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Liu Y, Ge H, Fan ZM, Lu T, He L, Li M, Zhao HR, Leng Q. Simvastatin inhibits proliferation and migration, promotes oxidative stress and ferroptosis in colon cancer. World J Gastrointest Oncol 2025; 17:104522. [DOI: 10.4251/wjgo.v17.i5.104522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 02/27/2025] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a major cause of cancer-related mortality, with limited therapeutic options for advanced stages. Simvastatin, primarily used to lower cholesterol, has shown potential as an anticancer agent. It may exert its effects by inhibiting SERPINE1, a protein implicated in CRC progression, and activating the cyclic guanosine monophosphate-protein kinase G (cGMP/PKG) signaling pathway. Given these findings, this study hypothesizes that simvastatin inhibits CRC cell proliferation and migration by downregulating SERPINE1 and activating the cGMP/PKG pathway, offering a novel therapeutic strategy for CRC management.
AIM To study the effects of simvastatin on the function of colon cancer cells and to uncover the underlying mechanisms.
METHODS NCM460, HCT-116, and SW620 cell lines were used for in vitro experiments with simvastatin at doses of 20 μM, 40 μM, and 80 μM. The Stitch database was used to analyze the target genes of simvastatin, whereas STRING was used to investigate SERPINE1 and its related pathways. HCT-116 and SW620 cells were transfected with single-cell RNA sequencing reveals SERPINE1 with or without Rp-8-Br-cGMP (a PKG inhibitor). Cell toxicity, proliferation, and migration were evaluated using the cell counting kit-8, colony formation, and Transwell assays, respectively. Apoptosis was analyzed via flow cytometry, and levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) were detected using commercial kits. Real-time polymerase chain reaction and western blotting were used to analyze gene expression.
RESULTS Simvastatin dose-dependently inhibited the proliferation and migration of HCT-116 and SW620 cells while promoting apoptosis. It downregulated Ki-67, proliferating cell nuclear antigen, MMP2, and MMP9, and upregulated Bax, particularly at higher doses. Simvastatin increased the ROS, MDA, and Fe2+ levels while decreasing the GSH levels. It downregulated SLC7A11 and ferroportin and upregulated TRF1. SERPINE1 was identified as a core target, with related genes enriched in the cGMP/PKG pathway. SERPINE1 knockdown increased GUCY1B1 and PRKG1 levels, decreased cell viability, and altered oxidative stress markers, with the effects being reversed by Rp-8-Br-cGMP.
CONCLUSION Simvastatin effectively inhibited the proliferation and migration of colon cancer cells and promoted apoptosis through the modulation of key targets, such as SERPINE1 and the cGMP/PKG signaling pathway.
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Affiliation(s)
- Ying Liu
- Department of Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Hao Ge
- Department of Traditional Chinese Medicine Surgery, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210038, Jiangsu Province, China
| | - Zhi-Min Fan
- Department of Anorectal Medicine, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Ting Lu
- Department of Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Lei He
- Department of Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Meng Li
- Department of Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Hao-Ran Zhao
- Department of Traditional Chinese Medicine Surgery, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210038, Jiangsu Province, China
| | - Qiang Leng
- Department of Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
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Kato H, Kawai K, Nakano D, Dejima A, Ise I, Natsume S, Takao M, Shibata S, Iizuka T, Akimoto T, Tsukada Y, Ito M. Does Colorectal Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer Increase Perineural Invasion? J Anus Rectum Colon 2024; 8:195-203. [PMID: 39086875 PMCID: PMC11286373 DOI: 10.23922/jarc.2023-057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 03/18/2024] [Indexed: 08/02/2024] Open
Abstract
Objectives To clarify whether self-expandable metallic stent (SEMS) placement for obstructive colorectal cancer (CRC) increases perineural invasion (PNI), thereby worsening the prognosis. Methods In total, 1022 patients with pathological T3 or T4 colon or rectosigmoid cancer who underwent resection were retrospectively reviewed. The study patients were divided into a no obstruction group (n=693), obstruction without stent group (n=251), and obstruction with stent group (n=78), and factors demonstrating an independent association with PNI, the difference in PNI incidence and severity between groups, and the association between PNI and the duration from SEMS placement to surgery were investigated. Survival analysis was performed for each group. Results On multivariate analysis, SEMS placement (hazard ratio [HR]: 2.08) was independently associated with PNI whereas SEMS placement was not. PNI occurred in 39%, 45%, and 68% of the no obstruction, obstruction without stent, and obstruction with stent group, respectively. In the obstruction with stent group, the proportion of PNI was not associated with the duration from SEMS placement to surgery. Extramural PNI, an advanced form of PNI, demonstrated no increase with increasing interval. The five-year OS was 86.3%, 76.7%, and 73.1% in no obstruction, obstruction without stent, and obstruction with stent group, respectively. On multivariate analysis, obstruction was an independent risk factor of decreased OS (HR: 1.57) whereas SEMS placement was not. Conclusions The prognosis was comparable between patients with SEMS placement and those with an obstruction who did not undergo SEMS placement, thus demonstrating that SEMS is a viable, therapeutic option for BTS.
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Affiliation(s)
- Hiroki Kato
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Daisuke Nakano
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Akira Dejima
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Ichiro Ise
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Soichiro Natsume
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Misato Takao
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Satomi Shibata
- Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Toshiro Iizuka
- Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Tetsuo Akimoto
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan
| | - Yuichiro Tsukada
- Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Masaaki Ito
- Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan
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Abstract
BACKGROUND It is unknown if the reduction in the expected number of cancer cases diagnosed during Swedish holidays are due to diagnostic delays, how different cancers are affected, and if the season of diagnosis influences long-term cancer survival. We aimed to quantify seasonal trends in incidence and excess mortality for a wide range of malignancies, requiring more or less urgent clinical management. MATERIAL AND METHODS This nationwide cohort study included all Swedish residents aged 20-84 in 1990-2019. Incidence and relative survival in pancreatic, colorectal, lung, urothelial, breast, and prostate cancer, together with malignant melanoma, non-Hodgkin lymphoma, and acute leukemia diagnosed during holiday and post-holiday were compared to working (reference) season. Incidence rate ratios (IRR) were estimated using Poisson regression and excess (cancer) mortality rate ratios using flexible parametric models. RESULTS We identified 882,980 cancer cases. Incidence declined during holiday season for all malignancies and the IRR ranged from 0.58 (95% CI 0.57-0.59 in breast to 0.92 (95% CI 0.89-0.94) in pancreatic cancer. A post-holiday increase was noted for acute leukemia, pancreatic, and lung cancer. For all malignancies except lung cancer, non-Hodgkin lymphoma, and acute leukemia, the excess mortality at 2 years from diagnosis was higher among those diagnosed during the holiday season. A tendency toward elevated short-term (0.5 years) excess mortality was noted in the post-holiday group, but long-term effects only persisted in breast cancer. CONCLUSION This study demonstrates lower holiday detection rates and higher mortality rates in various cancer types diagnosed during holiday season. Healthcare systems should offer a uniform level of cancer care independent of calendar season.
