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Qu W, Li L, Ma J, Li Y. Screening high-risk individuals for primary gastric carcinoma: evaluating overall survival probability score in the presence and absence of lymphatic metastasis post-gastrectomy. World J Surg Oncol 2024; 22:196. [PMID: 39054533 PMCID: PMC11271195 DOI: 10.1186/s12957-024-03481-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 07/17/2024] [Indexed: 07/27/2024] Open
Abstract
OBJECTIVE The aim of this study was to develop and validate prognostic models for predicting overall survival in individuals with gastric carcinoma, specifically focusing on both negative and positive lymphatic metastasis. METHODS A total of 1650 patients who underwent radical gastric surgery at Shanxi Cancer Hospital between May 2002 and December 2020 were included in the analysis. Multiple Cox Proportional Hazards analysis was performed to identify key variables associated with overall survival in both negative and positive lymphatic metastasis cases. Internal validation was conducted using bootstrapping to assess the prediction accuracy of the models. Calibration curves were used to demonstrate the accuracy and consistency of the predictions. The discriminative abilities of the prognostic models were evaluated and compared with the 8th edition of AJCC-TNM staging using Harrell's Concordance index, decision curve analysis, and time-dependent receiver operating characteristic curves. RESULTS The nomogram for node-negative lymphatic metastasis included variables such as age, pT stage, and maximum tumor diameter. The C-index for this model in internal validation was 0.719, indicating better performance compared to the AJCC 8th edition TNM staging. The nomogram for node-positive lymphatic metastasis included variables such as gender, age, maximum tumor diameter, neural invasion, Lauren classification, and expression of Her-2, CK7, and CD56. The C-index for this model was 0.674, also outperforming the AJCC 8th edition TNM staging. Calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis for both nomograms demonstrated excellent prediction ability. Furthermore, significant differences in prognosis between low- and high-risk groups supported the models' strong risk stratification performance. CONCLUSION This study provides valuable risk stratification models for lymphatic metastasis in gastric carcinoma, encompassing both node-positive and negative cases. These models can help identify low-risk individuals who may not require further intervention, while high-risk individuals can benefit from targeted therapies aimed at addressing lymphatic metastasis.
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Affiliation(s)
- Wenqing Qu
- Hepatobiliary, Pancreatic and Gastrointestinal Surgery, Shanxi Hospital Affiliated to Carcinoma Hospital, Chinese Academy of Medical Sciences, Shanxi Province Carcinoma Hospital, Carcinoma Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, P.R. China
| | - Ling Li
- Shanxi Medical University, 030013, Taiyuan, Shanxi, P.R. China
| | - Jinfeng Ma
- Hepatobiliary, Pancreatic and Gastrointestinal Surgery, Shanxi Hospital Affiliated to Carcinoma Hospital, Chinese Academy of Medical Sciences, Shanxi Province Carcinoma Hospital, Carcinoma Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, P.R. China.
| | - Yifan Li
- Hepatobiliary, Pancreatic and Gastrointestinal Surgery, Shanxi Hospital Affiliated to Carcinoma Hospital, Chinese Academy of Medical Sciences, Shanxi Province Carcinoma Hospital, Carcinoma Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, P.R. China.
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Díaz Del Arco C, Ortega Medina L, Estrada Muñoz L, Molina Roldán E, García Gómez de Las Heras S, Fernández Aceñero MJ. Prognostic role of the number of resected and negative lymph nodes in Spanish patients with gastric cancer. Ann Diagn Pathol 2023; 67:152209. [PMID: 37689040 DOI: 10.1016/j.anndiagpath.2023.152209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/01/2023] [Accepted: 09/03/2023] [Indexed: 09/11/2023]
Abstract
INTRODUCTION Lymph node (LN) involvement is one of the most critical prognostic factors in resected gastric cancer (GC). Some analyses, mainly conducted in Asian populations, have found that patients with a higher number of total lymph nodes (NTLN) and/or negative lymph nodes (NNLN) have a better prognosis, although other authors have failed to confirm these results. MATERIALS AND METHODS Retrospective study including all patients with GC resected in a tertiary hospital in Spain between 2001 and 2019 (n = 315). Clinicopathological features were collected and patients were categorized according to the NTLN and the NNLN. Statistical analyses were performed. RESULTS Mean NNLN was 17. The NNLN was significantly related to multiple clinicopathological variables, including recurrence and tumor-related death. The classification based on the NNLN (N1: ≥16, N2: 8-15, N3: ≤7) effectively stratified the entire cohort into three distinct prognostic groups and maintained its prognostic value within both the pN0 and pN+ patient subsets. Furthermore, it was an independent prognostic indicator for both overall and disease-free survival. Conversely, the mean NTLN was 21.9. Patients with ≤16 LN retrieved exhibited distinct clinicopathological features compared to those with >16 LN, but no significant differences were observed in terms of recurrence or disease-associated death. The application of alternative cut-off points for NTLN (10, 20, 25, 30, and 40) showed no prognostic significance. CONCLUSIONS In Spanish patients with resected GC the NNLN hold prognostic significance, while the NTLN does not appear to be prognostically significant. Incorporating the NNLN into GC staging may enhance the accuracy of the TNM system.
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Affiliation(s)
- Cristina Díaz Del Arco
- Pathology Teaching Unit, Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, Madrid, Spain; Department of Pathology, Hospital Clínico San Carlos; Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
| | - Luis Ortega Medina
- Pathology Teaching Unit, Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, Madrid, Spain; Department of Pathology, Hospital Clínico San Carlos; Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Lourdes Estrada Muñoz
- Department of Basic Medical Sciences, School of Medicine, Rey Juan Carlos University, Móstoles, Madrid, Spain; Department of Pathology, Rey Juan Carlos Hospital, Móstoles, Madrid, Spain
| | - Elena Molina Roldán
- Department of Pathology, Hospital Clínico San Carlos; Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Biobank, Hospital Clínico San Carlos, Madrid, Spain
| | | | - M Jesús Fernández Aceñero
- Pathology Teaching Unit, Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, Madrid, Spain; Department of Pathology, Hospital Clínico San Carlos; Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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Lopez J, Reategui ML, Rooper L, Koch W, Fakhry C, Mydlarz W, Tan M, Eisele DW, Mandal R, Vosler P, Gourin CG. Node Count as a Quality Indicator in Surgically Treated Mucosal Head and Neck Squamous Cell Cancer. Laryngoscope 2023; 133:2160-2165. [PMID: 36197005 DOI: 10.1002/lary.30429] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/12/2022]
Abstract
INTRODUCTION A yield of ≥18 nodes from neck dissection has been shown to be associated with improved locoregional recurrence rates and survival. We sought to determine factors associated with lymph node yields below this threshold. MATERIALS AND METHODS A retrospective review of patients who underwent neck dissection as part of definitive surgical treatment for mucosal head and neck squamous cell carcinoma (SCC) between January 2015 and December 2018 at an academic tertiary referral center was performed. Patients with a history of prior radiation or neck dissection were excluded. RESULTS There were 412 neck dissections performed in 323 patients. Specimens containing <18 nodes decreased from 16.2% in 2015-2016 to 7.4% of neck dissections in 2017-2018. The proportion of neck dissections removing <3 levels decreased from 9.1% of neck dissections in 2015-2016 to 4.0% in 2017-2018. Multivariable regression analysis demonstrated that dissection of ≥3 levels (OR = 0.2 [0.1-0.4]) and neck dissection in 2017-2018 compared to 2015-2016 (OR = 0.4 [0.2-0.8]) were significantly associated with a lower odds of <18 nodes. Stage, site, race, sex, human papillomavirus status, positive nodes, surgeon volume, and pathologist volume were not associated with neck dissection specimens with <18 nodes, after controlling for all other variables. CONCLUSIONS Increased recognition of the importance of node count as a quality indicator, and the extent of neck dissection is associated with increased nodal yield from neck dissection. These data suggest that node count can be used as a quality measure of neck dissection for mucosal SCC. LEVEL OF EVIDENCE 4 Laryngoscope, 133:2160-2165, 2023.
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Affiliation(s)
- Joseph Lopez
- Department of Plastic & Reconstructive Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Maria Laura Reategui
- Department of Plastic & Reconstructive Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Lisa Rooper
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Wayne Koch
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Carole Fakhry
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Wojtech Mydlarz
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Marietta Tan
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - David W Eisele
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Rajarsi Mandal
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Peter Vosler
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Christine G Gourin
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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Zeng Y, Cai F, Wang P, Wang X, Liu Y, Zhang L, Zhang R, Chen L, Liang H, Ye Z, Deng J. Development and validation of prognostic model based on extragastric lymph nodes metastasis and lymph node ratio in node-positive gastric cancer: a retrospective cohort study based on a multicenter database. Int J Surg 2023; 109:794-804. [PMID: 36999785 PMCID: PMC10389378 DOI: 10.1097/js9.0000000000000308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 02/14/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND Regional lymph node metastasis (LNM) is a competent and the most intensive predictor for the prognostic evaluation of patients after curative surgery. This study is based on the databases of two large medical centers in North and South China. It aims to establish a prognostic model based on extragastric LNM (ELNM) and lymph node ratio (LNR) in node-positive gastric cancer (GC). METHODS Clinical data of 874 GC patients with pathologically confirmed LNM in a large medical center in southern China, were included as the training cohort. In addition, the clinical data of 674 patients with pathologically confirmed LNM from a large medical center in northern China were used as the validation cohort. RESULTS In the training cohort, a modified N staging system (mNstage) based on ELNM and LNR was established; it has a significantly higher prognostic accuracy than the pN, LNR and ELNM staging system (Akaike Information Criterion, pN stage vs. LNR stage vs. ELNM stage vs. mN stage=5498.479 vs. 5537.815 vs. 5569.844 vs. 5492.123; Bayesian Information Criterion, pN stage vs. LNR stage vs. ELNM stage vs. mN stage=5512.799 vs. 5547.361 vs. 5574.617 vs. 5506.896; likelihood-ratio χ2 , pN stage vs. LNR stage vs. ELNM stage vs. mN stage=177.7 vs. 149.8 vs. 115.79 vs. 183.5). In the external validation, mNstage also has higher prognostic accuracy than the pN, LNR and ELNM staging system. Cox multivariate regression analysis showed that age, mNstage, pT stage, and perineural invasion were independent factors. A nomogram model was established according to the four factors (age, mNstage, pT stage, and perineural invasion). The nomogram model was greater than the traditional tumor-node-metastasis (TNM) staging in the training cohort [1-year area under the curve (AUC), American Joint Commission for Cancer (AJCC) 8th TNM vs. nomogram=0.692 vs. 0.746, 3-year AUC: AJCC 8th TNM vs. nomogram=0.684 vs. 0.758, 5-year AUC: AJCC 8th TNM vs. nomogram=0.725 vs. 0.762]. In the external validation, the nomogram also showed better prognostic value and greater prediction accuracy than the traditional TNM staging. CONCLUSION The prognostic model based on ELNM and LNR has good prognostic prediction in patients with node-positive GC.
