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Tustumi F, Pereira MA, Lisak AS, Ramos MFKP, Ribeiro Junior U, Dias AR. THE VALUE OF PREOPERATIVE PROGNOSTIC NUTRITIONAL INDEX IN GASTRIC CANCER AFTER CURATIVE RESECTION. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2024; 37:e1805. [PMID: 38896701 PMCID: PMC11182628 DOI: 10.1590/0102-6720202400012e1805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 03/23/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Predicting short- and long-term outcomes of oncological therapies is crucial for developing effective treatment strategies. Malnutrition and the host immune status significantly affect outcomes in major surgeries. AIMS To assess the value of preoperative prognostic nutritional index (PNI) in predicting outcomes in gastric cancer patients. METHODS A retrospective cohort analysis was conducted on patients undergoing curative-intent surgery for gastric adenocarcinoma between 2009 and 2020. PNI was calculated as follows: PNI=(10 x albumin [g/dL])+(0.005 x lymphocytes [nº/mm3]). The optimal cutoff value was determined by the receiver operating characteristic curve (PNI cutoff=52), and patients were grouped into low and high PNI. RESULTS Of the 529 patients included, 315 (59.5%) were classified as a low-PNI group (PNI<52) and 214 (40.5%) as a high-PNI group (PNI≥52). Older age (p=0.050), male sex (p=0.003), American Society of Anesthesiologists score (ASA) III/IV (p=0.001), lower hemoglobin level (p<0.001), lower body mass index (p=0.001), higher neutrophil-lymphocyte ratio (p<0.001), D1 lymphadenectomy, advanced pT stage, pN+ and more advanced pTNM stage were related to low-PNI patient. Furthermore, 30-day (1.4 vs. 4.8%; p=0.036) and 90-day (3.3 vs. 10.5%; p=0.002) mortality rates were higher in low-PNI compared to high-PNI group. Disease-free and overall survival were worse in low-PNI patients compared to high-PNI (p<0.001 for both). ASA III/IV score, low-PNI, pT3/T4, and pN+ were independent risk factors for worse survival. CONCLUSIONS Preoperative PNI can predict short- and long-term outcomes of patients with gastric cancer after curative gastrectomy. Low PNI is an independent factor related to worse disease-free and overall survival.
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Affiliation(s)
- Francisco Tustumi
- Universidade de São Paulo, Hospital das Clínicas, Instituto do Câncer do Estado de São Paulo, Department of Gastroenterology - São Paulo (SP), Brazil
| | - Marina Alessandra Pereira
- Universidade de São Paulo, Hospital das Clínicas, Instituto do Câncer do Estado de São Paulo, Department of Gastroenterology - São Paulo (SP), Brazil
| | - André Safatle Lisak
- Universidade de São Paulo, Hospital das Clínicas, Instituto do Câncer do Estado de São Paulo, Department of Gastroenterology - São Paulo (SP), Brazil
| | - Marcus Fernando Kodama Pertille Ramos
- Universidade de São Paulo, Hospital das Clínicas, Instituto do Câncer do Estado de São Paulo, Department of Gastroenterology - São Paulo (SP), Brazil
| | - Ulysses Ribeiro Junior
- Universidade de São Paulo, Hospital das Clínicas, Instituto do Câncer do Estado de São Paulo, Department of Gastroenterology - São Paulo (SP), Brazil
| | - André Roncon Dias
- Universidade de São Paulo, Hospital das Clínicas, Instituto do Câncer do Estado de São Paulo, Department of Gastroenterology - São Paulo (SP), Brazil
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Salazar BE, Pérez-Cala T, Gomez-Villegas SI, Cardona-Zapata L, Pazos-Bastidas S, Cardona-Estepa A, Vélez-Gómez DE, Justinico-Castro JA, Bernal-Cobo A, Dávila-Giraldo HA, Benítez-Guerra JC, Valencia-Cárdenas JT, Ospina EDJ, Castaño-Llano R, Bravo MM, Cataño-Correa JC, Zabaleta J, Trespalacios-Rangel AA, Cock-Botero AM, Roldán-Pérez MI, Martínez A. The OLGA-OLGIM staging and the interobserver agreement for gastritis and preneoplastic lesion screening: a cross-sectional study. Virchows Arch 2022; 480:759-769. [PMID: 35089403 DOI: 10.1007/s00428-022-03286-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/04/2022] [Accepted: 01/21/2022] [Indexed: 12/20/2022]
Abstract
Stomach cancer (SC) incidence and mortality are relevant public health issues worldwide. In Colombia, screening for preneoplastic lesions (PNL) and the presence of H. pylori is not routinely performed. Therefore, the aim of this study was to evaluate OLGA-OLGIM staging and the interobserver agreement in gastritis and preneoplastic lesions in patients with gastroduodenal symptoms from Colombia. A cross-sectional study was conducted in 272 patients with gastroduodenal symptoms. Gastric biopsies were taken following the Updated Sydney System with the OLGA-OLGIM classification, and the results were evaluated by two pathologists. Chronic gastritis and PNL were reported in 76% and 24% of the patients, respectively. Furthermore, 25% of the patients with PNL displayed gastric atrophy (GA) and 75% intestinal metaplasia (IM). Agreement in the histopathological reading for IM was good, whereas for OLGA was variable, and for the H. pylori quantity was poor. OLGA-OLGIM stages 0-II were the most frequent (96%), while stage III (4%) and SC (4%) were the least frequent. Age and coffee consumption were associated with a higher prevalence of PNL. This work determined that 4% of the population is at high risk of developing SC and would benefit from follow-up studies. Reinforcement of training programs to improve the agreement in histopathology readings is required.
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Affiliation(s)
- Beatriz E Salazar
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia.
