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Johannesen KMB, Fiehn AMK, Eiholm S. The topographical distribution of lymph node metastases in colon cancer resections. Ann Diagn Pathol 2023; 67:152205. [PMID: 37647771 DOI: 10.1016/j.anndiagpath.2023.152205] [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: 08/19/2023] [Accepted: 08/20/2023] [Indexed: 09/01/2023]
Abstract
In accordance with international guidelines all lymph nodes in colon cancer specimens must be examined to obtain accurate staging. This study aimed to determine the topographical location of lymph node metastases and evaluate if a more limited sampling approach could be an alternative. Partial colectomies received at the Department of Pathology, Zealand University Hospital during a six-month period were included. At the macroscopic examination, each specimen was divided into three different segments: a segment containing the index tumor and the tumor-feeding artery, an oral and an anal segment. The number of lymph nodes and lymph node metastases were registered separately for each segment. Resections from 93 patients were included. Of 2466 lymph nodes, 1839 (74.6 %) were located in the tumor segment, 308 (12.5 %) in the oral, and 319 (12.9 %) in the anal segment, respectively. In 133 (5,4 %) lymph nodes a metastasis was present. Of these 129 (97.0 %) were located in the tumor segment, one (0.8 %) in the oral segment, and three (2.3 %) in the anal segment. No patients had metastasis in the oral or anal segments without metastases also being present in the tumor segment leading to consideration of the need for lymph node harvest of the complete specimen upon initial examination. As such, the segment containing the index tumor and tumor-feeding artery could be regarded as a sentinel segment indicating a potential need for lymph node dissection in the oral and anal segments.
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Affiliation(s)
| | - Anne-Marie Kanstrup Fiehn
- Department of Pathology, Zealand University Hospital, Sygehusvej 9, 4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
| | - Susanne Eiholm
- Department of Pathology, Zealand University Hospital, Sygehusvej 9, 4000 Roskilde, Denmark
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Zhang C, Zhao S, Wang X. A Prognostic Nomogram for T3N0 Rectal Cancer After Total Mesorectal Excision to Help Select Patients for Adjuvant Therapy. Front Oncol 2021; 11:698866. [PMID: 34900666 PMCID: PMC8654784 DOI: 10.3389/fonc.2021.698866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 11/03/2021] [Indexed: 11/13/2022] Open
Abstract
Background The recurrence rate of T3N0 rectal cancer after total mesorectal excision (TME) is relatively low, meaning that not all patients need adjuvant therapy (AT) (radiotherapy, chemotherapy, or chemoradiotherapy). Methods Patients diagnosed with pT3N0M0 rectal cancer after TME were analyzed using the SEER database, of which 4367 did not receive AT and 2794 received AT. Propensity score matching was used to balance the two groups in terms of confounding factors. Cox proportional hazards regression analysis was used to screen independent prognostic factors, which were then used to establish a nomogram. The patients were then divided into three groups with X-tile software according to their risk scores. We enrolled 334 patients as external validation. Results The C-index of the model was 0.725 (95% confidence interval: 0.694–0.756). We divided the patients into three different risk layers based on the nomogram prediction scores, and found that AT did not improve the prognosis of low- and moderate-risk patients, while high-risk patients benefited from AT. External validation data also support the above conclusions. Conclusion This study developed a nomogram that effectively and comprehensively evaluates the prognosis of T3N0 rectal cancer patients after TME. After using the nomogram, we recommend AT for high-risk patients, but not for low- and moderate-risk patients.
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Affiliation(s)
- Chao Zhang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shutao Zhao
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Xudong Wang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
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Aisu Y, Kato S, Kadokawa Y, Yasukawa D, Kimura Y, Takamatsu Y, Kitano T, Hori T. Feasibility of Extended Dissection of Lateral Pelvic Lymph Nodes During Laparoscopic Total Mesorectal Excision in Patients with Locally Advanced Lower Rectal Cancer: A Single-Center Pilot Study After Neoadjuvant Chemotherapy. Med Sci Monit 2018; 24:3966-3977. [PMID: 29890514 PMCID: PMC6026381 DOI: 10.12659/msm.909163] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 01/29/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The feasibility of additional dissection of the lateral pelvic lymph nodes (LPLNs) in patients undergoing total mesorectal excision (TME) combined with neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC) is controversial. The use of laparoscopic surgery is also debated. In the present study, we evaluated the utility of laparoscopic dissection of LPLNs during TME for patients with LARC and metastatic LPLNs after NAC, based on our experience with 19 cases. MATERIAL AND METHODS Twenty-five patients with LARC with swollen LPLNs who underwent laparoscopic TME and LPLN dissection were enrolled in this pilot study. The patients were divided into 2 groups: those patients with NAC (n=19) and without NAC (n=6). Our NAC regimen involved 4 to 6 courses of FOLFOX plus panitumumab, cetuximab, or bevacizumab. RESULTS The operative duration was significantly longer in the NAC group than in the non-NAC group (648 vs. 558 minutes, respectively; P=0.022). The rate of major complications, defined as grade ≥3 according to the Clavien-Dindo classification, was similar between the 2 groups (15.8% vs. 33.3%, respectively; P=0.4016). No conversion to conventional laparotomy occurred in either group. In the NAC group, a histopathological complete response was obtained in 2 patients (10.5%), and a nearly complete response (Tis N0 M0) was observed in one patient (5.3%). Although the operation time was prolonged in the NAC group, the other perioperative factors showed no differences between the 2 groups. CONCLUSIONS Laparoscopic LPLN dissection is feasible in patients with LARC and clinically swollen LPLNs, even after NAC.
