tumors were invasive, and mice developed peritoneal carcinomatosis and lung metastases. GS-Wnt mice developed adenomatous tooth-like gastric cancer. Organoids derived from tumors of GS-TGBF and GS-Wnt mice were more resistant to docetaxel, whereas organoids from the CIN tumors were more resistant to trametinib. CONCLUSIONS Using a stomach-specific CreERT2 system, we created mice that develop tumors with morphologic similarities to subtypes of human gastric cancer. These tumors have different patterns of local growth, metastasis, and response to therapeutic agents. They can be used to study different subtypes of human gastric cancer.
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Affiliation(s)
- Therese Seidlitz
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Yi-Ting Chen
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Heike Uhlemann
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Sebastian Schölch
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany,Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany,German Cancer Consortium (DKTK), Dresden, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Susan Kochall
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Sebastian R. Merker
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Anna Klimova
- Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany,Core Unit for Data Management and Analytics (CDMA), National Center for Tumor Diseases (NCT), Dresden, Germany
| | - Alexander Hennig
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany,National Center for Tumor Diseases, Dresden, Germany
| | - Christine Schweitzer
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Kristin Pape
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Gustavo B. Baretton
- German Cancer Consortium (DKTK), Dresden, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany,Core Unit for Molecular Tumour Diagnostics, National Center for Tumor Diseases (NCT), Dresden, Germany,Institute of Pathology and Tumour and Normal Tissue Bank of the University Cancer Center, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,National Center for Tumor Diseases, Dresden, Germany
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Daniela E. Aust
- German Cancer Consortium (DKTK), Dresden, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany,Core Unit for Molecular Tumour Diagnostics, National Center for Tumor Diseases (NCT), Dresden, Germany,Institute of Pathology and Tumour and Normal Tissue Bank of the University Cancer Center, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,National Center for Tumor Diseases, Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany,German Cancer Consortium (DKTK), Dresden, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany,National Center for Tumor Diseases, Dresden, Germany
| | - Bon-Kyoung Koo
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria
| | - Daniel E. Stange
- Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany,German Cancer Consortium (DKTK), Dresden, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany,National Center for Tumor Diseases, Dresden, Germany,Reprint requests Address requests for reprints to: Daniel E. Strange, MD, PhD, Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
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22
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Hanada Y, Choi AY, Hwang JH, Draganov PV, Khanna L, Sethi A, Bartel MJ, Goel N, Abe S, De Latour RA, Park K, Melis M, Newman E, Hatzaras I, Reddy SS, Farma JM, Liu X, Schlachterman A, Kresak J, Trapp G, Ansari N, Schrope B, Lee JY, Dhall D, Lo S, Jamil LH, Burch M, Gaddam S, Gong Y, Del Portillo A, Tomizawa Y, Truong CD, Brewer Gutierrez OI, Montgomery E, Johnston FM, Duncan M, Canto M, Ahuja N, Lennon AM, Ngamruengphong S. Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria. Clin Gastroenterol Hepatol 2019; 17:1763-1769. [PMID: 30471457 DOI: 10.1016/j.cgh.2018.11.031] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 11/01/2018] [Accepted: 11/02/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.
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Affiliation(s)
- Yuri Hanada
- Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, Maryland
| | - Alyssa Y Choi
- Department of Medicine, University of Washington, Seattle, Washington
| | - Joo Ha Hwang
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, California
| | - Peter V Draganov
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida
| | - Lauren Khanna
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Amrita Sethi
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York
| | - Michael J Bartel
- Section of Gastroenterology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Neha Goel
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Seiichiro Abe
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Rabia A De Latour
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Kenneth Park
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Marcovalerio Melis
- Department of Surgery, New York University School of Medicine, New York, New York
| | - Elliot Newman
- Department of Surgery, New York University School of Medicine, New York, New York
| | - Ioannis Hatzaras
- Department of Surgery, New York University School of Medicine, New York, New York
| | - Sanjay S Reddy
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Jeffrey M Farma
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Xiuli Liu
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida
| | - Alexander Schlachterman
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Jesse Kresak
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida
| | - Garrick Trapp
- Department of Surgery, Columbia University Medical Center, New York, New York
| | - Nadia Ansari
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York
| | - Beth Schrope
- Department of Surgery, Columbia University Medical Center, New York, New York
| | - Jong Yeul Lee
- Digestive Diseases Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Deepti Dhall
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Simon Lo
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Laith H Jamil
- Digestive Diseases Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Miguel Burch
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Srinivas Gaddam
- Digestive Diseases Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Yulan Gong
- Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Armando Del Portillo
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
| | - Yutaka Tomizawa
- Division of Gastroenterology, University of Washington, Seattle, Washington
| | - Camtu D Truong
- Department of Pathology, University of Washington, Seattle, Washington
| | | | | | | | - Mark Duncan
- Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Marcia Canto
- Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, Maryland
| | - Nita Ahuja
- Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Anne Marie Lennon
- Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, Maryland
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23
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AlShammari A, Alam SF, Khan M, Aburahmah M. First endoscopic submucosal dissection of gastroesophageal junction carcinoma in a 72-year old male from Saudi Arabia. Int J Surg Case Rep 2019; 56:89-92. [PMID: 30861493 PMCID: PMC6411602 DOI: 10.1016/j.ijscr.2019.02.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 02/06/2019] [Accepted: 02/25/2019] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Esophageal and gastric tumors are very lethal malignancies. Their most common histology is adenocarcinoma for more than 90% of all gastroesophageal tumors. CASE PRESENTATION Herein, we report a case of endoscopic submucosal dissection for gastroesophageal junction carcinoma, the first of its kind to be performed in the Kingdom of Saudi Arabia for a 72-year-old patient, who was found to have a gastroesophageal junction mass extending to the cardia. Complete excision was performed via endoscopic submucosal dissection. There were no complications in the postoperative period and the patient was discharged in good condition. DISCUSSION Over time, the management of gastroesophageal junction carcinoma has evolved along with the surgical approach. Endoscopic submucosal dissection preserves the anatomical structures and not only leads to a better quality of life, but also decreases morbidity and mortality. The procedure shows favorable results for early-stage gastroesophageal junction carcinoma as a treatment option with excellent en bloc resection rates. CONCLUSION Endoscopic submucosal dissection is an acceptable management for T1 gastroesophageal junction carcinoma.
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Affiliation(s)
- Abdullah AlShammari
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh, 11533, Saudi Arabia; King Faisal Specialist Hospital and Research Center (KFSH&RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.
| | - Sreyoshi Fatima Alam
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh, 11533, Saudi Arabia.
| | - Mohamed Khan
- King Faisal Specialist Hospital and Research Center (KFSH&RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.
| | - Mohammad Aburahmah
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh, 11533, Saudi Arabia; King Faisal Specialist Hospital and Research Center (KFSH&RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.