| | - Tania Pérez-Cala
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Sara Isabel Gomez-Villegas
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Laura Cardona-Zapata
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Sebastián Pazos-Bastidas
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Alejandra Cardona-Estepa
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Diego Enrique Vélez-Gómez
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
| | | | - Andrés Bernal-Cobo
- Department of Pathology, School of Medicine, University of Antioquia, Medellín, Colombia
| | | | - Juan Carlos Benítez-Guerra
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia.,Promedan IPS, Medellín, Colombia
| | | | | | | | | | | | - Jovanny Zabaleta
- Department of Integrative Oncology and Department of Pediatrics, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | | | | | - Miguel Ignacio Roldán-Pérez
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia.,Department of Pathology, School of Medicine, University of Antioquia, Medellín, Colombia
| | - Alonso Martínez
- Bacteria & Cancer Group, Department of Microbiology, School of Medicine, University of Antioquia, Medellín, Colombia
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Application of Parametric Shared Frailty Models to Analyze Time-to-Death of Gastric Cancer Patients. J Gastrointest Cancer 2022; 54:104-116. [PMID: 35064523 DOI: 10.1007/s12029-021-00775-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Despite its declining incidence, gastric cancer (GC) is one of the world's leading malignancies and a major global health concern due to its high prevalence and fatality rate. Furthermore, it is the world's fourth most common cancer and the second leading cause of cancer death. Studying the determinants of time to death of gastric cancer patients will give clinicians more information to develop specific treatment plans, forecast prognosis, and track the progress of death cases. The application of the frailty model can help account for random variation in survival that may exist due to unobserved factors, as well as show the impact of latent factors on death risk. As a result, the purpose of this study was to assess the determinants of time to death of GC patients' by applying the parametric shared frailty models. METHODS The data for this study were obtained from gastric cancer patients admitted to the Tikur Anbesa Specialized Hospital, Addis Ababa, from January 1, 2015, to February 29, 2020. With the aim of coming up with an appropriate survival model that determines factors that affect the time to death of gastric cancer patients, various parametric shared frailty models were compared. In all of the frailty models, patient regions were used as a clustering variable. The current study implemented exponential, Weibull, log-logistic, and lognormal distributions for baseline hazard functions with gamma and inverse Gaussian's frailty distributions. The performance of all models was compared using the AIC and BIC criteria. R statistical software was used to conduct the analysis. RESULTS A retrospective study was undertaken on a total of 407 gastric cancer patients under follow-up at Tikur Anbesa Specialized Hospital. Of all 407 GC patients, 56.3% died while the remaining 43.7% were censored. The patients' median time to death was 21.9 months, with a maximum survival time of 49.6 months. In the current study, the clustering effect was significant in modeling the time to death from gastric cancer. The Weibull model with inverse Gaussian frailty has the minimum AIC and BIC value among the candidate models compared. The dependency within the clusters for the Weibull-inverse Gaussian frailty model was [Formula: see text] (13.4%). According to the results of our best model (Weibull-inverse Gaussian), the sex of the patient, the smoking status, the tumor size, the treatment taken, the vascular invasion, and the disease stage was found to be statistically significant at an alpha = 0.05 significance level. CONCLUSION Time to death of GC patient's data set was well described by the Weibull-inverse Gaussian shared frailty. Furthermore, Weibull baseline distribution best fits the GC data set as it enables proportional hazard and accelerated failure time model, for time to failure data. There is unobserved heterogeneity between clusters (patient regions), indicating the need to account for this clustering effect. In this study, survival time to death among GC patients was discovered to be small. Covariates like older age, being male, having higher (advanced) stage of GC disease (stage three and stage four), advanced tumor size, being smoker, infected by Helicobacter pylori, and existence of vascular invasion significantly accelerate the time to death of GC patients. In contrast, talking combination of more treatments prolongs the time to death of patients. To improve the health of patients, interventions should be taken based on significant prognostic factors, with special attention dedicated to patients with such factors to prevent GC death.
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Maubach G, Vieth M, Boccellato F, Naumann M. Helicobacter pylori-induced NF-κB: trailblazer for gastric pathophysiology. Trends Mol Med 2022; 28:210-222. [PMID: 35012886 DOI: 10.1016/j.molmed.2021.12.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/13/2021] [Accepted: 12/13/2021] [Indexed: 02/07/2023]
Abstract
NF-κB signaling pathways, induced by a variety of triggers, play a key role in regulating the expression of genes involved in the immune response and cellular responses to stress. The human pathogen Helicobacter pylori induces classical and alternative NF-κB signaling pathways via its effector ADP-L-glycero-β-D-manno-heptose (ADP-heptose). We review H. pylori- and NF-κB-dependent alterations in cellular processes and associated maladaptation leading to deleterious gastric pathophysiology that have implications for the diagnosis and treatment of gastric diseases. Therapeutic options for gastric cancer (GC) include clinically relevant small molecule inhibitors of NF-κB and epigenetic therapy approaches. In this context, gastric organoid biobanks originated from patient material, represent a valuable platform for translational applications to predict patient responses to chemotherapy, with a view to personalized medicine.
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Affiliation(s)
- Gunter Maubach
- Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Friedrich Alexander University, Erlangen-Nuremberg, 95445 Bayreuth, Germany
| | - Francesco Boccellato
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, OX37DQ Oxford, UK
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany.
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Zhang HH, Soyfoo MD, Cao JL, Sang HM, Xu SF, Jiang JX. Histopathological Characteristics and Therapeutic Outcomes of Endoscopic Submucosal Dissection for Gastric High-Grade Intraepithelial Neoplasia. J Laparoendosc Adv Surg Tech A 2021; 32:413-421. [PMID: 34962142 DOI: 10.1089/lap.2020.0035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Hai-Han Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Muhammad Djaleel Soyfoo
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiu-Liang Cao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Huai-Ming Sang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shun-Fu Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Kotelevets SM, Chekh SA, Chukov SZ. Updated Kimura-Takemoto classification of atrophic gastritis. World J Clin Cases 2021; 9:3014-3023. [PMID: 33969087 PMCID: PMC8080746 DOI: 10.12998/wjcc.v9.i13.3014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/01/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The Updated Sydney system for visual evaluation of gastric mucosal atrophy via endoscopic observation is subject to sampling error and interobserver variability. The Kimura-Takemoto classification system was developed to overcome these limitations.
AIM To compare the morphological classification of atrophic gastritis between the Kimura-Takemoto system and the Updated Sydney system.
METHODS A total of 169 patients with atrophic gastritis were selected according to diagnosis by the visual endoscopic Kimura-Takemoto method. Following the Updated Kimura-Takemoto classification system, one antrum biopsy and five gastric corpus biopsies were taken according to the visual stages of the Kimura-Takemoto system. The Updated Kimura-Takemoto classification system was then applied to each and showed 165 to have histological mucosal atrophy; the remaining 4 patients had no histological evidence of atrophy in any biopsy. The Updated Kimura-Takemoto classification was verified as a reference morphological method and applied for the diagnosis of atrophic gastritis. Adding one more biopsy from the antrum to the six biopsies according to the Updated Kimura-Takemoto classification, constitutes the updated combined Kimura-Takemoto classification and Sydney system.
RESULTS The sensitivity for degree of mucosal atrophy assessed by the Updated Sydney system was 25% for mild, 36% for moderate, and 42% for severe, when compared with the Updated Kimura-Takemoto classification of atrophic gastritis for morphological diagnosis. Four types of multifocal atrophic gastritis were identified: sequential uniform (type 1; in 28%), sequential non-uniform (type 2; in 7%), diffuse uniform (type 3; in 23%), diffuse non-uniform (type 4; in 24%), and "alternating atrophic – non-atrophic" (type 5; in 18%). The pattern of the spread of atrophy, sequentially from the antrum to the cardiac segment of the stomach, which was described by the Updated Kimura-Takemoto system, was histologically confirmed in 82% of cases evaluated.
CONCLUSION The Updated Sydney system is significantly inferior to the Updated Kimura-Takemoto classification for morphological verification of atrophic gastritis.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, Medical Institute, North Caucasus State Academy for Humanities and Technologies, Cherkessk 369000, Russia
| | - Sergey A Chekh
- Department of Software Development, Institute of Applied Mathematics and Information Technology, North Caucasus State Academy of Humanities and Technologies, Cherkessk 369000, Russia
- Department of Mathematics, Institute of Applied Mathematics and Information Technology, North Caucasus State Academy of Humanities and Technologies, Cherkessk 369000, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
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Fornaro L, Spallanzani A, de Vita F, D’Ugo D, Falcone A, Lorenzon L, Tirino G, Cascinu S, on behalf of GAIN (GAstric Cancer Italian Network). Beyond the Guidelines: The Grey Zones of the Management of Gastric Cancer. Consensus Statements from the Gastric Cancer Italian Network (GAIN). Cancers (Basel) 2021; 13:1304. [PMID: 33804024 PMCID: PMC8001719 DOI: 10.3390/cancers13061304] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/19/2021] [Accepted: 03/11/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Management of gastric and gastroesophageal junction (GEJ) adenocarcinoma remains challenging, because of the heterogeneity in tumor biology within the upper gastrointestinal tract. Daily clinical practice is full of grey areas regarding the complexity of diagnostic, staging, and therapeutic procedures. The aim of this paper is to provide a guide for clinicians facing challenging situations in routine practice, taking a multidisciplinary consensus approach based on available literature. METHODS The GAIN (GAstric cancer Italian Network) group was established with the aims of reviewing literature evidence, discussing key issues in prevention, diagnosis, and management of gastric and GEJ adenocarcinoma, and offering a summary of statements. A Delphi consensus method was used to obtain opinions from the expert panel of specialists. RESULTS Forty-nine clinical questions were identified in six areas of interest: role of multidisciplinary team; risk factors; diagnosis; management of early gastric cancer and multimodal approach to localized gastric cancer; treatment of elderly patients with locally advanced resectable disease; and treatment of locally advanced and metastatic cancer. CONCLUSIONS The statements presented may guide clinicians in practical management of this disease.
