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Luo WX, Chen Y, Li YT, Tang J, Ding J, Du Y, Wu Q, Liu JY. Selected proliferation markers correlated with dynamics of growth in colorectal cancer. Eur J Cancer Prev 2019; 28:181-187. [PMID: 29688906 DOI: 10.1097/cej.0000000000000448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
For treatment of metastatic colorectal cancer, the dynamics of tumor growth is an important factor for treatment decision. However, it is difficult to evaluate the dynamics of tumor growth, especially those of synchronous metastatic diseases. This study aimed to find some indicators related to tumor proliferation to judge the dynamics of tumor progression. The pathological reports and clinical data of 1205 patients with metastatic colorectal cancer were retrospectively reviewed; 75 patients with known relapse time after radical resection were included, and the expression of proliferation-associated proteins was detected by immunohistochemistry. Relapse-free time (RFT) from radical resection to relapse was obtained to analyze the relationship with expression of these factors. Kaplan-Meier univariate analysis showed that the overexpression of cyclin D1 and epidermal growth factor receptor (EGFR) and late pathological stage after surgery indicated shorter RFT. Multivariate analysis showed that EGFR and the stage were independent predictors of RFT. Expression of EGFR and cyclin D1 and the pathological stage were included as combination risk factors for RFT analysis; more risk factors were correlated with shorter RFT. EGFR and cyclin D1 seemed to be indicators of the dynamics of tumor growth, and overexpression of those molecules may suggest rapid growth and poor prognosis.
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Affiliation(s)
- Wu-Xia Luo
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
- Department of Medical Oncology, the First People's Hospital of Chengdu
| | - Ye Chen
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
| | - Yun-Tao Li
- Department of General Surgery, the Third People's Hospital of Chengdu, Chengdu, China
| | - Jie Tang
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
| | - Jing Ding
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
| | - Yang Du
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
| | - Qiang Wu
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
| | - Ji-Yan Liu
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University
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Tong GJ, Zhang GY, Liu J, Zheng ZZ, Chen Y, Niu PP, Xu XT. Comparison of the eighth version of the American Joint Committee on Cancer manual to the seventh version for colorectal cancer: A retrospective review of our data. World J Clin Oncol 2018; 9:148-161. [PMID: 30425940 PMCID: PMC6230917 DOI: 10.5306/wjco.v9.i7.148] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 08/30/2018] [Accepted: 10/09/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the survival trends in colorectal cancer (CRC) based on the different classifications recommended by the seventh and eighth editions of the American Joint Committee on Cancer staging system (AJCC-7th and AJCC-8th).
METHODS The database from our institution was queried to identify patients with pathologically confirmed stage 0-IV CRC diagnosed between 2006 and 2012. Data from 2080 cases were collected and 1090 cases were evaluated through standardized inclusion and exclusion criteria. CRC was staged by AJCC-7th and then restaged by AJCC-8th. Five-year disease-free survival (DFS) and overall survival (OS) were compared. SPSS 21.0 software was used for all data. DFS and OS were compared and analyzed by Kaplan-Meier and Log-rank test.
RESULTS Linear regression and automatic linear regression showed lymph node positive functional equations by tumor-node-metastasis staging from AJCC-7th and tumor-node-metastasis staging from AJCC-8th. Neurological invasion, venous infiltration, lymphatic infiltration, and tumor deposition put forward stricter requirements for pathological examination in AJCC-8th compared to AJCC-7th. After re-analyzing our cohort with AJCC-8th, the percentage of stage IVB cases decreased from 2.8% to 0.8%. As a result 2% of the cases were classified under the new IVC staging. DFS and OS was significantly shorter (P = 0.012) in stage IVC patients compared to stage IVB patients.
CONCLUSION The addition of stage IVC in AJCC-8th has shown that peritoneal metastasis has a worse prognosis than distant organ metastasis in our institution’s CRC cohort. Additional datasets should be analyzed to confirm these findings.