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24
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Seidlitz T, Merker SR, Rothe A, Zakrzewski F, von Neubeck C, Grützmann K, Sommer U, Schweitzer C, Schölch S, Uhlemann H, Gaebler AM, Werner K, Krause M, Baretton GB, Welsch T, Koo BK, Aust DE, Klink B, Weitz J, Stange DE. Human gastric cancer modelling using organoids. Gut 2019; 68:207-217. [PMID: 29703791 PMCID: PMC6352409 DOI: 10.1136/gutjnl-2017-314549] [Citation(s) in RCA: 228] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 04/07/2018] [Accepted: 04/10/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Gastric cancer is the second leading cause of cancer-related deaths and the fifth most common malignancy worldwide. In this study, human and mouse gastric cancer organoids were generated to model the disease and perform drug testing to delineate treatment strategies. DESIGN Human gastric cancer organoid cultures were established, samples classified according to their molecular profile and their response to conventional chemotherapeutics tested. Targeted treatment was performed according to specific druggable mutations. Mouse gastric cancer organoid cultures were generated carrying molecular subtype-specific alterations. RESULTS Twenty human gastric cancer organoid cultures were established and four selected for a comprehensive in-depth analysis. Organoids demonstrated divergent growth characteristics and morphologies. Immunohistochemistry showed similar characteristics to the corresponding primary tissue. A divergent response to 5-fluoruracil, oxaliplatin, irinotecan, epirubicin and docetaxel treatment was observed. Whole genome sequencing revealed a mutational spectrum that corresponded to the previously identified microsatellite instable, genomic stable and chromosomal instable subtypes of gastric cancer. The mutational landscape allowed targeted therapy with trastuzumab for ERBB2 alterations and palbociclib for CDKN2A loss. Mouse cancer organoids carrying Kras and Tp53 or Apc and Cdh1 mutations were characterised and serve as model system to study the signalling of induced pathways. CONCLUSION We generated human and mouse gastric cancer organoids modelling typical characteristics and altered pathways of human gastric cancer. Successful interference with activated pathways demonstrates their potential usefulness as living biomarkers for therapy response testing.
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Affiliation(s)
- Therese Seidlitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Sebastian R Merker
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Alexander Rothe
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Falk Zakrzewski
- Core Unit for Molecular Tumour Diagnostics (CMTD), National Center for Tumour Diseases (NCT) Dresden, Dresden, Germany
| | - Cläre von Neubeck
- Department of Radiotherapy and Radiation Oncology and National Center for Radiation Research in Oncology (OncoRay), University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Konrad Grützmann
- Core Unit for Molecular Tumour Diagnostics (CMTD), National Center for Tumour Diseases (NCT) Dresden, Dresden, Germany
| | - Ulrich Sommer
- Institute for Pathology and Tumour and Normal Tissue Bank of the University Cancer Center (UCC), University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Christine Schweitzer
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Sebastian Schölch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany,Partner Site Dresden, National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Heike Uhlemann
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Anne-Marlene Gaebler
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Kristin Werner
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Mechthild Krause
- Department of Radiotherapy and Radiation Oncology and National Center for Radiation Research in Oncology (OncoRay), University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany,Partner Site Dresden, National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Gustavo B Baretton
- Core Unit for Molecular Tumour Diagnostics (CMTD), National Center for Tumour Diseases (NCT) Dresden, Dresden, Germany,Institute for Pathology and Tumour and Normal Tissue Bank of the University Cancer Center (UCC), University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany,Partner Site Dresden, National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Bon-Kyoung Koo
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria
| | - Daniela E Aust
- Core Unit for Molecular Tumour Diagnostics (CMTD), National Center for Tumour Diseases (NCT) Dresden, Dresden, Germany,Institute for Pathology and Tumour and Normal Tissue Bank of the University Cancer Center (UCC), University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Barbara Klink
- Core Unit for Molecular Tumour Diagnostics (CMTD), National Center for Tumour Diseases (NCT) Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany,Partner Site Dresden, National Center for Tumor Diseases (NCT), Heidelberg, Germany,Institute for Clinical Genetics, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany,Partner Site Dresden, National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Daniel E Stange
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany,Partner Site Dresden, National Center for Tumor Diseases (NCT), Heidelberg, Germany
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25
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Huang Q, Li R, Xu GF, Zhou D, Fan XS, Zou XP. Emerging evidence supports grouping by location of early gastric carcinoma for appropriate clinical management in Chinese patients. J Dig Dis 2018; 19:730-736. [PMID: 30270559 DOI: 10.1111/1751-2980.12674] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Revised: 09/12/2018] [Accepted: 09/21/2018] [Indexed: 12/11/2022]
Abstract
Gastric cancer is common in China. At present, early detection with prompt resection of early gastric carcinoma (EGC) is crucial for improving patient's survival. Because of high heterogeneity of EGC in Chinese patients we reviewed recent clinicopathological and molecular evidence and proposed a grouping EGC in three subgroups according to their location for appropriate management. In group 1 (cardia), most patients with EGC in this small location were elderly men. The tumors originated in the cardiac mucosa with a high proportion of cases with slightly elevated gross patterns and intestinal adenocarcinoma histology with moderate to well differentiation. Poorly cohesive carcinoma was infrequent. As the risk for lymph node metastasis in this kind of tumor was significantly lower than that in the distal stomach, endoscopic therapy is preferred. Group 2 (fundus-corpus), many patients with EGC in this large location were young women. The EGCs originated in the oxyntic mucosa with pure and mixed poorly cohesive carcinomas that are more commonly present in this area than in any other. Most tumors were poorly differentiated with a high risk for lymph node metastasis. Thus, endoscopic therapy may be appropriate for intramucosal, but not for submucosal, carcinoma. Group 3 (antrum-pylorus). EGC tumors arose from the antral mucosa, primarily because of Helicobacter pylori infection, following the Correa gastric cancer tumorigenetic pathway. Erosive and ulcerated gross patterns were most frequently observed. While most EGCs in this location were mainly intestinal adenocarcinomas, poorly differentiated EGCs were substantial in number. Because the risk of lymph node metastasis remains to be illustrated, clinical management requires an individualized approach. This preliminary observation requires verification in large nationwide multicenter studies.
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Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School and Brigham and Women's Hospital, West Roxbury, Massachusetts, USA
| | - Rui Li
- Department of Gastroenterology, The Affiliated First Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Gui Fang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China
| | - Dan Zhou
- Quality Care Medical Consulting, LLC, Lexington, Massachusetts, USA
| | - Xiang Shan Fan
- Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital Affiliated to Nanjing, University Medical School, Nanjing, Jiangsu Province, China
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26
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Nieuwenhuis L, van den Brandt PA. Tree nut, peanut, and peanut butter consumption and the risk of gastric and esophageal cancer subtypes: the Netherlands Cohort Study. Gastric Cancer 2018; 21:900-912. [PMID: 29594821 DOI: 10.1007/s10120-018-0821-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 03/15/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nut consumption has been associated with reduced cancer-related mortality. However, it is unclear whether nut consumption also reduces the risk of esophageal and gastric cancer subtypes. We prospectively investigated the relationship of tree nut, peanut, and peanut butter intake with risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. METHODS In 1986, 120,852 males and females, aged 55-69 years, completed a baseline questionnaire on diet and cancer risk factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases, and 3,720 subcohort members were available for multivariable Cox regression analyses, using a case-cohort approach. RESULTS Increased total nut consumption was significantly associated with a decreased risk of ESCC and GNCA [HRs (95% CIs) for 10 + g/day vs. nonconsumers = 0.54 (0.30-0.96) and 0.73 (0.55-0.97), respectively], but not with EAC and GCA risk. Similar trends were observed for tree nut and peanut intake, which were mostly nonsignificant. For peanut butter intake, no significant associations were found. When excluding the first four years of follow-up to reduce the possible influence of reversed causation, the relation between nut consumption and ESCC risk attenuated, but remained inverse. CONCLUSIONS Our findings suggest that increased tree nut and peanut consumption is inversely associated with GNCA risk and possibly with ESCC risk, but not with the risk of the other esophageal and gastric cancer subtypes.