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Cox ML, Adam MA, Shenoi MM, Turner MC, Sun Z, Mantyh CR, Migaly J. Resected irradiated rectal cancers: Are twelve lymph nodes really necessary in the era of neoadjuvant therapy? Am J Surg 2017; 216:444-449. [PMID: 28890055 DOI: 10.1016/j.amjsurg.2017.08.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Revised: 08/10/2017] [Accepted: 08/21/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Our study aims to identify the minimum number of lymph nodes (LN) associated with improved survival in patients who underwent NRT for stage II-III rectal cancer. METHODS Adults with clinical stage II and III rectal adenocarcinoma in the National Cancer Data Base were stratified by NRT. Multivariable Cox regression modeling with restricted cubic splines was used to determine the minimum number of LNs associated with improved survival. RESULTS Of 38,363 patients, 76% received NRT. After adjustment, a LNY≥12 was associated with improved survival among patients receiving NRT (HR 0.79, p < 0.0001) and those without NRT (HR 0.88, p = 0.04). Among patients receiving NRT, factors independently associated with LNY≥12 were younger age, private insurance, low comorbidity score, a recent year of diagnosis, higher T stage and grade, APR resection, and academic institution. CONCLUSIONS A minimum LNY of 12 confers a survival benefit for rectal cancer patients regardless of receiving neoadjuvant radiation therapy.
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Affiliation(s)
- Morgan L Cox
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States.
| | - Mohamed A Adam
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States
| | - Mithun M Shenoi
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States
| | - Megan C Turner
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States
| | - Zhifei Sun
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States
| | - Christopher R Mantyh
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States
| | - John Migaly
- Department of General Surgery, Duke University Medical Center, Durham, NC, United States
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Lymphadenectomy in Colorectal Cancer: Therapeutic Role and How Many Nodes Are Needed for Appropriate Staging? CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0349-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Märkl B. Stage migration vs immunology: The lymph node count story in colon cancer. World J Gastroenterol 2015; 21:12218-12233. [PMID: 26604632 PMCID: PMC4649108 DOI: 10.3748/wjg.v21.i43.12218] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 10/26/2015] [Indexed: 02/06/2023] Open
Abstract
Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases, the number of harvested lymph nodes itself has prognostic relevance in stage II/III cancers. A stage migration effect caused by missed lymph node metastases has been postulated as most likely explanation for that. In order to avoid false negative node staging reporting of at least 12 lymph nodes is recommended. However, this threshold is met only in a minority of cases in daily practice. Due to quality initiatives the situation has improved in the past. This, however, had no influence on staging in several studies. While the numbers of evaluated lymph nodes increased continuously during the last decades the rate of node positive cases remained relatively constant. This fact together with other indications raised doubts that understaging is indeed the correct explanation for the prognostic impact of lymph node harvest. Several authors assume that immune response could play a major role in this context influencing both the lymph node detectability and the tumor’s behavior. Further studies addressing this issue are need. Based on the findings the recommendations concerning minimal lymph node numbers and adjuvant chemotherapy should be reconsidered.
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Bhatti ABH, Akbar A, Hafeez A, Syed AA, Khattak S, Jamshed A, Kazmi AS. Impact of lymph node ratio and number on survival in patients with rectal adenocarcinoma after preoperative chemo radiation. Int J Surg 2014; 13:65-70. [PMID: 25475873 DOI: 10.1016/j.ijsu.2014.11.038] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 11/26/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Retrieval of <12 lymph nodes after proctectomy and preoperative chemoradiation (C-XRT) may improve survival in good risk patients. The objective of this study was to determine impact of <12 retrieved lymph nodes and lymph node ratio (LNR) on survival in a population with certain poor prognostic features for rectal cancer. METHODS Patients who underwent surgery for rectal adenocarcinoma between 2005 and 2011 were divided them into <12 or >12 lymph node groups. The LNR groups were based on interquartile range. Clinicopathological and treatment outcomes were compared. Expected 5 year disease free and overall survival was calculated. Cox proportional hazard model was used to determine independent predictors. RESULTS More patients in <12 lymph nodes removed group had low tumors (<5 cm from anal verge) (75.5% versus 60.7%) (P=0.03) and underwent abdominoperineal resection (59.1% versus 42.9%) (P=0.02). Overall survival (OS) and disease free survival (DFS) was not different [(56% and 52% (P=0.7)] [(50% and 57% (P=0.5)]. LNR<0.15 was independent predictor of DFS while LNR ratio<0.12 for OS on multivariate analysis. CONCLUSION LNR and not number of retrieved nodes impacts survival in younger patients with predominance of anorectal tumors after C-XRT. A specific LNR cutoff remains to be defined.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan.