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Affiliation(s)
- Yi Zeng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
- Department of Gastrointestinal Surgical Oncology,Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital , Fuzhou, Fujian, China
| | - Fenglin Cai
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Pengliang Wang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Xinyu Wang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Yong Liu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Li Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Rupeng Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Luchuan Chen
- Department of Gastrointestinal Surgical Oncology,Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital , Fuzhou, Fujian, China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
| | - Zaisheng Ye
- Department of Gastrointestinal Surgical Oncology,Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital , Fuzhou, Fujian, China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin’s Clinical Research Center for Cancer, Tianjin
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Zeng Y, Chen LC, Ye ZS, Deng JY. Examined lymph node count for gastric cancer patients after curative surgery. World J Clin Cases 2023; 11:1930-1938. [PMID: 36998963 PMCID: PMC10044965 DOI: 10.12998/wjcc.v11.i9.1930] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/29/2023] [Accepted: 02/21/2023] [Indexed: 03/16/2023] Open
Abstract
Lymph node (LN) metastasis is the most common form of metastasis in gastric cancer (GC). The status and stage of LN metastasis are important indicators that reflect the progress of GC. The number of LN metastases is still the most effective index to evaluate the prognosis of patients in all stages of LN metastasis. Examined LN (ELN) count refers to the number of LNs harvested from specimens by curative gastrectomy for pathological examination. This review summarizes the factors that influence ELN count, including individual and tumor factors, intraoperative dissection factors, postoperative sorting factors, and pathological examination factors. Different ELN counts will lead to prognosis-related stage migration. Fine LN sorting and regional LN sorting are the two most important LN sorting technologies. The most direct and effective way to harvest a large number of LNs is for surgeons to perform in vitro fine LN sorting.
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Affiliation(s)
- Yi Zeng
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
| | - Lu-Chuan Chen
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
| | - Zai-Sheng Ye
- Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
| | - Jing-Yu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300202, China
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Li J, Xu Y, Zhang J, Wang S, Wang X, Guo H, Miao G. Prognostic value of the nodal yield in oral squamous cell carcinoma: a systematic review and meta-analysis. Expert Rev Anticancer Ther 2023; 23:339-345. [PMID: 36645663 DOI: 10.1080/14737140.2023.2168648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVES To systematically evaluate the prognostic value of the nodal yield in oral squamous cell carcinoma by meta-analysis. METHODS The meta-analysis was adherence to PRISMA. We searched MEDLINE, Embase, and Cochrane for studies published up to 20 April 2022. We collected evidences from observational studies regarding nodal yield in oral squamous cell carcinoma, and investigated its prognostic value by the routine methods of meta-analysis. RESULTS From seven studies, there was no significant impact of the lymph node yield on overall survival among patients with oral squamous cell carcinoma cases and <18 lymph nodes (hazard ratio (HR) = 1.019, 95% confidence interval (CI) = 0.786-1.320, p = 0.887), with significant heterogeneity (I2 = 80%). The pooled result indicated that a > 18-lymph node yield was a favorable prognostic factor (HR = 0.786, 95%CI = 0.646-0.956, p = 0.016; I2 = 39%). The lymph node yield was not associated with disease-specific survival (HR = 1.594, 95%CI = 0.996-2.552, p = 0.052; I2 = 81%) or disease-free survival (HR = 1.508, 95%CI = 0.924-2.460, p = 0.100; I2 = 41%). CONCLUSION A lymph node yield of ≥18 lymph nodes might be a favorable prognostic factor for the overall survival of patients with oral squamous cell carcinoma.
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Affiliation(s)
- Jiajia Li
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
| | - Yubo Xu
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
| | - Jie Zhang
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
| | - Shaohai Wang
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
| | - Xiaoyu Wang
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
| | - Huayan Guo
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
| | - Guojun Miao
- Department of Oral and Maxillofacial Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Tongji, China
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Prognostic value of the nodal yield in elective neck dissections in patients with head and neck carcinomas. Eur Arch Otorhinolaryngol 2021; 279:883-889. [PMID: 33938992 DOI: 10.1007/s00405-021-06819-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 04/09/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE The objective of this study is to assess the prognostic capacity of the nodal yield in elective neck dissections performed in patients with head and neck squamous cell carcinomas (HNSCC) without clinical or radiological evidence of regional involvement (cN0) at the time of diagnosis. METHODS Retrospective study including 647 patients with HNSCC treated with an elective neck dissection. RESULTS Patients with < 15 dissected nodes (n = 172, 26.6%) had a 5-year disease-specific survival of 64.9% (95% CI: 57.3-72.5%), while for patients with ≥ 15 dissected nodes (n = 475, 73.4%), it was of 81.9% (95% CI: 78.4-85.4%) (P = 0.0001). The nodal yield category had prognostic capacity on the disease-specific survival in patients with tumors located in the oral cavity (P = 0.001), the oropharynx (P = 0.023) and the hypopharynx (P = 0.034), while for patients with tumors located in the larynx, no significant differences appeared (P = 0.779). Differences in regional recurrence-free survival were also observed based on the nodal yield category in patients with extra-laryngeal tumors (5-year regional recurrence-free survival of 81.0% in patients with < 15 dissected nodes vs 89.0% in patients with ≥ 15 dissected nodes; P = 0.046). CONCLUSION The nodal yield in elective neck dissections in patients without evidence of lymph node disease (cN0) had prognostic capacity depending on the location of the primary tumor. For tumors located in the larynx, the number of dissected nodes did not significantly influence the prognosis. For tumors located in the oral cavity, oropharynx or hypopharynx, patients with < 15 dissected nodes had a disease-specific mortality 2.9 times higher than patients with ≥ 15 dissected nodes.
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Shannon AB, Straker RJ, Fraker DL, Roses RE, Miura JT, Karakousis GC. Ninety-day mortality after total gastrectomy for gastric cancer. Surgery 2021; 170:603-609. [PMID: 33789812 DOI: 10.1016/j.surg.2021.02.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 01/15/2021] [Accepted: 02/01/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Total gastrectomy for gastric cancer is associated with significant 30-day mortality, but this endpoint may underestimate the short-term mortality of the procedure. METHODS Retrospective analysis was performed using the National Cancer Database (2004-2015). Patients who underwent total gastrectomy for stage I to III gastric adenocarcinoma were identified and divided into cohorts based on 90-day mortality. Predictors of mortality were analyzed using multivariable logistic regression, and annual trends in mortality rates were calculated by Joinpoint Regression. RESULTS Of the 5,484 patients who underwent total gastrectomy, 90-day and 30-day mortality rates were 9.1% and 4.7%, respectively. Factors associated with 90-day mortality included increasing age (odds ratio 1.0, P < .001), income below the median (odds ratio 1.2, P = .039), Charlson-Deyo score ≥2 (odds ratio 1.4, P = .039), treatment at low-volume facilities (odds ratio 1.5, P < .001), N1 (odds ratio 2.0, P < .001), N2 (odds ratio 2.0, P < .001), or N3 (odds ratio 2.7, P < .001) stage disease, having <16 lymph nodes harvested (odds ratio 1.5, P < .001), and lack of treatment with chemotherapy (3.7, P < .001). Lack of health insurance (odds ratio 4.1, P = .080), and positive microscopic margins (odds ratio 1.3, P = .080) were correlated, but not significantly associated, with 90-day mortality. The 90-day mortality rate significantly declined from 14.3% in 2004 to 7.9% in 2015 (P = .006), and the 30-day mortality rate significantly declined from 7.7% in 2004 to 4.8% in 2015 (P = .009). CONCLUSION Nearly half of the deaths within 90 days after total gastrectomy for cancer occur beyond 30 days postoperative. Ninety-day mortality has improved over time, but rates remain high, suggesting the need for improved out-of-hospital postoperative care beyond 30 days.
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Affiliation(s)
- Adrienne B Shannon
- Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA
| | - Richard J Straker
- Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA
| | - Douglas L Fraker
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA
| | - Robert E Roses
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA
| | - John T Miura
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA
| | - Giorgos C Karakousis
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Pennsylvania, PA.
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Aurello P, Catracchia V, Petrucciani N, D'Angelo F, Leonardo G, Picchetto A, Antolino L, Magistri P, Terrenato I, Lauro A, Ramacciato G. What is the Role of Nodal Ratio as a Prognostic Factor for Gastric Cancer Nowadays? Comparison with New TNM Staging System and Analysis According to the Number of Resected Nodes. Am Surg 2020. [DOI: 10.1177/000313481307900523] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Nodal ratio (NR) has been demonstrated to be an important prognostic factor in patients with gastric cancer. The aim of this study is to evaluate the prognostic role of nodal ratio comparing it with the new TNM (2010) classification. One hundred forty-two patients were submitted to potentially curative gastrectomy for cancer. Patients with low performance status underwent D1.5 lymphadenectomy, whereas the other patients underwent D2–D2.5 lymphadenectomy. Nodal staging was classified according to 2010 International Union Against Cancer/American Joint Committee on Cancer classification. Kaplan-Meier method was used to evaluate survival, stratified for nodal classes and nodal status. Total gastrectomy was performed in 39 per cent of cases and distal gastrectomy in 61 per cent. Mean number of resected nodes was 25.5. Whereas N status was strictly related to the number of resected nodes, the NR was independent from the extension of the lymphadenectomy. Overall five-year survival was 81 per cent for N0 patients, 72 per cent for N1, and 26 and 23 per cent for N2 and N3, respectively. Patients with NR0 had 81 per cent five-year survival, whereas NR1 67 per cent, NR2 51 per cent, and NR3 22 per cent. NR seems to be a simple method to predict the prognosis of patients with gastric cancer; unlike N status, it is independent from the number of resected nodes, and therefore it is particularly useful in case of inadequate lymphadenectomy.
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Affiliation(s)
- Paolo Aurello
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Valeria Catracchia
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - NiccolÒ Petrucciani
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Francesco D'Angelo
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Giacomo Leonardo
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Andrea Picchetto
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Laura Antolino
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Paolo Magistri
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Irene Terrenato
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Augusto Lauro
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
| | - Giovanni Ramacciato
- From the Department of Surgery, Azienda Ospedaliera Sant'Andrea, University Sapienza of Rome, Faculty of Medicinand Psychology, Rome, Italy
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Lymph node yield and lymph node density for elective level II-IV neck dissections in laryngeal squamous cell carcinoma patients. Eur Arch Otorhinolaryngol 2019; 276:2923-2927. [PMID: 31317320 DOI: 10.1007/s00405-019-05560-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 07/11/2019] [Indexed: 12/21/2022]
Abstract
PURPOSE To determine the minimum lymph node yield (LNY) in patients with laryngeal squamous cell carcinoma (LSCCs). METHODS This retrospective study was performed in a tertiary care hospital setting and included 42 LSCC patients aged 39-81 years (females, n = 2; males, n = 40) who underwent a total or partial laryngectomy and elective bilateral level II-IV neck dissections (unilateral neck dissections: n = 84). RESULTS The average LNY in the unilateral level II-IV lymph node dissections was 25.9 ± 10, and the average metastatic LNY was 0.9 ± 1.9. The unilateral neck dissections were grouped according to the number of lymph nodes. There was no significant difference between the groups in terms of the metastatic LNY (p = 0.5). The metastatic lymph node density (LND) (metastatic lymph node yield/LNY) was 0.043 for unilateral neck level II-IV neck dissections. A Cox regression analysis revealed no significant relationship between survival and the LNY and LND in bilateral neck dissections (p = 0.4 and p = 0.8, respectively). CONCLUSIONS The results revealed no minimum number of lymph nodes that could reliably detect metastatic lymph nodes in LSCC patients.
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11
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de Kort WWB, Maas SLN, Van Es RJJ, Willems SM. Prognostic value of the nodal yield in head and neck squamous cell carcinoma: A systematic review. Head Neck 2019; 41:2801-2810. [PMID: 30969454 PMCID: PMC6767522 DOI: 10.1002/hed.25764] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 02/10/2019] [Accepted: 03/25/2019] [Indexed: 12/17/2022] Open
Abstract
Objective Literature analysis on the prognostic factor of the nodal yield (NY) in neck dissections (NDs), which in general surgical oncology is a strong prognosticator and quality‐of‐care marker. Methods We performed a systematic review of all PubMed and Embase publications until June 30, 2018 screening for data on NY as prognosticator and overall survival (OS) as outcome in patients with head and neck squamous cell carcinoma (HNSCC). Risk for bias was asserted by application of the Quality In Prognosis Studies tool. Results Of the 823 screened publications, 15 were included in this analysis. Five out of seven that compared NY ≥18 vs <18 as prognosticator, showed significantly improved survival if NY ≥18. Six studies used other cutoffs and three reported improved survival with each additionally harvested lymph node. Conclusion Increased NY in ND specimen for HNSCC, most commonly described as ≥18 lymph nodes, is associated with improved OS and could be used as a prognosticator and quality‐of‐care marker.
