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Maeda Y, Eto K, Yoshida N, Iwatsuki M, Iwagami S, Ogawa K, Sawayama H, Baba Y, Miyamoto Y, Baba H. The 5-factor modified frailty index is a novel predictive marker of death from other diseases after curative gastrectomy for gastric cancer. Geriatr Gerontol Int 2023; 23:750-756. [PMID: 37596938 DOI: 10.1111/ggi.14648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 06/23/2023] [Accepted: 07/14/2023] [Indexed: 08/21/2023]
Abstract
AIM The 5-factor modified frailty index (MFI-5) is a stratification tool to evaluate a patient's frailty. This study determined whether the MFI-5 is associated with short- and long-term outcomes after curative gastrectomy in patients with gastric cancer. METHODS We retrospectively reviewed 447 consecutive patients who underwent curative gastrectomy, and evaluated their overall survival (OS), relapse-free survival (RFS) and cancer-specific survival. RESULTS A total of 75 patients (16.8%) had high MFI-5 scores (MFI-5 ≥3). A high MFI-5 score was significantly associated with advanced age, male sex and severe postoperative complications. Patients with high MFI-5 scores had significantly poorer OS and RFS than those with low MFI-5 scores (5-year OS, 80.3% vs 59.7%, P < 0.01; 5-year RFS, 77.4% vs 54.9%, P < 0.01). Additionally, a high MFI-5 score was an independent predictor for OS (hazard ratio 1.69, 95% CI 1.09-2.61; P = 0.02) and RFS (hazard ratio, 1.80, 95% CI 1.19-2.74; P = 0.01). However, cancer-specific survival was not significantly different between the two groups. CONCLUSIONS The MFI-5 score can be predictive of postoperative morbidity and deaths from other disease after curative gastrectomy after curative gastrectomy for gastric cancer. Geriatr Gerontol Int 2023; 23: 750-756.
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Affiliation(s)
- Yuto Maeda
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsuhiro Ogawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiroshi Sawayama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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Xu SS, Chai NL, Tang XW, Linghu EQ, Wang SS, Feng XX, Li B. A predictive risk-scoring model for multiple synchronous early gastric cancers or gastric dysplasia before initial endoscopic resection. J Dig Dis 2021; 22:637-644. [PMID: 34480521 DOI: 10.1111/1751-2980.13050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 08/11/2021] [Accepted: 09/01/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To establish a new and easy-to-use risk-scoring predictive model to help identify high-risk patients with multiple synchronous gastric neoplasms (MSGN), including early gastric cancer (EGC) and gastric dysplasia (GD), before initial endoscopic resection (ER). METHODS We retrospectively enrolled 1361 patients with EGC or GD who had undergone ER from November 2006 to September 2019. The patients were randomly divided into the training (n = 681) and validation cohorts (n = 680). In the training phase a prediction score was constructed to assess the independent predictors of MSGN based on multivariate logistic regression analysis. The performance of the prediction model was evaluated using the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test. RESULTS Of the 1361 patients, 122 (9.0%) had MSGN. Three predictors for MSGN were scored and weighted, as follows: elderly male (≥65 y; three points), a family history of gastric cancer (two points) and surface redness (two points). Accordingly, patients were divided into the low (risk score, 0-3 points) or high-risk groups (risk score, 4-7 points). In the validation cohort, the incidence of MSGN in the low-risk and high-risk groups were 6.1% and 32.0%, respectively (P < 0.001). Our predictive risk-scoring model showed good discrimination (the area under the ROC curve [AUROC] 0.719, 95% confidence interval [CI] 0.634-0.794, P < 0.001) and calibration ability (Hosmer-Lemeshow test, χ2 = 6.539, P = 0.587) in the validation group. CONCLUSION This risk-scoring model has a good performance in predicting MSGN before the initial ER.
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Affiliation(s)
- Shan Shan Xu
- Nankai University School of Medicine, Nankai University, Tianjin, China
- Department of Gastroenterology and Hepatology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ning Li Chai
- Department of Gastroenterology and Hepatology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiao Wei Tang
- Department of Gastroenterology and Hepatology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - En Qiang Linghu
- Nankai University School of Medicine, Nankai University, Tianjin, China
- Department of Gastroenterology and Hepatology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Sha Sha Wang
- Nankai University School of Medicine, Nankai University, Tianjin, China
| | - Xiu Xue Feng
- Nankai University School of Medicine, Nankai University, Tianjin, China
| | - Bao Li
- Nankai University School of Medicine, Nankai University, Tianjin, China
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Dias AR, Pereira MA, Ramos MFKP, Ribeiro U, Zilberstein B, Cecconello I. IMPACT OF AGING IN THE SURGICAL OUTCOMES OF GASTRIC CANCER PATIENTS. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:93-99. [PMID: 33909804 DOI: 10.1590/s0004-2803.202100000-16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 10/27/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND As age advances, a higher burden of comorbidities and less functional reserve are expected, however, the impact of aging in the surgical outcomes of gastric cancer (GC) patients is unknown. OBJECTIVE The aim of this study is to evaluate surgical outcomes of GC patients according to their age group. METHODS Patients submitted to gastrectomy with curative intent due to gastric adenocarcinoma were divided in quartiles. Each group had 150 patients and age limits were: ≤54.8, 54.9-63.7, 63.8-72, >72. The outcomes assessed were: postoperative complications (POC), 90-day postoperative mortality, disease-free survival (DFS) and overall survival (OS). RESULTS Major surgical complications were 2.7% in the younger quartile vs 12% for the others (P=0.007). Major clinical complications raised according to the age quartile: 0.7% vs 4.7% vs 5.3% vs 7.3% (P<0.042). ASA score and age were independent risk factors for major POC. The 90-day mortality progressively increased according to the age quartile: 1.3% vs 6.0% vs 7.3% vs 14% (P<0.001). DFS was equivalent among quartile groups, while OS was significantly worse for those >72-year-old. D2 lymphadenectomy only improved OS in the three younger quartiles. Age >72 was an independent risk factor for worse OS (hazard ratio of 1.72). CONCLUSION Patients <55-year-old have less surgical complications. As age progresses, clinical complications and 90-day mortality gradually rise. OS is worse for those above age 72, and D2 lymphadenectomy should be individualized after this age.
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Affiliation(s)
- Andre Roncon Dias
- Instituto do Câncer, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. São Paulo, SP, Brasil
| | - Marina Alessandra Pereira
- Instituto do Câncer, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. São Paulo, SP, Brasil
| | | | - Ulysses Ribeiro
- Instituto do Câncer, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. São Paulo, SP, Brasil
| | - Bruno Zilberstein
- Instituto do Câncer, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. São Paulo, SP, Brasil
| | - Ivan Cecconello
- Instituto do Câncer, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. São Paulo, SP, Brasil
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Arai T. Do we need special viewpoints for intraoperative frozen section diagnosis? Virchows Arch 2020; 477:761-762. [PMID: 32524183 DOI: 10.1007/s00428-020-02862-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan.
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Tayanloo-Beik A, Sarvari M, Payab M, Gilany K, Alavi-Moghadam S, Gholami M, Goodarzi P, Larijani B, Arjmand B. OMICS insights into cancer histology; Metabolomics and proteomics approach. Clin Biochem 2020; 84:13-20. [PMID: 32589887 DOI: 10.1016/j.clinbiochem.2020.06.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/01/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023]
Abstract
Metabolomics as a post-genomic research area comprising different analytical methods for small molecules analysis. One of the underlying applications of metabolomics technology for better disease diagnosis and prognosis is discovering the metabolic pathway differences between healthy individuals and patients. On the other hand, the other noteworthy applications of metabolomics include its effective role in biomarker screening for cancer detection, monitoring, and prediction. In other words, emerging of the metabolomics field can be hopeful to provide a suitable alternative for the common current cancer diagnostic methods especially histopathological tests. Indeed, cancer as a major global issue places a substantial burden on the health care system. Hence, proper management can be beneficial. In this respect, formalin-fixed paraffin-embedded tissue specimens (in histopathological tests) are considered as a valuable source for metabolomics investigations. Interestingly, formalin-fixed paraffin-embedded tissue specimens can provide informative data for cancer management. In general, using these specimens, determining the cancer stage, individual response to the different therapies, personalized risk prediction are possible and high-quality clinical services are the promise of OMICS technologies for cancer disease. However, considering all of these beneficial characteristics, there are still some limitations in this area that need to be addressed in order to optimize the metabolomics utilizations and advancement.
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Affiliation(s)
- Akram Tayanloo-Beik
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Masoumeh Sarvari
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Moloud Payab
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Kambiz Gilany
- Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mahdi Gholami
- Department of Toxicology & Pharmacology, Faculty of Pharmacy; Toxicology and Poisoning Research Center, Tehran University of Medical Sciences, Tehran 1416753955, Iran.
| | - Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Joharatnam-Hogan N, Shiu KK, Khan K. Challenges in the treatment of gastric cancer in the older patient. Cancer Treat Rev 2020; 85:101980. [PMID: 32065879 DOI: 10.1016/j.ctrv.2020.101980] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 02/04/2020] [Accepted: 02/05/2020] [Indexed: 12/24/2022]
Abstract
Gastric cancer is considered an age-related disease, with the majority of new cases in the UK diagnosed in individuals over the age of 75. At present most guidance related to the management of gastric cancer is based on trials undertaken in the fit, younger patient. Historically the elderly have been underrepresented in clinical trials, which frequently have a restricted inclusion to an upper age limit of 75. The European Society for Medical Oncology (ESMO) recommends use of a geriatric assessment to determine functional age when initiating treatment in elderly patients with gastric cancer, which has been shown to be a better predictor of treatment response than chronological age. The physiological changes that occur with age, including reduced organ function and pharmacokinetic and pharmacodynamic variability, together with impaired functional status, necessitate a more individualised approach to treatment decisions in the older patient to provide them with the same advantages from radical treatment and palliative chemotherapy as younger patients. This review summarises the current evidence extrapolated from trial data on how best to optimise treatment for elderly patients with gastric cancer.