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Affiliation(s)
- Guo-Jun Tong
- General Surgery Department, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
- Central Laboratory, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Gui-Yang Zhang
- General Surgery Department, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Jian Liu
- General Surgery Department, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Zhao-Zheng Zheng
- General Surgery Department, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Yan Chen
- General Surgery Department, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Ping-Ping Niu
- Central Laboratory, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Xu-Ting Xu
- Central Laboratory, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
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Zhang H, Wang Z, Ma R, Wu J, Feng J. MicroRNAs as biomarkers for the progression and prognosis of colon carcinoma. Int J Mol Med 2018; 42:2080-2088. [PMID: 30066832 PMCID: PMC6108873 DOI: 10.3892/ijmm.2018.3792] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/10/2018] [Indexed: 12/14/2022] Open
Abstract
Early detection is critical for the treatment of colon carcinoma. However, current biomarkers for its diagnosis and prognosis are insufficient and improvement is required. Aberrantly expressed microRNAs (miRNAs/miRs) in colon carcinoma have been identified to function as potential diagnostic and prognostic biomarkers. In the present study, 245 differentially expressed miRNAs between colon carcinoma and normal tissues were identified by a bioinformatics analysis of a dataset from The Cancer Genome Atlas. A six-miRNA (miR-149, miR-3189, miR-3677, miR-3917, miR-4999 and miR-6854) prognostic prediction system was established, which is able to independently and effectively predict the prognosis of colon carcinoma patients [P<0.001, area under the receiver operating characteristic curve (AUC)=0.763]. Furthermore, the six miRNAs were highly correlated with the tumor-nodes-metastasis (TNM) stage and were able to distinguish between different stages (high vs. low TNM stage, P<0.001). Of note, combination of the six-miRNA signature and TNM stage provides an improved prediction of the patient's prognosis (AUC=0.797). Functional enrichment analysis revealed the possible mechanistic involvement of these predictive miRNAs in cancer-associated biological processes and pathways. Taken together, the present study demonstrated the promising potential of the novel six-miRNA model as an independent factor for the prediction of the progression and prognosis of colon carcinoma.
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Affiliation(s)
- Hui Zhang
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China
| | - Zhuo Wang
- Laboratory of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China
| | - Rong Ma
- Laboratory of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China
| | - Jianzhong Wu
- Laboratory of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China
| | - Jifeng Feng
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China
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Denost Q, Saillour F, Masya L, Martinaud HM, Guillon S, Kret M, Rullier E, Quintard B, Solomon M. Benchmarking trial between France and Australia comparing management of primary rectal cancer beyond TME and locally recurrent rectal cancer (PelviCare Trial): rationale and design. BMC Cancer 2016; 16:262. [PMID: 27044252 PMCID: PMC4820920 DOI: 10.1186/s12885-016-2286-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 03/18/2016] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Among patients with rectal cancer, 5-10% have a primary rectal cancer beyond the total mesorectal excision plane (PRC-bTME) and 10% recur locally following primary surgery (LRRC). In both cases, patients 'care remains challenging with a significant worldwide variation in practice regarding overall management and criteria for operative intervention. These variations in practice can be explained by structural and organizational differences, as well as cultural dissimilarities. However, surgical resection of PRC-bTME and LRRC provides the best chance of long-term survival after complete resection (R0). With regards to the organization of the healthcare system and the operative criteria for these patients, France and Australia seem to be highly different. A benchmarking-type analysis between French and Australian clinical practice, with regards to the care and management of PRC-bTME and LRRC, would allow understanding of patients' care and management structures as well as individual and collective mechanisms of operative decision-making in order to ensure equitable practice and improve survival for these patients. METHODS/DESIGN The current study is an international Benchmarking trial comparing two cohorts of 120 consecutive patients with non-metastatic PRC-bTME and LRRC. Patients with curative and palliative treatment intent are included. The study design has three main parts: (1) French and Australian cohorts including clinical, radiological and surgical data, quality of life (MOS SF36, FACT-C) and distress level (Distress thermometer) at the inclusion, 6 and 12 months; (2) experimental analyses consisting of a blinded inter-country reading of pelvic MRI to assess operatory decisions; (3) qualitative analyses based on MDT meeting observation, semi-structured interviews and focus groups of health professional attendees and conducted by a research psychologist in both countries using the same guides. The primary endpoint will be the clinical resection rate. Secondary end points will be concordance rate between French and Australian operative decisions based on the inter-country reading MRI, post-operative mortality and morbidity rates, oncological outcomes based on resection status and one-year overall and disease-free survival, patients' quality of life and distress level. Qualitative analysis will compare obstacles and facilitators of operative decision-making between both countries. DISCUSSION Benchmarking can be defined as a comparison and learning process which will allow, in the context of PRC-bTME and LRRC, to understand and to share the whole process management of these patientsbetween Farnce and Australia. TRIAL REGISTRATION NCT02551471 . (date of registration: 09/14/2015).