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Affiliation(s)
- Lorenzo Fornaro
- Department of Translational Medicine, Division of Medical Oncology, AOU Pisana, 56126 Pisa, Italy;
| | - Andrea Spallanzani
- Department of Oncology and Hematology, University Hospital of Modena, 41125 Modena, Italy;
| | - Ferdinando de Vita
- Department of Precision Medicine, Division of Medical Oncology, School of Medicine, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, Italy; (F.d.V.); (G.T.)
| | - Domenico D’Ugo
- General Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University, 00168 Rome, Italy; (D.D.); (L.L.)
| | - Alfredo Falcone
- Department of Translational Medicine, Division of Medical Oncology, University of Pisa, 56126 Pisa, Italy;
| | - Laura Lorenzon
- General Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University, 00168 Rome, Italy; (D.D.); (L.L.)
| | - Giuseppe Tirino
- Department of Precision Medicine, Division of Medical Oncology, School of Medicine, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, Italy; (F.d.V.); (G.T.)
| | - Stefano Cascinu
- Medical Oncology, Università Vita-Salute San Raffaele, 20132 Milan, Italy
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Kotelevets SM, Chekh SA. Screening, Monitoring, and Treatment of Precancerous Atrophic Gastritis in the Prospective Study for Seven Years. Asian Pac J Cancer Prev 2020; 21:331-336. [PMID: 32102507 PMCID: PMC7332137 DOI: 10.31557/apjcp.2020.21.2.331] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 02/01/2020] [Indexed: 02/05/2023] Open
Abstract
AIM Develop a program to identify, treat, and prevent severe atrophic gastritis to reduce gastric cancer incidence and mortality. MATERIALS AND METHODS In total, 2,847 people aged > 40 years old underwent serological noninvasive screening for atrophic gastritis by identifying postprandial gastrin-17 and pepsinogen-1 in the fasting state. Anti-H pylori IgG was found in 2,134 patients. Seven years later, 2,220 patientswho had undergone serological noninvasive screening were asked to fill out a questionnaire survey (were interviewed). We could not find any information on 627 of 2,847 patients. Next, 75 patients with multifocal atrophic gastritis who underwent gastroscopy and biopsies (the Updated Sydney System (USS)) were selected. To study gastrin-17 production, morpho-functional correlation was studies in 75 patients with multifocal atrophic gastritis. RESULTS During seven years, no reported case of gastric cancer was done among 2,220 persons who underwent serological screening and treatment. In the same population, 4.3 persons who did not receive screening during the same period, developed gastric cancer and died of it. In this study, we can say that 4.3 lives were saved out of 2,220 tested persons. The cost for screening this number of people amounted to €23,750. A comparison of the prevalence rate of the four stages of multifocal atrophic gastritis based on the data of the histopathology tests and noninvasive serologic screening in accordance with OLGA classification showed a strong correlation (the correlation coefficient is 0.812). This finding suggested that using this classification not only for histopathology tests for atrophic gastritis but also for serologic markers of antral mucosa and corpus ventriculi atrophy: gastrin-17 and pepsinogen-1. CONCLUSION Complex pathogenetic treatment of atrophic gastritis significantly reduced gastric cancer risk and incidence for such patients.
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Affiliation(s)
| | - Sergey A Chekh
- Department of Software Development, Department of Mathematics, Institute of Applied Mathematics and Information Technology, North Caucasus State Academy for Humanities and Technologies, Cherkessk, Stavropolskaya Street 36, Russian Federation.
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Prognostic Models for Predicting Overall Survival in Patients with Primary Gastric Cancer: A Systematic Review. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5634598. [PMID: 31641669 PMCID: PMC6766665 DOI: 10.1155/2019/5634598] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 08/23/2019] [Accepted: 09/05/2019] [Indexed: 02/06/2023]
Abstract
Background This study was designed to review the methodology and reporting of gastric cancer prognostic models and identify potential problems in model development. Methods This systematic review was conducted following the CHARMS checklist. MEDLINE and EMBASE were searched. Information on patient characteristics, methodological details, and models' performance was extracted. Descriptive statistics was used to summarize the methodological and reporting quality. Results In total, 101 model developments and 32 external validations were included. The median (range) of training sample size, number of death, and number of final predictors were 360 (29 to 15320), 193 (14 to 9560), and 5 (2 to 53), respectively. Ninety-one models were developed from routine clinical data. Statistical assumptions were reported to be checked in only nine models. Most model developments (94/101) used complete-case analysis. Discrimination and calibration were not reported in 33 and 55 models, respectively. The majority of models (81/101) have never been externally validated. None of the models have been evaluated regarding clinical impact. Conclusions Many prognostic models have been developed, but their usefulness in clinical practice remains uncertain due to methodological shortcomings, insufficient reporting, and lack of external validation and impact studies. Impact Future research should improve methodological and reporting quality and emphasize more on external validation and impact assessment.
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Rugge M, Sugano K, Scarpignato C, Sacchi D, Oblitas WJ, Naccarato AG. Gastric cancer prevention targeted on risk assessment: Gastritis OLGA staging. Helicobacter 2019; 24:e12571. [PMID: 30773732 DOI: 10.1111/hel.12571] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/08/2019] [Accepted: 01/10/2019] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) ranks among the most lethal epithelial malignancies, and its striking mortality rate prompts a global prevention strategy. Helicobacter pylori (H. pylori) gastritis is the main GC promoter, and the 2014 Global Kyoto conference recognized H. pylori gastritis as a (treatable) infectious disease. It is therefore plausible that any large-scale intervention for H. pylori eradication would result in cleansing the world of the fifth cause of cancer-related death. Atrophic gastritis is the cancerization field in which GCs (both intestinal and diffuse histotypes) mainly develop. Discontinuing the inflammatory cascade triggered by H. pylori is tantamount to preventing GC. For patients (still infected or eradicated) who have already developed gastric atrophy, the severity/topography of the atrophic changes correlates with their cancer risk. Gastritis OLGA (Operative Link for Gastritis Assessment) staging consistently ranks the atrophy-associated cancer risk, providing a solid clinical/biological rationale for establishing patient-specific surveillance programs. By combining primary and secondary prevention strategies, gastric cancer is a preventable disease.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy.,Veneto Tumor Registry (RTV), Veneto Regional Authority, Padova, Italy
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Carmelo Scarpignato
- Department of Medicine and Surgery, Clinical Pharmacology and Pathophysiology Unit, School of Medicine and Dentistry, University of Parma, Parma, Italy
| | - Diana Sacchi
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
| | | | - Antonio Giuseppe Naccarato
- Department of Translational Research and of New Surgical and Medical Technologies, Pathology Section, University of Pisa, Pisa, Italy
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den Hollander WJ, Holster IL, den Hoed CM, Capelle LG, Tang TJ, Anten MP, Prytz-Berset I, Witteman EM, Ter Borg F, Hartog GD, Bruno MJ, Peppelenbosch MP, Lesterhuis W, Doukas M, Kuipers EJ, Spaander MCW. Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions. Gut 2019; 68:585-593. [PMID: 29875257 DOI: 10.1136/gutjnl-2017-314498] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 05/05/2018] [Accepted: 05/10/2018] [Indexed: 12/13/2022]
Abstract
OBJECTIVE International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression. DESIGN Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17. RESULTS 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or invasive neoplasia (ie, gastric cancer) during follow-up. Two of these patients were successfully treated with endoscopic submucosal dissection, while the other two underwent a total gastrectomy. Compared with patients with extended AG/IM (PGI/II≤3 and/or OGLIM stage III-IV), patients with limited AG/IM (PG I/II>3 and OLGIM stage 0-II) did not develop high-grade adenoma/dysplasia or invasive neoplasia during follow-up (p=0.02). CONCLUSION In a low gastric cancer incidence area, a surveillance programme can detect gastric cancer at an early curable stage with an overall risk of neoplastic progression of 0.3% per year. Use of serological markers in endoscopic surveillance programmes may improve risk stratification.