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Affiliation(s)
- Nalinie Joharatnam-Hogan
- Gastrointestinal Oncology, Department of Medicine, University College London NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK
| | - Kai Keen Shiu
- Gastrointestinal Oncology, Department of Medicine, University College London NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK
| | - Khurum Khan
- Gastrointestinal Oncology, Department of Medicine, University College London NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
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Wang X, Zhao J, Fairweather M, Yang T, Sun Y, Wang J. Optimal treatment for elderly patients with resectable proximal gastric carcinoma: a real world study based on National Cancer Database. BMC Cancer 2019; 19:1079. [PMID: 31706283 PMCID: PMC6842542 DOI: 10.1186/s12885-019-6166-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 09/16/2019] [Indexed: 12/27/2022] Open
Abstract
Background High perioperative morbidity, mortality, and uncertain outcome of surgery in octogenarians with proximal gastric carcinoma (PGC) pose a dilemma for both patients and physicians. We aim to evaluate the risks and survival benefits of different strategies treated in this group. Methods Octogenarians (≥80 years) with resectable proximal gastric carcinoma who were recommended for surgery were identified from National Cancer Database during 2004–2013. Results Patients age ≥ 80 years with PGC were less likely to be recommended or eventually undergo surgery compared to younger patients. Patients with surgery had a significantly better survival than those without surgery (5-year OS: 26% vs. 7%, p < 0.001), especially in early stage patients. However, additional chemotherapy (HR: 0.94, 95% CI: 0.82–1.08, P = 0.36) or radiotherapy (HR: 0.97, 95% CI: 0.84–1.13, P = 0.72) had limited benefits. On multivariate analysis, surgery (HR: 0.66, 95% CI: 0.51–0.86, P = 0.002) was a significant independent prognostic factor, while extensive surgery had no survival benefit (Combined organ resection: HR: 1.88, 95% CI: 1.22–2.91, P = 0.004; number of lymph nodes examined: HR: 0.99, 95% CI: 0.97–1.00, P = 0.10). Surgery performed at academic and research (AR) medical center had the best survival outcome (5-year OS: 30% in AR vs. 18–27% in other programs, P < 0.001) and lowest risk (30-day mortality: 1.5% in AR vs. 3.6–6.6% in other programs, P < 0.001; 90-day mortality: 6.2% in AR vs. 13.6–16.4% in other programs, P < 0.001) compared to other facilities. Conclusions Less-invasive approach performed at academic and research medical center might be the optimal treatment for elderly patients aged ≥80 yrs. with early stage resectable PGC.
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Affiliation(s)
- Xuefei Wang
- Gastric Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
| | - Junjie Zhao
- Gastric Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Mark Fairweather
- Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
| | - Tingsong Yang
- Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 20072, China
| | - Yihong Sun
- Gastric Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Jiping Wang
- Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
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Risk stratification for lymph node metastasis using Epstein-Barr virus status in submucosal invasive (pT1) gastric cancer without lymphovascular invasion: a multicenter observational study. Gastric Cancer 2019; 22:1176-1182. [PMID: 31062195 DOI: 10.1007/s10120-019-00963-7] [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: 02/26/2019] [Accepted: 04/03/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Lymphovascular invasion (LVI) is a strong predictive factor for lymph node metastasis (LNM) in early gastric cancer (GC). This study investigated the risk for LNM in pT1b GC without LVI based on Epstein-Barr virus (EBV) status in addition to conventional clinicopathological parameters. METHODS In total, 847 consecutive patients of pT1b GC without LVI who underwent surgery at three high-volume centers between 2005 and 2014 were retrospectively analyzed. Clinicopathological parameters and EBV status were evaluated, and univariate and multivariate analyses were performed to estimate LNM risk. With regard to the presence of those three parameters, risk stratification for LNM was performed and compared with a previously proposed risk classification that included low-risk (LNM < 3.0%), intermediate-risk (LNM ≥ 3.0 and < 19.6%), and high-risk (LNM ≥ 19.6%) groups. RESULTS EBV-positive GC (EBVGC) accounted for 11.3% (96 of 847) of cases; LNM was lower in EBVGC than in non-EBVGC (1 of 96, 1.0% vs. 71/751, 9.5%). In the multivariate analysis, non-EBVGC [odds ratio (OR) 10.8, 95% confidence interval (CI) 1.48-78.9], age < 65 years (OR 2.13, 95% CI 1.30-3.48), and tumor diameter > 3 cm (OR 2.26, 95% CI 1.36-3.74) were independent risk factors for LNM. Patients with EBVGC were at low risk for LNM whereas those with all of three independent risk factors were at high risk (36 of 168, 21.4%, 95% CI 15.5-28.4). CONCLUSION LNM risk stratification that includes EBV status is useful for clinical decision-making in pT1b GC cases without LVI.
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Solid-type poorly differentiated adenocarcinoma of the stomach: clinicopathological and molecular characteristics and histogenesis. Gastric Cancer 2019; 22:314-322. [PMID: 30088163 DOI: 10.1007/s10120-018-0862-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 07/30/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite predominant microsatellite instability (MSI) in intestinal-type gastric carcinomas, we found the most frequent MSI in solid-type poorly differentiated adenocarcinoma (PDA). Although this tumor is classified as PDA, it is hypothesized to possess peculiar features among PDAs. The present study aimed to clarify the clinicopathological and molecular characteristics of this tumor. METHODS We examined the expression of p53, mismatch-repair proteins, and mucin core glycoproteins; microsatellite status; and mutations in KRAS and BRAF, as well as clinicopathological features, in 54 cases of PDA of the stomach (31 solid-type PDAs and 23 non-solid-type PDAs). RESULTS The proportion (51.6%) of MSI in solid-type PDA was significantly higher than that in non-solid-type PDA (4.5%) (p = 0.00022). The proportion of absent expression of MLH1 (58.1%) and PMS2 (51.6%) in solid-type PDA was significantly higher than that in non-solid-type PDA (4.5 and 8%) (p < 0.0001). No differences were found in the mutations of KRAS and BRAF among PDAs. MSI-positive solid-type PDA was significantly associated with older age, female predominance, lower third location, concordant glandular component, and absent MLH1 and PMS2 expression. CONCLUSIONS These results suggest that MSI-positive solid-type PDA has peculiar clinicopathological features and that MSI with absent MLH1 and PMS2 expression may play an important role in tumor development. In addition, from the viewpoint of histogenesis, MSI-positive solid-type PDA may originate from differentiated-type adenocarcinoma.
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Go SI, Ko GH, Lee WS, Lee JH, Jeong SH, Lee YJ, Hong SC, Ha WS. The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer. Cancer Res Treat 2019; 51:1411-1419. [PMID: 30913874 PMCID: PMC6790844 DOI: 10.4143/crt.2018.663] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 02/23/2019] [Indexed: 12/20/2022] Open
Abstract
Purpose We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC. Materials and Methods With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9-negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67–high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling. Results The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016). Conclusion This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.
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Affiliation(s)
- Se-Il Go
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
| | - Gyung Hyuck Ko
- Department of Pathology, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Won Sup Lee
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Jeong-Hee Lee
- Department of Pathology, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Sang-Ho Jeong
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
| | - Young-Joon Lee
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Soon Chan Hong
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Woo Song Ha
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
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Fanotto V, Fornaro L, Bordonaro R, Rosati G, Rimassa L, Di Donato S, Santini D, Tomasello G, Leone F, Silvestris N, Stragliotto S, Scartozzi M, Giampieri R, Nichetti F, Antonuzzo L, Cinieri S, Avallone A, Pellegrino A, Melisi D, Vasile E, Gerratana L, Aprile G. Second-line treatment efficacy and toxicity in older vs. non-older patients with advanced gastric cancer: A multicentre real-world study. J Geriatr Oncol 2018; 10:591-597. [PMID: 30551958 DOI: 10.1016/j.jgo.2018.11.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 11/04/2018] [Accepted: 11/28/2018] [Indexed: 01/06/2023]
Abstract
OBJECTIVES Although gastric cancer (GC) incidence rises with age, older patients are poorly represented in clinical trials, whose results are therefore difficult to translate into standard management of older patients. Purpose of this study was to compare clinico-pathological features and survival outcomes between older and non-older patients with advanced GC treated with at least two chemotherapy lines. MATERIALS AND METHODS Clinico-pathological characteristics, basal values, and treatment data of older (≥70 years at second-line start) and non-older patients were compared using chi-square test or 2-tailed Fisher exact test. The Kaplan-Meier estimation was used to calculate progression-free survival (PFS) and overall survival (OS), which were examined by log-rank test. RESULTS Older patients represented 31.8% of the population (N = 868). Intestinal type was more frequent in older patients (P = .02). Poorly differentiated tumours were more often observed in non-older patients (P = .009). At stage IV diagnosis, the rate of liver metastases was higher in older patients (P = .02), while peritoneal spread was more represented in non-older patients (P = .002). Although older patients were more often treated with monotherapy (P = .001), they had similar PFS (HR 0.86, 95%CI 0.71-1.03, P = .102) and OS (HR 0.82, 95%CI 0.65-1.02, P = .08) compared to the non-older counterpart. No statistical differences were observed in treatment-related adverse events, hospital admissions, or further treatment lines between age groups. CONCLUSION In our large cohort study, despite some differences in tumour characteristics and treatment intensity, no survival difference was found between older and non-older patients with advanced GC treated with at least two chemotherapy lines. Incidence of adverse events was similar between age groups.
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Affiliation(s)
- Valentina Fanotto
- Department of Oncology, University and General Hospital, Udine, Italy
| | - Lorenzo Fornaro
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | | | | | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano(MI), Italy
| | | | | | | | - Francesco Leone
- Medical Oncology, University of Turin, Candiolo Cancer Institute, FPO, IRCCS, Turin, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, National Cancer Institute IRCCS "Giovanni Paolo II", Bari, Italy
| | - Silvia Stragliotto
- UOC Oncologia Medica 1, Dip. di Oncologia, Istituto Oncologico Veneto - IRCCS, Padova, Italy
| | - Mario Scartozzi
- Medical Oncology, University of Cagliari, University Hospital, Cagliari, Italy
| | | | - Federico Nichetti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | | | | | - Antonio Avallone
- Experimental Abdomen Medical Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | | | | | - Enrico Vasile
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Lorenzo Gerratana
- Department of Oncology, University and General Hospital, Udine, Italy
| | - Giuseppe Aprile
- Department of Oncology, University and General Hospital, Udine, Italy; Department of Oncology, San Bortolo General Hospital, ULSS8 Berica - East District, Vicenza, Italy.
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12
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Sugimoto A, Nishida T, Osugi N, Takahashi K, Mukai K, Nakamatsu D, Matsubara T, Hayashi S, Yamamoto M, Nakajima S, Fukui K, Inada M. Prediction of survival benefit when deciding between chemotherapy and best supportive therapy in elderly patients with advanced gastric cancer: A retrospective cohort study. Mol Clin Oncol 2018; 10:83-91. [PMID: 30655981 PMCID: PMC6313942 DOI: 10.3892/mco.2018.1772] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 11/13/2018] [Indexed: 12/11/2022] Open
Abstract
It remains unclear whether elderly patients (EPs) with advanced gastric cancer (AGC) benefit from chemotherapy. The aim of the present study was to examine the prognostic factors for EPs with AGC in order to generate a prognosis-predicting scoring system. This single-center retrospective study examined consecutive patients with AGC between April 2012 and July 2017. Risk factors for survival in EPs aged ≥75 years were identified using a Cox proportional hazards model, and a prognostic scoring system was generated and retrospectively evaluated to determine its usefulness for predicting patient prognosis. A total of 61 patients were enrolled as EPs (mean age, 81 years) and compared with 80 non-EPs (mean age, 66 years). The median survival time (MST) was significantly longer for non-EPs compared with that for EPs (3.8 vs. 10.1 months, respectively; P=0.0447). Among the EPs, 29 (48%) received chemotherapy and 32 received best supportive care (BSC). A total of 68 non-EPs (85%) received chemotherapy and 12 non-EPs received BSC. Among EPs with AGC, age-adjusted multivariate analysis revealed that performance status (PS), neutrophil/lymphocyte ratio (NLR)<4, intestinal-type histology and chemotherapy were significant prognostic factors. To predict EPs too frail for chemotherapy prior to treatment, one point was assigned for a PS of 1, diffuse-type histology and NLR≥4, whereas 2 points were assigned for PS≥2, and the point totals for each patient were calculated. A cut-off point of 2 had the best P-value by the log-rank test and was used to divide the patients into low-risk (LoR: Score 0-1) and high-risk (HiR: Score 2-4) groups. The MST of the LoR and HiR groups was 23.6 and 3.6 months, respectively (P<0.001). As regards treatment strategies and risk groups, the LoR chemotherapy group had the best prognosis (P=0.0010), and LoR EPs who were administered chemotherapy had a longer MST (30.3 months) compared with EPs who received BSC (8.7 months). In conclusion, scoring systems using PS, histology and NLR may be useful when considering chemotherapy in EPs with AGC.