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Affiliation(s)
- Lisette Nieuwenhuis
- Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands.
| | - Piet A van den Brandt
- Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands.,Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
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27
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Pyo JH, Lee H, Min YW, Min BH, Lee JH, Kim KM, Yoo H, Ahn S, Kim JJ. Indication for endoscopic treatment based on the risk of lymph node metastasis in patients with Siewert type II/III early gastric cancer. Gastric Cancer 2018; 21:672-679. [PMID: 29243195 DOI: 10.1007/s10120-017-0789-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 12/07/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Because of the poor prognosis of proximal gastric cancers, there is debate as to whether the conventional indications for endoscopic resection can be used. METHODS Among subjects who underwent surgery for esophagogastric junction or gastric cardia cancer, 256 patients with T1 type II/III of the Siewert classification were included in this study. The association of lymph node metastasis (LNM) with each variable was analyzed using logistic regression models. A receiver operating characteristic curve was used to determine the discriminatory ability of the model. Propensity score-matched non-cardia cancer patients were selected to compare LNM and long-term survival rates. RESULTS Of the 256 patients with T1 Siewert II/III gastric cancer, 21 (8.2%) had LNM. Because there was no LNM in T1a cancers, risk factors were analyzed only in patients with T1b. Tumor size (OR 1.42, 95% CI 1.10-1.82, P = 0.007) and lymphovascular invasion (LVI) (OR 5.13, 95% CI 1.88-14.06, P = 0.002) were determined to be predictors of LNM (sensitivity = 66.7% and specificity = 81.6%). Among patients without LVI, the groups with negligible risk for LNM were mucosa-confined cancer, or SM1 cancer with a tumor size ≤3 cm. No LNM was observed in patients satisfying the absolute or extended criteria for endoscopic resection of early gastric cancers. LNM and long-term survival rates of patients with Siewert II/III did not differ significantly compared with matched non-cardia cancer patients. CONCLUSIONS Tumor size and LVI were associated with LNM in patients with early Siewert type II/III gastric cancer, and the expanded indication for endoscopic resection may be used.
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Affiliation(s)
- Jeung Hui Pyo
- Center for Health Promotion, Samsung Medical Center, Seoul, Republic of Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Heejin Yoo
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Soohyun Ahn
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
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28
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Arnold M, Laversanne M, Brown LM, Devesa SS, Bray F. Predicting the Future Burden of Esophageal Cancer by Histological Subtype: International Trends in Incidence up to 2030. Am J Gastroenterol 2017; 112:1247-1255. [PMID: 28585555 DOI: 10.1038/ajg.2017.155] [Citation(s) in RCA: 289] [Impact Index Per Article: 36.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 04/16/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Rapid increases in the incidence of esophageal adenocarcinoma (EAC) in high-income countries in the past decades have raised public health concerns. This study is the first to predict the future burden of esophageal cancer by histological subtype using international incidence data. METHODS Data on esophageal cancer incidence by year of diagnosis, sex, histology, and age group were extracted from 42 registries in 12 countries included in the last three volumes (VIII-X) of Cancer Incidence in Five Continents, contributing at least 15 years of consecutive data. Numbers of new cases and incidence rates were predicted up to 2030 by fitting and extrapolating age-period-cohort models; the differential impact of demographic vs. risk changes on future cases were examined. RESULTS The number of new AC cases is expected to increase rapidly 2005-2030 in all studied countries as a combined result of increasing risk and changing demographics. In contrast, the incidence of esophageal squamous cell carcinoma (ESCC) is predicted to continue decreasing in most countries. By 2030, 1 in 100 men in the Netherlands and the United Kingdom are predicted to be diagnosed with EAC during their lifetime. CONCLUSIONS The burden from EAC is expected to rise dramatically across high-income countries and has already or will surpass ESCC incidence in the coming years, especially among men. Notwithstanding the inherent uncertainties in trend-based predictions and in subtype misclassification, these findings highlight an ongoing transition in the epidemiology of esophageal cancer that is highly relevant to future cancer control planning and clinical practice.
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Affiliation(s)
- Melina Arnold
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Mathieu Laversanne
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Linda Morris Brown
- RTI International, Environmental and Health Sciences Unit, Biostatistics and Epidemiology Division, Rockville, Maryland, USA
| | - Susan S Devesa
- National Cancer Institute, Division of Cancer Epidemiology and Genetics, Biostatistics Branch, Bethesda, Maryland, USA
| | - Freddie Bray
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
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29
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Giacopuzzi S, Bencivenga M, Weindelmayer J, Verlato G, de Manzoni G. Western strategy for EGJ carcinoma. Gastric Cancer 2017; 20:60-68. [PMID: 28039533 DOI: 10.1007/s10120-016-0685-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 12/15/2016] [Indexed: 02/06/2023]
Abstract
In this paper, the epidemiological and clinicobiological behavior of esophagogastric junction (EGJ) adenocarcinoma in the West is compared and contrasted to that in the East, and an overview is provided of current therapeutic strategies employed for this type of tumor in Western countries. It is well known that multimodal treatment is the therapeutic standard in locally advanced EGJ adenocarcinoma, but whether neoadjuvant/perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) is the optimal approach is still debated. Neoadjuvant CRT improves local control in locally advanced Siewert type I and II tumors, so it should be considered the treatment of choice. In the subset of these patients with microscopic systemic disease at diagnosis, more intensive exclusive chemotherapy protocols could be of benefit. Therefore, there is an urgent need to identify these patients before planning the treatment. For Siewert type III tumors, perioperative chemotherapy is the standard. While there is general agreement on the optimal surgical approach for Siewert types I and III (a two-field Ivor Lewis operation and a total gastrectomy with distal esophagectomy, respectively), no standard surgical treatment has been defined for Siewert type II tumors. When data from Western series on proximal and circumferential resection margins and on nodal spread in Siewert type II tumors are taken into account, the optimal surgical approach appears to be Ivor Lewis esophagectomy. Whether the extent of esophageal invasion can correctly predict nodal involvement in middle-upper mediastinal stations as a means to restrict indications for transthoracic esophagectomy requires further investigation in the West.
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Affiliation(s)
- Simone Giacopuzzi
- General and Upper G.I. Surgery Division, Department of Surgery, University of Verona, Piazzale Stefani 1, 37126, Verona, Italy
| | - Maria Bencivenga
- General and Upper G.I. Surgery Division, Department of Surgery, University of Verona, Piazzale Stefani 1, 37126, Verona, Italy
| | - Jacopo Weindelmayer
- General and Upper G.I. Surgery Division, Department of Surgery, University of Verona, Piazzale Stefani 1, 37126, Verona, Italy
| | - Giuseppe Verlato
- Unit of Epidemiology and Medical Statistics, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
| | - Giovanni de Manzoni
- General and Upper G.I. Surgery Division, Department of Surgery, University of Verona, Piazzale Stefani 1, 37126, Verona, Italy.
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30
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Vasapolli R, Malfertheiner P, Kandulski A. Helicobacter pylori and non-malignant upper gastrointestinal diseases. Helicobacter 2016; 21 Suppl 1:30-3. [PMID: 27531536 DOI: 10.1111/hel.12337] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.