| | - Ali Akbar
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | | | - Aamir Ali Syed
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Shahid Khattak
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Arif Jamshed
- Department of Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Ather Saeed Kazmi
- Department of Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
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Gill AA, Zahm SH, Shriver CD, Stojadinovic A, McGlynn KA, Zhu K. Colon cancer lymph node evaluation among military health system beneficiaries: an analysis by race/ethnicity. Ann Surg Oncol 2014; 22:195-202. [PMID: 25059789 DOI: 10.1245/s10434-014-3939-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND The number of lymph nodes examined during colon cancer surgery falls below nationally recommended guidelines in the general population, with Blacks and Hispanics less likely to have adequate nodal evaluation in comparison to Whites. The Department of Defense's (DoD) Military Health System (MHS) provides equal access to medical care for its beneficiaries, regardless of racial/ethnic background. This study aimed to investigate whether racial/ethnic treatment differences exist in the MHS, an equal-access medical care system. METHODS Linked data from the DoD cancer registry and administrative claims databases were used and included 2,155 colon cancer cases. Multivariate logistic regression assessed the association between race/ethnicity and the number of lymph nodes examined (<12 and ≥12) overall and for stratified analyses. RESULTS No overall racial/ethnic differences in the number of lymph nodes examined was identified. Further stratified analyses yielded similar results, except potential racial/ethnic differences were found among persons with poorly differentiated tumors, where non-Hispanic Blacks tended to be less likely to have ≥12 lymph nodes dissected (odds ratio 0.34; 95 % confidence interval 0.14-0.80; p = 0.01) compared with non-Hispanic Whites. CONCLUSION Racial/ethnic disparities in the number of lymph nodes evaluated among patients with colon cancer were not apparent in an equal-access healthcare system. However, among poorly differentiated tumors there might be racial/ethnic differences in nodal yield, suggesting the possible effects of factors other than access to healthcare.
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Affiliation(s)
- Abegail A Gill
- John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA
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Destri GL, Carlo ID, Scilletta R, Scilletta B, Puleo S. Colorectal cancer and lymph nodes: The obsession with the number 12. World J Gastroenterol 2014; 20:1951-1960. [PMID: 24587671 PMCID: PMC3934465 DOI: 10.3748/wjg.v20.i8.1951] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Lymphadenectomy of colorectal cancer is a decisive factor for the prognostic and therapeutic staging of the patient. For over 15 years, we have asked ourselves if the minimum number of 12 examined lymph nodes (LNs) was sufficient for the prevention of understaging. The debate is certainly still open if we consider that a limit of 12 LNs is still not the gold standard mainly because the research methodology of the first studies has been criticized. Moreover many authors report that to date both in the United States and Europe the number “12” target is uncommon, not adequate, or accessible only in highly specialised centres. It should however be noted that both the pressing nature of the debate and the dissemination of guidelines have been responsible for a trend that has allowed for a general increase in the number of LNs examined. There are different variables that can affect the retrieval of LNs. Some, like the surgeon, the surgery, and the pathology exam, are without question modifiable; however, other both patient and disease-related variables are non-modifiable and pose the question of whether the minimum number of examined LNs must be individually assigned. The lymph nodal ratio, the sentinel LNs and the study of the biological aspects of the tumor could find valid application in this field in the near future.