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Affiliation(s)
- Aya Sugimoto
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Naoto Osugi
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Kei Takahashi
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Kaori Mukai
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Dai Nakamatsu
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Tokuhiro Matsubara
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Shiro Hayashi
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Masashi Yamamoto
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Sachiko Nakajima
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Koji Fukui
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Masami Inada
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
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13
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Xu G, Feng F, Liu S, Wang F, Zheng G, Wang Q, Cai L, Guo M, Lian X, Zhang H. Clinicopathological features and prognosis in elderly gastric cancer patients: a retrospective cohort study. Onco Targets Ther 2018; 11:1353-1362. [PMID: 29559793 PMCID: PMC5856060 DOI: 10.2147/ott.s152471] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background Little is known about the clinicopathological features and prognosis in elderly gastric cancer (GC) patients aged 65–79 years. The aim of this study was to evaluate clinicopathological features and prognosis in elderly GC patients. Patients and methods From May 2008 to December 2014, a total of 5,282 GC patients were enrolled in our present study. Patients were divided into elderly and middle-aged groups. The clinicopathological features and clinical outcomes were analyzed. Results The proportion of dysphagia was significantly higher in elderly patients than that in middle-aged patients (P=0.002), whereas the proportion of abdominal pain and heartburn was significantly lower in elderly patients than that in middle-aged patients (P<0.001 vs P=0.038, respectively). The proportion of patients with carbohydrate antigen (CA) 19-9 was significantly higher in elderly patients than that in middle-aged patients (P=0.009). There was no significant difference in clinicopathological features between elderly and middle-aged patients with D2 gastrectomy (all P>0.05). Age, tumor size, histological type, tumor depth, lymph node metastasis, carcinoembryonic antigen, alpha fetoprotein, CA19-9, and CA125 were independent risk factors for the prognosis of GC patients in univariate and multivariate analyses. Overall survival in elderly patients was significantly reduced compared with middle-aged patients (P=0.001), especially in patients with tumor size >5 cm (P=0.002), poorly differentiated tumor (P<0.000), stage III tumor (P=0.002), or normal levels of carcinoembryonic antigen (P=0.009), alpha fetoprotein (P=0.002), CA19-9 (P=0.002), and CA125 (P=0.004). Conclusion The clinicopathological features of elderly patients were different to those of middle-aged patients. The prognosis for elderly GC patients was significantly worse than for middle-aged patients.
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Affiliation(s)
- Guanghui Xu
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Fan Feng
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Shushang Liu
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Fei Wang
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi.,Department of General Surgery, No 534 Hospital of PLA, Luoyang
| | - Gaozan Zheng
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Qiao Wang
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi.,Department of Surgery, No 91 Center Hospital of PLA, Jiaozuo, Henan, China
| | - Lei Cai
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Man Guo
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Xiao Lian
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
| | - Hongwei Zhang
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi
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Characteristics of advanced gastric cancer with negative or only perigastric lymph node metastasis in elderly patients. Aging Clin Exp Res 2018; 30:161-168. [PMID: 28455621 DOI: 10.1007/s40520-017-0767-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 04/22/2017] [Indexed: 12/13/2022]
Abstract
OBJECTIVES After gastrectomy with extended lymph node (LN) dissection, the damage of celiac plexus seems to cause of disorder of eating habits. To clarify the indication of gastrectomy with limited LN dissection for elderly patients, the pathological characteristics of advanced gastric cancer in elderly patients were examined in this study. METHODS Forty-seven patients aged ≥80 years with advanced gastric cancer (deeper than pT2) who underwent curative gastrectomy from 1998 to 2015 were enrolled. Patients were classified into two groups by extent of LN metastasis: Group A, with N0 or only perigastric LN metastasis (n = 33); Group B, LN metastasis beyond the perigastric area (n = 14). Pathological factors were then evaluated. RESULTS No significant differences were observed in age, sex, body mass index, American Society of Anesthesiologists physical status classification, serum level of carcinoembryonic antigen, surgical procedure, extent of LN dissection, and number of dissected LNs. Pathological findings showed no significant differences in tumor location, macroscopic type, histologic type, and lymphovascular invasion. However, significant differences were observed in tumor maximum diameter at the cut-off level of 40 mm (Group A: ≤40 mm, n = 10 and >40 mm, n = 23; Group B: ≤40 mm, n = 0 and >40 mm, n = 14; P = 0.02). CONCLUSION In the elderly patients, LN metastasis in advanced gastric cancer of ≤40 mm in diameter was limited to be within the perigastric area. Gastrectomy with only perigastric LN dissection may be adopted in these patients.
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15
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Otsuka Y, Akahoshi K, Yasunaga K, Kubokawa M, Gibo J, Osada S, Tokumaru K, Miyamoto K, Sato T, Shiratsuchi Y, Oya M, Koga H, Ihara E, Nakamura K. Clinical outcomes of Clutch Cutter endoscopic submucosal dissection for older patients with early gastric cancer. World J Gastrointest Oncol 2017; 9:416-422. [PMID: 29085568 PMCID: PMC5648985 DOI: 10.4251/wjgo.v9.i10.416] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 07/24/2017] [Accepted: 08/04/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the clinical outcome of endoscopic submucosal dissection using the Clutch Cutter (ESDCC) in older patients.
METHODS We reviewed 232 consecutive patients with early gastric cancer who underwent ESDCC between June 2010 and February 2014 at Aso Iizuka Hospital. We divided patients into two groups according to age: Older patients (> 80 years, n = 64) and non-older patients (≤ 80 years, n = 168). We retrospectively compared the prevalence rates of pre-existing comorbidities, anticoagulant therapy, en bloc resection, mean duration of hospitalization, incidence of ESDCC-related complications, change in performance status (PS) before and after ESDCC, and financial cost of admission.
RESULTS The older group comprised 64 patients with a mean age of 84.1 years, and the non-older group comprised 168 patients with a mean age of 69.5 years. Older patients had significantly more pre-existing comorbidities than did non-older patients, specifically heart disease (P < 0.05). The en bloc resection rate in non-older patients was significantly higher than that in older patients (100% vs 95.3%, P = 0.02). There were no significant differences between the older and non-older groups in the incidence of ESDCC-related complications (i.e., postoperative bleeding and perforation) and the post-ESDCC change in PS. There were also no significant differences between the older and non-older groups in the mean duration of hospitalization (11.4 and 10.7 d, respectively) and financial cost of admission (657040 JPY and 574890 JPY, respectively).
CONCLUSION ESDCC has a good clinical outcome in older patients.
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Affiliation(s)
- Yoshihiro Otsuka
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Kazuya Akahoshi
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Kayoko Yasunaga
- Diagnosis Procedure Combination Coding Management Office, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Masaru Kubokawa
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Junya Gibo
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Shigeki Osada
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Kayo Tokumaru
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Kazuaki Miyamoto
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Takao Sato
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Yuki Shiratsuchi
- Department of Gastroenterology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Masafumi Oya
- Department of Pathology, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Hidenobu Koga
- Clinical Research Supportive Office, Aso Iizuka Hospital, Iizuka 820-8505, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Kazuhiko Nakamura
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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16
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Ko GH, Go SI, Lee WS, Lee JH, Jeong SH, Lee YJ, Hong SC, Ha WS. Prognostic impact of Ki-67 in patients with gastric cancer-the importance of depth of invasion and histologic differentiation. Medicine (Baltimore) 2017; 96:e7181. [PMID: 28640099 PMCID: PMC5484207 DOI: 10.1097/md.0000000000007181] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 05/24/2017] [Accepted: 05/24/2017] [Indexed: 01/01/2023] Open
Abstract
Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic biomarker has not been established in gastric cancer. The present study was performed to investigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC).With tissue microarray for 320 patients with gastric cancer, we performed immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. For validation, we performed bootstrap resampling.The median follow-up duration was 72 months (range: 3-120 months). Ki-67-high group showed worse prognosis than Ki-67-low group in EGC (5-YSR, 78.9% vs 92.0%, P = .018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs 59.2%, P = .951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-high group was considerably worse than that for Ki-67-low group (5-YSR, 67.0% vs 94.4%, P = .012), but not in those with moderately differentiated (P = .504) and poorly differentiated histology (P = .905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r = 0.215, P = .002). Multivariate analysis also revealed that the high-Ki-67 expression serves as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397-13.515, P = .011), especially in the well-differentiated histology, but not in all the patients (P = .171). Bootstrap resampling internally validated this result (P = .011).This study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC with well-differentiated histologic type.
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Affiliation(s)
| | | | | | | | - Sang-Ho Jeong
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Young-Joon Lee
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Soon Chan Hong
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Woo Song Ha
- Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
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17
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Ruspi L, Galli F, Pappalardo V, Inversini D, Martignoni F, Boni L, Dionigi G, Rausei S. Lymphadenectomy in elderly/high risk patients: should it be different? Transl Gastroenterol Hepatol 2017; 2:5. [PMID: 28217755 DOI: 10.21037/tgh.2016.12.07] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 12/27/2016] [Indexed: 12/26/2022] Open
Abstract
The global aging of population will lead a greater number of elderly patients to undergo surgical procedure in a near future. Concerning gastric cancer, the impact of lymphadenectomy on survival has been demonstrated in RCTs, and extended lymphadenectomy is now considered as gold standard of treatment in non-early tumors. However, the role of age as a prognostic factor and the benefit of extended surgery in elderly/high-risk patients are not clearly defined yet. From our revision of literature, it seems that surgery for gastric cancer may have a further tailorization, considering not only the stage of disease, but also patients' age and comorbidities.