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Affiliation(s)
- Wouter J den Hollander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - I Lisanne Holster
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Caroline M den Hoed
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Lisette G Capelle
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Tjon J Tang
- Department of Gastroenterology and Hepatology, IJsselland Hospital, Capelle aan den IJssel, The Netherlands
| | - Marie-Paule Anten
- Department of Gastroenterology and Hepatology, Sint Franciscus Hospital, Rotterdam, The Netherlands
| | - Ingrid Prytz-Berset
- Department of Gastroenterology, More and Romsdal Trust Ålesund, Ålesund, Norway
| | - Ellen M Witteman
- Deparment of Gastroenterology and Hepatology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Frank Ter Borg
- Department of Gastroenterology and Hepatology, Deventer Hospital, Deventer, The Netherlands
| | - Gijsbert den Hartog
- Department of Gastroenterology and Hepatology, Rijnstate, Arnhem, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Maikel Petrus Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Wilco Lesterhuis
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Michael Doukas
- Department of Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.,Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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12
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Rugge M, Meggio A, Pravadelli C, Barbareschi M, Fassan M, Gentilini M, Zorzi M, Pretis GD, Graham DY, Genta RM. Gastritis staging in the endoscopic follow-up for the secondary prevention of gastric cancer: a 5-year prospective study of 1755 patients. Gut 2019; 68:11-17. [PMID: 29306868 DOI: 10.1136/gutjnl-2017-314600] [Citation(s) in RCA: 120] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 11/21/2017] [Accepted: 11/26/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Operative link on gastritis assessment (OLGA) staging for gastritis ranks the risk for gastric cancer (GC) in progressive stages (0-IV). This prospective study aimed at quantifying the cancer risk associated with each gastritis stage. DESIGN A cohort of 1755 consecutive patients with dyspepsia underwent initial (T-0) oesophagogastroduodenoscopy with mapped gastric biopsies, OLGA staging and assessment of Helicobacter pylori infection. Patients were followed for 55 months (median); patients with stages II III and IV underwent a second endoscopy/restaging (T-1), and those with stages 0 and I were followed clinically and through in-depth clinical and record checking. Endpoints were OLGA stage at T-1 and development of gastric epithelial neoplasia. RESULTS At T-0, 77.6% of patients had stage 0, 14.4% stage I, 5.1% stage II, 2.1% stage III and 0.85% stage IV. H. pylori infection was detected in 603 patients at T-0 and successfully eradicated in 602 of them; 220 had a documented history of H. pylori eradication; and 932 were H. pylori naïve-negative. Incident neoplastic lesions (prevalence=0.4%; low-grade intraepithelial neoplasia (IEN)=4; high-grade IEN=1; GC=2) developed exclusively in patients with stages III-IV. The risk for epithelial neoplasia was null in patients at stages 0, I and II (95% CI 0 to 0.4), 36.5 per 1000 person-years in patients at stage III (95% CI 13.7 to 97.4) and 63.1 per 1000 person-years in patients at stage IV (95% CI 20.3 to 195.6). CONCLUSIONS This prospective study confirms that OLGA staging reliably predicts the risk for development of gastric epithelial neoplasia. Although no neoplastic lesions arose in H. pylori-naïve patients, the H. pylori eradication in subjects with advanced stages (III-IV) did not abolish the risk for neoplastic progression.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine (DIMED), Pathology Unit, University of Padua, Padova, Italy
- Veneto Tumor Registry, Veneto Region, Padova, Italy
| | - Alberto Meggio
- Department of Gastroenterology, Trento and Rovereto Hospital, Trento, Italy
| | - Cecilia Pravadelli
- Department of Gastroenterology, Trento and Rovereto Hospital, Trento, Italy
| | | | - Matteo Fassan
- Department of Medicine (DIMED), Pathology Unit, University of Padua, Padova, Italy
| | | | - Manuel Zorzi
- Veneto Tumor Registry, Veneto Region, Padova, Italy
| | - Giovanni De Pretis
- Department of Gastroenterology, Trento and Rovereto Hospital, Trento, Italy
| | - David Y Graham
- Department of Medicine, Michael E DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA
| | - Robert M Genta
- Miraca Life Sciences Research Institute, Irving, Texas, USA
- Departments of Pathology and Medicine, Baylor College of Medicine, Houston, Texas, USA
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13
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Yun CY, Kim N, Lee J, Lee JY, Hwang YJ, Lee HS, Yoon H, Shin CM, Park YS, Kim JW, Lee DH. Usefulness of OLGA and OLGIM system not only for intestinal type but also for diffuse type of gastric cancer, and no interaction among the gastric cancer risk factors. Helicobacter 2018; 23:e12542. [PMID: 30303591 DOI: 10.1111/hel.12542] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/20/2018] [Accepted: 09/04/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND The operative link on gastric atrophy (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) stages have been suggested for risk estimation of gastric cancer (GC). However, usefulness of OLGA/OLGIM systems in diffuse type of GC was not investigated so far. The aims of this study were to evaluate the OLGA/OLGIM systems in estimating the GC risk according to Lauren's classification and to investigate the interaction among the risk factors. MATERIALS AND METHODS The OLGA/OLGIM stages were evaluated in 1398 (765 control and 633 GC patients) who were prospectively enrolled in the Seoul National University Bundang Hospital. Synergistic interaction among the risk factors for GC was calculated using an additive model. RESULTS Among 387 intestinal-type GC patients, 71 (18.3%) were high-risk OLGA stages (III, IV) and 113 (29.2%) were high-risk OLGIM stages (III, IV). Of the 246 patients with diffuse-type GC, 36 (14.6%) were high-risk OLGA stages and 39 (15.9%) were high-risk OLGIM stages. Multivariable analysis revealed family history of GC, Helicobacter pylori infection, high-risk OLGA stages, and high-risk OLGIM stages as independent risk factors for GC regardless of histologic type (odds ratios [ORs] 1.78, 1.94, 2.63, and 3.18, respectively). There was no significant risk modification among the H. pylori infection, family history of GC, and high-risk OLGA/OLGIM stages. CONCLUSION High-risk OLGA/OLGIM stages are important prediction markers for GC regardless of H. pylori infection or family history of GC not only for the intestinal type but also for diffuse-type GC.