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Affiliation(s)
- Riccardo Vasapolli
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Arne Kandulski
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
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31
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Clinicopathological characterisation of small (2 cm or less) proximal and distal gastric carcinomas in a Chinese population. Pathology 2016; 47:526-32. [PMID: 26166663 PMCID: PMC4699347 DOI: 10.1097/pat.0000000000000276] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
SummaryClinicopathological characteristics of small gastric carcinoma have not been well defined in Chinese patients. The aim of this study was to investigate and compare small proximal (PGC, n = 111) with distal (DGC, n = 202) gastric carcinoma in 313 consecutive surgically resected small (≤2 cm) gastric carcinomas diagnosed with the WHO criteria. PGC patients were significantly older (average age 63 years versus 59 in DGCs) with a male/female ratio of 3:1. Most tumours were clustered along the lesser curvature (74% in PGCs and 65% in DGCs). Compared to DGCs, PGCs showed a protruded gross pattern significantly more frequently and were significantly better differentiated with a significantly wider histomorphological spectrum. Surprisingly, PGCs were composed of significantly fewer signet-ring cell carcinomas (1% versus 16% in DGCs) but were significantly more deeply invasive, compared to DGCs. Lymph node metastasis was detected in 23% overall, but was significantly less frequent in PGCs (16%) than in DGCs (26%) (p < 0.05). However, the difference in survival between the two groups was not statistically significant. Our results demonstrate that in Chinese patients, PGCs display distinct clinicopathological characteristics, compared to DGCs.
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32
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Doorakkers E, Lagergren J, Engstrand L, Brusselaers N. Eradication of Helicobacter pylori and Gastric Cancer: A Systematic Review and Meta-analysis of Cohort Studies. J Natl Cancer Inst 2016; 108:djw132. [PMID: 27416750 DOI: 10.1093/jnci/djw132] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 04/15/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is associated with an increased risk of gastric adenocarcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma and a decreased risk of esophageal adenocarcinoma. We aimed to assess how eradication therapy for H. pylori influences the risk of developing these cancers. METHODS This was a systematic review and meta-analysis. We searched PubMed, Web of Science, Embase, and the Cochrane Library and selected articles that examined the risk of gastric cancer, MALT lymphoma, or esophageal cancer following eradication therapy, compared with a noneradicated control group. RESULTS Among 3629 articles that were considered, nine met the inclusion criteria. Of these, eight cohort studies assessed gastric cancer while one randomized trial assessed esophageal cancer. Out of 12 899 successfully eradicated patients, 119 (0.9%) developed gastric cancer, compared with 208 (1.1%) out of 18 654 noneradicated patients. The pooled relative risk of gastric cancer in all eight studies was 0.46 (95% confidence interval [CI] = 0.32 to 0.66, I(2) = 32.3%) favoring eradication therapy. The four studies adjusting for time of follow-up and confounders showed a relative risk of 0.46 (95% CI = 0.29 to 0.72, I(2) = 44.4%). CONCLUSIONS This systematic review and meta-analysis indicates that eradication therapy for H. pylori prevents gastric cancer. There was insufficient literature for meta-analysis of MALT lymphoma or esophageal cancer.
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Affiliation(s)
- Eva Doorakkers
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (ED, JL, NB); Division of Cancer Studies, King's College London, London, UK (JL); Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden (LE)
| | - Jesper Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (ED, JL, NB); Division of Cancer Studies, King's College London, London, UK (JL); Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden (LE)
| | - Lars Engstrand
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (ED, JL, NB); Division of Cancer Studies, King's College London, London, UK (JL); Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden (LE)
| | - Nele Brusselaers
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (ED, JL, NB); Division of Cancer Studies, King's College London, London, UK (JL); Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden (LE)
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33
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Arnold M, Colquhoun A, Cook MB, Ferlay J, Forman D, Soerjomataram I. Obesity and the Incidence of Upper Gastrointestinal Cancers: An Ecological Approach to Examine Differences across Age and Sex. Cancer Epidemiol Biomarkers Prev 2016; 25:90-7. [PMID: 26494763 PMCID: PMC4713286 DOI: 10.1158/1055-9965.epi-15-0753] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 10/15/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Esophageal and gastric cancers differ in their epidemiology but have several risk factors in common. The aim of this study was to assess age and sex differences in the burden of esophageal and gastric cancers in the context of the global obesity epidemic. METHODS Data from 50 countries were obtained from Cancer Incidence in Five Continents Volume X and GLOBOCAN 2012. Age-specific and age-standardized incidence rates of esophageal adenocarcinoma and squamous cell carcinoma (ESCC), as well as cardia (CGC) and noncardia (NCGC) gastric cancer, were estimated. Countries were grouped and analyzed according to their obesity prevalence. RESULTS A gradient across quartiles of obesity prevalence was found for esophageal adenocarcinoma, with the highest incidence rates in high prevalence countries (ASR 3.0 vs. 0.8 per 100,000 in highest vs. lowest obesity quartiles, males). In contrast, for ESCC as well as for CGC and NCGC the reverse was true, with the highest rates observed in countries with the lowest obesity prevalence (ESCC, 2.2 vs. 11.5; CGC, 2.8 vs. 7.8; NCGC, 3.9 vs. 17.4 in highest vs. lowest obesity quartiles, males). Although for esophageal adenocarcinoma, sex and age differences in incidence were most pronounced in countries with a high prevalence of obesity, these differences were much smaller for the other cancer sites assessed. CONCLUSIONS Variation in obesity prevalence may partly explain age and sex differences in the incidence of esophageal adenocarcinomas. IMPACT Ecologic studies can help assess relationships between risk factors and cancer, and generate new hypotheses that may be pursued through more directed research.
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Affiliation(s)
- Melina Arnold
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.