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Affiliation(s)
- Laura Ruspi
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Federica Galli
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Vincenzo Pappalardo
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Davide Inversini
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Francesco Martignoni
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Luigi Boni
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Gianlorenzo Dionigi
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
| | - Stefano Rausei
- Department of General Surgery, University of Insubria, 21100 Varese, Italy; Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
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Watanabe K, Hikichi T, Nakamura J, Takagi T, Suzuki R, Sugimoto M, Waragai Y, Kikuchi H, Konno N, Asama H, Takasumi M, Obara K, Ohira H. Endoscopic submucosal dissection for early gastric cancer in very elderly patients age 85 or older. Endosc Int Open 2017; 5:E17-E24. [PMID: 28191493 PMCID: PMC5292875 DOI: 10.1055/s-0042-122960] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background and study aims The safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in very elderly patients remains unclear. The aim of this study was to evaluate the safety and efficacy of ESD for EGC in patients age 85 years and older. Patients and methods Patients who underwent ESD for EGC between September 2003 and April 2015 were divided into 3 groups: the very elderly (≥ 85 years; 43 patients), the elderly (65 - 84 years; 511 patients), and the non-elderly ( ≤ 64 years; 161 patients). Adverse events (AEs) were used as the primary endpoint to assess the safety of ESD, and the ESD treatment outcomes (i. e., en bloc resection rate, complete en bloc resection rate, and curative resection rate) and the overall survival rate after ESD were the secondary endpoints. These parameters were retrospectively evaluated in the 3 groups. Results There were no significant differences in AEs (non-elderly, elderly, and very elderly: 7.3, 9.5, and 12.5 %, respectively, P = 0.491) or in the en bloc resection and complete en bloc resection rates among the three groups. However, there was a significant difference in the curative resection rates (non-elderly, elderly, and very elderly: 91.5, 84.1, and 77.1 %, respectively, P = 0.014). Regarding overall survival, there was a significant difference among the three groups (1-, 5-, and 10-year overall survival rates: non-elderly: 98.6, 90.2, and 74.7 %; elderly: 97.2, 86.2, and 61.9 %; and very elderly: 92.7, 66.8, and 34.4 %, respectively, P = 0.001). Moreover, the overall survival rate in the very elderly patients with cardiovascular disease was significantly lower than that in the very elderly patients without cardiovascular disease (P < 0.001). Conclusions ESD is an acceptable treatment for EGC in patients 85 years of age or older in terms of safety. However, the overall survival after ESD in the very elderly patients with cardiovascular disease was short.
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Affiliation(s)
- Ko Watanabe
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan; Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Jun Nakamura
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan; Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Tadayuki Takagi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Rei Suzuki
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Mitsuru Sugimoto
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yuichi Waragai
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hitomi Kikuchi
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan; Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Naoki Konno
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan; Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hiroyuki Asama
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Mika Takasumi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Katsutoshi Obara
- Department of Advanced Gastrointestinal Endoscopy, Fukushima Medical University, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
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Clinical Characteristics and Outcomes of Gastric Cancer Patients Aged over 80 Years: A Retrospective Case-Control Study. PLoS One 2016; 11:e0167615. [PMID: 27942044 PMCID: PMC5152853 DOI: 10.1371/journal.pone.0167615] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 11/17/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS The average human life expectancy is increasing worldwide, thus the proportion of elderly gastric cancer patients is also increasing. In this case-control study, we investigated the clinical and oncologic outcomes of gastric cancer in patients over 80 years old. METHODS From January 2004 to December 2010, 291 patients aged over 80 years old (case group) were diagnosed and treated with gastric cancer at Asan Medical Center, Seoul, Korea. From the same period, 291 patients aged 18 to 80 years old were selected as the control group. The clinical findings and clinical outcomes of gastric cancer were retrospectively reviewed and compared between the two groups. RESULTS There were significant differences in the overall 5-year survival rate between the case and control groups (30.9% vs. 73.8%, respectively; P<0.001). In patients who received the curative treatment, overall 3- and 5-year survival rates showed 74.3% and 57.9% in case group and 91.6% and 86.5% in the control group. When analysis was confined to resectable elderly patients with a favorable performance, the curative resection group showed significantly better overall 3- and 5-year survival rates than the conservative treatment group (73.7% and 58.8% vs. 29.8% and 0%, respectively). CONCLUSIONS Although elderly gastric cancer patients show an advanced stage at diagnosis and poor prognosis compared with non-elderly patients, elderly patients with good performance could benefit from curative resection. Thus, the clinical decision whether to undergo curative resection or conservative management should be made on an individualized basis.
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20
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Chang SH, Kim SN, Choi HJ, Park M, Kim RB, Go SI, Lee WS. Adjuvant Chemotherapy for Advanced Gastric Cancer in Elderly and Non-elderly Patients: Meta-Analysis of Randomized Controlled Trials. Cancer Res Treat 2016; 49:263-273. [PMID: 27384158 PMCID: PMC5266393 DOI: 10.4143/crt.2016.054] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 05/27/2016] [Indexed: 02/07/2023] Open
Abstract
PURPOSE This study evaluated the benefits of adjuvant chemotherapy on elderly patients with advanced gastric cancer (AGC) using meta-analysis of well-designed randomized controlled clinical studies. MATERIALS AND METHODS PubMed, Embase, and Cochrane were searched to retrieve clinical studies evaluating the benefits of adjuvant chemotherapy in the elderly with AGC. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across studies using a fixed-effects model. RESULTS Two studies were included in this meta-analysis to estimate HR for the overall survival (OS), and relapse-free survival (RFS) between adjuvant chemotherapy and surgery in elderly and non-elderly patients. HR for OS in the elderly and non-elderly was 0.745 (95% CI, 0.552 to 1.006, p=0.055) and 0.636 (95% CI, 0.522 to 0.776; p < 0.001), respectively, which showed no heterogeneity regarding HR between the two groups (pinteraction=0.389). HR for RFS in the elderly and non-elderly was 0.613 (95% CI, 0.466 to 0.806; p < 0.001) and 0.633 (95% CI, 0.533 to 0.753; p < 0.001), respectively (pinteraction=0.846). CONCLUSION Meta-analysis suggests that the benefit of adjuvant chemotherapy to the elderly is not big enough to reach statistical significance while the HR for OS is less than 1 (0.745) and no heterogeneity are observed regarding the HR between the elderly and non-elderly patients.
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Affiliation(s)
- Seong-Hwan Chang
- Department of Surgery, Konkuk University School of Medicine, Seoul, Korea
| | - Soo-Nyung Kim
- Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea
| | - Hye Jung Choi
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Misuk Park
- Medical Library, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Rock Bum Kim
- Department of Preventive Medicine and Environmental Health, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Se-Il Go
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Won Sup Lee
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
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Sohn IW, Jung DH, Kim JH, Chung HS, Park JC, Shin SK, Lee SK, Lee YC. Analysis of the Clinicopathological Characteristics of Gastric Cancer in Extremely Old Patients. Cancer Res Treat 2016; 49:204-212. [PMID: 27384160 PMCID: PMC5266408 DOI: 10.4143/crt.2016.163] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 06/07/2016] [Indexed: 12/19/2022] Open
Abstract
PURPOSE Gastric cancer is the third-leading cause of cancer-related death in Korea. As the Korean population is ageing, the number of extremely old patients with this disease is increasing. This study examined the clinicopathological characteristics of gastric cancer in extremely old (over 85 years) patients who received treatment or conservative observations and compared the treatment outcomes according to the treatment modality. MATERIALS AND METHODS A total of 170 patients over 85 years of age were diagnosed with gastric cancer. Of these, 81 underwent treatment for gastric cancer and 89 received conservative observations. The clinicopathological characteristics of the treatment and conservative groupswere compared. RESULTS The mean age of the patients was 86.5 years. The conservative group included significantly more patients with older ages, macroscopically advanced cancer and upper-middle located cancer. The overall survival rate of the treatment group was significantly higher than that of the conservative group. The disease-specific mortality rate was significantly lower in the treatment group than in the conservative group. Multivariate analysis revealed the clinical course, alarm sign, and macroscopic classification to be independent prognosis factors. CONCLUSION By itself, the chronological age should not be used as a strategy to determine whether treatmentwill be administered for gastric cancer. Patients who have early gastric cancer or lower-risk preexisting comorbidities should not be discouraged from treatment, even if they are older than 85 years.
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Affiliation(s)
- Il Woong Sohn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Da Hyun Jung
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Soo Chung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Chul Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Kwan Shin
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Kil Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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El Hanafy E, El Nakeeb A, Ezzat H, Hamdy E, Atif E, Kandil T, Fouad A, Wahab MA, Monier A. How does epidemiological and clinicopathological features affect survival after gastrectomy for gastric cancer patients-single Egyptian center experience. World J Gastrointest Surg 2016; 8:444-451. [PMID: 27358677 PMCID: PMC4919712 DOI: 10.4240/wjgs.v8.i6.444] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 03/19/2016] [Accepted: 04/06/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the clinicopathological features and the significance of different prognostic factors which predict surgical overall survival in patients with gastric carcinoma.
METHODS: This retrospective study includes 80 patients diagnosed and treated at gastroenterology surgical center, Mansoura University, Egypt between February 2009 to February 2013. Prognostic factors were assessed by cox proportional hazard model.
RESULTS: There were 57 male and 23 female. The median age was 57 years (24-83). One, 3 and 5 years survival rates were 71%, 69% and 46% respectively. The median survival was 69.96 mo. During the follow-up period, 13 patients died (16%). Hospital morbidity was reported in 10 patients (12.5%). The median number of lymph nodes removed was 22 (4-41). Lymph node (LN) involvement was found in 91% of cases. After R0 resection, depth of wall invasion, LN involvement and the number (> 15) of retrieved LN, LN ratio and tumor differentiation predict survival. In multivariable analysis, tumor differentiation, curability of resection and a number of resected LN superior to 15 were found to be independent prognostic factors.
CONCLUSION: Surgery remains the cornerstone of treatment. Tumor differentiation, curability of resection and a number of resected LN superior to 15 were found to be independent prognostic factors. Extended LN dissection does not increase the morbidity or mortality rate but markedly improves long term survival.
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Long-term prognosis after endoscopic submucosal dissection for early gastric cancer in super-elderly patients. Surg Endosc 2016; 30:4321-9. [PMID: 26850026 DOI: 10.1007/s00464-016-4751-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2015] [Accepted: 01/11/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND No previous study has confirmed the safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the super-elderly patient population. The current study aimed to evaluate the validity of ESD for EGC in super-elderly patients aged ≥85 years with comorbidities. METHODS Our study group included 85 super-elderly patients (102 EGCs) who were diagnosed at Hiroshima University Hospital between April 2002 and October 2014. We evaluated the en bloc resection rates, R0 resection rates, complication rates, and prognosis in relation to the degree of comorbidities (group A-H, patients with high-risk comorbidities; group A-L, patients with low-risk comorbidities; group B, patients without comorbidities; and group C, patients followed without ESD). RESULTS The en bloc resection rates were 100, 96, and 100 % in groups A-H, A-L, and B, respectively. R0 resection rates were 94, 96, and 94 % in groups A-H, A-L, and B, respectively. There were no severe complications related to ESD. During the follow-up period, there was a significantly higher frequency of death in group A than in group B (p < 0.01), and there were no significant differences between groups A-H and A-L. However, there were no cases of death related to gastric cancer. CONCLUSIONS ESD was performed safely, and death related to gastric cancer was prevented in super-elderly patients with comorbidities, regardless of the degree of the disease. However, patients with comorbidities are at a high risk of poor prognosis.