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Affiliation(s)
- Ida Wikén
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Therese M-L Andersson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Cecilia Radkiewicz
- Upper Gastrointestinal Surgery/Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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Kang BM, Park JS, Kim HJ, Park SY, Yoon G, Choi GS. Prognostic Value of Mesorectal Lymph Node Micrometastases in ypN0 Rectal Cancer After Chemoradiation. J Surg Res 2022; 276:314-322. [DOI: 10.1016/j.jss.2022.02.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 02/11/2022] [Accepted: 02/17/2022] [Indexed: 11/24/2022]
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Kohl VKB, Weber K, Brunner M, Geppert CI, Fietkau R, Grützmann R, Semrau S, Merkel S. Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma. Int J Colorectal Dis 2022; 37:1355-1365. [PMID: 35545701 PMCID: PMC9167202 DOI: 10.1007/s00384-022-04174-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/23/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE This single-centre cohort study was designed to identify factors that can predict primary tumour downstaging by neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. METHODS Prospectively collected data from 555 patients with clinical T category (cT) cT3-4 rectal carcinoma treated between 1995 and 2019 were retrospectively analysed. All patients received long-term neoadjuvant chemoradiotherapy followed by surgery with curative intent at the Department of Surgery, University Hospital Erlangen, Germany. Patient-, tumour- and treatment-related factors with a potential impact on the downstaging of rectal carcinoma to pathological T category (pT) ≤ ypT2 and ypT0 were analysed in univariate and multivariate logistic regression analyses. The prognosis of patients with and without downstaging of the primary tumour was compared. RESULTS A total of 288 (51.9%) patients showed downstaging to ≤ ypT2. Eighty-six (15.5%) patients achieved clinical complete regression (ypT0). In the multivariate logistic regression analysis, the factors cT category, BMI, ECOG score, CEA, histological type, extension in the rectum and year of the start of treatment were found to be independent factors for predicting downstaging to ≤ ypT2 after neoadjuvant chemoradiotherapy. The year of treatment initiation also remained an independent significant predictor for pathological complete regression. The prognosis was superior in patients with downstaging to ≤ ypT2 in terms of locoregional and distant recurrence as well as disease-free and overall survival. CONCLUSION Factors predicting downstaging after long-term nCRT could be identified. This may be helpful for counselling patients and selecting the optimal treatment for patients with advanced rectal carcinoma.
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Affiliation(s)
- Valerie K. B. Kohl
- Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany ,Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany
| | - Klaus Weber
- Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany ,Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany
| | - Maximilian Brunner
- Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany ,Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany
| | - Carol I. Geppert
- Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany ,Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Rainer Fietkau
- Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany ,Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Robert Grützmann
- Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany ,Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany
| | - Sabine Semrau
- Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany ,Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Susanne Merkel
- Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany ,Comprehensive Cancer Center Erlangen–European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany ,Department of Surgery, University Hospital Erlangen, Krankenhausstr. 12, 91054 Erlangen, Germany
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Chen K, Collins G, Wang H, Toh JWT. Pathological Features and Prognostication in Colorectal Cancer. Curr Oncol 2021; 28:5356-5383. [PMID: 34940086 PMCID: PMC8700531 DOI: 10.3390/curroncol28060447] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/01/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
The prognostication of colorectal cancer (CRC) has traditionally relied on staging as defined by the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging classifications. However, clinically, there appears to be differences in survival patterns independent of stage, suggesting a complex interaction of stage, pathological features, and biomarkers playing a role in guiding prognosis, risk stratification, and guiding neoadjuvant and adjuvant therapies. Histological features such as tumour budding, perineural invasion, apical lymph node involvement, lymph node yield, lymph node ratio, and molecular features such as MSI, KRAS, BRAF, and CDX2 may assist in prognostication and optimising adjuvant treatment. This study provides a comprehensive review of the pathological features and biomarkers that are important in the prognostication and treatment of CRC. We review the importance of pathological features and biomarkers that may be important in colorectal cancer based on the current evidence in the literature.
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Affiliation(s)
- Kabytto Chen
- Discipline of Surgery, Faculty of Medicine and Health, The University of Sydney, Westmead 2145, Australia; (G.C.); (H.W.)
- Division of Colorectal Surgery, Department of Surgery, Westmead Hospital, Westmead 2145, Australia
| | - Geoffrey Collins
- Discipline of Surgery, Faculty of Medicine and Health, The University of Sydney, Westmead 2145, Australia; (G.C.); (H.W.)
- Division of Colorectal Surgery, Department of Surgery, Westmead Hospital, Westmead 2145, Australia
| | - Henry Wang
- Discipline of Surgery, Faculty of Medicine and Health, The University of Sydney, Westmead 2145, Australia; (G.C.); (H.W.)
- Division of Colorectal Surgery, Department of Surgery, Westmead Hospital, Westmead 2145, Australia
| | - James Wei Tatt Toh
- Discipline of Surgery, Faculty of Medicine and Health, The University of Sydney, Westmead 2145, Australia; (G.C.); (H.W.)