| | - Amy Colquhoun
- School of Public Health, University of Alberta, Edmonton, Canada
| | - Michael B Cook
- Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland
| | - Jacques Ferlay
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - David Forman
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Isabelle Soerjomataram
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
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34
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Kandulski A, Venerito M, Malfertheiner P. Helicobacter pylori
and esophageal neoplasia. ESOPHAGEAL CANCER AND BARRETT'S ESOPHAGUS 2015:79-86. [DOI: 10.1002/9781118655153.ch8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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35
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Han J, Jiang Y, Liu X, Meng Q, Xi Q, Zhuang Q, Han Y, Gao Y, Ding Q, Wu G. Dietary Fat Intake and Risk of Gastric Cancer: A Meta-Analysis of Observational Studies. PLoS One 2015; 10:e0138580. [PMID: 26402223 PMCID: PMC4581710 DOI: 10.1371/journal.pone.0138580] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 09/01/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Consumption of dietary fat has been reported to be associated with gastric cancer risk, but the results of epidemiologic studies remain inconsistent. We conducted a meta-analysis to summarize the evidence regarding the association between dietary fat intake and gastric cancer risk. METHODS A comprehensive search of PubMed and EMBASE was performed to identify observational studies providing quantitative estimates between dietary fat and gastric cancer risk. Random effects model was used to calculate the summary relative risk(SRR) in the highest versus lowest analysis. Categorical dose-response analysis was conducted to quantify the association between dietary fat intake and gastric cancer risk. Heterogeneity among studies was evaluated using I2 and tau2(between study variance)statistics. Subgroup analysis and publication bias analysis were also performed. RESULTS Twenty-two articles were included in the meta-analysis. The SRR for gastric cancer was 1.18 for individuals with highest intake versus lowest intake of total fat (95% confidence interval [CI]: 0.999-1.39; n = 28; P< 0.001; tau2 = 0.12; I2 = 69.5%, 95% CI: 55%-79%) and 1.08 with a daily increase in total fat intake (20 g/d) (95%CI: 1.02-1.14; n = 6; P = 0.09; tau2 = 0.002; I2 = 46.8%, 95% CI: 0%-79%). Positive association between saturated fat intake (SRR = 1.31; 95%CI: 1.09-1.58;n = 18;P<0.001; tau2 = 0.08; I2 = 60.6%, 95% CI: 34%-76%), inverse association between polyunsaturated fat intake (SRR = 0.77; 95%CI: 0.65-0.92; n = 16; P = 0.003; tau2 = 0.06; I2 = 56.2%, 95% CI: 23%-75%) and vegetable fat intake (SRR = 0.55; 95%CI: 0.41-0.74; n = 4;P = 0.12; tau2 = 0.04; I2 = 48.6%, 95% CI: 0%-83%), and no association between monounsaturated fat intake (SRR = 1.00; 95%CI: 0.79-1.25; n = 14; P< 0.001; tau2 = 0.10; I2 = 63.0%, 95% CI: 34%-79%) and animal fat intake (SRR = 1.10; 95%CI: 0.90-1.33; n = 6; P = 0.13;tau2 = 0.02; I2 = 42.0%, 95% CI: 0%-70%) and gastric cancer risk were observed. CONCLUSIONS Our results suggest that intake of total fat is potentially positively associated with gastric cancer risk, and specific subtypes of fats account for different effects. However, these findings should be confirmed by further well-designed cohort studies with detailed dietary assessments and strict control of confounders.
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Affiliation(s)
- Jun Han
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Yi Jiang
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Xiao Liu
- Nursing Department, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Qingyang Meng
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Qiulei Xi
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Qiulin Zhuang
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Yusong Han
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Ying Gao
- Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Qiurong Ding
- Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Guohao Wu
- The Clinical Nutrition Center of Shanghai, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
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Xiao JW, Liu ZL, Ye PC, Luo YJ, Fu ZM, Zou Q, Wei SJ. Clinical comparison of antrum-preserving double tract reconstruction vs roux-en-Y reconstruction after gastrectomy for Siewert types II and III adenocarcinoma of the esophagogastric junction. World J Gastroenterol 2015; 21:9999-10007. [PMID: 26379405 PMCID: PMC4566393 DOI: 10.3748/wjg.v21.i34.9999] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 07/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore a reasonable method of digestive tract reconstruction, namely, antrum-preserving double-tract reconstruction (ADTR), for patients with adenocarcinoma of the esophagogastric junction (AEG) and to assess its efficacy and safety in terms of long-term survival, complications, morbidity and mortality.
METHODS: A total of 55 cases were retrospectively collected, including 18 cases undergoing ADTR and 37 cases of Roux-en-Y reconstruction (RY) for AEG (Siewert types II and III) at North Sichuan Medical College. The cases were divided into two groups. The clinicopathological characteristics, perioperative outcomes, postoperative complications, morbidity and overall survival (OS) were compared for the two different reconstruction methods.
RESULTS: Basic characteristics including sex, age, body mass index (BMI), Siewert type, pT status, pN stage, and lymph node metastasis were similar in the two groups. No significant differences were found between the two groups in terms of perioperative outcomes (including the length of postoperative hospital stay, operating time, and intraoperative blood loss) and postoperative complications (consisting of anastomosis-related complications, wound infection, respiratory infection, pleural effusion, lymphorrhagia, and cholelithiasis). For the ADTR group, perioperative recovery indexes such as time to first flatus (P = 0.002) and time to resuming a liquid diet (P = 0.001) were faster than those for the RY group. Moreover, the incidence of reflux esophagitis was significantly decreased compared with the RY group (P = 0.048). The postoperative morbidity and mortality rates for overall postoperative complications and the rates of tumor recurrence and metastasis were not significantly different between the two groups. Survival curves plotted using the Kaplan-Meier method and compared by log-rank test demonstrated similar outcomes for the ADTR and RY groups. Multivariate analysis of significantly different factors that presented as covariates on Cox regression analysis to assess the survival and recurrence among AEG patients showed that age, gender, BMI, pleural effusion, time to resuming a liquid diet, lymphorrhagia and tumor-node-metastasis stage were important prognostic factors for OS of AEG patients, whereas the selection of surgical method between ADTR and RY was shown to be a similar prognostic factor for OS of AEG patients.
CONCLUSION: ADTR by jejunal interposition presents similar rates of tumor recurrence, metastasis and long-term survival compared with classical reconstruction with RY esophagojejunostomy; however, it offers considerably improved near-term quality of life, especially in terms of early recovery and decreased reflux esophagitis. Thus, ADTR is recommended as a worthwhile digestive tract reconstruction method for Siewert types II and III AEG.
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Bornschein J, Dingwerth A, Selgrad M, Venerito M, Stuebs P, Frauenschlaeger K, Achilleos A, Roessner A, Malfertheiner P. Adenocarcinomas at different positions at the gastro-oesophageal junction show distinct association with gastritis and gastric preneoplastic conditions. Eur J Gastroenterol Hepatol 2015; 27:492-500. [PMID: 25822856 DOI: 10.1097/meg.0000000000000299] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Adenocarcinomas at the gastro-oesophageal junction (GOJ) are currently stratified by tumour location. This retrospective study examines the association of preneoplastic conditions and inflammation of the gastric mucosa with GOJ cancer at different locations and compares them with nonjunctional gastric cancers. PATIENTS AND METHODS A total of 520 patients with junctional and nonjunctional gastric cancer were assessed for the presence and degree of intestinal metaplasia, glandular atrophy and inflammation in the stomach. Histopathological data were complete for 428 patients (68.9% men, median age 67.7 years), including 172 patients with GOJ cancer (GOJ1: 1-5 cm proximal to the junction, GOJ2: 'true' junctional, GOJ3: 2-5 cm distal to the junction). Gastric inflammation and preneoplastic conditions were scored according to the updated Sydney classification and further stratified into respective operative link on gastritis assessment (OLGA) and operative link on gastritis assessment on intestinal metaplasia (OLGIM) stages. RESULTS The prevalence and degree of gastric atrophy and intestinal metaplasia were significantly lower in GOJ1 than GOJ3 (P<0.01). Preneoplastic conditions in the stomach were similar in GOJ3 compared with nonjunctional gastric cancer. GOJ1 were almost exclusively (98.4%) of the intestinal type, whereas GOJ2 and GOJ3 were the diffuse type in 22.6 and 22.4% of the patients (P<0.001). Of all patients, only 8.5 and 12.7% presented with stage III/IV according to OLGA and OLGIM, respectively. However, data for OLGA and OLGIM staging were only available in 61.2 and 67.9% of patients, respectively. CONCLUSION GOJ1 are less likely to be associated with gastric pathology compared with GOJ3 or nonjunctional gastric cancer. OLGA or OLGIM staging in patients with advanced gastro-oesophageal cancer seems to be of limited value.