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Urasaki T, Kodaira M, Hibino M, Yamagata S, Watanabe Y, Terazawa Y, Sano M, Kuriki K. Poorly Differentiated Gastric Adenocarcinoma Can Mimic Hilar Cholangiocarcinoma. Intern Med 2016; 55:1559-64. [PMID: 27301505 DOI: 10.2169/internalmedicine.55.5888] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
This report describes two cases with obstructive jaundice caused by poorly differentiated gastric adenocarcinoma. Computed tomography scans showed circumferential stenosis in the hilar bile ducts. Endoscopic retrograde cholangiopancreatography showed dilatation of the bilateral hepatic ducts and stenosis of the common hepatic ducts from the bifurcation of the bilateral hepatic ducts. The first diagnoses were hilar cholangiocarcinoma and biliary drainage decreased serum bilirubin; however, both patients died of cancer within a short period of time. Autopsies revealed lymphatic vessel invasion and possible subepithelial invasion by gastric adenocarcinoma into the hilar bile ducts. A differential diagnosis should thus be required in suspected cases of hilar cholangiocarcinoma.
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25
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Surgical outcomes and survival after gastrectomy in octogenarians with gastric cancer. J Surg Res 2015; 198:80-6. [DOI: 10.1016/j.jss.2015.05.046] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 05/14/2015] [Accepted: 05/22/2015] [Indexed: 12/14/2022]
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Sekiguchi M, Kushima R, Oda I, Suzuki H, Taniguchi H, Sekine S, Fukagawa T, Katai H. Clinical significance of a papillary adenocarcinoma component in early gastric cancer: a single-center retrospective analysis of 628 surgically resected early gastric cancers. J Gastroenterol 2015; 50:424-34. [PMID: 25142800 DOI: 10.1007/s00535-014-0991-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Accepted: 08/07/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND We recently reported that the presence of a papillary adenocarcinoma (pap) component was an independent risk factor for lymphatic involvement in endoscopically resected early gastric cancer (EGC). This study aimed to investigate the potential association between the presence of a pap component in EGC and lymph node metastasis (LNM). METHODS In order to evaluate the association between LNM and clinicopathological features, including a pap component, we reviewed 628 surgically resected EGCs at our institution between 2009 and 2012. Clinicopathological features included age, gender, tumor location, macroscopic type, tumor size, histological type, depth, ulcerative findings, and lymphatic and venous involvement. In addition, the association between clinicopathological features and lymphatic involvement was also evaluated. RESULTS LNM was observed in 52 cases (8.3%). Univariate analyses revealed a significant correlation between a pap component and LNM as well as tumor size, depth, macroscopic type, a poorly differentiated adenocarcinoma component, and lymphatic and venous involvement. The percentage of positive LNM among the EGC cases with a pap component was significantly higher than in those without the component (18.2 vs. 7.3%, P = 0.010). Via multivariate analyses lymphatic involvement was identified as the strongest risk factor for LNM [odds ratio (OR) 14.1] and a pap component was revealed as an independent risk factor for lymphatic involvement (OR 3.1). CONCLUSION Our study revealed that EGC cases with a pap component were at higher risk of lymphatic involvement and showed a higher percentage of positive LNM. More attention should be paid to a pap component in EGC.
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Affiliation(s)
- Masau Sekiguchi
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan,
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Jeuck TLA, Wittekind C. Gastric carcinoma: stage migration by immunohistochemically detected lymph node micrometastases. Gastric Cancer 2015; 18:100-8. [PMID: 24550066 DOI: 10.1007/s10120-014-0352-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Accepted: 02/01/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Immunohistochemically detected micrometastases of the regional lymph nodes in previously pN0-classified gastric cancer have been incorporated in the TNM staging system. This study aims to determine the incidence of such micrometastases in gastric carcinoma and to investigate their impact on stage grouping and prognosis. METHODS Ninety-five patients with gastric carcinoma classified as pN0 by conventional histological examination were enrolled. All patients underwent gastric resection with regional lymphadenectomy between 2006 and 2010. A total of 2018 lymph nodes was obtained (median, 20 Lymph nodes) and immunohistostained with anti-pan cytokeratin antibody (KL1). RESULTS Micrometastases were detected in regional lymph nodes by immunohistostaining in 16 out of all 95 patients. Fourteen patients were upstaged by micrometastasis-positive regional lymph nodes. Three patients demonstrated lymph nodes with isolated tumor cells alone. A significantly higher incidence of micrometastases was observed in patients with diffuse histologic type (p = 0.007) and total gastrectomy (p = 0.007). When isolated tumor cells were also regarded as lymph node involvement, the recurrence rate was significantly higher for node-positive than for node-negative patients and for those younger than 70 years (33.3 and 6.7 %, respectively; p = 0.026; n = 39). Overall survival analysis revealed no significant difference between micrometastasis-positive and micrometastasis-negative patients. CONCLUSION Immunohistostaining of regional lymph nodes in node-negative gastric carcinoma patients leads to an increased detection of micrometastases with significant implications for the staging system. Although no impact on survival time was shown, the higher recurrence rate for node-positive patients younger than 70 years indicates a prognostic value of immunohistochemically detectable micrometastases.
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Affiliation(s)
- Theresa L A Jeuck
- Institute of Pathology, University Hospital Leipzig, Liebigstrasse 24, 04103, Leipzig, Germany,
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Lim JH, Lee DH, Shin CM, Kim N, Park YS, Jung HC, Song IS. Clinicopathological features and surgical safety of gastric cancer in elderly patients. J Korean Med Sci 2014; 29:1639-45. [PMID: 25469063 PMCID: PMC4248584 DOI: 10.3346/jkms.2014.29.12.1639] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 08/20/2014] [Indexed: 11/30/2022] Open
Abstract
Gastric cancer is one of the most common cancers, especially among the elderly. However little is known about gastric cancer in elderly patients. This study was designed to evaluate the specific features of gastric cancer in elderly patients. Medical records of 1,107 patients who had radical gastrectomy for gastric cancer between June 2005 and December 2009 were reviewed. They were divided into young (<65 yr, n=676), young-old (65-74 yr, n=332), and old-old age group (≥75 yr, n=99). Increased CA 19-9 (5.6%, 13.4%, 14.6%, P=0.001), advanced diseases (42.5%, 47.0%, and 57.6, P=0.014), and node metastasis (37.6%, 38.9%, 51.5%, P=0.029) were more common in the young-old and old-old age groups. There were no significant differences in Helicobacter pylori status (63.6%, 56.7%, 61.2%, P=0.324) between the three groups. Surgery-related complication rates were similar in the three groups (5.3%, 5.1%, 8.1%, P=0.497). Microsatellite instability (P<0.001) and p53 overexpression (P<0.001) were more common among the elderly. The elderly group had more synchronous tumors (7.5%, 10.2%, 17.2%; P=0.006). Surgery can be applied to elderly gastric cancer without significant risk of complications. However, considering the more advanced disease and synchronous tumors among the elderly, care should be taken while deciding the extent of surgery for elderly gastric cancer.
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Affiliation(s)
- Joo Hyun Lim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Korea
| | - In Sung Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Santoro R, Ettorre GM, Santoro E. Subtotal gastrectomy for gastric cancer. World J Gastroenterol 2014; 20:13667-13680. [PMID: 25320505 PMCID: PMC4194551 DOI: 10.3748/wjg.v20.i38.13667] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 06/10/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Although a steady decline in the incidence and mortality rates of gastric carcinoma has been observed in the last century worldwide, the absolute number of new cases/year is increasing because of the aging of the population. So far, surgical resection with curative intent has been the only treatment providing hope for cure; therefore, gastric cancer surgery has become a specialized field in digestive surgery. Gastrectomy with lymph node (LN) dissection for cancer patients remains a challenging procedure which requires skilled, well-trained surgeons who are very familiar with the fast-evolving oncological principles of gastric cancer surgery. As a matter of fact, the extent of gastric resection and LN dissection depends on the size of the disease and gastric cancer surgery has become a patient and “disease-tailored” surgery, ranging from endoscopic resection to laparoscopic assisted gastrectomy and conventional extended multivisceral resections. LN metastases are the most important prognostic factor in patients that undergo curative resection. LN dissection remains the most challenging part of the operation due to the location of LN stations around major retroperitoneal vessels and adjacent organs, which are not routinely included in the resected specimen and need to be preserved in order to avoid dangerous intra- and postoperative complications. Hence, the surgeon is the most important non-TMN prognostic factor in gastric cancer. Subtotal gastrectomy is the treatment of choice for middle and distal-third gastric cancer as it provides similar survival rates and better functional outcome compared to total gastrectomy, especially in early-stage disease with favorable prognosis. Nonetheless, the resection range for middle-third gastric cancer cases and the extent of LN dissection at early stages remains controversial. Due to the necessity of a more extended procedure at advanced stages and the trend for more conservative treatments in early gastric cancer, the indication for conventional subtotal gastrectomy depends on multiple variables. This review aims to clarify and define the actual landmarks of this procedure and the role it plays compared to the whole range of new and old treatment methods.
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Terazawa T, Iwasa S, Takashima A, Nishitani H, Honma Y, Kato K, Hamaguchi T, Yamada Y, Shimada Y. Impact of adding cisplatin to S-1 in elderly patients with advanced gastric cancer. J Cancer Res Clin Oncol 2013; 139:2111-6. [PMID: 24129809 DOI: 10.1007/s00432-013-1537-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2013] [Accepted: 10/04/2013] [Indexed: 01/09/2023]
Abstract
PURPOSE We retrospectively examined the efficacy and safety of S-1 alone or S-1 plus cisplatin (SP) for elderly patients with advanced gastric cancer because the benefit of adding cisplatin in these patients still remains unclear. PATIENTS AND METHODS Among 175 patients aged 70 years or older who received S-1 alone or SP as a first-line therapy between April 2000 and November 2010 at our institution, 104 patients who met eligibility criteria were examined. We investigated safety and efficacy of S-1 and SP. RESULTS Among these 104 patients, 73 patients received S-1 and 31 patients received SP. The median age was 75 years in the S-1 group and 74 years in the SP group. The response rate was 26.3 % in the S-1 group and 44.0 % in the SP group. Major grade 3 or higher adverse events were observed as follows (S-1 vs. SP): nausea (1.4 vs. 16.1 %), anorexia (16.4 vs. 41.9 %), neutropenia (4.1 vs. 35.5 %), and febrile neutropenia (0 vs. 9.7 %). The median overall survival (OS) was 10.4 months in the S-1 group and 17.8 months in the SP group. Treatment of SP and histology of intestinal type were detected as independent, good prognostic factors in multivariate analysis. CONCLUSION SP might improve OS with some added toxicity compared to S-1 alone in elderly patients with advanced gastric cancer.