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Affiliation(s)
- Willem W B de Kort
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Sybren L N Maas
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Robert J J Van Es
- Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Head and Neck Surgical Oncology, Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Stefan M Willems
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Head and Neck Surgical Oncology, Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands
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A Simplified Two-Step Technique for Extended Lymphadenectomy During Resection of Gastroesophageal Malignancy: Early Results Compared to En Bloc Dissection. J Gastrointest Surg 2019; 23:393-401. [PMID: 30603860 DOI: 10.1007/s11605-018-4056-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 11/13/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Extended lymph node dissection (ELND) remains an important component of curative intent resection of mid-stage gastric cancer (GC). Benefits include enhanced staging accuracy, extending regional disease control, and optimizing potential curability. ELND during gastrectomy remains underutilized in US centers due to a low prevalence of GC operations. METHODS The traditional en bloc ELND was modified into a two-step technique to facilitate greater ease of dissection with better exposure. After completion of the gastrectomy component, retrogastric nodes are dissected in a separate, contiguous specimen. Resulting data were compared to outcomes after en bloc resection. RESULTS Of 179 consecutive patients undergoing gastrectomy, 129 underwent an ELND (73%). There were 97 men and 32 women, with a median age of 64 years (range 24-98). The median total LN count was 25 (3-86). The two-step dissection yielded an average of 18.3 (± 8.5 S.D.) perigastric and 12.1 (± 5.8) retrogastric nodes. Two-step LND was associated with lower estimated blood loss (265 vs. 448 ml, p = 0.0005), lower transfusion requirements (6 vs. 28%, p = 0.007), greater mean total LN counts (30 vs. 26, p = 0.03), and a greater rate of obtaining at least 15 or 20 LNs (91 vs. 77% and 83 vs. 65%, p = 0.05). Major morbidity (overall 16%), length of stay, and survival outcomes were not different. CONCLUSIONS The two-step LND technique as described was found to be associated with favorable operative and postoperative outcome parameters and an excellent LN yield. It can be recommended for standard ELND indications in the absence of macroscopically abnormal LNs.
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13
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Cozzaglio L, Doci R, Celotti S, Roncalli M, Gennari L. Gastric Cancer: Extent of Lymph Node Dissection and Requirements for a Correct Staging. TUMORI JOURNAL 2018; 90:467-72. [PMID: 15656331 DOI: 10.1177/030089160409000505] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Aims and Background Lymphatic spread is an important prognostic factor in gastric cancer. The TNM classification requires at least 15 lymph nodes to stage and identify three prognostic groups according to the number of metastatic lymph nodes: N1 (1-6), N2 (7-15), N3 (>15). The aim of this study was to investigate which type of lymph node dissection allows an accurate staging. Methods From 1996 to 2001, we treated 140 gastric cancer patients, 27 with D1 and 113 with D2 dissection. We evaluated lymph node count, status and ratio between metastatic and total number of excised lymph nodes, keeping 20% as the cutoff value. Results The mean number of lymph nodes was 18 and 33 respectively for D1 and D2 (P <0.001), 41% of patients in D1 and 5% in D2 had less than 15 lymph nodes (P <0.001). 59% in D1 and 73% in D2 (P = 0.145) had lymph node metastases, but this incidence decreased to 36% (P = 0.045) and 16% (P <0.001) respectively for D, and D2 when less than 15 lymph nodes were available. Considering the ratio between metastatic and total number of lymph nodes, 45% of D1 versus 3% of D2 (P <0.001) in the N1 group exceeded 20%. Conclusions D2 lymph node dissection is better than D1 in providing at least 15 lymph nodes required for a correct staging. We confirm the risk of a downstage when less than 15 lymph nodes are available.
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Affiliation(s)
- Luca Cozzaglio
- Department of General Surgery, Istituto Clinico Humanitas, Rozzano, Milan, Italy.
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Radical Gastrectomy: Still the Cornerstone of Curative Treatment for Gastric Cancer in the Perioperative Chemotherapy Era-A Single Institute Experience over a Decade. Int J Surg Oncol 2018; 2018:9371492. [PMID: 29568650 PMCID: PMC5820646 DOI: 10.1155/2018/9371492] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 11/27/2017] [Indexed: 12/26/2022] Open
Abstract
Background and Objectives Most gastric cancer patients now undergo perioperative chemotherapy (POCT) based on the MAGIC trial results. POCT consists of neoadjuvant chemotherapy (NACT) as well as postoperative adjuvant chemotherapy. This study assessed the applicability of perioperative chemotherapy and the impact of radical gastrectomy encompassing a detailed lymph-node resection on outcomes of gastric cancer. Methods Medical and pathology records of all gastric carcinoma resections were reviewed from 2006 onwards. Pathological details, number of lymph-nodes resected, and proportion of involved nodes, reasons for nonadministration of NACT, complications, recurrence, and survival data were analysed. Results Only twenty-eight (37.8%) out of 74 patients underwent NACT and only nine completed POCT. NACT was declined due to comorbidities/patient refusal n = 24, early stage n = 14, and emergency presentation n = 8. Patients receiving NACT were much younger. Anastomotic leaks, hospital-mortality, lymph-node yield, and proportion of involved lymph-nodes were similar in both groups. Thirty-two patients died due to recurrence with lymph-node involvement heralding higher recurrence risk and much poorer survival (HR 2.66; p = 0.013). Conclusion More than 60% patients with resectable gastric carcinoma did not undergo NACT. Radical gastrectomy with lymphadenectomy remained the cornerstone of treatment in this period.
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Ho AS, Kim S, Tighiouart M, Gudino C, Mita A, Scher KS, Laury A, Prasad R, Shiao SL, Van Eyk JE, Zumsteg ZS. Metastatic Lymph Node Burden and Survival in Oral Cavity Cancer. J Clin Oncol 2017; 35:3601-3609. [PMID: 28880746 PMCID: PMC5791830 DOI: 10.1200/jco.2016.71.1176] [Citation(s) in RCA: 193] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Purpose Current staging systems for oral cavity cancers incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigated the independent impact of numerical metastatic LN burden on survival. Methods Adult patients with oral cavity squamous cell carcinoma undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004 and 2013. A neck dissection of a minimum of 10 LNs was required. Multivariable models were constructed to assess the association between the number of metastatic LNs and survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Results Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs (HR, 1.34; 95% CI, 1.29 to 1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20 to 1.65; P < .001) and lower neck involvement (HR, 1.16; 95% CI, 1.06 to 1.27; P < .001) also predicted increased mortality. Increasing number of nodes examined was associated with improved survival, plateauing at 35 LNs (HR, 0.98; 95% CI, 0.98 to 0.99; P < .001). In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality. A novel nodal staging system derived by recursive partitioning analysis exhibited greater concordance than the American Joint Committee on Cancer (8th edition) system. Conclusion The number of metastatic nodes is a critical predictor of oral cavity cancer mortality, eclipsing other features such as LN size and contralaterality in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions.
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Affiliation(s)
- Allen S. Ho
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
| | - Sungjin Kim
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
| | | | - Cynthia Gudino
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
| | - Alain Mita
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
| | - Kevin S. Scher
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
| | - Anna Laury
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
| | - Ravi Prasad
- All authors: Cedars-Sinai Medical Center, Los Angeles, CA
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Bouliaris K, Rachiotis G, Diamantis A, Christodoulidis G, Polychronopoulou E, Tepetes K. Lymph node ratio as a prognostic factor in gastric cancer patients following D1 resection. Comparison with the current TNM staging system. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2017; 43:1350-1356. [PMID: 28433495 DOI: 10.1016/j.ejso.2017.03.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 01/03/2017] [Accepted: 03/10/2017] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Nodal ratio (NR) has been demonstrated to be an independent prognostic factor in patients with gastric cancer. We evaluated the prognostic role of NR comparing it with the current TNM (2010) classification in gastric cancer patients treated with curative (R0) D1 resection. MATERIALS AND METHODS We retrospectively reviewed 110 patients who underwent R0 resection for gastric cancer at University Hospital of Larissa between 2002 and 2011. All patients had a D1 lymphadenectomy plus the nodes along the left gastric artery. Factors affecting survival as well as correlations between the N status, NR status and resected nodes were investigated. RESULTS In univariate analysis the N and NR status but not the numbers of retrieved nodes were significant prognostic factors. Inside N1 and N2 categories, patients with different NR groups were present and survival of some of these subpopulations was statistically different at long-rank test. There was a correlation between the nodes retrieved and N status but not with the NR category. In multivariate analysis both N status (HR=1.45; 95% C.I. = 1.19-1.89) and NR (HR=4.53; 95% C.I. = 1.86-11.03) found to be independent prognostic factors of survival. CONCLUSION Prognostic significance of N status and NR status was comparable. Unlike N status, NR is independent by the number of resected nodes, and therefore it is particularly useful in case of conventional lymphadenectomy.
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Affiliation(s)
- K Bouliaris
- Surgical Department, University Hospital of Larissa, Mezurlo 41110, Thessaly, Greece.
| | - G Rachiotis
- Department of Hygiene and Epidemiology, Medical Faculty School of Health Science, University of Thessaly, Larissa 41222, Greece.
| | - A Diamantis
- Surgical Department, University Hospital of Larissa, Mezurlo 41110, Thessaly, Greece.
| | - G Christodoulidis
- Surgical Department, University Hospital of Larissa, Mezurlo 41110, Thessaly, Greece.
| | - E Polychronopoulou
- Internal Medicine Department, University Hospital of Larissa, Mezurlo 41110, Thessaly, Greece.
| | - K Tepetes
- Surgical Department, University Hospital of Larissa, Mezurlo 41110, Thessaly, Greece.