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Affiliation(s)
- Chang Yong Yun
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University Seoul, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University Seoul, South Korea
| | - Jaebong Lee
- Division of Statistics in Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Young Jae Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hye Seung Lee
- Departments of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University Seoul, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University Seoul, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University Seoul, South Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University Seoul, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University Seoul, South Korea
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14
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Rugge M, Genta RM, Fassan M, Valentini E, Coati I, Guzzinati S, Savarino E, Zorzi M, Farinati F, Malfertheiner P. OLGA Gastritis Staging for the Prediction of Gastric Cancer Risk: A Long-term Follow-up Study of 7436 Patients. Am J Gastroenterol 2018; 113:1621-1628. [PMID: 30333540 DOI: 10.1038/s41395-018-0353-8] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 07/20/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Gastritis OLGA-staging ranks the risk for gastric cancer (GC) in progressive stages (0-IV). This long-term follow-up study quantifies the GC risk associated with each OLGA stage. METHODS Consecutive patients (7436) underwent esophagogastroscopy (T-0), with mapped gastric biopsies, OLGA staging, and H. pylori status assessment. Patients with neoplastic lesion (invasive or non-invasive) at the index endoscopy (and/or within 12 months) were excluded. All patients were followed-up (T-1) by combining different sources of clinical/pathological information (Regional Registries of: (i) esophagogastroduodenoscopies; (ii) pathology reports; (iii) cancer, (iv) mortality). The endpoint was histologically documented development of gastric epithelial neoplasia. RESULTS At T-0, the patients' distribution by OLGA stage was: Stage 0 = 80.8%; Stage I = 12.6%; Stage II = 4.3%; Stage III = 2.0%; Stage IV = 0.3%; H. pylori infection was detected in 25.9% of patients. At the end of the follow-up (mean/median = 6.3/6.6 years), 28 incident neoplasia were documented (overall prevalence = 0.60 per 103/person-years; low-grade intraepithelial neoplasia = 17/28; high-grade intraepithelial neoplasia = 4/28; GC = 7/28). By OLGA stage at the enrollment, the rate of incident neoplasia was: Stage 0 = 1 case; rate/103 person-years = 0.03; 95%CI: 0.004-0.19; Stage I = 2 cases; rate/103 person-years = 0.34; 95%CI: 0.09-1.36; Stage II = 3 cases; rate/103 person-years = 1.48; 95%CI: 0.48-4.58; Stage III = 17 cases; rate/103 person-years = 19.1; 95%CI: 11.9-30.7; Stage IV = 5 cases; rate/103 person-years = 41.2; 95%CI: 17.2-99.3. Multivariate analysis including gender, age, H. pylori status, and OLGA stage at enrollment only disclosed OLGA stage as predictor of neoplastic progression (OLGA stage III: HR = 712.4, 95%CI = 92.543-5484.5; OLGA stage IV: HR = 1450.7, 95%CI = 166.7-12626.0). CONCLUSIONS Among 7436 patients, OLGA stages at the enrollment correlated significantly with different risk for gastric neoplasia. Based on the obtained results, gastritis staging is a critical adjunct in endoscopy follow-up protocols aimed at GC secondary prevention.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Robert M Genta
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Elisa Valentini
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Irene Coati
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Stefano Guzzinati
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Edoardo Savarino
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Manuel Zorzi
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Fabio Farinati
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Medicine (DIMED), Surgical pathology & Cytopathology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Veneto Tumor Registry, Veneto Region, Padova, Italy. Departments of Pathology and Medicine, Baylor College of Medicine, Houston, TX, USA. Inform Diagnostics Research Institute, Irving, TX, USA. Department of Oncology and Gastroenterology (DISGOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
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15
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Elghali MA, Gouader A, Bouriga R, Mahjoub M, Jarrar MS, Ziadi S, Mokni M, Hamila F, Ltaeif R. Gastric Adenocarcinomas in Central Tunisia: Evolution Specificities through Two Decades and Relation with Helicobacter pylori. Oncology 2018; 95:121-128. [PMID: 29694966 DOI: 10.1159/000488488] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 03/15/2018] [Indexed: 12/20/2022]
Abstract
INTRODUCTION In developed countries, authors have reported variations over time in the seat and histological type of gastric adenocarcinomas, which were explained by Helicobacter pylori infection (HPI) incidence changes. In North-African countries and the Arabic world, epidemiological changes in gastric adenocarcinomas are still unknown. Our study aims to explore and to describe those changes in central Tunisia. MATERIALS AND METHODS This is a retrospective observational and descriptive study including 876 cases based on the National Central Tunisian Register of Cancers over a period of 21 years. Two groups were formed and compared (group A: 337 patients from 1995 to 2005; group B: 539 patients from 2006 to 2015). RESULTS HPI decreased from 32.6% in group A to 11.2% in group B (p < 0.05). Signet ring cell carcinomas increased in 2 decades from 14% in group A to 36% in group B (p < 0.05). Proximal cancers were 16.61% in group A and increased to 19.66% in group B (p = 0.3). Total gastrectomy rate was 10.4% in group A versus 23.2% in group B (p < 0.05). CONCLUSION This study has shown a significant increase of signet ring cell carcinomas with a simultaneous decrease in HPI in the last decade in central Tunisia.
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Affiliation(s)
| | - Amine Gouader
- Department of Digestive Surgery, Farhat Hached University Hospital, Sousse, Tunisia
| | - Rym Bouriga
- Department of Medical Oncology, Farhat Hached University Hospital, Sousse, Tunisia
| | - Mohamed Mahjoub
- Department of Epidemiology and Hospital Hygiene, Farhat Hached University Hospital, Sousse, Tunisia
| | - Mohamed Salah Jarrar
- Department of Digestive Surgery, Farhat Hached University Hospital, Sousse, Tunisia
| | - Sonia Ziadi
- Department of Pathology, Farhat Hached University Hospital, Sousse, Tunisia
| | - Moncef Mokni
- Department of Pathology, Farhat Hached University Hospital, Sousse, Tunisia
| | - Fahmi Hamila
- Department of Digestive Surgery, Farhat Hached University Hospital, Sousse, Tunisia
| | - Rached Ltaeif
- Department of Digestive Surgery, Farhat Hached University Hospital, Sousse, Tunisia
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16
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Abstract
CONTEXT - Comprehensive molecular investigations of mainstream carcinogenic processes have led to the use of effective molecular targeted agents in most cases of solid tumors in clinical settings. OBJECTIVE - To update readers regarding the evolving role of the pathologist in the therapeutic decision-making process and the introduction of next-generation technologies into pathology practice. DATA SOURCES - Current literature on the topic, primarily sourced from the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database, were reviewed. CONCLUSIONS - Adequate evaluation of cytologic-based and tissue-based predictive diagnostic biomarkers largely depends on both proper pathologic characterization and customized processing of biospecimens. Moreover, increased requests for molecular testing have paralleled the recent, sharp decrease in tumor material to be analyzed-material that currently comprises cytology specimens or, at minimum, small biopsies in most cases of metastatic/advanced disease. Traditional diagnostic pathology has been completely revolutionized by the introduction of next-generation technologies, which provide multigene, targeted mutational profiling, even in the most complex of clinical cases. Combining traditional and molecular knowledge, pathologists integrate the morphological, clinical, and molecular dimensions of a disease, leading to a proper diagnosis and, therefore, the most-appropriate tailored therapy.