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Affiliation(s)
- Tetsuji Terazawa
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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Liang YX, Deng JY, Guo HH, Ding XW, Wang XN, Wang BG, Zhang L, Liang H. Characteristics and prognosis of gastric cancer in patients aged ≥ 70 years. World J Gastroenterol 2013; 19:6568-6578. [PMID: 24151383 PMCID: PMC3801370 DOI: 10.3748/wjg.v19.i39.6568] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2013] [Revised: 07/28/2013] [Accepted: 08/04/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To elucidate the prognostic value of age for gastric cancer and identify the optimal treatment for elderly gastric cancer patients. METHODS We enrolled 920 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2007 in our center. Patients were categorized into three groups: younger group (age < 50 years), middle-aged group (50-69 years), and elderly group (≥ 70 years). Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed. The log-rank test was used to assess statistical differences between curves. Independent prognostic factors were identified by the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of age on survival at each stage. Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer. We analyzed the potential prognostic factors for patients aged ≥ 70 years. Finally, the impact of extent of lymphadenectomy and postoperative chemotherapy on survival for each age group was evaluated. RESULTS In the elderly group, there was a male predominance. At the same time, cancers of the upper third of the stomach, differentiated type, and less-invasive surgery were more common than in the younger or middle-aged groups. Elderly patients were more likely to have advanced tumor-node-metastasis (TNM) stage and larger tumors, but less likely to have distant metastasis. Although 5-year overall survival (OS) rate specific to gastric cancer was not significantly different among the three groups, elderly patients demonstrated a significantly lower 5-year OS rate than the younger and middle-aged patients (elderly vs middle-aged vs younger patients = 22.0% vs 36.6% vs 38.0%, respectively). In the TNM-stratified analysis, the differences in OS were only observed in patients with II and III tumors. In multivariate analysis, only surgical margin status, pT4, lymph node metastasis, M1 and sex were independent prognostic factors for elderly patients. The 5-year OS rate did not differ between elderly patients undergoing D1 and D2 lymph node resection, and these patients benefited little from chemotherapy. CONCLUSION Age ≥ 70 years was an independent prognostic factor for gastric cancer after gastrectomy. D1 resection is appropriate and postoperative chemotherapy is possibly unnecessary for elderly patients with gastric cancer.
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Tural D, Selçukbiricik F, Serdengeçti S, Büyükünal E. A comparison of patient characteristics, prognosis, treatment modalities, and survival according to age group in gastric cancer patients. World J Surg Oncol 2012; 10:234. [PMID: 23121731 PMCID: PMC3542166 DOI: 10.1186/1477-7819-10-234] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Accepted: 10/18/2012] [Indexed: 12/15/2022] Open
Abstract
Background The aim of this study was to investigate age-specific incidence rates and to compare disease stage, treatment, and survival according to age group in patients with gastric adenocarcinoma. Methods Gastric cancer patients treated at our hospital between 1999 and 2010 were retrospectively evaluated. We divided the cases into two subgroups: group 1 consisted of patients older than 70 years at the time of treatment, and group 2 included patients aged 70 years or younger. In all, 151 patients over 70 years of age and 715 patients age 70 years or younger were analyzed. Categorical and continuous variables were summarized using descriptive statistics and compared using statistical software. Overall survival rates were estimated via the Kaplan-Meier method. Results Median age at diagnosis was 58 years (range: 22 to 90 years). Between 1999 and 2002 the annual median age for patients aged older than70 years was 9.8%, which increased to 20% between 2007 and 2010. The one-year survival rate for patients with metastatic disease (stage IV) was 10.9% (95% CI: 8.9% to 12.9%) and 27.8% (95% CI: 17.3% to 38.2%) in groups 1 and 2, respectively (P = 0.015). The five-year survival rate for patients with non-metastatic disease (in whom curative surgery was performed) was 15.5% (95% CI = 12% to 19%) and 26.9% (95% CI = 25.9% to 27.9%) in groups 1 and 2, respectively (P = 0.03). There were no significant differences in gender, tumor localization in the stomach, tumor histology, perineural invasion (PNI), lymphovascular invasion (LVI), tumor stage, or type of surgery between the two groups. However, fewer of the patients in group 1 underwent adjuvant treatment (P = 0.02) and palliative chemotherapy (P = 0.007) than group 2 patients that were non-metastatic and metastatic at presentation, respectively. Conclusions Groups 1 and 2 were similar in terms of histopathological features and surgical modality; however, the survival rate was lower in group 1 than in group 2. The incidence of gastric cancer was higher in the patients older than 70 years of age. Additional randomized studies are needed to further assess the safety and clinical benefit of chemotherapy in gastric cancer patients older than70 years of age.
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Affiliation(s)
- Deniz Tural
- Department of Internal Medicine, Division of Medical Oncology, Cerrahpasa Medical School, Istanbul University, Istanbul, 34098, Turkey.
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Lu Z, Lu M, Zhang X, Li J, Zhou J, Gong J, Gao J, Li J, Zhang X, Li Y, Shen L. Advanced or metastatic gastric cancer in elderly patients: clinicopathological, prognostic factors and treatments. Clin Transl Oncol 2012; 15:376-83. [PMID: 23054754 DOI: 10.1007/s12094-012-0938-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2012] [Accepted: 08/30/2012] [Indexed: 01/29/2023]
Abstract
PURPOSE To analyze the clinicopathological features, prognostic factors, treatment efficacy and safety among elderly patients with advanced or metastatic gastric cancer. METHODS Three hundred and nineteen patients aged 65 years and older, diagnosed with advanced or metastatic gastric cancer, were followed and data were retrospectively collected, reviewed and analyzed. RESULTS The elderly patients carried specific clinicopathological characteristics. Body mass index (BMI), number of metastatic lesions, ascites, Karnofsky performance score (KPS), tumor differentiation grade, lactate dehydrogenase (LDH) level, local treatment, and chemotherapy were the independent prognostic factors. Serum LDH level was superior to the serum CEA level in the prognosis of advanced or metastatic gastric cancer in older patients. Cisplatin-based regimen, chemotherapy cycles, metastatic lesions, LDH level, and supraclavicular lymph node metastasis were the independent prognostic factors in 220 patients receiving chemotherapy. The toxicity was mild and tolerable. CONCLUSION KPS, BMI and a well-differentiated histopathology were factors favoring longer survival, whereas elevated serum LDH and a greater number of metastatic lesions were associated with poor prognosis among those elderly patients. Cisplatin-based chemotherapy provided survival benefits and mild toxicity.
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Affiliation(s)
- Z Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Beijing, 100142, China
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Hsu JT, Liu MS, Wang F, Chang CJ, Hwang TL, Jan YY, Yeh TS. Standard radical gastrectomy in octogenarians and nonagenarians with gastric cancer: are short-term surgical results and long-term survival substantial? J Gastrointest Surg 2012; 16:728-737. [PMID: 22350724 DOI: 10.1007/s11605-012-1835-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Accepted: 02/02/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND The high incidence of gastric cancer among the octogenarians and nonagenarians (oldest old; age ≥ 80 years) is emerging as an important management issue. Herein, we report both the short-term outcomes and long-term survival results of standard radical gastrectomy in this group of patients. METHODS This was a retrospective review of 164 oldest old patients (older group) and 2,258 younger patients (age <80 years; younger group) with gastric cancer who underwent curative resection between January 1994 and December 2006. Clinicopathologic data, long-term survival, and prognostic factors were analyzed. RESULTS Clinical tumor stage did not differ between the two groups at the time of diagnosis. Higher Charlson comorbidity index scores (≥ 5) were observed in the older group than in the younger group; this was associated with higher postoperative morbidity (P = 0.035) and in-hospital mortality rates (P = 0.015) in the older group. At a median follow-up of 37.8 months, the overall survival rate for the older group was lower than that for the younger group (P < 0.001). However, the cumulative incidence of gastric cancer-related deaths was comparable between the two groups. Nodal involvement and metastatic to retrieved lymph node ratio were the only independent predictors of survival in the older group. CONCLUSIONS Patients in the older group had a higher postoperative morbidity rate but comparable cancer-specific survival. Careful patient selection for gastrectomy is warranted in elderly patients, particularly those with high-grade nodal involvement.
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Affiliation(s)
- Jun-Te Hsu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5 Fushing Street, Kweishan Shiang, Taoyuan, 333, Taiwan
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Tokioka S, Umegaki E, Murano M, Takeuchi N, Takeuchi T, Kawakami K, Yoda Y, Kojima Y, Higuchi K. Utility and problems of endoscopic submucosal dissection for early gastric cancer in elderly patients. J Gastroenterol Hepatol 2012; 27 Suppl 3:63-9. [PMID: 22486874 DOI: 10.1111/j.1440-1746.2012.07075.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM Endoscopic submucosal dissection (ESD) is reported to be a safe and reliable procedure for the elderly, but these reports could have already had a bias at the time ESD was performed. However, the reports have not clearly stated the criteria of indications. In the present study, we retrospectively elucidated the usefulness and problems of ESD for early gastric cancer in elderly patients (≥ 65 years) in comparison with non-elderly patients. METHODS The subjects were selected from 412 consecutive patients with early gastric cancer (515 lesions) for which ESD was performed between June 2002 and February 2010. The following were used for analysis between groups: pre- and postoperative performance status (PS) of subjects, prevalence rates of pre-existing comorbidities, characteristics of lesions, treatment outcomes, durations of hospitalization, operating times, incidence rates of complications and durations of hospitalization, and postoperative hemorrhage rates, and duration of hospitalization in patients with anticoagulant therapy. RESULTS Of the lesions in the elderly, four patients (1.0%) were elderly with a PS of 3. The PS increased to six patients (1.6%) after the procedure. None of the non-elderly had a PS of 3 before or after the procedure. The ratio of patients with a pre-existing comorbidity was higher in the elderly than in the non-elderly. There were no differences between the two groups in the characteristics of the lesions, their duration of hospitalization, their operating times, or the incidence rates of complications. However, the elderly with perforations had a significantly longer hospitalization than the comparable non-elderly. The percentage of the patients taking anticoagulant drugs was significantly higher among the elderly. Of the patients on anticoagulant therapy, the duration of hospitalization tended to be longer in the elderly but no significant difference was found. None of the non-elderly with postoperative hemorrhage had received anticoagulant therapy. In the elderly with postoperative hemorrhage, 15.8% of the lesions were in those who had received anticoagulant therapy, indicating a significantly higher percentage of such lesions in the elderly group. CONCLUSION We conclude that ESD is useful in elderly patients because there is a similar risk as for the non-elderly if the approach is individualized, and the following are taken into consideration when making the final decision of performing ESD in an elderly patient: patients should have a PS of 0, 1, or 2; determine whether or not anticoagulant therapy can be discontinued and whether or not treatment can be performed reliably without complications.