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Pou JD, Barton BM, Lawlor CM, Frederick CH, Moore BA, Hasney CP. Minimum lymph node yield in elective level I-III neck dissection. Laryngoscope 2017; 127:2070-2073. [DOI: 10.1002/lary.26545] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 01/23/2016] [Accepted: 01/27/2016] [Indexed: 11/07/2022]
Affiliation(s)
- Jason D. Pou
- Department of Otolaryngology-Head and Neck Surgery; Tulane University School of Medicine; New Orleans Louisiana
| | - Blair M. Barton
- Department of Otolaryngology-Head and Neck Surgery; Tulane University School of Medicine; New Orleans Louisiana
| | - Claire M. Lawlor
- Department of Otolaryngology-Head and Neck Surgery; Tulane University School of Medicine; New Orleans Louisiana
| | - Christopher H. Frederick
- Department of Otolaryngology-Head and Neck Surgery; Tulane University School of Medicine; New Orleans Louisiana
| | - Brian A. Moore
- Department of Otolaryngology-Head and Neck Surgery; Tulane University School of Medicine; New Orleans Louisiana
- Department of Otorhinolaryngology; Ochsner Clinic Foundation; New Orleans Louisiana U.S.A
| | - Christian P. Hasney
- Department of Otolaryngology-Head and Neck Surgery; Tulane University School of Medicine; New Orleans Louisiana
- Department of Otorhinolaryngology; Ochsner Clinic Foundation; New Orleans Louisiana U.S.A
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Nelen SD, Heuthorst L, Verhoeven RHA, Polat F, Kruyt PM, Reijnders K, Ferenschild FTJ, Bonenkamp JJ, Rutter JE, de Wilt JHW, Spillenaar Bilgen EJ. Impact of Centralizing Gastric Cancer Surgery on Treatment, Morbidity, and Mortality. J Gastrointest Surg 2017; 21:2000-2008. [PMID: 28815471 PMCID: PMC5698358 DOI: 10.1007/s11605-017-3531-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Accepted: 07/31/2017] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Centralization of gastric cancer surgery is thought to improve outcome and has been imposed in the Netherlands since 2012. This study analyzes the effect of centralization in terms of treatment outcome and survival in the Eastern part of the Netherlands. METHODS All gastric cancer patients without distant metastases who underwent a gastrectomy in six hospitals in the Eastern part of the Netherlands between 2008 and 2011 (pre-centralization) and 2013-2016 (post-centralization) were selected from the Netherlands Cancer Registry. Patient and tumor characteristics and treatment outcomes (duration of surgery, blood loss, resection margin, lymphadenectomy, chemotherapy, postoperative complications and hospital stay, and overall and disease-free survival) were analyzed and compared between pre- and post-centralization. RESULTS One hundred forty-four patients were included pre-centralization and 106 patients post-centralization. Patient and tumor characteristics were almost similar in the two periods. After centralization, more patients were treated with perioperative chemotherapy (25 vs. 42% p < 0.01). The proportion of patients treated with an adequate lymphadenectomy (21 vs. 93% p < 0.01) and laparoscopic surgery (6 vs. 40% p < 0.01) increased significantly (p < 0.01). The amount of cardiac complications (16 vs. 7.5% p < 0.05) decreased; however, complications needing a re-intervention were comparable (42 vs. 40% p = 0.79). Median hospital stay decreased from 10 to 8 days (p < 0.01). A 30-day mortality did not differ significantly (4.2 vs. 1.9%). A 1-year overall (78 vs. 80% p = 0.17) and disease-free survival (73 vs. 74% p = 0.66) remained stable. DISCUSSION Centralizing gastric cancer treatment in the Eastern part of the Netherlands resulted in improved lymph node harvesting and a successful introduction of laparoscopic gastrectomies. Centralization has not translated into improved mortality, and other variables may also have led to these improved outcomes. Further research using a nationwide population-based study will be needed to confirm these data.
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Affiliation(s)
- S. D. Nelen
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein 10, Route 618, P.O. 9101, 6500 HB Nijmegen, the Netherlands
| | - L. Heuthorst
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein 10, Route 618, P.O. 9101, 6500 HB Nijmegen, the Netherlands
| | - R. H. A. Verhoeven
- Department of Research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - F. Polat
- Department of Surgery, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Ph. M. Kruyt
- Department of Surgery, Gelderse Vallei Hospital, Ede, the Netherlands
| | - K. Reijnders
- Department of Surgery, Slingeland Hospital, Doetinchem, the Netherlands
| | - F. T. J. Ferenschild
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein 10, Route 618, P.O. 9101, 6500 HB Nijmegen, the Netherlands ,Department of Surgery, Maasziekenhuis Pantein, Boxmeer, the Netherlands
| | - J. J. Bonenkamp
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein 10, Route 618, P.O. 9101, 6500 HB Nijmegen, the Netherlands
| | - J. E. Rutter
- Department of Surgery, Rijnstate Hospital, Arnhem, the Netherlands
| | - J. H. W. de Wilt
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein 10, Route 618, P.O. 9101, 6500 HB Nijmegen, the Netherlands
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Herrera-Almario G, Patane M, Sarkaria I, Strong VE. Initial report of near-infrared fluorescence imaging as an intraoperative adjunct for lymph node harvesting during robot-assisted laparoscopic gastrectomy. J Surg Oncol 2016; 113:768-70. [PMID: 27021142 DOI: 10.1002/jso.24226] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 03/03/2016] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Adequate lymphadenectomy is a fundamental aspect of oncologically sound gastrectomies. Robot-assisted laparoscopic gastrectomy is a minimally invasive alternative that allows functional imaging to be easily integrated to the surgical field and may aid in intraoperative identification of lymphovascular bundles. METHODS Indocyanine green application and near-infrared fluorescence imaging were used during robot-assisted laparoscopic gastrectomy as an adjunct for the identification of relevant lymph node basins in real time. RESULTS A total of 31 patients were included. Twenty-nine gastrectomies were performed for adenocarcinoma and two wedge resections for neuroendocrine tumors. The mean lymph node retrieval was twenty-nine (range 17-61) for adenocarcinoma and five for neuroendocrine tumors. In all cases, at least five lymph nodes were seen along the main nodal basins, which provided real time intraoperative feedback regarding lymph node identification. Average time for indocyanine green application and functional imaging was less than 10 min. CONCLUSIONS Near-infrared fluorescent imaging may provide an improved method to help visualize lymph nodes intraoperatively during robot-assisted laparoscopic gastrectomy, thus adding a potentially valuable adjunct for lymphadenectomy and overall lymph node retrieval. J. Surg. Oncol. 2016;113:768-770. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | - Michael Patane
- Department of Surgery, Memorial Sloan Kettering Cancer, New York, New York
| | - Inderpal Sarkaria
- Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vivian E Strong
- Department of Surgery, Memorial Sloan Kettering Cancer, New York, New York
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Böttcher A, Dommerich S, Sander S, Olze H, Stromberger C, Coordes A, Jowett N, Knopke S. Nodal yield of neck dissections and influence on outcome in laryngectomized patients. Eur Arch Otorhinolaryngol 2016; 273:3321-9. [DOI: 10.1007/s00405-016-3928-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Accepted: 02/05/2016] [Indexed: 12/15/2022]
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Lemieux A, Kedarisetty S, Raju S, Orosco R, Coffey C. Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma. Otolaryngol Head Neck Surg 2015; 154:465-72. [DOI: 10.1177/0194599815622409] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 11/24/2015] [Indexed: 12/11/2022]
Abstract
Objective Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Study Design Case series with chart review. Setting Administrative database analysis. Subjects and Methods The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. Results A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). Conclusion These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy.
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Affiliation(s)
- Aaron Lemieux
- School of Medicine, University of California San Diego, La Jolla, California, USA
| | - Suraj Kedarisetty
- School of Medicine, University of California San Diego, La Jolla, California, USA
| | - Sharat Raju
- School of Medicine, University of California San Diego, La Jolla, California, USA
| | - Ryan Orosco
- Division of Head and Neck Surgery, University of California San Diego, La Jolla, California, USA
| | - Charles Coffey
- Division of Head and Neck Surgery, University of California San Diego, La Jolla, California, USA
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Mocellin S, McCulloch P, Kazi H, Gama‐Rodrigues JJ, Yuan Y, Nitti D. Extent of lymph node dissection for adenocarcinoma of the stomach. Cochrane Database Syst Rev 2015; 2015:CD001964. [PMID: 26267122 PMCID: PMC7263417 DOI: 10.1002/14651858.cd001964.pub4] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The impact of lymphadenectomy extent on the survival of patients with primary resectable gastric carcinoma is debated. OBJECTIVES We aimed to systematically review and meta-analyze the evidence on the impact of the three main types of progressively more extended lymph node dissection (that is, D1, D2 and D3 lymphadenectomy) on the clinical outcome of patients with primary resectable carcinoma of the stomach. The primary objective was to assess the impact of lymphadenectomy extent on survival (overall survival [OS], disease specific survival [DSS] and disease free survival [DFS]). The secondary aim was to assess the impact of lymphadenectomy on post-operative mortality. SEARCH METHODS We searched CENTRAL, MEDLINE and EMBASE until 2001, including references from relevant articles and conference proceedings. We also contacted known researchers in the field. For the updated review, CENTRAL, MEDLINE and EMBASE were searched from 2001 to February 2015. SELECTION CRITERIA We considered randomized controlled trials (RCTs) comparing the three main types of lymph node dissection (i.e., D1, D2 and D3 lymphadenectomy) in patients with primary non-metastatic resectable carcinoma of the stomach. DATA COLLECTION AND ANALYSIS Two authors independently extracted data from the included studies. Hazard ratios (HR) and relative risks (RR) along with their 95% confidence intervals (CI) were used to measure differences in survival and mortality rates between trial arms, respectively. Potential sources of between-study heterogeneity were investigated by means of subgroup and sensitivity analyses. The same two authors independently assessed the risk of bias of eligible studies according to the standards of the Cochrane Collaboration and the quality of the overall evidence based on the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. MAIN RESULTS Eight RCTs (enrolling 2515 patients) met the inclusion criteria. Three RCTs (all performed in Asian countries) compared D3 with D2 lymphadenectomy: data suggested no significant difference in OS between these two types of lymph node dissection (HR 0.99, 95% CI 0.81 to 1.21), with no significant difference in postoperative mortality (RR 1.67, 95% CI 0.41 to 6.73). Data for DFS were available only from one trial and for no trial were DSS data available. Five RCTs (n = 3 European; n = 2 Asian) compared D2 to D1 lymphadenectomy: OS (n = 5; HR 0.91, 95% CI 0.71 to 1.17) and DFS (n=3; HR 0.95, 95% CI 0.84 to 1.07) findings suggested no significant difference between these two types of lymph node dissection. In contrast, D2 lymphadenectomy was associated with a significantly better DSS compared to D1 lymphadenectomy (HR 0.81, 95% CI 0.71 to 0.92), the quality of the body of evidence being moderate; however, D2 lymphadenectomy was also associated with a higher postoperative mortality rate (RR 2.02, 95% CI 1.34 to 3.04). AUTHORS' CONCLUSIONS D2 lymphadenectomy can improve DSS in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic benefit.
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Affiliation(s)
- Simone Mocellin
- University of PadovaMeta‐Analysis Unit, Department of Surgery, Oncology and GastroenterologyVia Giustiniani 2PadovaVenetoItaly35128
| | - Peter McCulloch
- John Radcliffe HospitalNuffield Department of Surgery6th floorHeadingtonOxfordUKOX3 9DU
| | - Hussain Kazi
- University of LiverpoolAcademic DepartmentLiverpoolUK
| | - Joaquin J Gama‐Rodrigues
- Hospital de ClinicasDepartment of Digestive SurgeryRua Manuel da Nobrega, 1564Sao PauloSao PauloBrazil04001005
| | - Yuhong Yuan
- McMaster UniversityDepartment of Medicine, Division of Gastroenterology1280 Main Street WestRoom HSC 4N50HamiltonONCanadaL8S 4K1
| | - Donato Nitti
- University of PadovaClinica Chirurgica IIVia Giustiniani 2PadovaItaly35128
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Cohen DJ, Leichman L. Controversies in the treatment of local and locally advanced gastric and esophageal cancers. J Clin Oncol 2015; 33:1754-9. [PMID: 25918302 DOI: 10.1200/jco.2014.59.7765] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Despite overall progress in the therapy of local and locally advanced esophageal, gastroesophageal junction, and gastric adenocarcinomas, death as a result of these tumors remains a common outcome. Most randomized phase III trials on which level-one evidence has been built have included the heterogeneous histologies and locations associated with these tumors. However, the different etiologies, molecular biology, and recurrence patterns associated with gastroesophageal malignancies suggest the need to split rather than lump. Biologic and response differences exist between squamous and adenocarcinomas, as well as diffuse and intestinal histologies. This may be a cause behind conflicting outcomes in similar trials. The accepted standard of chemoradiotherapy for locally advanced esophageal and gastroesophageal junction cancers is based on a few positive trials, with the best chemotherapy and total dose of radiation remaining controversial. In the West, the staging evaluations of locally advanced gastric cancer are not uniform. Yet, these evaluations will inform the results of preoperative and perioperative treatments. Although postoperative chemoradiotherapy for gastric cancer has been an accepted treatment option for the last decade, more recent studies have called into question the need for radiotherapy. In perioperative strategies, it has yet to be determined whether histologic or molecular changes in the operative specimen should inform postoperative treatment. An appropriate place for targeted therapy needs to be found in preoperative and postoperative treatment regimens. Finally, because so much is lost when trials are forced to close for lack of accrual, it is imperative to build multidisciplinary consensus before they are launched.