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Affiliation(s)
- Matteo Fassan
- From the Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy
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17
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Lario S, Brunet-Vega A, Quílez ME, Ramírez-Lázaro MJ, Lozano JJ, García-Martínez L, Pericay C, Miquel M, Junquera F, Campo R, Calvet X. Expression profile of circulating microRNAs in the Correa pathway of progression to gastric cancer. United European Gastroenterol J 2018; 6:691-701. [PMID: 30083331 DOI: 10.1177/2050640618759433] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 01/17/2018] [Indexed: 12/23/2022] Open
Abstract
Background Helicobacter pylori infection causes long-term chronic active gastritis, a risk factor for the intestinal and diffuse forms of gastric cancer. Most gastric cancers develop in a stepwise progression from chronic active gastritis to precursor lesions of gastric cancer. The early detection of gastric cancer improves survival. Studies with recent evidence have proposed circulating-microRNAs as biomarkers of cancer. Objective The purpose of this study was to explore the circulating-microRNA profile from H. pylori infection to gastric adenocarcinoma. Methods One hundred and twenty-three patients were enrolled and assigned to the discovery or the validation sets. In the discovery phase, circulating-microRNAs were measured by dye-based quantitative polymerase chain reaction and a selection of circulating-microRNAs was validated by probe-based quantitative polymerase chain reaction. A quality control protocol was used. Results One hundred and sixty-seven circulating-microRNAs were detected. Precursor lesions of gastric cancer and gastric cancer patients showed the downregulation of eight and five circulating-microRNAs, respectively. We further validated the deregulation of miR-196a-5p in precursor lesions of gastric cancer and the deregulation of miR-134-5p, miR-144-3p and miR-451a in gastric cancer. However, circulating-microRNAs exhibited moderate diagnostic performance due to the overlap of circulating-microRNA expression between non-cancer and cancer patients. miR-144-3p/miR-451a expression levels were correlated. Interestingly, these microRNAs are in 17q11.2, a site of rearrangements associated with gastric cancer. Conclusion Circulating-microRNAs are deregulated in precancerous and gastric cancer patients but efforts are needed to improve their diagnostic accuracy.
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Affiliation(s)
- Sergio Lario
- Fundació Parc Taulí, Spain.,Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain
| | - Anna Brunet-Vega
- Fundació Parc Taulí, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain.,Oncology Service, Hospital de Sabadell, Sabadell, Spain
| | - María E Quílez
- Fundació Parc Taulí, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain.,Oncology Service, Hospital de Sabadell, Sabadell, Spain
| | - María J Ramírez-Lázaro
- Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain
| | - Juan J Lozano
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Bioinformatics Platform, CIBEREHD, Madrid, Spain
| | - Lorena García-Martínez
- Fundació Parc Taulí, Spain.,Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain
| | - Carles Pericay
- Institut Universitari Parc Taulí-UAB, Sabadell, Spain.,Oncology Service, Hospital de Sabadell, Sabadell, Spain
| | - Mireia Miquel
- Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain
| | - Félix Junquera
- Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain
| | - Rafael Campo
- Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain
| | - Xavier Calvet
- Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Institut Universitari Parc Taulí-UAB, Sabadell, Spain.,Departament de Medicina, UAB, Sabadell, Spain
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Mescoli C, Gallo Lopez A, Taxa Rojas L, Jove Oblitas W, Fassan M, Rugge M. Gastritis staging as a clinical priority. Eur J Gastroenterol Hepatol 2018; 30:125-129. [PMID: 29215433 DOI: 10.1097/meg.0000000000001015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The elective background for gastric adenocarcinoma is the atrophic transformation of the gastric mucosa. The extent of mucosal atrophy basically parallels the risk of developing gastric cancer. This means that either noninvasive (serology) or invasive (endoscopy/histology) methods enabling the atrophic transformation to be quantified can be used theoretically to assess a given patient's gastric cancer risk. This review aims to focus on the reliability of histology gastritis Operative Link for Gastritis Assessment -staging system for assessing the 'personalized' cancer risk in individuals with (atrophic) gastritis.
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Affiliation(s)
- Claudia Mescoli
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova
| | - Aly Gallo Lopez
- Proyecta Diagnostico Scientific Research Center-CONCYTEC Instituto de Investigación de la Facultad de Medicina Humana de la Universidad de San Martín de Porres
| | - Luis Taxa Rojas
- Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas INEN, Lima
| | | | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova
| | - Massimo Rugge
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova
- Veneto Tumor Registry (RTV), Veneto Regional Authority, Padova, Italy
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19
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Rugge M, Genta RM, Di Mario F, El-Omar EM, El-Serag HB, Fassan M, Hunt RH, Kuipers EJ, Malfertheiner P, Sugano K, Graham DY. Gastric Cancer as Preventable Disease. Clin Gastroenterol Hepatol 2017; 15:1833-1843. [PMID: 28532700 DOI: 10.1016/j.cgh.2017.05.023] [Citation(s) in RCA: 135] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/26/2017] [Accepted: 05/16/2017] [Indexed: 02/07/2023]
Abstract
Gastric cancer, 1 of the 5 most common causes of cancer death, is associated with a 5-year overall survival rate less than 30%. A minority of cancers occurs as part of syndromic diseases; more than 90% of adenocarcinomas are considered as the ultimate consequence of a longstanding mucosal inflammation. Helicobacter pylori infection is the leading etiology of non-self-limiting gastritis, which may result in atrophy of the gastric mucosa and impaired acid secretion. Gastric atrophy establishes a field of cancerization prone to further molecular and phenotypic changes, possibly resulting in cancer growth. This well-understood natural history provides the clinicopathologic rationale for primary and secondary cancer prevention strategies. A large body of evidence demonstrates that combined primary (H pylori eradication) and secondary (mainly endoscopy) prevention efforts may prevent or limit the progression of gastric oncogenesis. This approach, which is tailored to different country-specific gastric cancer incidence, socioeconomic, and cultural factors, requires that the complementary competences of gastroenterologists, oncologists, and pathologists be amalgamated into a common strategy of health policy.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine (DIMED), University of Padua, Padua, Italy; Veneto Tumor Registry, Veneto Region, Padua, Italy.
| | - Robert M Genta
- Miraca Life Sciences Research Institute, Irving, and Departments of Pathology and Medicine, Baylor College of Medicine, Houston, Texas
| | - Francesco Di Mario
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy
| | - Emad M El-Omar
- St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Hashem B El-Serag
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas
| | - Matteo Fassan
- Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Richard H Hunt
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | | | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas
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20
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Attar M, Mansoori M, Shahbazi M. Interleukin-6 Genetic Variation and Susceptibility to Gastric Cancer in an Iranian Population. Asian Pac J Cancer Prev 2017; 18:3025-3029. [PMID: 29172275 PMCID: PMC5773787 DOI: 10.22034/apjcp.2017.18.11.3025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background: Despite recent decrease in the incidence of gastric cancer, it is still a common type of cancer in the north of Iran. Many evaluations have shown that polymorphisms of cytokine genes like that for interleukin 6 (IL-6), which play important roles in regulation of the immune response, can increase the risk of gastric cancer. This study examined the role of the IL-6-174 gene polymorphism in susceptibility in an Iranian population. Method: Genomic DNA was extracted from peripheral whole blood of 100 patients and 361 healthy controls. Genotyping was accomplished by the sequence-specific primer-polymerase chain reaction (SSP-PCR) method and statistical analyses were carried out using Fisher’s exact test. Frequencies of the IL-6-174 G/C genotypes were determined under co-dominant, dominant, and recessive genetic models. Results: An association between the polymorphism of IL-6 -174 G/C and susceptibility to gastric cancer was observed. The frequency of G allele was higher in patients (78%) than in controls (70.5 %) (OR=1.48, 95% CI=1.01-2.20, P=0.04). Conclusions: The high G allele and G/G genotype frequency in patients compared to control subjects suggests that the IL-6 -174 G/C polymorphism may influence the susceptibility to gastric cancer. In addition, the demographic information showed that most of the subjects were male (69.0%) that gastric cancer is related to environmental factors.