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Affiliation(s)
- Jan Bornschein
- aDepartment of Gastroenterology, Hepatology and Infectious Diseases bDepartment of General, Visceral and Vascular Surgery cInstitute of Pathology, Otto-von-Guericke University, Magdeburg, Germany dCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
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Abstract
OBJECTIVE The two major histological types of oesophageal cancer--adenocarcinoma (AC) and squamous cell carcinoma (SCC)--are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence estimates for individual subtypes are still lacking. This study for the first time quantified the global burden of oesophageal cancer by histological subtype. DESIGN Where available, data from Cancer Incidence in Five Continents Vol. X (CI5X) were used to compute, age-specific, sex-specific and country-specific proportions of AC and SCC. Nine regional averages were computed for countries without CI5X data. The proportions were then applied to all oesophageal cancer cases from GLOBOCAN 2012 and age-standardised incidence rates calculated for both histological types. RESULTS Worldwide, an estimated 398,000 SCCs and 52,000 ACs of the oesophagus occurred in 2012, translating to incidence rates of 5.2 and 0.7 per 100,000, respectively. Although SCCs were most common in South-Eastern and Central Asia (79% of the total global SCC cases), the highest burden of AC was found in Northern and Western Europe, Northern America and Oceania (46% of the total global AC cases). Men had substantially higher incidence than women, especially in the case of AC (male to female ratio AC: 4.4; SCC: 2.7). CONCLUSIONS These first global estimates of oesophageal cancer incidence by histology suggested a high concentration of AC in high-income countries with men being at much greater risk. This quantification of incidence will aid health policy makers to plan appropriate cancer control measures in the future.
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Affiliation(s)
- Melina Arnold
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Isabelle Soerjomataram
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Jacques Ferlay
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - David Forman
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
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Lin R, Xiao D, Guo Y, Tian D, Yun H, Chen D, Su M. Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis. Oncotarget 2015; 6:2856-64. [PMID: 25650663 PMCID: PMC4413622 DOI: 10.18632/oncotarget.3091] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 12/25/2014] [Indexed: 02/05/2023] Open
Abstract
Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.
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Affiliation(s)
- Runhua Lin
- Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
- The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China
| | - Dejun Xiao
- Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
- Clinical Laboratory of Ganzhou People's Hospital, Ganzhou, Jiangxi, PR China
| | - Yi Guo
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, PR China
| | - Dongping Tian
- Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
- The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China
| | - Hailong Yun
- Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
- The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China
| | - Donglin Chen
- Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
- The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China
| | - Min Su
- Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
- The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China
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Li-Chang HH, Kasaian K, Ng Y, Lum A, Kong E, Lim H, Jones SJ, Huntsman DG, Schaeffer DF, Yip S. Retrospective review using targeted deep sequencing reveals mutational differences between gastroesophageal junction and gastric carcinomas. BMC Cancer 2015; 15:32. [PMID: 25656989 PMCID: PMC4322811 DOI: 10.1186/s12885-015-1021-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 01/14/2015] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Adenocarcinomas of both the gastroesophageal junction and stomach are molecularly complex, but differ with respect to epidemiology, etiology and survival. There are few data directly comparing the frequencies of single nucleotide mutations in cancer-related genes between the two sites. Sequencing of targeted gene panels may be useful in uncovering multiple genomic aberrations using a single test. METHODS DNA from 92 gastroesophageal junction and 75 gastric adenocarcinoma resection specimens was extracted from formalin-fixed paraffin-embedded tissue. Targeted deep sequencing of 46 cancer-related genes was performed through emulsion PCR followed by semiconductor-based sequencing. Gastroesophageal junction and gastric carcinomas were contrasted with respect to mutational profiles, immunohistochemistry and in situ hybridization, as well as corresponding clinicopathologic data. RESULTS Gastroesophageal junction carcinomas were associated with younger age, more frequent intestinal-type histology, more frequent p53 overexpression, and worse disease-free survival on multivariable analysis. Among all cases, 145 mutations were detected in 31 genes. TP53 mutations were the most common abnormality detected, and were more common in gastroesophageal junction carcinomas (42% vs. 27%, p = 0.036). Mutations in the Wnt pathway components APC and CTNNB1 were more common among gastric carcinomas (16% vs. 3%, p = 0.006), and gastric carcinomas were more likely to have ≥3 driver mutations detected (11% vs. 2%, p = 0.044). Twenty percent of cases had potentially actionable mutations identified. R132H and R132C missense mutations in the IDH1 gene were observed, and are the first reported mutations of their kind in gastric carcinoma. CONCLUSIONS Panel sequencing of routine pathology material can yield mutational information on several driver genes, including some for which targeted therapies are available. Differing rates of mutations and clinicopathologic differences support a distinction between adenocarcinomas that arise in the gastroesophageal junction and those that arise in the stomach proper.
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Affiliation(s)
- Hector H Li-Chang
- University of British Columbia, Vancouver, Canada.
- Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 855 12 Ave W, Vancouver, BC, V5Z 1 M9, Canada.
- Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, Canada.
| | - Katayoon Kasaian
- University of British Columbia, Vancouver, Canada.
- Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
| | - Ying Ng
- Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, Canada.
| | - Amy Lum
- Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, Canada.
| | - Esther Kong
- Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, Canada.
| | - Howard Lim
- University of British Columbia, Vancouver, Canada.
- Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
| | - Steven Jm Jones
- Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
| | - David G Huntsman
- University of British Columbia, Vancouver, Canada.
- Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 855 12 Ave W, Vancouver, BC, V5Z 1 M9, Canada.
- Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, Canada.
- Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, Canada.
| | - David F Schaeffer
- University of British Columbia, Vancouver, Canada.
- Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 855 12 Ave W, Vancouver, BC, V5Z 1 M9, Canada.
| | - Stephen Yip
- University of British Columbia, Vancouver, Canada.
- Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 855 12 Ave W, Vancouver, BC, V5Z 1 M9, Canada.
- Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, Canada.
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Olefson S, Moss SF. Obesity and related risk factors in gastric cardia adenocarcinoma. Gastric Cancer 2015; 18:23-32. [PMID: 25209115 DOI: 10.1007/s10120-014-0425-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Accepted: 08/23/2014] [Indexed: 02/07/2023]
Abstract
Over recent decades, the incidence of cancers of the gastroesophageal junction, including gastric cardia tumors, has increased markedly. This is a trend that has been well documented, especially in studies from the USA and northern Europe that have also demonstrated a concomitant rise in the ratio of cardia to distal gastric cancers. The rise in the prevalence of gastric cardia adenocarcinoma has been paralleled by the worldwide obesity epidemic, with almost all epidemiological studies reporting increased body mass index and obesity increase the risk of cardia cancer development. However, the strength of this association is less marked than the link between obesity and esophageal adenocarcinoma, and the mechanisms remain poorly understood. Other possible confounders of the relationship between obesity and cardia cancer include the decline in Helicobacter pylori infection and the widespread use of proton pump inhibitors, although these have rarely been controlled for in case-control and cohort studies investigating associations between obesity and cardia cancer. We review these epidemiological trends and discuss proposed mechanisms for the association, drawing attention to controversies over the difficulty of defining cardia cancer. The relative paucity of high-quality epidemiological studies from other regions of the world should prompt further investigation of this issue, especially in populations undergoing rapid socioeconomic change.