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Lörincz BB, Langwieder F, Möckelmann N, Sehner S, Knecht R. The impact of surgical technique on neck dissection nodal yield: making a difference. Eur Arch Otorhinolaryngol 2015; 273:1261-7. [PMID: 25784183 DOI: 10.1007/s00405-015-3601-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Accepted: 03/02/2015] [Indexed: 11/26/2022]
Abstract
The nodal yield of neck dissections is an independent prognostic factor in several types of head and neck cancer. The authors aimed to determine whether the applied dissection technique has a significant impact on nodal yield. This is a single-institution, prospective study with internal control group (level of evidence: 2A). Data of 150 patients undergoing 223 neck dissections between February 2011 and March 2013 have been collected in a comprehensive cancer centre. Eighty-two patients underwent neck dissection with unwrapping the cervical fascia from lateral to medial, while 68 patients were operated without specifically unwrapping the fascia, in a caudal to cranial fashion. The standardised, horizontal neck dissection technique along the fascial planes resulted in a significantly higher nodal count in Levels I, II, III and IV, as well as in terms of overall nodal yield (mean: n = 22.53) than that of the vertical dissection applied in the control group (mean: n = 15.00). This is the first publication showing a direct correlation between neck dissection nodal yield and surgical technique. Therefore, it is paramount to optimise the applied surgical concept to maximise the oncological benefit.
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Affiliation(s)
- Balazs B Lörincz
- Head and Neck Cancer Centre of the Hubertus Wald University Cancer Centre Hamburg, Hamburg, Germany
- Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Felix Langwieder
- Head and Neck Cancer Centre of the Hubertus Wald University Cancer Centre Hamburg, Hamburg, Germany
- Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Nikolaus Möckelmann
- Head and Neck Cancer Centre of the Hubertus Wald University Cancer Centre Hamburg, Hamburg, Germany
- Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Susanne Sehner
- Department of Medical Biometry and Epidemiology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Rainald Knecht
- Head and Neck Cancer Centre of the Hubertus Wald University Cancer Centre Hamburg, Hamburg, Germany.
- Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
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Ronellenfitsch U, Najmeh S, Andalib A, Perera RM, Rousseau MC, Mulder DS, Ferri LE. Functional outcomes and quality of life after proximal gastrectomy with esophagogastrostomy using a narrow gastric conduit. Ann Surg Oncol 2014; 22:772-9. [PMID: 25212836 DOI: 10.1245/s10434-014-4078-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND The best surgical approach for tumors of the proximal stomach remains controversial. For proximal gastrectomy (PG), the evidence regarding quality of life (QoL) and functional outcomes is controversial. Moreover, there are limited data from non-Asian settings. METHODS All patients who underwent PG from September 2005 to July 2013 were identified from an institutional database. Demographic, perioperative and pathologic characteristics were retrieved. Symptom scores (0 = best/4 = worst) for reflux symptoms, dysphagia and validated QoL metrics (FACT scale, where a higher score is better) were assessed during early and late follow-up. Eligible patients for analysis were those with no evidence of recurrence. RESULTS Of 465 upper gastrointestinal cancer resections, 50 were PG for adenocarcinoma (42; 84%), neuroendocrine carcinoma (5; 10%) or other pathologies (3; 6%). R0 resection was achieved in 44 (89.8%) of 49 patients with malignant tumors. Median lymph node collection was 32 (range 7-57). QoL scores did not differ from preoperative to early follow-up but increased compared to both at late follow-up [preoperative, 125 (interquartile range 105-140); early follow-up, 122.5 (97-142); late follow-up, 147 (132-159); p < 0.05]. At early and late follow-up, 9 (21.4%) of 42 and 10 (33.3%) of 30 patients reported reflux symptoms, but most were mild. Endoscopic signs of esophagitis were found in 7 (29%) of 24 patients, but only two of these reported reflux symptoms. Conversely only three of eight patients with reflux symptoms had esophagitis on endoscopy. CONCLUSIONS Global QoL is not reduced early after PG, and increases compared to baseline at late follow-up. Although reflux symptoms are reported by a quarter of patients, most are mild, and there is little correlation with esophagitis. PG should remain a viable option in the management of proximal gastric tumors.
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Affiliation(s)
- Ulrich Ronellenfitsch
- Department of Surgery, Medical Faculty Mannheim of the University of Heidelberg, University Medical Centre Mannheim, Mannheim, Germany
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Datta J, Lewis RS, Mamtani R, Stripp D, Kelz RR, Drebin JA, Fraker DL, Karakousis GC, Roses RE. Implications of inadequate lymph node staging in resectable gastric cancer: a contemporary analysis using the National Cancer Data Base. Cancer 2014; 120:2855-65. [PMID: 24854027 DOI: 10.1002/cncr.28780] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 03/20/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND National guidelines recommend examination of ≥ 15 lymph nodes for adequate staging of resectable gastric adenocarcinoma (GA). The relevance of these guidelines, which were established before the increasing use of multimodality therapy, and the impact of inadequate lymph node staging (LNS) in a contemporary cohort have not been extensively explored. METHODS Stage I-III GA patients who underwent gastrectomy from 1998 to 2011 were identified using the National Cancer Data Base. Trends in LNS adequacy, predictors of inadequate LNS (< 15 LN examined) and the relationship between LNS and overall survival (OS) were analyzed. RESULTS In 22,409 patients, compliance with LNS guidelines was poor (inadequate LNS in 61.2% of cases, median LN harvested in 11.0%). Subtotal/partial gastrectomy was the strongest predictor of inadequate LNS (OR = 2.01, P < .001). Survival analyses included 9139 patients with minimum 5 years follow-up; median, 1-year, and 5-year survival was 35.6 months, 75.5%, and 39.7%, respectively. LN positivity (HR = 1.90) and age > 76 years (HR = 1.73) were the strongest predictors of worse OS (both P < .001). Inadequate LNS was independently associated with worse OS (HR = 1.33, P < .001). Median OS after inadequate compared to adequate LNS was significantly worse (33.3 months versus 42.0 months, P < .001), regardless of AJCC clinical stage subgroup or tumor T classification (both P < .001). CONCLUSIONS Adequate LNS is achieved in a minority of patients. Inadequate LNS was independently associated with worse OS. Examination of ≥ 15 LN is a reproducible prognosticator of gastric cancer outcomes in the United States and should continue to serve as a benchmark for quality of care.
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Affiliation(s)
- Jashodeep Datta
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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27
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Ebrahimi A, Clark JR, Amit M, Yen TC, Liao CT, Kowalski LP, Kreppel M, Cernea CR, Bachar G, Villaret AB, Fliss D, Fridman E, Robbins KT, Shah JP, Patel SG, Gil Z. Minimum Nodal Yield in Oral Squamous Cell Carcinoma: Defining the Standard of Care in a Multicenter International Pooled Validation Study. Ann Surg Oncol 2014; 21:3049-55. [DOI: 10.1245/s10434-014-3702-x] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Indexed: 12/13/2022]
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Giuliani A, Miccini M, Basso L. Extent of lymphadenectomy and perioperative therapies: Two open issues in gastric cancer. World J Gastroenterol 2014; 20:3889-3904. [PMID: 24744579 PMCID: PMC3983445 DOI: 10.3748/wjg.v20.i14.3889] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 11/23/2013] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is one of the leading causes of death for cancer worldwide, although geographical variations in incidence exist. Over the last decades, its incidence and mortality have gradually decreased in Western countries, while these have increased, or remained stable, in the other world regions. Gastric cancer is often diagnosed at an advanced stage, with the only notable exception of Japan, where nationwide screening programs are enforced, due to local high incidence. Curative- intent surgery (i.e., gastrectomy, total or partial, and lymphadenectomy) remains the cornerstone of treatment of gastric cancer. Much has been debated about the extent of lymph node dissection and, although it is a valuable contribution to staging and cure, operative treatment only represents one aspect of overall effective management, as the risk of both locoregional and distant recurrences are high, and bear a poor prognosis. As a matter of fact, surgery, as a single modality treatment, has probably achieved its maximum efficacy for local control and survival, while other accompanying nonsurgical treatment modalities have to be taken into account, although their role is still the subject of considerable debate. The authors in this review present an update on the outcome of treatment of gastric cancer in relation to the extent of lymphadenectomy and of various nonsurgical preoperative, intraoperative, and postoperative strategies.
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Jaber JJ, Zender CA, Mehta V, Davis K, Ferris RL, Lavertu P, Rezaee R, Feustel PJ, Johnson JT. Multi-institutional investigation of the prognostic value of lymph nodel yield in advanced-stage oral cavity squamous cell carcinoma. Head Neck 2014; 36:1446-52. [PMID: 24038739 DOI: 10.1002/hed.23475] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Revised: 07/11/2013] [Accepted: 08/21/2013] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND Although existing literature provides surgical recommendations for treating occult disease (cN0) in early-stage oral cavity squamous cell carcinoma (SCC), a focus on late-stage oral cavity SCC is less pervasive. METHODS The medical records of 162 patients with late-stage oral cavity SCC pN0 who underwent primary neck dissections were reviewed. Lymph node yield as a prognosticator was examined. RESULTS Despite being staged pN0, patients that had a higher lymph node yield had an improved regional/distant control rates, disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Lymph node yield consistently outperformed all other standard variables as being the single best prognostic factor with a tight risk ratio range (RR = 0.95-0.98) even when correcting for the number of lymph nodes examined. CONCLUSION The results of this study showed that lower regional recurrence rates and improved survival outcomes were seen as lymph node yield increased for advanced T classification oral cavity SCC pN0. This suggests that increasing lymph node yield with an extended cervical lymphadenectomy may result in lower recurrence rates and improved survival outcomes for this advanced stage group.
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Affiliation(s)
- James J Jaber
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Otolaryngology - Head and Neck Surgery, Loyola University Medical Center, Chicago, Illinois
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How many lymph nodes should be assessed in patients with gastric cancer? A systematic review. Gastric Cancer 2012; 15 Suppl 1:S70-88. [PMID: 22895615 DOI: 10.1007/s10120-012-0169-y] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Accepted: 06/01/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nodal status is one of the most important prognostic factors in gastric adenocarcinoma (GC). As such, it is important to assess an appropriate number of lymph nodes (LNs) in order to accurately stage patients. However, the number of LNs assessed in each GC case varies, and in many cases the number examined per gastric specimen is less than current recommendations. PURPOSE We aimed to identify and synthesize findings from all articles evaluating the association of clinicopathological features and long-term outcomes with the number of LNs assessed among GC patients. METHODS Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. RESULTS Twenty-five articles were included in this review. Extensive resection, increased tumor size, and greater TNM staging were all associated with a greater number of LNs assessed. The disease-free survival was longer and recurrence rate was lower in patients with more LNs assessed. Overall survival, as well as survival by TNM and clinical stage, was improved among patients with an increased number of LNs assessed, but much of this appears to be due to stage migration, with the effect more pronounced in more advanced disease. CONCLUSION More LNs assessed resulted in less stage migration and possibly better long-term outcomes. Although current guidelines suggest 16 LNs to be assessed, especially in advanced GC, a higher number of LNs should be assessed.