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Affiliation(s)
- Marzieh Attar
- Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran
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Lin P, Xiong DD, Dang YW, Yang H, He Y, Wen DY, Qin XG, Chen G. The anticipating value of PLK1 for diagnosis, progress and prognosis and its prospective mechanism in gastric cancer: a comprehensive investigation based on high-throughput data and immunohistochemical validation. Oncotarget 2017; 8:92497-92521. [PMID: 29190933 PMCID: PMC5696199 DOI: 10.18632/oncotarget.21438] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 08/23/2017] [Indexed: 12/26/2022] Open
Abstract
Polo-like kinase 1 (PLK1) is a multi-functional protein and its aberrant expression is a driver of cancerous transformation and progression. To increase our understanding of the clinical value and potential molecular mechanism of PLK1 in gastric cancer (GC), we performed this comprehensive investigation. A total of 25 datasets and 12 publications were finally incorporated. Additional immunohistochemistry was conducted to validate the expression pattern of PLK1 in GC. The pooled standard mean deviation (SMD) indicated that PLK1 mRNA was up-regulated in GC (SMD=1.21, 95% CI: 0.65-1.77, P< 0.001). Similarly, the pooled odds ratio (OR) revealed that PLK1 protein was overexpressed in GC compared with normal gastric tissue (OR=12.12, 95% CI: 5.41-27.16, P<0.001). The area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.86. Furthermore, our results demonstrated that GC patients with PLK1 overexpression were significantly associated with unfavorable overall survival (HR =1.54, 95% CI: 1.30–1.83, P<0.001), lymph node metastasis (OR = 1.78, 95% CI: 1.13–2.80, P=0.013) and advanced TNM stage (OR=1.48, 95% CI: 1.02-2.15, P=0.038). Altogether, 100 similar genes were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and further with gene-set enrichment analysis. These genes were related to gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways relevant to the cell cycle. Gene set enrichment analysis (GSEA) indicated that PLK1 is associated with various cancer-related pathways. Collectively, this study suggests that PLK1 overexpression could play vital roles in the carcinogenesis and deterioration of GC via regulating tumor-related pathways.
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Affiliation(s)
- Peng Lin
- Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Dan-Dan Xiong
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Yi-Wu Dang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Hong Yang
- Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Yun He
- Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Dong-Yue Wen
- Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Xin-Gan Qin
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
| | - Gang Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
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Fassan M, Saraggi D, Balsamo L, Realdon S, Scarpa M, Castoro C, Coati I, Salmaso R, Farinati F, Guzzardo V, Arcidiacono D, Munari G, Gasparini P, Veronese N, Luchini C, Valeri N, Rugge M. Early miR-223 Upregulation in Gastroesophageal Carcinogenesis. Am J Clin Pathol 2017; 147:301-308. [PMID: 28395057 DOI: 10.1093/ajcp/aqx004] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES To test miR-223 upregulation during gastric (intestinal-type) and Barrett esophageal carcinogenesis. METHODS miR-223 expression was assessed by quantitative reverse transcription polymerase chain reaction in a series of 280 gastroesophageal biopsy samples representative of the whole spectrum of phenotypic changes involved in both carcinogenetic cascades. The results were further validated by in situ hybridization on multiple tissue specimens obtained from six surgically treated gastroesophageal adenocarcinomas. miR-223 expression was also assessed in plasma samples from 30 patients with early stage (ie, stages I and II) gastroesophageal adenocarcinoma and relative controls. RESULTS In both gastric and esophageal models, miR-223 expression significantly increased along with the severity of the considered lesions (analysis of variance, P < .001). Among atrophic gastritis and long-segment Barrett esophagus samples, miR-223 overexpression was significantly associated with the score of intestinal metaplasia. miR-223 plasma levels were significantly upregulated in patients with cancer compared with controls ( t test, both P < .001). CONCLUSIONS miR-223 early upregulation observed in tissue samples and its diagnostic value in discriminating patients with early adenocarcinoma by plasma testing provide a solid rationale for further exploring the diagnostic reliability of this microRNA as a novel biomarker in gastroesophageal adenocarcinoma secondary prevention strategies.
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Affiliation(s)
- Matteo Fassan
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | - Deborah Saraggi
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | - Laura Balsamo
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | | | - Marco Scarpa
- Surgery Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Carlo Castoro
- Surgery Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Irene Coati
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | - Roberta Salmaso
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | - Fabio Farinati
- Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit
| | - Vincenza Guzzardo
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | - Diletta Arcidiacono
- Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit
- Venetian Institute of Molecular Medicine
| | - Giada Munari
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
| | - Pierluigi Gasparini
- Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus
| | - Nicola Veronese
- Department of Medicine (DIMED), Geriatrics Division, University of Padua, Padua, Italy
| | - Claudio Luchini
- Surgical Pathology Unit, Santa Chiara Hospital, Trento, Italy
| | - Nicola Valeri
- Gastrointestinal Oncology and Lymphoma, Royal Mardsen Hospital, London and Sutton, UK
- Department of Molecular Pathology, Institute of Cancer Research, London and Sutton, UK
| | - Massimo Rugge
- From the Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit
- Veneto Tumour Registry, Padua, Italy
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Baniak N, Senger JL, Ahmed S, Kanthan SC, Kanthan R. Gastric biomarkers: a global review. World J Surg Oncol 2016; 14:212. [PMID: 27514667 PMCID: PMC4982433 DOI: 10.1186/s12957-016-0969-3] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 08/02/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes. MAIN BODY This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability. CONCLUSION A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.
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Affiliation(s)
- Nick Baniak
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
| | - Jenna-Lynn Senger
- Department of Surgery, University of Alberta, 116 St & 85 Ave, Edmonton, T6G 2R3, T6G 2B7 AB Canada
| | - Shahid Ahmed
- Division of Medical Oncology, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
| | - S. C. Kanthan
- Department of General Surgery, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
| | - Rani Kanthan
- Department of General Surgery, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK S7N 0W8 Canada
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24
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Histologic types of gastric cancer among migrants from the former Soviet Union and the general population in Germany: what kind of prevention do we need? Eur J Gastroenterol Hepatol 2016; 28:863-70. [PMID: 27187801 DOI: 10.1097/meg.0000000000000645] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVE The incidence of gastric cancer (GC) is high among migrants from Eastern Europe and Asia, but a detailed picture of disease characteristics is missing. Our study examined the incidence of histologic types among resettlers from the former Soviet Union and the general population in Germany to draw conclusions on risk factors and possible prevention strategies. METHODS Between 1990 and 2009, all GC diagnoses among a cohort of 18 619 resettlers residing in the Saarland were identified in the Saarland Cancer Registry database. Age-standardized incidence rates (ASRs) of the entire Saarland population and standardized incidence ratios (SIRs) of resettlers compared with the Saarland population were calculated for types according to Laurén. In addition, ASRs and SIRs were modeled using Poisson's regression to investigate time trends. RESULTS The ASR of intestinal GC in the Saarland population decreased over time, whereas the ASR of diffuse GC remained unchanged. Resettlers' incidence of intestinal GC was elevated among men [SIR: 3.04, 95% confidence interval (CI): 2.05-4.50] and women (SIR: 2.78, 95% CI: 1.61-4.79), whereas diffuse GC was elevated only among women (SIR: 1.98, 95% CI: 1.07-3.69). No time trends for SIRs could be observed in regression analysis. CONCLUSION Different trends of diffuse GC incidence in Germany and the USA underline the importance of environmental risk factors. The continuously elevated risk of GC among male resettlers is probably associated with risk factors affecting exclusively the intestinal type such as a low intake of fruit and vegetables and heavy alcohol consumption. Future prevention programs for resettlers should include dietary measures.