- Division of Colorectal Surgery, Department of Surgery, Westmead Hospital, Westmead 2145, Australia
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Adams K, Chapuis PH, Keshava A, Rickard MJFX, Stewart P, Suen M, Chan C, Dent OF. Recurrence and colon cancer-specific death in patients with large bowel obstruction requiring urgent operation: a competing risks analysis. Colorectal Dis 2021; 23:2604-2618. [PMID: 34252253 DOI: 10.1111/codi.15807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/19/2021] [Accepted: 07/06/2021] [Indexed: 02/08/2023]
Abstract
AIM Clinical presentation with large bowel obstruction has been proposed as a predictor of poor long-term oncological outcomes after resection for colorectal cancer. This study examines the association between obstruction and recurrence and cancer-specific death after resection for colon cancer. METHOD Consecutive patients who underwent resection for colon cancer between 1995 and 2014 were drawn from a prospectively recorded hospital database with all surviving patients followed for at least 5 years. The outcomes of tumour recurrence and colon cancer-specific death were assessed by competing risks multivariable techniques with adjustment for potential clinical and pathological confounding variables. RESULTS Recurrence occurred in 271 of 1485 patients who had a potentially curative resection. In bivariate analysis, obstruction was significantly associated with recurrence [hazard ratio (HR) 2.23, CI 1.52-3.26, p < 0.001] but this association became nonsignificant after adjustment for confounders (HR 1.53, CI 0.95-2.46, p = 0.080). Colon cancer-specific death occurred in 238 of 295 patients who had a noncurative resection. Obstruction was not significantly associated with cancer-specific death (HR 1.02, CI 0.72-1.45, p = 0.903). In patients who had a noncurative resection, the competing risks incidence of colon cancer-specific death was not significantly greater in obstructed than in unobstructed patients (HR 1.02, CI 0.72-1.45, p = 0.903). CONCLUSION Whilst the immediate clinical challenge of an individual patient presenting with large bowel obstruction must be addressed by the surgeon, the patient's long-term oncological outcomes are unrelated to obstruction per se.
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Affiliation(s)
- Katie Adams
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Pierre H Chapuis
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Department of Surgery, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Anil Keshava
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Department of Surgery, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Matthew J F X Rickard
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Department of Surgery, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Peter Stewart
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Department of Surgery, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Michael Suen
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Charles Chan
- Division of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Department of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Owen F Dent
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Department of Surgery, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
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González N, Loroño A, Aguirre U, Lázaro S, Baré M, Redondo M, Briones E, Sarasqueta C, Bilbao A, de Larrea NF, Quintana JM. Risk scores to predict mortality 2 and 5 years after surgery for colorectal cancer in elderly patients. World J Surg Oncol 2021; 19:252. [PMID: 34446044 PMCID: PMC8394051 DOI: 10.1186/s12957-021-02356-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/01/2021] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND The aim of this study was to identify predictors of mortality in elderly patients undergoing colorectal cancer surgery and to develop a risk score. METHODS This was an observational prospective cohort study. Individuals over 80 years diagnosed with colorectal cancer and treated surgically were recruited in 18 hospitals in the Spanish National Health Service, between June 2010 and December 2012, and were followed up 1, 2, 3, and 5 years after surgery. Sociodemographic and clinical data were collected. The primary outcomes were mortality at 2 and between 2 and 5 years after the index admission. RESULTS The predictors of mortality 2 years after surgery were haemoglobin ≤ 10 g/dl and colon locations (HR 1.02; CI 0.51-2.02), ASA class of IV (HR 3.55; CI 1.91-6.58), residual tumour classification of R2 (HR 7.82; CI 3.11-19.62), TNM stage of III (HR 2.14; CI 1.23-3.72) or IV (HR 3.21; CI 1.47-7), LODDS of more than - 0.53 (HR 3.08; CI 1.62-5.86)) and complications during admission (HR 1.73; CI 1.07-2.80). Between 2 and 5 years of follow-up, the predictors were no tests performed within the first year of follow-up (HR 2.58; CI 1.21-5.46), any complication due to the treatment within the 2 years of follow-up (HR 2.47; CI 1.27-4.81), being between 85 and 89 and not having radiotherapy within the second year of follow-up (HR 1.60; CI 1.01-2.55), no colostomy closure within the 2 years of follow-up (HR 4.93; CI 1.48-16.41), medical complications (HR 1.61; CI 1.06-2.44), tumour recurrence within the 2 years of follow-up period (HR 3.19; CI 1.96-5.18), and readmissions at 1 or 2 years of follow-up after surgery (HR 1.44; CI 0.86-2.41). CONCLUSION We have identified variables that, in our sample, predict mortality 2 and between 2 and 5 years after surgery for colorectal cancer older patients. We have also created risks scores, which could support the decision-making process. TRIAL REGISTRATION ClinicalTrials.gov , NCT02488161 .