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Ghahramani L, Moaddabshoar L, Razzaghi S, Hamedi SH, Pourahmad S, Mohammadianpanah M. Prognostic Value of Total Lymph Node Identified and Ratio of Lymph Nodes in Resected Colorectal Cancer. ACTA ACUST UNITED AC 2013. [DOI: 10.17795/acr-15311] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Adequacy of Lymph Node Staging in Colorectal Cancer: Analysis of 250 Patients and Analytical Literature Review. ACTA ACUST UNITED AC 2013. [DOI: 10.5812/acr.11495] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Shia J, Wang H, Nash GM, Klimstra DS. Lymph node staging in colorectal cancer: revisiting the benchmark of at least 12 lymph nodes in R0 resection. J Am Coll Surg 2012; 214:348-55. [PMID: 22225644 DOI: 10.1016/j.jamcollsurg.2011.11.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Revised: 11/16/2011] [Accepted: 11/23/2011] [Indexed: 12/18/2022]
Affiliation(s)
- Jinru Shia
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
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Fan L, Levy M, Aguilar CE, Mertens RB, Dhall D, Frishberg DP, Wang HL. Lymph node retrieval from colorectal resection specimens for adenocarcinoma: is it worth the extra effort to find at least 12 nodes? Colorectal Dis 2011; 13:1377-83. [PMID: 20969717 DOI: 10.1111/j.1463-1318.2010.02472.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
AIM Retrieval of a minimum of 12 lymph nodes has been recommended for adequately staging a node-negative colorectal cancer (CRC). This study was designed to determine whether the extra effort expended to recover more nodes for histological examination improves the accuracy of staging. METHOD Pathology reports, histology worklists, and haematoxylin and eosin (H&E) slides of 334 CRC resections were reviewed. The total number of nodes and the number of positive nodes harvested from the first and additional searches were recorded for each patient. RESULTS The number of nodes retrieved from the 334 resections at the first search ranged from 0 to 57 (mean: 14.2), with 195 patients (58.4%) having ≥ 12 nodes. Nodal metastasis was found in 122 (33.6%) patients. Additional searches were performed on 115 patients, including 91 with < 12 nodes. The mean number of nodes recovered in these patients increased significantly, from 9.1 to 14.2 (P < 0.0001). Thirty-one additional positive nodes were found in 19 patients following the further searches, and 12 (63.2%) of the 19 patients were upstaged using the American Joint Committee on Cancer (AJCC) 6th edition (2002) staging criteria. The total number of nodes retrieved and the probability of obtaining ≥ 12 nodes correlated negatively with the age of the patient and the rectosigmoid location of the tumours, but positively with the specimen length, the pericolic/perirectal fat width, female gender and tumour size. CONCLUSION Although a number of patient and specimen variables influence the number of lymph nodes retrieved, our observations support the importance of a thorough search for nodes in CRC specimens in order to achieve accurate tumour staging.
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Affiliation(s)
- L Fan
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
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Steele SR, Chen SL, Stojadinovic A, Nissan A, Zhu K, Peoples GE, Bilchik A. The impact of age on quality measure adherence in colon cancer. J Am Coll Surg 2011; 213:95-103; discussion 104-5. [PMID: 21601492 DOI: 10.1016/j.jamcollsurg.2011.04.013] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2010] [Revised: 04/13/2011] [Accepted: 04/13/2011] [Indexed: 12/28/2022]
Abstract
BACKGROUND Recently lymph node yield (LNY) has been endorsed as a quality measure of colon cancer resection adequacy. It is unclear whether this measure is relevant to all ages. We hypothesized that total lymph node yield (LNY) is negatively correlated with increasing age and overall survival (OS). STUDY DESIGN The Surveillance, Epidemiology and End Results (SEER) database was queried for all nonmetastatic colon cancer patients diagnosed from 1992 to 2004 (n = 101,767), grouped by age (<40, 41 to 45, 46 to 50, and in 5-year increments until 86+ years). Proportions of patients meeting the 12 LNY minimum criterion were determined in each age group and analyzed with multivariate linear regression adjusting for demographics and American Joint Committee on Cancer (AJCC) 6(th) Edition stage. OS comparisons in each age category were based on the guideline of 12 LNY. RESULTS Mean LNY decreased with increasing age (18.7 vs 11.4 nodes/patient, youngest vs oldest group, p < 0.001). The proportion of patients meeting the 12 LNY criterion also declined with each incremental age group (61.9% vs 35.2% compliance, youngest vs oldest, p < 0.001). Multivariate regression demonstrated a negative effect of each additional year in age and log (LNY) with coefficient of -0.003 (95% CI -0.003 to -0.002). When stratified by age and nodal yield using the 12 LNY criterion, OS was lower for all age groups in stage II colon cancer with less than 12 LNY, and each age group over 60 years with less than 12 LNY for stage III colon cancer (p < 0.05). CONCLUSIONS Every attempt to adhere to proper oncologic principles should be made at the time of colon cancer resection regardless of age. The prognostic significance of the 12 LN minimum criterion should be applied even to elderly colon cancer patients.
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Affiliation(s)
- Scott R Steele
- Department of Surgery, Division of Colorectal Surgery, Madigan Army Medical Center, Tacoma, WA, USA
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Downing SR, Cadogan KA, Ortega G, Jaji Z, Bolorunduro OB, Oyetunji TA, Chang DC, Ford DH, Frederick WA. The Number of Lymph Nodes Examined Debate in Colon Cancer: How Much is Enough? J Surg Res 2010; 163:264-9. [DOI: 10.1016/j.jss.2010.03.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2010] [Revised: 03/01/2010] [Accepted: 03/04/2010] [Indexed: 11/27/2022]
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