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Affiliation(s)
- Satoshi Tokioka
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
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36
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Dittmar Y, Rauchfuss F, Götz M, Scheuerlein H, Jandt K, Settmacher U. Impact of clinical and pathohistological characteristics on the incidence of recurrence and survival in elderly patients with gastric cancer. World J Surg 2012; 36:338-345. [PMID: 22205105 DOI: 10.1007/s00268-011-1395-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Gastric cancer is one of the most frequent malignant tumors worldwide. Despite improvements in diagnostic procedures, as well as the introduction of multimodal treatment strategies, the overall prognosis remains poor. The role of gastric resection in elderly patients with gastric cancer has not been clearly defined as yet. The goal of the present study was to assess whether specific pathohistological features result in different outcomes for younger patients and elderly patients. METHODS A total of 272 patients with advanced gastric cancer treated surgically in our hospital between 1998 and 2009 were included in the study. Data were analyzed from a prospectively maintained database. RESULTS Median overall survival was 84 months in the younger subgroup and 37 months in the elderly subgroup (P = 0.038), whereas local recurrence occurred more frequently in younger patients (33% vs. 23%). We identified positive lymph nodes at the contralateral curvature, perilymphonodular tumor cells, and positive lymph node conglomerates as strong negative prognostic factors. There were few pathohistological characteristics that affected survival and the incidence of tumor recurrence differently in elderly and younger patients. Although only a few elderly patients underwent chemotherapy plus gastric resection (7% vs. 28% of the younger patients), there was a trend toward longer survival for those who received multimodal treatment. CONCLUSIONS Our results suggest that there is no tumor-related prognostic difference between young and elderly patients that would preclude radical surgery in elderly patients, as long as they are generally fit for surgery.
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Affiliation(s)
- Yves Dittmar
- Department of General, Visceral and Vascular Surgery, University of Jena, Erlanger Allee 101, 07740, Jena, Germany.
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Kim HS, Lee H, Jeung HC, Noh SH, Chung HC, Roh JK, Nam CM, Rha SY. Advanced detection of recent changing trends in gastric cancer survival: up-to-date comparison by period analysis. Jpn J Clin Oncol 2012; 41:1344-50. [PMID: 22128316 DOI: 10.1093/jjco/hyr153] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVE To establish a comprehensive cancer treatment and prevention policy, data collection should be performed in a timely manner, and survival analysis needs to reflect changes in treatment strategy. Therefore, we introduced the concept of period analysis for gastric cancer, the most prevalent cancer in Korea. We estimated 5- and 10-year survival trend of gastric cancer, based on data from the Yonsei Cancer Center Tumor Registry between 1990 and 2004. METHODS We compared the differences in survival between cohort, complete and period analyses for two different periods, 1995-99 and 2000-04. RESULTS A total of 11 724 cases were included. The median age of cancer diagnosis gradually increased over time, and more patients were diagnosed with Stage I disease in recent years. In the basic comparison of three estimated analytic methods (cohort, complete and period), period analysis (45.8%) was most similar to the actual 5-year observed survival rate (48.5%), when compared with cohort (43.6%) and complete (44.8%) analyses. When we compared survival between different 10-year periods (1990-99 and 1995-2004), period analysis demonstrated a greater difference than complete analysis (9.0 versus 3.9%). Subgroup analysis indicated that the survival improvement was determined by period analysis, and it was more pronounced for the age group <74 years and in Stages III-IV patients. CONCLUSIONS We observed that period analysis demonstrates the most similar results to the actual observed survival and is, therefore, a useful method to derive precise cancer survival in gastric cancer. This information is useful to understand survival differences that are influenced by changing treatment strategy.
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Affiliation(s)
- Hyo Song Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 120-752, Korea
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Sasaki S, Yashima K, Hayashi A, Takeda Y, Yasugi A, Koda M, Kawaguchi K, Harada K, Ito H, Murawaki Y. Clinicopathological and patient characteristics of early gastric neoplasia endoscopically resected with loss of Mlh1 expression. Oncol Lett 2010; 2:217-222. [PMID: 22866067 DOI: 10.3892/ol.2010.231] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2010] [Accepted: 12/06/2010] [Indexed: 02/06/2023] Open
Abstract
Hypermethylation of the promoter region of the MLH1 gene leads to loss of Mlh1 protein expression and plays a key role in the development of gastric cancer. Little is known about the association between Mlh1 expression and the clinicopathological and patient characteristics in early gastric neoplasia, particularly in endoscopically resected tumors. Immunohistochemistry was used to examine Mlh1 expression in 140 early gastric neoplasias obtained by endoscopic resection and comprising 31 gastric adenomas (GAs) and 109 early gastric cancers (EGCs), and compared them to corresponding clinicopathological and patient data. P53 expression and phenotypic profiles were also analyzed. The rate of reduced Mlh1 expression and P53 overexpression was 9.6 and 6.5% in GAs, and 27.5 and 27.5% in EGCs, respectively. In elderly patients (≥65 years of age), the aberrant expression of Mlh1 in EGCs was more significant in female than in male patients (59.9 vs. 29.8%; P=0.016). In addition, the frequency of aberrant Mlh1 expression in EGCs increased significantly in patients with oncological family histories and elevated gross type (P=0.033 and P=0.04, respectively). Moreover, a significant correlation was observed among aberrant Mlh1, P53-negative and HGM expression. The present findings suggest that loss of Mlh1 expression is associated with age, gender, oncological family history and tumor growth pattern in EGC. Patient and tumor characteristics are key factors in the screening, surveillance and diagnosis of early gastric neoplasia, particularly in elderly individuals.
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Affiliation(s)
- Shuji Sasaki
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
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Arai T, Kasahara I, Sawabe M, Honma N, Aida J, Tabubo K. Role of methylation of the hMLH1 gene promoter in the development of gastric and colorectal carcinoma in the elderly. Geriatr Gerontol Int 2010; 10 Suppl 1:S207-12. [PMID: 20590835 DOI: 10.1111/j.1447-0594.2010.00590.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The occurrence of malignant neoplasms increases with advancing age. Although aging and carcinogenesis are basically different processes, they share phenomena such as the accumulation of DNA damage and abnormal proteins. Recent advances in molecular biology have shown an accumulation of genetic and epigenetic changes in both aging and carcinogenesis, as well as the alteration of metabolism, immunosenescence and shortened telomeres. DNA methylation is a representative epigenetic phenomenon and is frequently involved in controlling gene functions during development and tumorigenesis. We herein focused on methylation of genes in the development of gastrointestinal carcinomas in the elderly. The proportion of gastric and colorectal carcinomas with hypermethylation of the hMLH1 promoter increases with age, reaching 25-30% of all carcinomas of the stomach and large intestine in elderly patients. These tumors have clinicopathological and molecular characteristics such as loss of hMLH1 expression, microsatellite instability, poorly differentiated histology, peritumoral inflammatory cell infiltration, low incidence of lymph node metastasis and favorable prognosis. However, methylation-related carcinogenesis accounts for up to approximately one-third of tumors, and other mechanisms; for example chromosomal instability as a result of telomere dysfunction, are responsible for the development of most carcinomas in the elderly.
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Affiliation(s)
- Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
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Saif MW, Makrilia N, Zalonis A, Merikas M, Syrigos K. Gastric cancer in the elderly: an overview. Eur J Surg Oncol 2010; 36:709-17. [PMID: 20542657 DOI: 10.1016/j.ejso.2010.05.023] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2009] [Revised: 01/27/2010] [Accepted: 05/17/2010] [Indexed: 12/13/2022] Open
Abstract
AIMS Gastric cancer in the elderly represents a distinct entity with specific clinicopathological characteristics and the majority of affected patients belong to this age group. Subtotal or total gastrectomy with radical lymph node dissection, adjuvant chemoradiotherapy or perioperative chemotherapy represent the only potentially curative treatment options and seem to be performed with acceptable morbidity and mortality rates in selected elderly patients. Published research is very limited due to the strict selection and under-representation of elderly patients in clinical trials. A review of current recommendations and practice was performed. METHODS A comprehensive literature review was performed searching Medline for articles published since 1974, using "gastric cancer", "elderly" and "treatment" as keywords. OBSERVATIONS The data suggest that elderly patients that fulfill the inclusion criteria of clinical trials experience the same advantages and toxicities from chemotherapy as younger patients. Fit elderly patients with operable gastric cancer should be candidates for the standard surgical resection provided that preoperative comorbidities are taken into account. Perioperative chemotherapy or postoperative chemoradiotherapy should be added in case of locally advanced disease. Palliative systemic chemotherapy seems to prolong survival in recurrent and metastatic disease. CONCLUSIONS Chronological age alone is not sufficient reason to withhold curative or palliative treatment from an elderly gastric cancer patient. Performance status does not suffice in order to estimate the general condition of elderly patients and cofactors regarding their functional, social and mental status have to be considered.
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Affiliation(s)
- M W Saif
- Department of Clinical Oncology, Yale University School of Medicine New Haven, CT, USA
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Tanaka N, Katai H, Taniguchi H, Saka M, Morita S, Fukagawa T, Gotoda T. Trends in characteristics of surgically treated early gastric cancer patients after the introduction of gastric cancer treatment guidelines in Japan. Gastric Cancer 2010; 13:74-7. [PMID: 20602192 DOI: 10.1007/s10120-009-0536-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Accepted: 12/02/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND The gastric cancer treatment guidelines (Guidelines) of the Japanese Gastric Cancer Association allow endoscopic treatment and a modified gastrectomy for the treatment of early gastric cancer (EGC). Endoscopic treatment is indicated for EGC with a minimal chance of nodal metastasis. Consequently, surgeons will likely treat an increasing number of EGC patients with greater chance of nodal metastasis using a reduced extent of lymphadenectomy. The aim of this study was to investigate the trends in characteristics and long-term oncological outcomes of surgically treated EGC patients after the introduction of the Guidelines. METHODS Between 2001 and 2003, 696 patients underwent a gastrectomy according to the Guidelines. These 696 patients (the Guidelines group) were retrospectively compared with 635 patients (the control group) who had undergone a gastrectomy between 1991 and 1995 (before the introduction of the Guidelines). RESULTS The incidence of nodal metastasis in mucosal cancers was higher in the Guidelines group than in the control group (6.5% vs 2.6%). The proportion of D2 or greater extended lymphadenectomy in the Guidelines group was lower than that in the control group (29.7% vs 62.5%). Nevertheless, the 5-year survival rate in the Guidelines group was similar to that in the control group (94.2% vs 92.3%). CONCLUSION Surgeons treated more cases of mucosal cancer with nodal metastasis after the introduction of the Guidelines. The long-term oncological outcomes for patients with EGC remained excellent. So far, the Guidelines for the treatment of EGC appear acceptable.