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Affiliation(s)
- Quentin Denost
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, F-33075, France. .,Université Bordeaux Segalen, Bordeaux, F-33076, France. .,Service de Chirurgie Digestive, Hôpital Saint-André, 33075, Bordeaux, France.
| | - Florence Saillour
- Unité Méthodes Evaluation en Santé, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Lindy Masya
- Surgical Outcome Research Centre (SOuRCe), Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Helene Maillou Martinaud
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, F-33075, France.,Université Bordeaux Segalen, Bordeaux, F-33076, France
| | - Stephanie Guillon
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, F-33075, France.,Université Bordeaux Segalen, Bordeaux, F-33076, France
| | - Marion Kret
- Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du CHU de Bordeaux (USMR), Université Bordeaux Segalen, Case 75, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Eric Rullier
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, F-33075, France.,Université Bordeaux Segalen, Bordeaux, F-33076, France
| | - Bruno Quintard
- Laboratory of Psychology, Université Victor Segalen Bordeaux 2, Bordeaux, France
| | - Michael Solomon
- Surgical Outcome Research Centre (SOuRCe), Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Bilchik AJ, Wainberg ZA, Nissan A, Slamon DJ, Protic M, Avital I, Chen HW, Chen D, Sim M, Elashoff D, Stojadinovic A. Value of primary tumor gene signatures in colon cancer when national quality standards are adhered to: preliminary results of an international prospective multicenter trial. Ann Surg Oncol 2014; 22:535-42. [PMID: 25190115 DOI: 10.1245/s10434-014-4013-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Indexed: 11/18/2022]
Abstract
BACKGROUND The purpose of this study was to determine if gene signatures are informative in colon cancer (CC) when National Quality Standards (NQS) are adhered to. Several studies have demonstrated the prognostic potential of gene signatures in primary CC. This has never been evaluated prospectively with adherence to NQS. METHODS This was a prospective, international, multicenter trial. Eligibility criteria were: no distant metastasis, ≥12 lymph nodes (LNs), and no adjuvant chemotherapy for LN-negative CC. RNA from frozen tumor samples was considered reliable if RNA Integrity Number >9. Using an Agilent whole human genome array, 44,000 genes were analyzed in primary tumors for differential gene expression (DGE). ANOVA applied at 2-fold expression level was performed in at least 8 experiments to obtain the DGEs. RESULTS Molecular analysis was completed in 113 of 128 patients. With median follow-up of 27 months, 11.5 % recurred within 3 years after surgery. Significant DGE was identified in recurrent tumors reflected by upregulation (UR) in cellular proliferation and by downregulation (DR) in prodifferentiating panel of 9 genes, independent of T or N classification. By multivariate analysis 3-year disease-free survival was 12.5 % in the UR/DR group versus 93.4 % in the non-UR/DR group (p < .0001; HR = 24.2; 95 % CI 4.8-120.4). CONCLUSIONS This is the first prospective trial to evaluate gene signatures in CC with adherence to a 12-node minimum quality standard. Certain molecular pathways may be prognostically relevant if both surgery and pathology are standardized, regardless of T or N classification. Careful consideration should be made to include surgical quality measures when planning clinical trials to evaluate the true effect of molecular markers in CC.