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Affiliation(s)
- Nerea González
- Osakidetza Basque Health Service, Galdakao – Usansolo Hospital (Research Unit), Galdakao, Basque Country Spain
- Kronikgune Institute for Health Services Research, Barakaldo, Basque Country Spain
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
| | - Ane Loroño
- Osakidetza Basque Health Service, Galdakao – Usansolo Hospital (Research Unit), Galdakao, Basque Country Spain
| | - Urko Aguirre
- Osakidetza Basque Health Service, Galdakao – Usansolo Hospital (Research Unit), Galdakao, Basque Country Spain
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
| | - Santiago Lázaro
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
- Osakidetza Basque Health Service, Galdakao–Usansolo Hospital (Surgery Department), Galdakao, Basque Country Spain
| | - Marisa Baré
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
- Clinical Epidemiology and Cancer Screening, Parc Taulí University Hospital, Parc del Taulí, 1, 08208 Sabadell, Barcelona, Spain
| | - Maximino Redondo
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
- Andalusian Health Service, Resarch Unit, Costa del Sol Hospital, Autovía A-7 Km, 187-29603 Marbella, Malaga Spain
| | - Eduardo Briones
- UDG Public Health, AP Sevilla district, Av. de Jerez, 41013 Sevilla, Spain
| | - Cristina Sarasqueta
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
- Biodonostia Health Research Institute, Donostia Universitary Hospital, Begiristain Doktorea Pasealekua, 20014 Donostia-San Sebastian, Guipuzkoa Spain
| | - Amaia Bilbao
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
- Osakidetza Basque Health Service, Research Unit, Basurto Universitary Hospital, Montevideo Etorb., 18, 48013 Bilbao, Bizkaia Spain
| | - Nerea Fernández de Larrea
- Epidemiology National Centre, Institute of Health Carlos III, Calle de Melchor Fernández Almagro, 5, 28029 Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - José María Quintana
- Osakidetza Basque Health Service, Galdakao – Usansolo Hospital (Research Unit), Galdakao, Basque Country Spain
- Health Services Research on Chronic Patients Network, REDISSEC, Galdakao, Basque Country Spain
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Psoas Muscle Index Defined by Computer Tomography Predicts the Presence of Postoperative Complications in Colorectal Cancer Surgery. ACTA ACUST UNITED AC 2021; 57:medicina57050472. [PMID: 34064607 PMCID: PMC8151336 DOI: 10.3390/medicina57050472] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 05/01/2021] [Accepted: 05/07/2021] [Indexed: 12/25/2022]
Abstract
Background and Objectives: Sarcopenia is a recognized prognostic factor for both complications and survival in cancer patients. This study aims to analyze the relationship between sarcopenia measured by psoas muscle index on computer tomography scans and the presence of postoperative complications in colorectal cancer surgery. Materials and Methods: In a prospective study we recorded data from 51 patients who underwent colorectal cancer surgery in the Mures County Clinical Hospital, Romania. Total psoas muscle area and psoas density were measured at the level of the third lumbal vertebra (L3) for further index calculation. We also evaluated the general characteristics and laboratory analyses to obtain more information about status of the patients. Short-term postoperative complications were scored according to the Clavien-Dindo classification. Results: The majority of the 51 patients were male (61%) and the median age was 65 years. More than half of the cancer was located in the rectum (56.9%), a quarter in the right colon (25.5%), the rest in the sigmoid (11.8%), and the left colon (5.9%). Twenty-one patients (41.2%) developed a complication, five (9.8%) of these were Clavien-Dindo grade 3, 4 or 5 (high grade) and sixteen (31.3%) grade 1 or 2 (low grade). The low- and high-grade groups showed a significantly lower right psoas muscle area, left psoas muscle area, total psoas muscle area, and psoas muscle index (p < 0.001 in all cases). Among laboratory analyses, a significantly lower perioperative hematocrit, hemoglobin, and albumin level were found in patients who developed complications. Furthermore we observed that an elevated serum C-reactive protein level was associated with a higher grade of complication (p < 0.043). Conclusions: The psoas muscle index (PMI) influence on the postoperative outcome is an important factor in our single center prospective study and it appears to be a good overall predictor in colorectal surgery. A lower PMI is directly associated with a low or high grade complication by Clavien-Dindo classification. Perioperative inflammatory and nutritional status evidenced by serum C-reactive protein (CRP) and albumin level influences the presence of postoperative complications.
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Manceau G, Voron T, Mege D, Bridoux V, Lakkis Z, Venara A, Beyer-Berjot L, Abdalla S, Sielezneff I, Lefèvre JH, Karoui M. Prognostic factors and patterns of recurrence after emergency management for obstructing colon cancer: multivariate analysis from a series of 2120 patients. Langenbecks Arch Surg 2019; 404:717-729. [PMID: 31602503 DOI: 10.1007/s00423-019-01819-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 08/21/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE At equal TNM stage, obstructing colon cancer (OCC) is associated with worse prognosis in comparison with uncomplicated cancer. Our aim was to identify prognostic factors of overall (OS) and disease-free survival (DFS) in patients treated for OCC. METHODS From 2000 to 2015, 2325 patients were treated for OCC in French surgical centers, members of the French National Surgical Association (AFC). Patients with palliative management were excluded. The main endpoints were OS and DFS. A multivariate analysis, using Cox proportional hazards regression model, was performed to determine independent prognostic factors. RESULTS The cohort included 2120 patients. The median of follow-up was 13.2 months. In multivariate analysis, age > 75 years, ASA score ≥ 3, ECOG score ≥ 3, right-sided colon cancer, presence of synchronous metastases, anastomotic leakage, and absence of adjuvant chemotherapy were independent OS factors. Age > 75 years, ASA score ≥ 3, right-sided colon cancer, presence of synchronous metastases, and absence of postoperative chemotherapy were independent factors of poor OS after exclusion of patients who died postoperatively. Age ≥ 75 years, ASA score ≥ 3, ECOG score ≥ 3, right-sided colon cancer, lymph node involvement, presence of vascular, lymphatic or perineural invasion, less than 12 harvested lymph nodes, and absence of adjuvant chemotherapy were independent DFS factors. CONCLUSIONS Management of OCC should take into account prognostic factors related to the patient (age, comorbidities), tumor location, and tumor stage. Adjuvant chemotherapy administration plays an important role. For patients undergoing initial defunctionning stoma, neoadjuvant chemotherapy could be an option to improve prognosis.
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Affiliation(s)
- Gilles Manceau
- Sorbonne Université, Assistance Publique Hôpitaux de Paris, Department of Digestive Surgery, Pitié Salpêtrière University Hospital, Paris, France
| | - Thibault Voron
- Sorbonne Université, Assistance Publique Hôpitaux de Paris, Saint Antoine University Hospital, Department of Digestive Surgery, Paris, France
| | - Diane Mege
- Timone University Hospital, Department of Digestive Surgery, Marseille, France
| | - Valérie Bridoux
- Charles Nicolle University Hospital, Department of Digestive Surgery, Rouen, France
| | - Zaher Lakkis
- Besançon University Hospital, Department of Digestive Surgery, Besançon, France
| | - Aurélien Venara
- Angers University Hospital, Department of Digestive Surgery, Angers, France
| | - Laura Beyer-Berjot
- Assistance Publique Hôpitaux de Marseille, North University Hospital, Department of Digestive Surgery, Marseille, France
| | - Solafah Abdalla
- Université Paris-Sud, Assistance Publique Hôpitaux de Paris, Bicêtre University Hospital, Department of Digestive Surgery, Le Kremlin Bicêtre, France
| | - Igor Sielezneff
- Timone University Hospital, Department of Digestive Surgery, Marseille, France
| | - Jeremie H Lefèvre
- Sorbonne Université, Assistance Publique Hôpitaux de Paris, Saint Antoine University Hospital, Department of Digestive Surgery, Paris, France
| | - Mehdi Karoui
- Sorbonne Université, Assistance Publique Hôpitaux de Paris, Department of Digestive Surgery, Pitié Salpêtrière University Hospital, Paris, France.