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Affiliation(s)
- Sidney Olefson
- Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA
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Al-Haddad S, Chang AC, De Hertogh G, Grin A, Langer R, Sagaert X, Salemme M, Streutker CJ, Soucy G, Tripathi M, Upton MP, Vieth M, Villanacci V. Adenocarcinoma at the gastroesophageal junction. Ann N Y Acad Sci 2014; 1325:211-25. [DOI: 10.1111/nyas.12535] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Sahar Al-Haddad
- Department of Laboratory Medicine and Pathobiology; St. Michael's Hospital; Toronto Canada
| | - Andrew C. Chang
- Section of Thoracic Surgery; University of Michigan Medical Center; Ann Arbor Michigan
| | - Gert De Hertogh
- Department of Morphology and Molecular Pathology; University Hospitals of K.U. Leuven; Leuven Belgium
| | | | - Rupert Langer
- Institute of Pathology; University of Bern; Bern Switzerland
| | - Xavier Sagaert
- Department of Morphology and Molecular Pathology; University Hospitals of K.U. Leuven; Leuven Belgium
| | | | - Catherine J. Streutker
- Department of Laboratory Medicine and Pathobiology; St. Michael's Hospital; Toronto Canada
| | - Geneviève Soucy
- Département de Pathologie - Pathologie Gastro-intestinale; Centre Hospitalier de l'Université de Montréal; Montréal Canada
| | - Monika Tripathi
- Department of Cellular Pathology; Oxford University Hospitals NHS Trust; Oxford United Kingdom
| | - Melissa P. Upton
- Department of Pathology; University of Washington; Seattle Washington
| | - Michael Vieth
- Institute of Pathology; Klinikum Bayreuth; Bayreuth Germany
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Cook MB, Corley DA, Murray LJ, Liao LM, Kamangar F, Ye W, Gammon MD, Risch HA, Casson AG, Freedman ND, Chow WH, Wu AH, Bernstein L, Nyrén O, Pandeya N, Whiteman DC, Vaughan TL. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). PLoS One 2014; 9:e103508. [PMID: 25075959 PMCID: PMC4116205 DOI: 10.1371/journal.pone.0103508] [Citation(s) in RCA: 113] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 06/30/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. METHODS Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. RESULTS Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. CONCLUSIONS This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
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Affiliation(s)
- Michael B. Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America
- * E-mail:
| | - Douglas A. Corley
- Division of Research and Oakland Medical Center, Kaiser Permanente, Northern California, Oakland, California, United States of America
| | - Liam J. Murray
- Centre for Public Health, Queen’s University, Belfast, Northern Ireland
| | - Linda M. Liao
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America
| | - Farin Kamangar
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America
- Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, United States of America
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Marilie D. Gammon
- Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina, United States of America
| | - Harvey A. Risch
- Yale University School of Medicine, Department of Epidemiology and Public Health, New Haven, Connecticut, United States of America
| | - Alan G. Casson
- Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Neal D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America
| | - Wong-Ho Chow
- The University of Texas MD Anderson Cancer Center, Department of Epidemiology, Houston, Texas, United States of America
| | - Anna H. Wu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America
| | - Leslie Bernstein
- Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, United States of America
| | - Olof Nyrén
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Nirmala Pandeya
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | - Thomas L. Vaughan
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
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Abstract
PURPOSE OF REVIEW The purpose of the review is to discuss key studies conducted on the intriguing relationship between Helicobacter pylori and gastroesophageal reflux disease. RECENT FINDINGS Epidemiological studies have repeatedly described a negative association between H. pylori infection and erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, but not between H. pylori and gastroesophageal reflux disease symptoms. Especially, infection with CagA-positive strains appears to protect the distal esophagus by causing fundic gland atrophy and impaired gastric acid secretion. Although earlier reports suggested the development of erosive esophagitis after H. pylori eradication, more recent studies discuss that H. pylori eradication usually does not have an important clinical impact on gastroesophageal reflux disease. SUMMARY Gastric atrophy is the most widely accepted mechanism by which the distal esophagus is protected from abnormal acid exposure in patients with H. pylori infection. The clinical impact of H. pylori infection on the prevalence of erosive esophagitis and Barrett's esophagus remains a matter of debate. In areas with a high prevalence of H. pylori-induced atrophic gastritis, the protection that this infection may afford against gastroesophageal reflux disease is not comparable to the risk that H. pylori poses for the development of gastric cancer.
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Niu X, Wei WQ, Hao CQ, Song GH, Li J, Hua ZL, Li YW, Chang J, Wang XZ, Zhao DL, Wang GQ, Hsieh E, Qiao YL. Evaluation of routine biopsies in endoscopic screening for esophagogastric junction cancer. World J Gastroenterol 2014; 20:5074-5081. [PMID: 24803821 PMCID: PMC4009543 DOI: 10.3748/wjg.v20.i17.5074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 01/21/2014] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore whether routine biopsies at the high incidence spot of esophagogastric junction (EGJ) cancer are justified in endoscopic screening.
METHODS: This was a multicenter population-based study conducted in eight high-risk areas in China. A total of 37396 participants underwent endoscopic examination. Biopsies were obtained from visible mucosal abnormalities or from normal-appearing mucosa at the high incidence spot of esophagogastric junction cancer when no abnormality was detected. Specimens showing high-grade intraepithelial neoplasia (HIN) or higher grade lesions were deemed as pathologically “positive”. The ratios of positive pathologic diagnosis between participants with abnormal and normal-appearing mucosa were compared using the Pearson χ2 test. Odds ratios and 95% confidence intervals, adjusted for potential confounders, were calculated using logistic regression.
RESULTS: A total of 37520 individuals participated in this study and 37396 (99.7%) participants had full information and were suitable for analysis. During endoscopic examinations, 9.11% (3405/37396) participants were found to have visible mucosal lesions. Of the participants who had normal-appearing mucosa at the EGJ, only 0.28% (94/33991) were diagnosed with HIN or higher grade lesions, whereas 6.05% (206/3405) of participants with abnormalities at the EGJ had a positive pathologic result. After controlling for other variables, visible abnormal mucosa detected under endoscopy strongly predicted a positive pathologic result (OR = 32.51, 95%CI: 23.96-44.09). The proportion of participants with “positive” pathologic diagnoses increased as the total number of endoscopic examinations performed by the doctors increased (< 5000 cases vs 5000-10000 cases vs > 10000 cases, Z = -2.7207, P = 0.0065, Cochran Armiger trend test). The same trend was found between the proportion of participants with positive pathologic diagnoses and the total number of years the doctors performed endoscopy (< 5 years vs 5-10 years vs > 10 years, Z = -10.3222, P < 0.001, Cochran Armiger trend test).
CONCLUSION: Additional routine biopsies from the high incidence spot of EGJ cancer are of limited value and are unjustified.