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Affiliation(s)
- Norimitsu Tanaka
- Gastric Surgery Division, National Cancer Center Hospital, Chuo-ku, Tokyo, 104-0045, Japan
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Ha TK, An JY, Youn HG, Choi MG, Noh JH, Sohn TS, Kim S. Missed lesions in synchronous multiple gastric cancer. ANZ J Surg 2010; 80:276-9. [DOI: 10.1111/j.1445-2197.2009.05108.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Nakamura Y, Migita T, Hosoda F, Okada N, Gotoh M, Arai Y, Fukushima M, Ohki M, Miyata S, Takeuchi K, Imoto I, Katai H, Yamaguchi T, Inazawa J, Hirohashi S, Ishikawa Y, Shibata T. Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression. Int J Cancer 2009; 125:1859-67. [PMID: 19588488 DOI: 10.1002/ijc.24538] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Krüppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a significant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures.
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Affiliation(s)
- Yu Nakamura
- Cancer Genomics Project, National Cancer Center Research Institute, Tokyo 104-0045, Japan
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Nitta T, Egashira Y, Akutagawa H, Edagawa G, Kurisu Y, Nomura E, Tanigawa N, Shibayama Y. Study of clinicopathological factors associated with the occurrence of synchronous multiple gastric carcinomas. Gastric Cancer 2009; 12:23-30. [PMID: 19390928 DOI: 10.1007/s10120-008-0493-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2008] [Accepted: 11/20/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND Multiple gastric carcinomas often arise in gastric mucosa with chronic gastritis, particularly severe intestinal metaplasia. In regard to such characteristics, several clinicopathological risk factors for multiple carcinomas have been reported, but no clinically useful criteria are available at present for assessing the onset of multiple gastric carcinomas. If the risk for multiple gastric carcinomas could be accurately assessed, efficient and accurate surveillance could be performed following minimally invasive therapies. METHODS In the present study, we investigated clinicopathological differences between 94 cases of multiple early gastric carcinomas and 285 cases of solitary early gastric carcinoma. We tested 379 specimens of gastric carcinomas that had been surgically resected at the Department of General and Gastroenterological Surgery of Osaka Medical College, Japan, from April 1999 to December 2006. RESULTS Univariate analysis of clinicopathological factors in the present study showed that multiple gastric carcinomas were significantly correlated to old age (> or =65 years), well- and moderately differentiated histological type, mucin phenotype (intestinal type), distribution of atrophic mucosa in the stomach (severe), degree of intestinal metaplasia in the surrounding mucosa (severe), and heterotopic glandular cysts. Multivariate analysis using the stepwise method identified age (> or =65 years) and degree of intestinal metaplasia in the surrounding mucosa (severe) as significant independent risk factors for multiple gastric carcinomas. CONCLUSION While other studies have shown risk factors for multiple gastric carcinomas, the present study is unique in showing risk assessment criteria based on a combination of risk factors for multiple gastric carcinomas.
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Butte JM, Duarte I, Crovari F, Guzmán S, Llanos O. [Gastric cancer in patients older than 75 years. Surgical treatment and long-term survival]. Cir Esp 2008; 82:341-5. [PMID: 18053503 DOI: 10.1016/s0009-739x(07)71744-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
INTRODUCTION The characteristics and results of radical gastrectomy for gastric cancer in elderly patients are controversial. Aim. To analyze the clinicopathologic characteristics and the results of gastrectomy for cancer in a group of patients > or = 75 year old. MATERIAL AND METHOD A series of 442 patients who underwent surgery for gastric cancer was divided into group A (< 75 years old) and group B (> or = 75 years old). The clinicopathologic characteristics, results of gastrectomy, and long-term survival were compared. RESULTS The mean age was 62 +/- 13 years. There were 361 patients in group A and 81 patients in group B. Tumoral location in the upper third of the stomach was more frequent in group A than in group B (36.8% vs 24.7%), while localization in the lower third of the stomach was more frequent in group B than in group A (50.6% vs 29.4%) (p < 0.05). Total gastrectomy was performed in 66% of patients in group A and in 38% of those in group B (p < 0.05); 27.3 +/- 3.5 nodes were resected in group A and 19.5 +/- 0.7 in group B (p < 0.05). No differences were found in the frequency of complications (16%) or in overall operative mortality between the two groups. However, mortality in total gastrectomy was higher in group B (6.4%) than in group A (3.8%) (p < 0.05). No differences in 5-year survival were found between the two groups (44.3% in group A and 44.4% in group B). CONCLUSIONS In patients aged more than 75 years old, tumors were more frequently located in the distal third of the stomach. Age above 75 years does not seem to be a prognostic factor and long-term results depend more on disease stage.
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Affiliation(s)
- Jean M Butte
- Departamento de Cirugía Digestiva, División de Cirugía, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
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Arai T, Sawabe M, Hosoi T, Tanaka N. Role of DNA repair systems in malignant tumor development in the elderly. Geriatr Gerontol Int 2008; 8:65-72. [DOI: 10.1111/j.1447-0594.2008.00450.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Arai T, Takubo K. Clinicopathological and molecular characteristics of gastric and colorectal carcinomas in the elderly. Pathol Int 2007; 57:303-14. [PMID: 17539960 DOI: 10.1111/j.1440-1827.2007.02101.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The occurrence of malignant neoplasms increases with advancing age. Although aging and carcinogenesis are basically different processes, there are phenomena common to each such as accumulation of DNA damage and abnormal proteins. Gastric and colorectal carcinomas are representative tumors in which the prevalence and the number of patients increase significantly with age. Compared with gastric and colorectal cancers occurring in younger patients, those occurring in older patients have clinicopathological differences in tumor location, gender distribution, histological type, histological diversity, multiplicity, incidence of lymph node metastasis, and prognosis. In the elderly there are peculiar types of carcinoma such as medullary-type poorly differentiated colorectal adenocarcinoma and solid-type poorly differentiated gastric adenocarcinoma, both of which occur in older women. Methylation, apoptosis, and telomere dysfunction play important roles in the development of gastric and colorectal cancers in the elderly.
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Affiliation(s)
- Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Sakaecho, Tokyo, Japan.
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Gretschel S, Estevez-Schwarz L, Hünerbein M, Schneider U, Schlag PM. Gastric cancer surgery in elderly patients. World J Surg 2006; 30:1468-74. [PMID: 16850149 DOI: 10.1007/s00268-005-0633-5] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND To investigate the value of individual risk-adapted therapy in geriatric patients, we performed a consecutive analysis of 363 patients undergoing potentially curative surgery for gastric cancer. PATIENTS AND METHODS All patients underwent extensive preoperative workup to assess surgical risk. The following criteria were evaluated in 3 age groups (<60 years, 60-75 years, and >75 years): comorbidity, tumor characteristics, type of resection, postoperative morbidity and mortality, recurrence rate, overall survival, and disease-free survival. RESULTS There was an increased rate of comorbidity in the higher age groups (51% vs 76% vs 83%; P<0.05). Cardiovascular and pulmonary diseases were most common. There was a decrease in the rate of both total gastrectomy (74%, 54%, 46%; P<0.05) and D2 lymphadenectomy (78%, 53%, 31%; P<0.05). The 30-day mortality in the 3 age groups was 0%, 1%, and 8%, respectively (P<0.05). There was only a slight difference in tumor recurrence rate (35%, 37%, and 27%; P=0.437), with no significant difference in 5-year cancer-related survival (61%, 53%, 61%; P=0.199). CONCLUSIONS Patient selection and risk-adapted surgery in elderly patients can result in acceptable therapeutic results comparable to younger patients. Limited surgery in elderly gastric cancer patients with high comorbidity does not necessarily compromise oncological outcome.
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Affiliation(s)
- Stephen Gretschel
- Department of Surgery and Surgical Oncology, Charité, University Medicine Berlin, Campus Buch, Robert-Rössle-Cancer Hospital, HELIOS Klinikum, Berlin, Germany
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Matsukawa Y, Semba S, Kato H, Ito A, Yanagihara K, Yokozaki H. Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer. Cancer Sci 2006; 97:484-91. [PMID: 16734726 PMCID: PMC11159019 DOI: 10.1111/j.1349-7006.2006.00203.x] [Citation(s) in RCA: 176] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Overexpression of the enhancer of zeste homolog 2 (EZH2) protein, a known repressor of gene transcription, has been reported to be associated with biological malignancy of prostate cancer and several other cancers. The purpose of this study was to examine the expression of EZH2 and analyze its relationship with the clinicopathological features of human gastric cancers. Expression levels of EZH2 mRNA and protein were examined in 13 gastric cancer cell lines and in 83 surgically removed human gastric cancer tissues. Immunohistochemical analysis of the 83 tissue samples and corresponding non-cancerous gastric mucosa showed that EZH2 was more highly expressed in the cancerous than in the non-cancerous tissues, and the expression levels of EZH2 were highly correlated with tumor size, depth of invasion, vessel invasion, lymph node metastasis and clinical stages. Univariate analysis of survival rate calculated by the Kaplan-Meier method revealed that gastric cancer patients with high-level EZH2 expression had poorer prognosis than those expressing no or low levels of EZH2 (P = 0.0271). These findings suggest that overexpression of EZH2 may contribute to the progression and oncogenesis of human gastric cancers, and thus immunohistochemical study of EZH2 expression may serve as a new biomarker for predicting the prognosis of gastric cancers.
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Affiliation(s)
- Yasuko Matsukawa
- Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
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Gasparini G, Inelmen EM, Enzi G, Santoro C, Sergi G, Cardin F, Terranova O. Clinical and prognostic aspects of gastric carcinoma in the elderly. J Gastrointest Surg 2006; 10:395-401. [PMID: 16504885 DOI: 10.1016/j.gassur.2005.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2005] [Revised: 07/06/2005] [Accepted: 07/06/2005] [Indexed: 02/06/2023]
Abstract
The aim of the present study was to analyze the influence of various factors on the prognosis for elderly patients with gastric carcinoma. Forty-eight patients aged > or =65 years admitted to Padova General Hospital were divided into two groups by age (<75 or >75 years). They all had a histologically confirmed diagnosis of gastric adenocarcinoma. Information on their clinicopathological characteristics was collected from the Padova Hospital medical records. On univariate analysis, significant prognostic factors in the two age groups were gender, stage, histotype (Lauren's intestinal type), Charlson index, and type of surgery (curative resection, palliative resection, and no surgery). On multivariate analysis, independent prognostic factors were the Charlson index, tumor stage, and age group. The 52-month survival rate was 72.7% for females and 12.5% for males for patients > or =75 years (P = 0.01), while for the whole series of patients it was 67.5% for females and 29.9% for males (P = 0.003). The 17-month survival rate was 55.6% for surgically treated patients and 0% for the untreated cases in stage 4 (P = 0.03). Gastric cancer should be treated with conventional surgery even in the very elderly, since the survival rate for this age group does not differ significantly from the figures for younger patients.
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Affiliation(s)
- Giulia Gasparini
- Department of Medical and Surgical Sciences, Geriatrics Section, University of Padua, Ospedale Giustinaneo 2 piano, Via Giustiniani 2, 35100 Padua, Italy
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