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Samawi HH, Yin Y, Speers CH, Cheung WY. Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based Study. Clin Colorectal Cancer 2018; 17:e711-e717. [DOI: 10.1016/j.clcc.2018.07.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/12/2018] [Accepted: 07/16/2018] [Indexed: 11/26/2022]
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12
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Braun R, Benecke C, Nolde J, Kleemann M, Zimmermann M, Keck T, Laubert T. Gender-related differences in patients with colon cancer resection. Eur Surg 2018. [DOI: 10.1007/s10353-018-0513-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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13
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Quirt JS, Nanji S, Wei X, Flemming JA, Booth CM. Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice. ACTA ACUST UNITED AC 2017; 24:e15-e23. [PMID: 28270728 DOI: 10.3747/co.24.3410] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. METHODS Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). RESULTS The study population included 7249 patients who underwent resection of colon cancer; 49% (n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. CONCLUSIONS Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.
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Affiliation(s)
- J S Quirt
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute
| | - S Nanji
- The departments of Oncology, Queen's University, Kingston, ON.; Surgery, Queen's University, Kingston, ON
| | - X Wei
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute
| | - J A Flemming
- Medicine, Queen's University, Kingston, ON.; Public Health Sciences, Queen's University, Kingston, ON
| | - C M Booth
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute; The departments of Oncology, Queen's University, Kingston, ON.; Medicine, Queen's University, Kingston, ON.; Public Health Sciences, Queen's University, Kingston, ON
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Steele M, Voutsadakis IA. Pre-treatment platelet counts as a prognostic and predictive factor in stage II and III rectal adenocarcinoma. World J Gastrointest Oncol 2017; 9:42-49. [PMID: 28144399 PMCID: PMC5241527 DOI: 10.4251/wjgo.v9.i1.42] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 08/20/2016] [Accepted: 11/02/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate if pre-treatment platelet counts could provide prognostic information in patients with rectal adenocarcinoma that received neo-adjuvant treatment.
METHODS Platelet number on diagnosis of stage II and III rectal cancer was evaluated in 51 patients receiving neo-adjuvant treatment and for whom there were complete follow-up data on progression and survival, as well as pathologic outcome at the time of surgery. Pathologic responses on the surgical specimen of patients with lower platelet counts (150-300 × 109/L) were compared with these of patients with higher platelet counts (> 300 × 109/L) by the χ2 test. Overall and progression free survival Kaplan-Meier curves of the two groups were constructed and compared with the Log-Rank test.
RESULTS A significant difference was present between the two groups in regards to pathologic response with patients with lower platelet counts being more likely to exhibit a good or complete response to neo-adjuvant treatment than patients with higher platelet counts (P = 0.015). Among other factors evaluated, there was also a significant difference between the carcinoembryonic antigen (CEA) at presentation of patients that exhibited a good or complete response and those that had no response or a minimal to moderate response. Patients with a good or complete response were more likely to present with a CEA of less than 5 μg/L (P = 0.00066). There was no significant difference in overall and progression free survival between the two platelet count groups (Log-Rank tests P = 0.42 and P = 0.35, respectively).
CONCLUSION In this retrospective analysis of stage II and III rectal cancer patients, platelet counts at the time of diagnosis had prognostic value for neo-adjuvant treatment pathologic response. Pre-treatment CEA also held prognostic value in regards to treatment effect.
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Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients. Sci Rep 2016; 6:24517. [PMID: 27075165 PMCID: PMC4830949 DOI: 10.1038/srep24517] [Citation(s) in RCA: 110] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Accepted: 03/31/2016] [Indexed: 12/30/2022] Open
Abstract
Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.
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Sucullu I, Ozdemir Y, Cuhadar M, Balta AZ, Yucel E, Filiz AI, Gulec B. Comparison of emergency surgeries for obstructed colonic cancer with elective surgeries: A retrospective study. Pak J Med Sci 2015; 31:1322-1327. [PMID: 26870090 PMCID: PMC4744275 DOI: 10.12669/pjms.316.8277] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Revised: 08/04/2015] [Accepted: 08/28/2015] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Colon cancer patients presented with obstruction were known to have worse postoperative morbidity and mortality rates, but conflicting data has been reported in recent years. We aimed to investigate postoperative complication rates, and short and long-term oncological outcomes in patients with colon cancer treated with either emergency surgery due to obstruction or elective surgery. METHODS Two hundred fifty two patients were analyzed. Patients presented with obstruction and underwent an emergency surgery, and patients operated under elective circumstances were compared according to their demographic variables, tumor characteristics, and short and long term treatment outcomes. RESULTS Distribution of age, gender and comorbidities were similar between both the groups. Need for an end colostomy was significantly higher in obstructed patients (22.7% vs 1.6%, respectively). Obstructed patients were tending to be at an advanced stage. Postoperative morbidity and mortality, and prognosis of colon cancer patients presented with obstruction is worse than patients operated under elective circumstances. CONCLUSIONS Colon cancer patients presented with obstruction constitutes more than one quarter of all patients. These patients have significantly higher morbidity and mortality rates. Obstructed colon cancer usually appears at advanced stage. Primary resection and anastomosis is safe in most of the cases.