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25
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Fassan M, Saraggi D, Balsamo L, Cascione L, Castoro C, Coati I, De Bernard M, Farinati F, Guzzardo V, Valeri N, Zambon CF, Rugge M. Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis. Oncotarget 2016; 7:4915-4924. [PMID: 26701848 PMCID: PMC4826253 DOI: 10.18632/oncotarget.6642] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 11/27/2015] [Indexed: 12/11/2022] Open
Abstract
Aberrant let-7c microRNA (miRNA) expression has been observed in Helicobacter pylori-related gastric cancer (GC) but fragmentary information is available on the let-7c dysregulation occurring with each phenotypic change involved in gastric carcinogenesis. Let-7c expression was assessed (qRT-PCR) in a series of 175 gastric biopsy samples representative of the whole spectrum of phenotypic changes involved in H. pylori-related gastric oncogenesis including: i) normal gastric mucosa, as obtained from dyspeptic controls (40 biopsy samples); ii) non-atrophic gastritis (40 samples); iii) atrophic-metaplastic gastritis (35 samples); iv) intra-epithelial neoplasia (30 samples); v) GC (30 samples). Let-7c expression was also tested in 20 biopsy samples obtained from 10 patients before and after H. pylori eradication therapy (median follow-up: 10 weeks; range: 7-14). The results obtained were further validated by in situ hybridization on multiple tissue specimens obtained from 5 surgically treated H. pylori-related GCs. The study also included 40 oxyntic biopsy samples obtained from serologically/histologically confirmed autoimmune gastritis (AIG: 20 corpus-restricted, non-atrophic; 20 corpus-restricted, atrophic-metaplastic). Let-7c expression dropped from non-atrophic gastritis to atrophic-metaplastic gastritis, intra-epithelial neoplasia, and invasive GC (p<0.001). It rose again significantly following H. pylori eradication (p=0.009). As in the H. pylori model, AIG also featured a significant let-7c down-regulation (p<0.001). The earliest phases of the two pathways to gastric oncogenesis (H. pylori-environmental and autoimmune host-related) are characterized by similar let-7c dysregulations. In H. pylori infection, let-7c down-regulation regresses after the bacterium's eradication, while it progresses significantly with the increasing severity of the histological lesions.
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Affiliation(s)
- Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Deborah Saraggi
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Laura Balsamo
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Luciano Cascione
- Institute of Oncology Research and Swiss Institute of Bioinformatics, Lymphoma & Genomics Group, Bellinzona, Switzerland
| | - Carlo Castoro
- Istituto Oncologico Veneto, IOV-IRCCS, Surgery Unit, Padua, Italy
| | - Irene Coati
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | | | - Fabio Farinati
- Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy
| | - Vincenza Guzzardo
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Nicola Valeri
- Molecular Pathology Division, Institute of Cancer Research, London and Sutton, UK
| | - Carlo Federico Zambon
- Department of Medicine (DIMED), Clinical Pathology Unit, University of Padua, Padua, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
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Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 908:441-78. [PMID: 27573785 DOI: 10.1007/978-3-319-41388-4_22] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model.
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27
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Coati I, Fassan M, Farinati F, Graham DY, Genta RM, Rugge M. Autoimmune gastritis: Pathologist's viewpoint. World J Gastroenterol 2015; 21:12179-12189. [PMID: 26576102 PMCID: PMC4641135 DOI: 10.3748/wjg.v21.i42.12179] [Citation(s) in RCA: 114] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 06/15/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.
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28
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Rugge M. Gastric Cancer Risk in Patients with Helicobacter pylori Infection and Following Its Eradication. Gastroenterol Clin North Am 2015; 44:609-24. [PMID: 26314671 DOI: 10.1016/j.gtc.2015.05.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
As Helicobacter pylori is a first-class carcinogen, eradication of the infection would be expected to be a beneficial measure for the (primary) prevention of gastric cancer. Given the natural history of gastric cancer, it is plausible that eradication before gastric atrophy sets in offers the best chance for cancer risk reduction. The beneficial effects of eradication may, nevertheless, still be achievable in more advanced disease. The reversibility of inflammatory lesions has been supported by undeniable evidence; the regression of mucosal atrophy/metaplasia has also been confirmed by several recent histologic studies.
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Affiliation(s)
- Massimo Rugge
- Surgical Pathology & Cytopathology Unit, Department of Medicine - DIMED, University of Padova, Via Aristide Gabelli, 61, Padova 35121, Italy.
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29
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Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers. DISEASE MARKERS 2015; 2015:503762. [PMID: 26379360 PMCID: PMC4563069 DOI: 10.1155/2015/503762] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Revised: 07/22/2015] [Accepted: 07/26/2015] [Indexed: 12/17/2022]
Abstract
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade.
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30
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Jian-Cheng T, Bo Z, Jian F, Liang Z. Delta-Shaped Gastroduodenostomy in Fully Laparoscopic Distal Gastrectomy: A Retrospective Study. Medicine (Baltimore) 2015; 94:e1153. [PMID: 26181558 PMCID: PMC4617079 DOI: 10.1097/md.0000000000001153] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 06/17/2015] [Accepted: 06/19/2015] [Indexed: 12/18/2022] Open
Abstract
This study aims to explore the technical feasibility, safety, and clinical efficacy of delta-shaped anastomosis for digestive tract reconstruction during totally laparoscopic distal gastrectomy. Clinical data of 24 patients who received totally laparoscopic distal gastrectomy with delta-shaped anastomosis (laparoscopic gastrectomy group, LG group) and 30 patients who received open distal gastrectomy for gastric cancer (open gastrectomy group, OG group) from April 2013 to April 2014 were retrospectively analyzed. Operation time, intraoperative blood loss, postoperative time to intestinal function recovery, postoperative pain, postoperative hospital stay, and incidence of postoperative complications (infection, obstruction, and delayed gastric emptying) were compared between these 2 groups. Patients in both groups were discharged without marked complications. No patients who initially selected laparoscopy were converted to laparotomy. Patients in the LG group had longer operation times (175.3 ± 64.7 minutes versus 120.1 ± 43.4 minutes, P < 0.05), lower intraoperative blood loss (50.8 ± 25.3 mL versus 95.6 ± 20.7 mL, P < 0.05), faster recovery of intestinal function (1.2 ± 0.5 days versus 2.6 ± 1.0 days, P < 0.05), less postoperative pain (5.6 ± 0.7 versus 9.5 ± 0.3, P < 0.05), and shorter length of postoperative hospital stay (8.5 ± 2.2 days versus 12.2 ± 3.8 days, P < 0.05), compared with patients in the OG group. There were no significant differences with respect to surgical margins achieved, the number of lymph nodes retrieved or incidence of postoperative complications (infection, obstruction, and delayed gastric emptying) between the 2 groups (P > 0.05). Laparoscopic reconstruction of the digestive tract through delta-shaped anastomosis appears to be safe, feasible, and associated to rapid recovery. These data argue for more wide-spread implementation of this procedure.
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Affiliation(s)
- Tu Jian-Cheng
- From the Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu Province, P.R. China (TJ-C, ZB, FJ, ZL)
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