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Yang SI, Lee SH. Clinical Outcome of Positive Margin of Postgastrectomy with Adenocarcinoma of Stomach. KOSIN MEDICAL JOURNAL 2012. [DOI: 10.7180/kmj.2012.27.1.31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
<sec><title>Objectives</title> Many investigators have recommended adequate resection margin and lymphadenectomy for radical curative resection. The aim of this study is to evaluate clinical characteristics of positive resection margin (proximal or distal) of postgastrectomy in advanced gastric cancer. </sec><sec><title>Methods</title> We studied 17 patients with gastric cancer who were diagnosed positive resection margin by intraoperative frozen biopsy or permanent biopsy report from January 2005 to December 2007, retrospectively. Surgical margin monitored by endoscopy. </sec><sec><title>Results</title> Distal gastrectomy was performed in 13 patients and total gastrectomy in 4. Gastrectomy with combined resection including splenectomy was performed in 3, distal pancreatectomy in 2, transverse colon segmental resection in 1, and cholecystectomy in 2. Positive Proximal margin was found in 12, positive distal margin in 3, and both in 2. Palliative chemotherapy was performed in 8 patients. Postoperative follow up endoscopy was established in only 8 patients. Malignant results from endoscopic biopsy in gastroenteric or esophagoenteric anastomotic line were proven in 2 patients during follow up. 9 patients were not performed follow-up endoscopy. Among total 17 patients, 2 patients are alive. Fifteen patients died of aggravation of disease in 13 and postoperative complication in 2. </sec><sec><title>Conclusions</title> Although positive surgical margin in far advanced gastric cancer were found, it can consider that does not further resection to obtain microscopic clear anastomotic margin. </sec>
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McCulloch P, Nita ME, Kazi H, Gama-Rodrigues JJ. WITHDRAWN: Extended versus limited lymph nodes dissection technique for adenocarcinoma of the stomach. Cochrane Database Syst Rev 2012; 1:CD001964. [PMID: 22258947 DOI: 10.1002/14651858.cd001964.pub3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Surgeons disagree about the merits and risks of radical lymph node clearance during gastrectomy for cancer. OBJECTIVES To evaluate survival and peri-operative mortality after limited or extended lymph node removal during gastrectomy for cancer. SEARCH METHODS We searched MEDLINE, EMBASE, CancerLit, LILACS, Central Medical Journal Japanese Database and the Cochrane register, references from relevant articles and conference proceedings. We contacted known workers in the field. For the updated review, the Cochrane Library, M EDLINE , E MBASE and LILACS were searched from 2001 to April 2009. SELECTION CRITERIA Studies published after 1970 which reported 5 year survival or postoperative mortality rates, and clearly defined the node dissection performed, were considered. We excluded studies which overtly included patients receiving perioperative chemotherapy, and comparisons with clear systematic treatment allocation bias. Randomised controlled trials (RCTs), non-randomised comparisons and observational studies were considered separately. DATA COLLECTION AND ANALYSIS Three reviewers selected trials for inclusion. Quality assessment and data extraction were performed independently by two reviewers. Results of trials of similar design were pooled. Meta-analysis was performed separately for randomised and non-randomised comparisons. MAIN RESULTS Two randomised and two non-randomised comparisons of limited (D1) versus extended (D2) node dissection and 11 cohort studies of either D1 or D2 resection were analysed. Meta-analysis of randomised trials did not reveal any survival benefit for extended lymph node dissection (Risk ratio = 0.95 (95% CI 0.83 - 1.09), but showed increased postoperative mortality (RR 2.23, 95% CI 1.45 - 3.45). Pre-specified subgroup analysis suggested a possible benefit in stage T3+ tumours (RR = 0.68, 95% CI 0.42-1.10). Non-randomised comparisons showed no significant survival benefit for extended dissection (RR 0.92, 95% CI 0.83 -1.02), but decreased mortality (RR 0.65, 95% CI 0.45-0.93). Subgroup analysis showed apparent benefit in UICC stage II and IIIa. Observational studies of D2 resection reported much better mortality and survival than those of D1 surgery, but the settings were strikingly different. AUTHORS' CONCLUSIONS D2 dissection carries increased mortality risks associated with spleen and pancreas resection, and probably with inexperience and low case volumes. Randomised studies show no evidence of overall survival benefit, but possible benefit in T3+ tumours. These results may be confounded by surgical learning curves and poor surgeon compliance. Non-randomised comparisons suggest a possible survival benefit for D2 in intermediate UICC stages. Observational studies show high 5 year survival and low operative mortality after D2 dissection in experienced units, and poor results after D1 dissection in non-specialist units. Further studies, with precautions to eliminate learning curve effects, contamination and non-compliance, are needed to evaluate D2 dissection in intermediate stage gastric cancer.
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Affiliation(s)
- Peter McCulloch
- Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, UK
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Shao YS, Peng KQ, Zhang YT, Yu Y, Feng Y, Zhu L, Liu W, Wu WL. Lymph node metastasis in advanced proximal gastric cancer: an analysis of 86 cases. Shijie Huaren Xiaohua Zazhi 2011; 19:1300-1306. [DOI: 10.11569/wcjd.v19.i12.1300] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the pattern of lymph node metastasis in advanced proximal gastric cancer to guide the extent of stomach resection (proximal or total gastrectomy) and to evaluate the necessity of splenectomy.
METHODS: The clinicopathological data for 86 patients with advanced proximal gastric cancer who underwent radical gastrectomy at our hospital from January 1989 to September 2010 were retrospectively analyzed. The number and size of detected lymph nodes were recorded. The total and average number of detected lymph nodes, total rate of lymph node metastasis, and metastasis rates of Nos. 1-16 lymph nodes were calculated.
RESULTS: A total of 4 756 (30-157) lymph nodes were detected in the surgical specimens from 86 patients with advanced proximal gastric cancer, and the average number of detected lymph nodes was 55.30 ± 20.23. Of 4 756 detected lymph nodes, 3 859 (81.14%) had a size of ≤5 mm. Seventy of 86 cases had lymph node metastasis, and the total rate of lymph node metastasis was 81.40%. Of 912 metastatic lymph nodes, 556 (60.96%) had a size of ≤5 mm. The metastasis rates of Nos. 1-4 and 7-9 lymph nodes (39.53%-80.23%) were higher than those of Nos. 12-15 (0.00%-2.33%). The metastasis rates of Nos 5, 6, 10, 11 and 16 lymph nodes were 22.09%, 15.12%, 33.72%, 18.60% and 15.12%, respectively.
CONCLUSION: Analysis of the pattern of lymph node metastasis in proximal advanced gastric cancer has an appreciable value in guiding lymphadenectomy. Total gastrectomy plus splenectomy is a feasible radical surgery for proximal advanced gastric cancer because of the requirement of resection of Nos. 5-6 and Nos. 10-11 lymph nodes.
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Three-step method for lymphadenectomy in gastric cancer surgery: a single institution experience of 120 patients. J Am Coll Surg 2011; 212:200-8. [PMID: 21276533 DOI: 10.1016/j.jamcollsurg.2010.09.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2010] [Revised: 09/08/2010] [Accepted: 09/10/2010] [Indexed: 02/03/2023]
Abstract
BACKGROUND Gastric cancer is one of the most common malignancies and a leading cause of cancer death. Complete resection is still the only treatment to offer a cure for patients with gastric cancer. Lymphadenectomy is the most important part of curative resection, but lymphadenectomy is also very difficult in gastric cancer surgery. The aim of this study was to report our 3-step method for lymphadenectomy and clarify its safety and value in gastric cancer. STUDY DESIGN A total of 120 consecutive patients underwent our 3-step method for lymphadenectomy at the Second Affiliated Hospital Zhejiang University College of Medicine between February 2006 and July 2007. The main surgical procedure was performed from right to left and from caudal to cranial. Clinical factors, surgical variables, postoperative morbidity, and hospital (30-day) mortality were analyzed retrospectively. RESULTS Total gastrectomy was performed in 41 patients; combined adjacent organ resection was performed in 9 patients. The mean operation time was 201.8 minutes, and the mean blood loss was 376.7 mL. The median postoperative hospital stay was 14.9 ± 4.3 days. A total of 3,569 lymph nodes (LNs) were removed and examined, and 2,879 were negative. More than 15 LNs were examined in all 120 patients. The median number of examined LNs was 29 (range 17 to 64; mean 29.7 ± SD 9.6) per patient, and the median number of positive LNs was 5 (range 0 to 37; mean 5.8 ± SD 7.1) per patient. The overall incidence of postoperative complications was 10.8%, and the rate of hospital death was 0%. The median follow-up period for those patients was 34.3 months (range 10 to 53 months), and the overall 3-year survival rate was 40.6%. CONCLUSIONS The 3-step method for lymphadenectomy is easy to perform and is a safe and useful procedure for gastric cancer surgery.
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35
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Ebrahimi A, Zhang WJ, Gao K, Clark JR. Nodal yield and survival in oral squamous cancer: Defining the standard of care. Cancer 2011; 117:2917-25. [PMID: 21246523 DOI: 10.1002/cncr.25834] [Citation(s) in RCA: 114] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2010] [Revised: 10/21/2010] [Accepted: 10/28/2010] [Indexed: 11/05/2022]
Abstract
BACKGROUND Elective neck dissection (END) is commonly used as a staging and therapeutic procedure for oral squamous cell carcinoma (SCC) at high risk of nodal metastases. The authors aimed to determine whether the extent of lymphadenectomy, as defined by nodal yield, is a prognostic factor in this setting. METHODS A retrospective database review identified 225 patients undergoing END with curative intent for oral SCC between 1987 and 2009. Nodal yield was studied as a categorical variable for association with overall, disease-specific, and disease-free survival in univariate and multivariate analyses. RESULTS Nodal yield <18 was associated with 5-year overall survival of 51% compared with 74% in those with nodal yield ≥ 18 (P = .009). Five-year disease-specific survival rates were 69% in those with <18 nodes and 87% in patients with ≥ 18 nodes (P = .022). Similar results were obtained for disease-free survival, with 5-year rates of 44% with <18 nodes versus 71% with ≥ 18 nodes (P = .043). After adjusting for the effect of age, nodal status, T stage, and adjuvant radiotherapy on multivariate analysis, nodal yield <18 was associated with reduced overall (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1-3.6; P = .020), disease-specific (HR, 2.2; 95% CI, 1.1-4.5; P = .043), and disease-free survival (HR, 1.7; 95% CI, 1.1-2.8; P = .040). In the pathologically lymph node-negative subgroup (n = 148), similar results were obtained. CONCLUSIONS Nodal yield is an independent prognostic factor in patients undergoing END for oral SCC. These results suggest that an adequate lymphadenectomy in this setting should include at least 18 nodes.
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Abstract
BACKGROUND Surgery in gastric cancer (GC) aims to achieve resection of the primary tumor and its lymphatic drain, with a minimal adverse effect on morbidity and mortality, and the best possible quality of life. METHODS From June 1993 to May 2008, 113 patients with a preoperative diagnosis of the GC were considered for laparoscopic gastrectomy at our institution. There was a predominance of males and mean age was 60 years. After peritoneal cavity inspection, laparoscopic ultrasound was used to determine the presence of deep liver metastasis. Total gastrectomy and Roux-en-Y reconstruction were performed in upper and middle-third tumors, and subtotal gastrectomy, either with Billroth II or Roux-en-Y reconstruction, in tumors affecting the lower third of the stomach. D2 lymphadenectomy was performed in both cases. RESULTS There were 21 cases (18.5%) with distant metastases and/or an unresectable tumor due to the invasion of adjacent organs. In these patients the procedure was limited to laparoscopic biopsy in 16 cases and laparoscopic gastrojejunostomy in 5 cases. Laparoscopic gastrectomy was performed in 92 patients with a mean surgical time of 162 minutes and a mortality rate of 5.4%. Conversion was necessary in 7 cases (7.6%). CONCLUSIONS The benefits and safety of laparoscopic gastrectomy are evident, with similar outcomes to conventional surgery and all the advantages of minimally invasive access. The learning curve is long. Laparoscopic gastrectomy is a safe and effective option for the treatment of GC, avoiding nontherapeutic laparotomy in patients with advanced disease. Comparative prospective studies evaluating the long-term survival of these patients are still necessary.