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Affiliation(s)
- Ilker Sucullu
- Ilker Sucullu, Associate Professor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
| | - Yavuz Ozdemir
- Yavuz Ozdemir, Assistant Professor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
| | - Mehmet Cuhadar
- Mehmet Cuhadar, Resident Doctor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
| | - Ahmet Ziya Balta
- Ahmet Ziya Balta, Associate Professor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
| | - Ergun Yucel
- Ergun Yucel, Associate Professor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
| | - Ali Ilker Filiz
- Ali Ilker Filiz, Associate Professor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
| | - Bulent Gulec
- Bulent Gulec, Professor, Department of General Surgery, GATA Haydarpasa Training Hospital, Istanbul, Turkey
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17
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Kleemann M, Benecke C, Helfrich D, Bruch HP, Keck T, Laubert T. Prospective Analysis of More than 1,000 Patients with Rectal Carcinoma: Are There Gender-Related Differences? VISZERALMEDIZIN 2015; 30:118-24. [PMID: 26288586 PMCID: PMC4513819 DOI: 10.1159/000362680] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background Since the beginning of the new millennium gender medicine has become more and more relevant. The goal has been to unveil differences in presentation, treatment response, and prognosis of men and women with regard to various diseases. Methods This study encompassed 1,061 patients who underwent surgery for rectal cancer at the Department of Surgery, University Medical Center Schleswig-Holstein Campus Lübeck, Germany, between January 1990 and December 2011. Prospectively documented demographic, clinical, pathological, and follow-up data were obtained. Analysis encompassed the comparison of clinical, histopathological, and oncological parameters with regard to the subcohorts of male and female patients. Results No statistically significant differences could be found for clinical and histopathological parameters, location of tumor, resection with or without anastomosis, palliative or curative treatment, conversion rates, duration of surgery, and long-term survival. For the entire cohort, gender-related statistically significant differences in complications encompassed anastomotic leakage, burst abdomen, pneumonia, and urinary tract complications all of which occurred more often in men. Conclusion Data obtained in this study suggest that there are no gender-related differences in the oncologic surgical treatment of patients with rectal carcinoma. However, male sex seems to be a risk factor for increased early postoperative morbidity.
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Affiliation(s)
- Markus Kleemann
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| | - Claudia Benecke
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| | - Diana Helfrich
- Lübeck Medical School, University of Lübeck, Berlin, Germany
| | - Hans-Peter Bruch
- Berufsverband der Deutschen Chirurgen e.V. (BDC), Berlin, Germany
| | - Tobias Keck
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| | - Tilman Laubert
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
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The impact of osteopontin on prognosis and clinicopathology of colorectal cancer patients: a systematic meta-analysis. Sci Rep 2015; 5:12713. [PMID: 26234583 PMCID: PMC4522607 DOI: 10.1038/srep12713] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Accepted: 06/01/2015] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide. Up to now, no biomarker has been used to predict the prognosis and surveillance of patients with CRC. Recently, the association between osteopontin (OPN) overexpression and the prognosis of CRC was investigated widely, but the results were inconsistent. Therefore, the aim of present meta-analysis was to assess the prognostic effect of osteopontin in patients with CRC. PubMed, EMBASE, Web of Science, Scopus and Chinese Medical Database were systematically searched. A total of 15 studies containing 1698 patients were included in our meta-analysis. The pooled data of studies showed that high OPN expression was significantly associated with high tumor grades (OR = 2.24, 95% CI 1.55–3.23), lymph node metastasis (OR = 2.36, 95% CI 1.71–3.26) and tumor distant metastasis (OR = 2.38, 95% CI 1.01–5.60). Moreover, high OPN expression was significantly associated with the 2-year (HR 1.97, 95% CI 1.30–3.00), 3-year (HR 1.82, 95% CI 1.24–2.68), 5 year (HR 1.53, 95% CI 1.28–1.82) survival rates and overall survival (OS, HR 1.70, 95% CI 1.12–2.60), respectively. These results indicated that OPN could serve as a prognostic biomarker and as a potential therapeutic target for CRC.
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19
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Hu F, Yang S, Lv S, Peng Y, Meng L, Gou L, Zhang X. Analysis of AC3-33 gene expression in multiple organ cancer and adjacent normal tissue by RNA in situ hybridization. Oncol Lett 2015; 9:2795-2798. [PMID: 26137149 DOI: 10.3892/ol.2015.3112] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 02/23/2015] [Indexed: 11/06/2022] Open
Abstract
The AC3-33 gene encodes a secretory protein that can inhibit Elk1 transcriptional activity via the ERK1/2 pathway. In the current study, in situ RNA hybridization was used to detect the AC3-33 gene expression in multiple organ cancer and cancer-adjacent normal tissue. The results showed that the expression level of AC3-33 varies across different tissues. AC3-33 exhibited positive expression in squamous cell carcinoma of the esophagus, adenocarcinoma of the rectum, hepatocellular carcinoma, squamous cell carcinoma (SCC) of the lung, cancer-adjacent normal hepatic tissue, clear cell carcinoma of the kidney, invasive ductal carcinoma of the breast, SCC of the uterine cervix and cancer-adjacent normal kidney tissue. Negative expression of AC3-33 was observed in adenocarcinoma of the stomach and colon, cancer-adjacent normal esophageal tissue, cancer-adjacent normal gastric tissue, cancer-adjacent normal colon tissue, cancer-adjacent normal rectal tissue, serous adenocarcinoma of the ovary and cancer-adjacent normal ovarian tissue. However, the expression of AC3-33 in cancer adjacent normal breast tissue was partially positive. In conclusion, the AC3-33 gene does exhibit positive expression in certain carcinomas, which may indicate that AC3-33 has a significant involvement in the development and progression of these carcinomas.