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Affiliation(s)
- Anton J Bilchik
- John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA,
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Demir L, Ekinci N, Erten C, Somali I, Can A, Dirican A, Cokmert S, Bayoglu V, Akyol M, Kucukzeybek Y, Alacacioglu A, Tarhan MO. The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer. J Surg Oncol 2014; 109:665-75. [DOI: 10.1002/jso.23563] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 12/21/2013] [Indexed: 01/31/2023]
Affiliation(s)
- Lutfiye Demir
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
- Department of Basic Oncology; Institute of Oncology; Dokuz Eylul University Medical Faculty; Izmir Turkey
| | - Nese Ekinci
- Department of Pathology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Cigdem Erten
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Isil Somali
- Department of Medical Oncology; Institute of Oncology; Dokuz Eylul University Medical Faculty; Izmir Turkey
| | - Alper Can
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Ahmet Dirican
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Suna Cokmert
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Vedat Bayoglu
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Murat Akyol
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Yuksel Kucukzeybek
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Ahmet Alacacioglu
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
| | - Mustafa Oktay Tarhan
- Department of Medical Oncology; Ataturk Training and Resarch Hospital; Katip Celebi University; Izmir Turkey
- Department of Preventive Oncology; Institute of Oncology; Dokuz Eylul University Medical Faculty; Izmir Turkey
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Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, Bilchik AJ. AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg 2013; 217:181-90. [PMID: 23768788 DOI: 10.1016/j.jamcollsurg.2013.04.018] [Citation(s) in RCA: 217] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 04/09/2013] [Accepted: 04/09/2013] [Indexed: 01/11/2023]
Abstract
BACKGROUND The 7th edition of the AJCC Cancer Staging Manual (AJCC-7) includes substantial changes for colon cancer (CC), which are particularly complex in patients with stage II and III disease. We used a national cancer database to determine if these changes improved prediction of survival. STUDY DESIGN The database of the Surveillance, Epidemiology and End Results Program was queried to identify patients with pathologically confirmed stage I to III CC diagnosed between 1988 and 2008. Colon cancer was staged by the 6(th) edition of the AJCC Cancer Staging Manual (AJCC-6) and then restaged by AJCC-7. Five-year disease-specific survival and overall survival were compared. RESULTS After all exclusion criteria were applied, AJCC-6 and AJCC-7 staging was possible in 157,588 patients (68.9%). Bowker's test of symmetry showed that the number of patients per substage was different for AJCC-6 and AJCC-7 (p < 0.001). The Akaike information criteria comparison showed superior fit with the AJCC-7 model (p < 0.001). However, although AJCC-7 staging yielded a progressive decrease in disease-specific survival and overall survival of patients with stage IIA (86.3% and 72.4%, respectively), IIB (79.4% and 63.2%, respectively), and IIC (64.9% and 54.6%, respectively) CC, disease-specific survival and overall survival of patients with stage IIIA disease increased (89% and 79%, respectively). Subset analysis of patients with >12 lymph nodes examined did not affect this observation. CONCLUSIONS The AJCC-7 staging of CC does not address all survival discrepancies, regardless of the number of lymph nodes examined. Consideration of other prognostic factors is critical for decisions about therapy, particularly for patients with stage II CC.
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Affiliation(s)
- Danielle M Hari
- Gastrointestinal Research Program, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA
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Abstract
BACKGROUND Approximately 10% of patients with colorectal cancer have locally advanced disease with peritoneal involvement (T4a) or invasion of adjacent organs (T4b) at the time of diagnosis. Of patients who undergo resection with curative intent, between 7 and 33% develop isolated locoregional recurrences. R0 surgical excision is potentially curative. METHODS We reviewed the literature relating to multivisceral resection for T4 or recurrent colorectal cancer. RESULTS Comprehensive staging to identify the local and systemic extent of disease is essential to determine resectability and patient suitability for a curative approach. PET scans and pelvic MRI (rectal) staging and a coordinated multispecialty input to neoadjuvant treatment, multivisceral surgical resection, reconstruction and adjuvant chemotherapy are essential. Intraoperative radiotherapy and hyperthermic intraperitoneal chemotherapy may have a role in selected patients. R0 resection can achieve 5-year local control rates for primary locally advanced and recurrent colorectal cancer of up to 89 and 38%, respectively, and overall 5-year survival up to 66 and 25%, respectively. CONCLUSION An aggressive surgical strategy as part of a multimodal strategy in the treatment of locally advanced or recurrent colorectal cancer in the absence of incurable metastatic disease affords the best prospect for long-term survival in selected patients.
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Affiliation(s)
- J O Larkin
- Surgical Professorial Unit, St. Vincent's University Hospital and UCD School of Medicine and Medical Sciences, Dublin, Ireland
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