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Abstract
OBJECTIVE About 20 years ago, the scientific community was first alerted to an enigmatic increase of oesophageal adenocarcinomas in the UK and USA. Subsequently, a virtual epidemic-still unexplained-was confirmed in several western countries. Detailed descriptive data might provide clues to its causes. DESIGN We collected data on incident cases of oesophageal adenocarcinoma from population-based cancer registries in Australia, Europe, North America and Asia. We calculated age-standardised incidence rates and fitted log-linear Poisson models to assess annual rate of increase and to disentangle age-period-cohort effects, linear spine models to estimate rate of increase since 1985, and Joinpoint models to identify possible inflection points. RESULTS With considerable between-registry variation in magnitude and timing, we found a consistent dramatic increase in incidence with an observed or estimated start between 1960 and 1990. The average annual increase ranged from 3.5% in Scotland to 8.1% in Hawaii with similar proportional increase among men and women in most registries and a maintained three to sixfold higher incidence among men. Generally, calendar period was a more important determinant of incidence trends than birth cohort. Where possible to conduct, Joinpoint analyses indicated that the onset of the epidemic varied considerably even between neighbouring countries. CONCLUSIONS Given the preponderant period effect and the abrupt onset observed or inferred in most populations, the epidemic appears to be caused by some exposure that was first introduced around 1950. At least 30 years' variation in estimated time of onset opens prospects for hypothesis-generating ecological analyses.
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Affiliation(s)
- Gustaf Edgren
- Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts, USA
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de Martel C, Forman D, Plummer M. Gastric cancer: epidemiology and risk factors. Gastroenterol Clin North Am 2013; 42:219-40. [PMID: 23639638 DOI: 10.1016/j.gtc.2013.01.003] [Citation(s) in RCA: 275] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastric cancer is one of the major malignancies in the world. This article summarizes the current understanding of the worldwide burden of this disease, its geographic variation, and temporal trends. An overview is presented of known risk factors, including genetic, dietary, and behavioral, but focuses on Helicobacter pylori infection as the most important factor in noncardia gastric cancer. When the data and the literature allow, we distinguish between cardia and noncardia sub-sites, as it is now clear that these two anatomic locations present distinct and sometimes opposite epidemiological characteristics.
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Cook MB, Kamangar F, Weinstein SJ, Albanes D, Virtamo J, Taylor PR, Abnet CC, Wood RJ, Petty G, Cross AJ, Dawsey SM. Iron in relation to gastric cancer in the Alpha-tocopherol, Beta-carotene Cancer Prevention Study. Cancer Epidemiol Biomarkers Prev 2012; 21:2033-42. [PMID: 23001240 PMCID: PMC3493744 DOI: 10.1158/1055-9965.epi-12-0799] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Iron is an essential micronutrient that can have carcinogenic effects when at high or low concentrations. Previous studies of iron in relation to gastric cancer have not assessed subtype-specific relationships. We used the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to assess whether iron metrics were associated with gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). METHODS We selected 341 incident gastric cancer cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of follow-up, and 341 individually matched controls. We measured prediagnostic serum iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total iron-binding capacity (TIBC) and transferrin saturation were estimated from these metrics. Dietary iron exposures were estimated from a food frequency questionnaire. Multivariable logistic regression was used for analysis. RESULTS Serum iron metrics were not associated with GCC, except for a potential "n"-shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and, possibly, transferrin saturation. TIBC appeared to share a "u"-shaped relationship with GNCC (global P = 0.033). Dietary iron exposures were not associated with either subsite. Adjustment for Helicobacter pylori and gastric atrophy had little effect on observed associations. CONCLUSIONS We found little evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC was associated with an iron profile similar to that of iron deficiency. IMPACT Our findings indicate that inverse associations between iron metrics and gastric cancer are driven by associations with GNCC. Further elucidation of potential mechanisms is warranted.
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Affiliation(s)
- Michael B Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS/Suite 550/Room 5014, Bethesda, MD 20852-7234, USA.
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Huang Q, Fan X, Agoston AT, Feng A, Yu H, Lauwers G, Zhang L, Odze RD. Comparison of gastro-oesophageal junction carcinomas in Chinese versus American patients. Histopathology 2012; 59:188-97. [PMID: 21884197 DOI: 10.1111/j.1365-2559.2011.03924.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS To compare the clinical and pathological features of gastro-oesophageal junction (GEJ) carcinomas in Chinese and American patients. METHODS AND RESULTS Eighty consecutive patients with a GEJ carcinoma (43 from mainland China, and 37 from the USA) were evaluated for association with Barrett oesophagus (BO), chronic Helicobacter pylori gastritis, intestinal metaplasia, and outcome. GEJ carcinomas were defined as tumours that were located within 20 mm of, and crossed, the GEJ. Overall, GEJ carcinomas from Chinese patients revealed significantly more frequent location in the proximal stomach, higher pathological stage, larger size, younger patient age, and association with chronic H. pylori gastritis. In contrast, GEJ cancers from American patients showed a strong association with distal oesophageal location, BO, and associated intestinal metaplasia and dysplasia. Pathologically, GEJ carcinomas from American patients were predominantly adenocarcinomas, whereas Chinese patients showed a higher proportion of mucinous, adenosquamous, acinar or neuroendocrine tumours. Overall, 3- and 5-year survival rates were statistically similar between both patient groups, but upon multivariate analysis, Chinese patients showed statistically better survival rates for stage III tumours. CONCLUSIONS Most GEJ carcinomas in patients from China represent proximal gastric cancers associated with chronic H. pylori gastritis, and BO-associated carcinomas are rare among this patient population.
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Affiliation(s)
- Qin Huang
- Department of Pathology of the Nanjing Drum Tower Hospital, Nanjing, China
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Schouten LJ, Steevens J, Huysentruyt CJR, Coffeng CE, Keulemans YCA, van Leeuwen FE, Driessen ALC, van den Brandt PA. Total cancer incidence and overall mortality are not increased among patients with Barrett's esophagus. Clin Gastroenterol Hepatol 2011; 9:754-61. [PMID: 21570484 DOI: 10.1016/j.cgh.2011.04.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2011] [Revised: 03/30/2011] [Accepted: 04/05/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Barrett's esophagus (BE) increases risk for esophageal adenocarcinoma, but it is not clear how it affects risk for other cancers or overall mortality. We analyzed data from a population-based cohort of subjects with BE. METHODS The Netherlands Cohort Study was initiated in 1986 and included 120,852 participants (55-69 years old at baseline). Until December 2002, 626 incident cases of BE (excluding nonintestinal metaplasia) were identified by record linkage with the nationwide Pathology Registry. This cohort was followed for a median period of 5.7 years; data on cancer and mortality were obtained from record linkage to the Netherlands Cancer Registry and Statistics Netherlands. The expected number of cases was calculated using national cancer incidence and mortality data. RESULTS In the BE cohort, 13 individuals developed esophageal cancer and 5 developed gastric cancer. The ratio of observed:expected (O:E) incidence of esophageal and gastric cancer was 10.0 (95% confidence interval [CI], 5.3-17.1) and 1.8 (95% CI, 0.6-4.2), respectively. Total cancer incidence (excluding esophageal and gastric cancer) increased in the BE cohort, although not by a statistically significant amount (O:E, 1.3; 95% CI, 1.0-1.6). Of cancer subtypes, incidences of small intestinal and pancreatic cancer increased in subjects with BE, but not by a statistically significant amount, after exclusion of data from the first 6 months of follow-up. During the follow-up period, 225 individuals with BE died. Mortality from all causes (excluding esophageal and gastric cancer) was not increased among subjects with BE (O:E, 1.0; 95% CI, 0.9-1.2), nor was mortality from specific causes of death. CONCLUSIONS The incidence of esophageal cancer was increased in a population-based cohort of subjects with BE. However, when esophageal and gastric cancers were excluded, total cancer incidence and overall mortality were not increased among subjects with BE.
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Affiliation(s)
- Leo J Schouten
- Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
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