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Affiliation(s)
- Fen Hu
- College of Life Sciences, College of Psychology, Hebei United University, Tangshan, Hebei 063000, P.R. China
| | - Shaoqing Yang
- College of Life Sciences, College of Psychology, Hebei United University, Tangshan, Hebei 063000, P.R. China
| | - Shaobo Lv
- College of Life Sciences, College of Psychology, Hebei United University, Tangshan, Hebei 063000, P.R. China
| | - Yan Peng
- College of Life Sciences, College of Psychology, Hebei United University, Tangshan, Hebei 063000, P.R. China
| | - Lijun Meng
- Department of Environment and Chemical Engineering, Tangshan College, Tangshan, Hebei 063000, P.R. China
| | - Lixia Gou
- College of Life Sciences, College of Psychology, Hebei United University, Tangshan, Hebei 063000, P.R. China
| | - Xiujun Zhang
- College of Life Sciences, College of Psychology, Hebei United University, Tangshan, Hebei 063000, P.R. China
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20
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Choi JM, Lee C, Han YM, Lee M, Choi YH, Jang DK, Im JP, Kim SG, Kim JS, Jung HC. Long-term oncologic outcomes of endoscopic stenting as a bridge to surgery for malignant colonic obstruction: comparison with emergency surgery. Surg Endosc 2014; 28:2649-55. [PMID: 24789126 DOI: 10.1007/s00464-014-3517-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Accepted: 03/10/2014] [Indexed: 01/04/2023]
Abstract
BACKGROUND Self-expandable metallic stents (SEMS) are now regarded as an effective and safe intervention for malignant colorectal obstruction (MCO). However, manipulation of the tumor might lead to the spillage of tumor cells and result in distant metastases. We aimed to compare the long-term oncologic outcomes of SEMS as a bridge to surgery with those of emergency surgery for MCO. METHODS Between June 2005 and December 2011, 60 patients who underwent elective curative resection after endoscopic SEMS insertion were included in the "SEMS group". The SEMS group was matched to 180 patients who underwent emergency curative surgery for MCO during the same period ["Emergency surgery (ES) group"]. The clinicopathologic characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between the two groups. RESULTS There were no significant differences in demographics, tumor stage, location, and histology between the SEMS group and the ES group. The median follow-up times were 41.4 months (IQR, 22.2-60.0 months) for the SEMS group and 45.0 months (IQR, 20.9-68.1 months) for the ES group. The proportions of patients who received postoperative adjuvant chemotherapy were comparable (SEMS group vs. ES group, 68.3 % vs. 77.8 %; P = 0.210). The long-term prognosis did not significantly differ between two groups in either the 5-year RFS rate (79.6 % vs. 70.2 %; P = 0.218) or the 5-year OS rate (97.8 % vs. 94.3 %; P = 0.469). CONCLUSIONS Long-term oncologic outcomes of SEMS insertion as a bridge to surgery were comparable to those of primary curative surgery.
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Affiliation(s)
- Ji Min Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea,
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Role for gender in colorectal cancer risk: a Taiwan population-based study. Int J Colorectal Dis 2013; 28:1001-8. [PMID: 23371332 DOI: 10.1007/s00384-013-1647-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/21/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Gender differences in the prognosis of colorectal cancer (CRC) remain controversial. The aim of this study was to complete a comprehensive analysis of gender differences in CRC survival derived from population registries in Taiwan. MATERIALS AND METHODS We analyzed survival data for patients diagnosed with CRC between 1998 and 2005 derived from the Taiwan Cancer Registry database. During this time period, 65,113 patients were registered, and 62,060 patients were eligible. Gender differences in overall survival and cancer-specific survival were analyzed by use of the Kaplan-Meier method. We then modeled the risk in different genders by use of a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. RESULTS The 5-year period overall and cancer-specific survivals were significantly higher in women than in men [51.84% (95% confidence interval (CI), 51.22-52.46) vs. 47.68% (95% CI, 47.14-48.22), log-rank p < 0.001; and 56.44% (95% CI, 55.82-57.07) vs. 53.47 % (95 % CI, 52.92-54.01), log-rank p < 0.001, respectively]. Subgroup analysis revealed higher overall and cancer-specific survivals in women between 50 and 80 years age and those with adenocarcinomas (p < 0.001). By use of Cox modeling, we noted a decreased hazard ratio (HR) for death from CRC in women compared with men (HR, 0.820-0.971), especially in the 50-80-year age group. All estimated HRs, after adjusting for age, tumor histology, and tumor site, had significant trends of a decreasing risk of death from CRC in women. CONCLUSIONS Our findings suggest that overall and cancer-specific survival advantage was most evident in women between 50 and 80 years of age.
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Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels. Anal Chim Acta 2013; 779:64-71. [DOI: 10.1016/j.aca.2013.03.060] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Revised: 03/21/2013] [Accepted: 03/25/2013] [Indexed: 11/17/2022]
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Ahn BK, Lee KH. Characteristics and Prognoses of Small Obstructing Colorectal Cancers: The Combination of Gross Findings Has Value in Predicting Recurrence after Curative Therapy. Am Surg 2013. [DOI: 10.1177/000313481307900535] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Byung Kyu Ahn
- Department of Surgery Hanyang University Medical Center Seoul, Korea
| | - Kang Hong Lee
- Department of Surgery Hanyang University Medical Center Seoul, Korea
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Nouguerède E, Berenguer C, Garcia S, Bennani B, Delfino C, Nanni I, Dahan L, Gasmi M, Seitz JF, Martin PM, Ouafik L. Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo. Cancer Med 2013; 2:196-207. [PMID: 23634287 PMCID: PMC3639658 DOI: 10.1002/cam4.51] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Revised: 11/08/2012] [Accepted: 11/09/2012] [Indexed: 12/17/2022] Open
Abstract
Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM22-52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target.