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Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol 2010; 28:5210-8. [PMID: 21060024 PMCID: PMC3020693 DOI: 10.1200/jco.2009.26.6114] [Citation(s) in RCA: 527] [Impact Index Per Article: 35.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2009] [Accepted: 09/01/2010] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines. PATIENTS AND METHODS Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required. RESULTS This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466). CONCLUSION This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).
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Affiliation(s)
- Christoph Schuhmacher
- Klinikum rechts der Isar, Chirurgische Klinik der TU München, Ismaningerstr. 22, D-81675 München, Germany.
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Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol 2010. [PMID: 21060024 DOI: 10.1200/jco2009.26.6114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
PURPOSE Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines. PATIENTS AND METHODS Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required. RESULTS This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466). CONCLUSION This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).
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Affiliation(s)
- Christoph Schuhmacher
- Klinikum rechts der Isar, Chirurgische Klinik der TU München, Ismaningerstr. 22, D-81675 München, Germany.
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Zhao D, Xu H, Li K, Sun Z. Prognostic factors for patients after curative resection for proximal gastric cancer. ACTA ACUST UNITED AC 2010; 30:530-5. [PMID: 20714884 DOI: 10.1007/s11596-010-0463-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2009] [Indexed: 12/14/2022]
Abstract
The factors influencing the long-term survival of patients with proximal gastric cancer (PGC) after curative resection were investigated. Data from 171 patients who underwent curative resection for PGC were retrospectively analyzed. The patients were grouped according to the clinicopathological factors and operative procedures. The tumor depth (T stage) and lymph node metastasis (pN stage) were graded according to the fifth edition of TNM Staging System published by UICC in 1997. The metastatic lymph node ratio (MLR) was divided into four levels: 0%, <10%, 10%-30% and >30%. The data of survival rate were analyzed by Kaplan-Meier method (log-rank test) and Cox regression model. The 5-year overall survival rate of 171 patients was 37.32%. The univariate analysis demonstrated that the survival time of the postoperative patients with PGC was related to tumor size (chi2=4.57, P=0.0325), gross type (chi2=21.38, P<0.001), T stage (chi2=27.91, P<0.001), pN stage (chi2=44.72, P<0.001), MLR (chi2=61.12, P<0.001), TNM stage (chi2=44.91, P<0.001), and range of gastrectomy (chi2=4.36, P=0.0368). Multivariate analysis showed that MLR (chi2=10.972, P=0.001), pN stage (chi2=6.640, P=0.010), TNM stage (chi2=7.081, P=0.007), T stage (chi2=7.687, P=0.006) and gross type (chi2=6.252, P=0.012) were the independent prognostic factors. In addition, the prognosis of patients who underwent total gastrectomy (TG) was superior to that of patients who underwent proximal gastrectomy (PG) for the cases of tumor>or=5 cm (chi2=6.31, P=0.0120), Borrmann III/IV (chi2=7.96, P=0.0050), T4 (chi2=4.57, P=0.0325), pN2 (chi2=5.52, P=0.0188), MLR 10%-30% (chi2=4.46, P=0.0347), MLR>30% (chi2=13.34, P=0.0003), TNM III (chi2=14.05, P=0.0002) or TNM IV stage (chi2=4.37, P=0.0366); and combining splenectomy was beneficial to the cases of T3 (chi2=5.68, P=0.0171) or MLR>30% (chi2=6.11, P=0.0134). It was concluded that MLR, pN stage, TNM stage, T stage, and gross type had advantages in providing a precise prognostic evaluation for patients undergoing curative resection for PGC, in which MLR was the most valuable index. TG and combining splenectomy were useful to improve the prognosis to patients with PGC of TNM III/IV stage, serosa invasion, or extensive regional lymph node metastasis.
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Affiliation(s)
- Donghui Zhao
- Department of Surgical Oncology, Research Unit of General Surgery, First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
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Jensen LS, Nielsen H, Mortensen PB, Pilegaard HK, Johnsen SP. Enforcing centralization for gastric cancer in Denmark. Eur J Surg Oncol 2010; 36 Suppl 1:S50-4. [PMID: 20598495 DOI: 10.1016/j.ejso.2010.06.025] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Accepted: 06/09/2010] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Population-based data on the early postoperative outcome after surgery for gastric cancer are very sparse. We examined the development in the quality of surgery and early postoperative outcomes in Denmark following centralization of gastric cancer surgery and implementation of national clinical guidelines. METHODS All patients in Denmark who underwent resection with curative intent for gastric cancer between 1st July 2003 and 31st December 2008 in one of five university hospitals were registered in a national database. Data on surgical quality and mortality were obtained from the database and compared with the results from the period before centralization (1999-2003). RESULTS A total of 416 patients underwent resection in the study period. The risk of anastomotic leakages for the whole period was 5.0% (95%CI; 3.2-7.7) compared to 6.1% (95%CI; 4.3-8.6) before centralization, whereas the 30-days hospital mortality was 2.4% (95%CI; 1.2-4.4) compared to 8.2% (95%CI; 6.0-10.4) before centralization. In addition, the percentage of patients with at least 15 lymph nodes removed increased during the study period from 19 in 2003 to 76 in 2008. CONCLUSIONS Centralization of gastric cancer surgery in Denmark and implementation of national clinical guidelines monitored by a national database was associated with improvements in surgical quality and substantially lower in-hospital mortality.
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Affiliation(s)
- L S Jensen
- Department of Surgery, Aarhus University Hospital, Nørrebrogade 44, Aarhus C, Denmark.
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Deng J, Liang H, Sun D, Pan Y. The prognostic analysis of lymph node-positive gastric cancer patients following curative resection. J Surg Res 2010; 161:47-53. [PMID: 19783008 DOI: 10.1016/j.jss.2008.12.019] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2008] [Revised: 12/10/2008] [Accepted: 12/12/2008] [Indexed: 12/13/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the appropriate prognostic indicators of lymph node-positive gastric cancer patients following curative resection. METHODS A retrospective study of 196 lymph node-positive patients who underwent radical gastrectomy (R0) for gastric cancer from January 1997 to December 2000 was analyzed statistically to identify the intensive indictors of prognosis. RESULTS In 196 evaluable patients, 5-year survival rate was 33.2%. A total of 4048 lymph nodes were examined (median, 20.6; range, 15-49), and 1661 lymph nodes were positive (median, 8.5; range, 1-37). The median survival was 29 months. With multivariate analysis, we found number and ratio of metastatic lymph nodes were associated with overall survival (OS) of lymph node-positive patients after curative surgery. However, we ultimately identified that ratio of metastatic lymph nodes was more appropriate to evaluate OS of lymph node-positive patients than number of metastatic lymph nodes by using the case-control matched fashion. One hundred forty-four (73.5%) patients had recurrence after curative surgery. The median disease-free time was 18 month, and the median survival after recurrence was 4 month. With multivariate analysis (logistic regression model), we found number of metastatic lymph nodes was associated with recurrence after curative surgery. CONCLUSION Ratio and number of metastatic lymph nodes were important indicators of OS and recurrence of lymph node-positive gastric cancer patients following curative resection, respectively.
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Affiliation(s)
- Jingyu Deng
- Gastrointestinal Cancer Surgery Division, Tianjin Medical University Cancer Hospital and City Key Laboratory of Tianjin Cancer Center, Tianjin, China
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The node ratio as prognostic factor after curative resection for gastric cancer. J Gastrointest Surg 2010; 14:614-9. [PMID: 20101526 DOI: 10.1007/s11605-009-1142-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2009] [Accepted: 12/14/2009] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The depth of the tumor invasion and nodal involvement are the two main prognostic factors in gastric cancer. Staging systems differ among countries and new tools are needed to interpret and compare results and to reduce stage migration. The node ratio (NR) has been proposed as a new prognostic factor. MATERIALS AND METHODS We retrospectively reviewed 282 patients who underwent curative resection for gastric cancer at Parma University Hospital between 2000 and 2007. TNM stage, NR, overall survival, survival according to nodal status, and survival according to the total number of nodes retrieved were calculated. RESULTS At univariate analysis, the TNM stage, number of metastatic nodes, NR, and depth of tumor invasion, but not the number of nodes retrieved, were significant prognosis factors. Patients with more than 15 nodes retrieved in the specimen survived significantly longer (p < 0.04). This was confirmed for all N or NR classes within N groups. There was a correlation between the number of nodes retrieved and N but not with the NR category. NR was an independent prognostic factor at Cox regression. CONCLUSION NR is a reliable and sensitive tool to differentiate patients with similar characteristics, probably more so than the TNM system. NR is not strictly related to the number of nodes retrieved and this may potentially decrease the stage migration phenomenon. More trials are needed to validate this factor.
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Huang CM, Lin BJ, Lu HS, Zhang XF, Li P, Xie JW. Effect of lymphadenectomy extent on advanced gastric cancer located in the cardia and fundus. World J Gastroenterol 2008; 14:4216-4221. [PMID: 18636669 PMCID: PMC2725385 DOI: 10.3748/wjg.14.4216] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2008] [Revised: 05/16/2008] [Accepted: 05/23/2008] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the prognostic impact of lymphade-nectomy extent in advanced gastric cancer located in the cardia and fundus. METHODS Two hundred and thirty-six patients with advanced gastric cancer located in the cardia and fundus who underwent D2 curative resection were analyzed retrospectively. Relationships between the numbers of lymph nodes (LNs) dissected and survival was analyzed among different clinical stage subgroups. RESULTS The 5-year overall survival rate of the entire cohort was 37.5%. Multivariate prognostic variables were total LNs dissected (P < 0.0001; or number of negative LNs examined, P < 0.0001), number of positive LNs (P < 0.0001), T category (P < 0.0001) and tumor size (P = 0.015). The greatest survival differences were observed at cutoff values of 20 LNs resected for stage II (P = 0.0136), 25 for stage III(P < 0.0001), 30 for stage IV (P = 0.0002), and 15 for all patients (P = 0.0024). Based on the statistically assumed linearity as best fit, linear regression showed a significant survival enhancement based on increasing negative LNs for patients of stages III (P = 0.013) and IV (P = 0.035). CONCLUSION To improve the long-term survival of patients with advanced gastric cancer located in the cardia and fundus, removing at least 20 LNs for stage II, 25 LNs for stage III, and 30 LNs for stage IV patients during D2 radical dissection is recommended.
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Biffi R, Chiappa A, Luca F, Pozzi S, Lo Faso F, Cenciarelli S, Andreoni B. Extended lymph node dissection without routine spleno-pancreatectomy for treatment of gastric cancer: low morbidity and mortality rates in a single center series of 250 patients. J Surg Oncol 2006; 93:394-400. [PMID: 16550575 DOI: 10.1002/jso.20495] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES To verify the hypothesis that avoidance of routine splenectomy and distal pancreatectomy in a modified D-2 resection for gastric cancer can significantly lower the complications rate of this procedure in a population of Western patients. METHODS A series of 250 consecutive Italian patients suffering from localized, histology-proven gastric cancer was submitted to gastrectomy and extended D-2 lymphadenectomy for treatment of their disease during an 8-year period (1994-2002) at the European Institute of Oncology in Milano, Italy. Caudal pancreas and spleen were routinely preserved, unless the tumor was not closely adjacent to or directly invading these organs. Postoperative morbidity, overall mortality, and length of hospital stay were recorded. RESULTS One hundred forty patients underwent total gastrectomy and 110 a subtotal distal one; splenectomy was performed in 8 cases and spleno-pancreatectomy in 15. The postoperative morbidity rate was 18%, the mortality rate was 1.2% and 9 patients experienced re-operation. The median length of stay was 14.8 days. CONCLUSIONS These results compete favorably with those reported after standard D-1 gastrectomy in Western patients series. D-2 gastrectomy with spleen and pancreas routine preservation can be considered a safe treatment for gastric cancer in Western patients, at least in experienced centers.
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Affiliation(s)
- Roberto Biffi
- Division of General Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
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Dicken BJ, Graham K, Hamilton SM, Andrews S, Lai R, Listgarten J, Jhangri GS, Saunders LD, Damaraju S, Cass C. Lymphovascular invasion is associated with poor survival in gastric cancer: an application of gene-expression and tissue array techniques. Ann Surg 2006; 243:64-73. [PMID: 16371738 PMCID: PMC1449982 DOI: 10.1097/01.sla.0000194087.96582.3e] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To examine a population-based cohort for the association between clinicopathologic predictors of survival and immunohistochemical markers (IHC), and to assess changes in gene expression that are associated with lymphovascular invasion (LVI). SUMMARY BACKGROUND DATA LVI has been associated with poor survival and aggressive tumor behavior. The molecular changes responsible for the behavior of gastric cancer have yet to be determined. Characterization of IHC markers and gene expression profiles may identify molecular alterations governing tumor behavior. METHODS : Clinicopathologic and survival data of 114 patients were reviewed. Archival specimens were used to construct a multitumor tissue array that was subjected to IHC of selected protein targets. Correlation of IHC with tumor thickness (T status), LVI and prognosis was studied. Microarray analysis of fresh gastric cancer tissue was conducted to examine the gene expression profile with respect to LVI. RESULTS In a multivariate analysis, nodal status (N), metastasis (M), and LVI were independent predictors of survival. LVI was associated with a 5-year survival of 13.9% versus 55.9% in patients in whom it was absent. LVI correlated with advancing T status (P = 0.001) and N status (P < 0.001). IHC staining of cyclooxygenase-2 (COX-2) correlated with T status, tumor grade, lymph node positivity, and IHC staining of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Microarray analyses suggested differential expression of oligophrenin-1 (OPHN1) and ribophorin-II (RPNII) with respect to LVI. CONCLUSION LVI was an independent predictor of survival in gastric cancer. Expression of COX-2 may facilitate tumor invasion through MMP-2 and MMP-9 activation. OPHN1 and RPN II appeared to be differentially expressed in gastric cancers exhibiting LVI. The reported function of OPHN1 and RPN II makes these gene products promising candidates for future studies involving LVI in gastric cancer.
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Affiliation(s)
- Bryan J Dicken
- Department of Surgery, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada
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Ichikura T, Chochi K, Sugasawa H, Mochizuki H. Modified radical lymphadenectomy (D1.5) for T2-3 gastric cancer. Langenbecks Arch Surg 2005; 390:397-402. [PMID: 16041552 DOI: 10.1007/s00423-005-0570-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2005] [Accepted: 06/09/2005] [Indexed: 12/28/2022]
Abstract
BACKGROUND The operative mortality in gastric cancer surgery has been reported to be higher with D2 lymphadenectomy than with D1 in the West. The modified radical lymphadenectomy (D1.5) may be safer than D2 under these circumstances. This study was aimed to determine whether D1.5 would deteriorate long-term survival as compared with D2. METHOD Since the concept of the extent of lymphadenectomy varied among the surgeons, 461 patients who underwent curative gastrectomy for T2-4 gastric adenocarcinoma were retrospectively categorized into three groups according to the surgeon: D1 with dissection along the left gastric and common hepatic arteries (D1.5); lymphadenectomy between D1.5 and D2; D2 or more extended dissection. RESULTS No differences were found in the survival rates among the three groups within each of the T2a, T2b, and T3 categories. According to a multivariate analysis using Cox's proportional hazard model, the classification according to the surgeons had no survival impact (p>0.8). CONCLUSION D1.5 lymphadenectomy resulted in a survival rate that was almost equal to that of D2. The use of D1.5 instead of D2 can be an attractive option to be compared with D1 in future trials.
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Affiliation(s)
- Takashi Ichikura
- Department of Surgery I, National Defense Medical College Hospital, 3-2, Namiki, Tokorozawa, 359-8513, Japan.
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DiSiena MR, Taneja C, Wanebo HJ. Radical Gastrectomy and Lymphadenectomy: Historic Overview, Surgical Trends, and Lessons from the Past. Surg Oncol Clin N Am 2005; 14:511-32, vi-vii. [PMID: 15978427 DOI: 10.1016/j.soc.2005.05.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Michael R DiSiena
- Department of Surgery, Roger Williams Medical Center, 825 Chalkstone Avenue, Providence, RI 02908, USA
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Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg 2005; 241:27-39. [PMID: 15621988 PMCID: PMC1356843 DOI: 10.1097/01.sla.0000149300.28588.23] [Citation(s) in RCA: 501] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE This update reviews the epidemiology and surgical management, and the controversies of gastric adenocarcinoma. We provide the relevance of outcome data to surgical decision-making and discuss the application of gene-expression analysis to clinical practice. SUMMARY BACKGROUND DATA Gastric cancer mortality rates have remained relatively unchanged over the past 30 years, and gastric cancer continues to be one of the leading causes of cancer-related death. Well-conducted studies have stimulated changes to surgical decision-making and technique. Microarray studies linked to predictive outcome models are poised to advance our understanding of the biologic behavior of gastric cancer and improve surgical management and outcome. METHODS We performed a review of the English gastric adenocarcinoma medical literature (1980-2003). This review included epidemiology, pathology and staging, surgical management, issues and controversies in management, prognostic variables, and the application of outcome models to gastric cancer. The results of DNA microarray analysis in various cancers and its predictive abilities in gastric cancer are considered. RESULTS Prognostic studies have provided valuable data to better the understanding of gastric cancer. These studies have contributed to improved surgical technique, more accurate pathologic characterization, and the identification of clinically useful prognostic markers. The application of microarray analysis linked to predictive models will provide a molecular understanding of the biology driving gastric cancer. CONCLUSIONS Predictive models generate important information allowing a logical evolution in the surgical and pathologic understanding and therapy for gastric cancer. However, a greater understanding of the molecular changes associated with gastric cancer is needed to guide surgical and medical therapy.
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Affiliation(s)
- Bryan J Dicken
- Department of Surgery, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada
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McCulloch P, Nita ME, Kazi H, Gama-Rodrigues J. Extended versus limited lymph nodes dissection technique for adenocarcinoma of the stomach. Cochrane Database Syst Rev 2004:CD001964. [PMID: 15495024 DOI: 10.1002/14651858.cd001964.pub2] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Surgeons disagree about the merits and risks of radical lymph node clearance during gastrectomy for cancer. OBJECTIVES To evaluate survival and peri-operative mortality after limited or extended lymph node removal during gastrectomy for cancer. SEARCH STRATEGY We searched MEDLINE, EMBASE, CancerLit, LILACS, Central Medical Journal Japanese Database and the Cochrane register, references from relevant articles and conference proceedings. We contacted known workers in the field. SELECTION CRITERIA Studies published after 1970 which reported 5 year survival or postoperative mortality rates, and clearly defined the node dissection performed, were considered. We excluded studies which overtly included patients receiving perioperative chemotherapy, and comparisons with clear systematic treatment allocation bias. Randomised controlled trials (RCTs), non-randomised comparisons and observational studies were considered separately. DATA COLLECTION AND ANALYSIS Three reviewers selected trials for inclusion. Quality assessment and data extraction were performed independently by two reviewers. Results of trials of similar design were pooled. Meta-analysis was performed separately for randomised and non-randomised comparisons. MAIN RESULTS Two randomised and two non-randomised comparisons of limited (D1) versus extended (D2) node dissection and 11 cohort studies of either D1 or D2 resection were analysed. Meta-analysis of randomised trials did not reveal any survival benefit for extended lymph node dissection (Risk ratio = 0.95 (95% CI 0.83 - 1.09), but showed increased postoperative mortality (RR 2.23, 95% CI 1.45 - 3.45). Pre-specified subgroup analysis suggested a possible benefit in stage T3+ tumours (RR = 0.68, 95% CI 0.42-1.10). Non-randomised comparisons showed no significant survival benefit for extended dissection (RR 0.92, 95% CI 0.83 -1.02), but decreased mortality (RR 0.65, 95% CI 0.45-0.93). Subgroup analysis showed apparent benefit in UICC stage II and IIIa. Observational studies of D2 resection reported much better mortality and survival than those of D1 surgery, but the settings were strikingly different. REVIEWERS' CONCLUSIONS D2 dissection carries increased mortality risks associated with spleen and pancreas resection, and probably with inexperience and low case volumes. Randomised studies show no evidence of overall survival benefit, but possible benefit in T3+ tumours. These results may be confounded by surgical learning curves and poor surgeon compliance. Non-randomised comparisons suggest a possible survival benefit for D2 in intermediate UICC stages. Observational studies show high 5 year survival and low operative mortality after D2 dissection in experienced units, and poor results after D1 dissection in non-specialist units. Further studies, with precautions to eliminate learning curve effects, contamination and non-compliance, are needed to evaluate D2 dissection in intermediate stage gastric cancer.
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Affiliation(s)
- P McCulloch
- Academic Unit of Surgery, University of Liverpool, Aintree, Lower Lane, L9 7AL, Liverpool, UK.
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Dicken BJ, Saunders LD, Jhangri GS, de Gara C, Cass C, Andrews S, Hamilton SM. Gastric cancer: establishing predictors of biologic behavior with use of population-based data. Ann Surg Oncol 2004; 11:629-35. [PMID: 15150070 DOI: 10.1245/aso.2004.09.002] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Tumor thickness and nodal status are important predictors of survival following curative resection for gastric cancer. Lymphovascular invasion (LVI) is a potential predictor of biological behavior. The relationship between LVI and tumor thickness (T status) has not been established in population-based studies. METHODS Clinicopathological and survival data of 577 patients at nine centers, from between 1991 and 1997, was collected from patient records and a Provincial Cancer Registry. The primary endpoint of the study was death. A secondary analysis of a node-negative subgroup examined the significance of LVI with respect to T status. RESULTS The population disease-specific survival was 28%. In a multivariate analysis, T, N, M, esophageal margin, tumor morphology, and residual tumor category were independent predictors of survival. LVI was documented in 58% of resected tumors. LVI correlated with advancing T and N status but was not significant in a multivariate population model. Subgroup analysis of node-negative gastric cancer found T status and LVI to be independent predictors of survival. LVI was associated with a 5-year survival of 8%, versus 43% among patients in whom it was absent (P <.001). CONCLUSIONS T status and N status were the most important independent predictors of survival in a population-based study of gastric cancer. LVI correlated with advancing N and T status. Multivariate analysis of node-negative patients showed LVI and T status are independent predictors of survival.
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Affiliation(s)
- B J Dicken
- 2D2 Walter C. Mackenzie Health Sciences Center, 8440-112 St. University of Alberta Hospital, Edmonton, Alberta, Canada T6G 2B7
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