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Affiliation(s)
| | | | - Stéphane Garcia
- Laboratoire d'Anapathologie, CHU Nord (AP-HM)Marseille, F-13000, France
| | - Bahia Bennani
- Laboratoire de Biologie du Cancer, Faculté de Médecine et de PharmacieBP 1893, Route de Sidi Harazem, Fès, Maroc
| | | | - Isabelle Nanni
- Laboratoire de Transfert d'Oncologie Biologique (AP-HM)Marseille, F-13000, France
| | - Laetitia Dahan
- Service d'oncologie digestive, CHU la Timone (AP-HM)Marseille, F-13000, France
| | - Mohamed Gasmi
- Service de Gastro-entérologie, CHU Nord (AP-HM)Marseille, F-13000, France
| | - Jean-François Seitz
- Service d'oncologie digestive, CHU la Timone (AP-HM)Marseille, F-13000, France
| | - Pierre-Marie Martin
- Inserm, UMR 911-CRO2Marseille, F-13000, France
- Laboratoire de Transfert d'Oncologie Biologique (AP-HM)Marseille, F-13000, France
| | - L'Houcine Ouafik
- Inserm, UMR 911-CRO2Marseille, F-13000, France
- Laboratoire de Transfert d'Oncologie Biologique (AP-HM)Marseille, F-13000, France
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Al-Ahwal MS, Shafik YH, Al-Ahwal HM. First national survival data for colorectal cancer among Saudis between 1994 and 2004: what's next? BMC Public Health 2013; 13:73. [PMID: 23351644 PMCID: PMC3577472 DOI: 10.1186/1471-2458-13-73] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Accepted: 01/23/2013] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the second most common malignancy in the Saudi population. This study aimed to review CRC data from the Saudi Cancer Registry (SCR) in order to evaluate the prognostic factors for CRC survival in Saudi patients. METHODS This study was a retrospective censored overall survival (OS) analysis of CRC data for the period 1994-2004 obtained from the SCR. Data were collected from all 13 administrative regions of the Kingdom of Saudi Arabia (KSA) by the SCR in collaboration with the National Information Center of the Ministry of Interior. The Kaplan-Meier method was used to calculate the cumulative survival rate, which was then stratified by gender and by period (1994-1999 versus 2000-2004). The clinico-pathological variables that might affect CRC survival were analyzed by Cox regression analysis. RESULTS Between 1994 and 2004, 549 CRC cases were diagnosed (363 [66.1%] in males and 186 [33.9%] in females). The OS for CRC during this period was 44.6% (44.7% for 1994-1999 and 44.3% for 2000-2004 [p=0.7]). There was a significant (p=0.003) discrepancy of 9.6% between the male five-year OS (41.0%) and the female five-year OS (50.6%). The five-year OS was 63.3% for patients with localized disease, 50.2% for those with regional disease, and 14.7% for patients with metastases. By Cox regression analysis, age and extent were significant prognostic factors of survival in patients with colon cancer; the risk was higher in patients with distant metastasis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.17-5.45; p=0.01). In patients with rectal cancer, the risk was lower in males (HR, 0.66; CI, 0.45-0.98; p=0.04), but higher in patients with unknown tumor extent (HR, 3.70; 95% CI, 1.66-8.24; p=0.01). CONCLUSIONS The five-year OS for 1994-2004 was 44.6% for patients with CRC. More so, five-year OS based on CRC stage was generally lower than the typically reported survival rates. The establishment of a national screening program and increased access to specialized medical faculties may be necessary to improve CRC survival in the KSA.
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Affiliation(s)
- Mahmoud S Al-Ahwal
- Department of Medicine, Colon Cancer Chair, Faculty of Medicine, King Abdulaziz University (KAU), Jeddah, Kingdom of Saudi Arabia.
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26
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Bustin SA, Murphy J. RNA biomarkers in colorectal cancer. Methods 2013; 59:116-25. [DOI: 10.1016/j.ymeth.2012.10.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2012] [Revised: 09/28/2012] [Accepted: 10/04/2012] [Indexed: 02/08/2023] Open
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Chang HC, Horng JT, Lin WC, Lai HW, Chang CW, Chen TA. Evaluation of the appropriate age range of colorectal cancer screening based on the changing epidemiology in the past 20 years in taiwan. ISRN GASTROENTEROLOGY 2012; 2012:960867. [PMID: 22970382 PMCID: PMC3437287 DOI: 10.5402/2012/960867] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2012] [Accepted: 07/31/2012] [Indexed: 01/22/2023]
Abstract
Introduction. According to the recommendation of the United States Preventative Services Task Force, most countries provide average-risk screening for colorectal cancers (CRCs) between the ages of 50 and 75 years. However, the age range of screening should be modified because of an increasing life span. Methods. Totally 124,314 CRC cases were registered in Taiwan Cancer Registry from 1988 to 2007. The 20-year study period was divided into four 5-year increments. We divided the patients into four age groups (under age 50, age 50–74, age 74–84, and over age 85) in each increment to determine whether there were changes in the age distribution. Results. In the subgroup of patients under age 50, the number of CRC cases increased, but they accounted for a decreasing proportion of the total CRCs. In the 50–74 age group, the proportion of CRC cases also dropped. In contrast, the proportion increased in the 75–84 age group. Therefore, 43.63% of CRC patients would not be delegated to screen in the period of 2003–2007 if the CRC screening were restricted in the 50–74 age group. Conclusions. CRC screening for healthy individuals aged over 75 years is necessary.
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Affiliation(s)
- Huan-Cheng Chang
- Department of Family Medicine, Taiwan Landseed Hospital, Ping-Jen City, Taoyuan 32449, Taiwan
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Pharmacogenetics of oxaliplatin as adjuvant treatment in colon carcinoma: are single nucleotide polymorphisms in GSTP1, ERCC1, and ERCC2 good predictive markers? Mol Diagn Ther 2012; 15:277-83. [PMID: 21958378 DOI: 10.1007/bf03256419] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Adjuvant chemotherapy improves survival in stage III colon cancer patients. However, a subgroup of patients still develops recurrent disease at some point in time, partly because of the ineffectiveness of the chemotherapy. Predictive markers of response are therefore crucial. Our aim was to study the predictive value of functional polymorphisms in genes involved in the metabolism of oxaliplatin and in DNA repair in stage III colon cancer patients. MATERIALS AND METHODS Normal DNA was isolated from 98 patients diagnosed with stage III colon carcinoma. Single nucleotide polymorphisms (SNPs) in three genes (the excision repair cross-complementing genes ERCC1 [19007T>C] and ERCC2 [2251A>C], and the glutathione S-transferase pi 1 gene [GSTP1 313A>G]) were tested by PCR followed by digestion with restriction enzymes or by direct sequencing. These genes and SNPs were selected on the basis of their reported associations with oxaliplatin response in colorectal cancer. RESULTS The genotype frequencies were in Hardy-Weinberg equilibrium. GSTP1 and ERCC2 polymorphisms were significantly associated with sex. The AA genotype of GSTP1 313A>G was more frequent in men than in women (59% vs 30%, p = 0.02), and the CC genotype of ERCC2 2251A>C was significantly more frequent in women than in men (24% vs 6%, p = 0.02). In univariate and multivariate survival analysis, none of the tested polymorphisms seemed to influence disease-free survival. The GSTP1 AA genotype had different effects on survival between men and women; homozygous A men had significantly worse cancer-specific survival and overall survival than women with the same genotype (log rank p = 0.029 and p = 0.015, respectively). CONCLUSION None of the tested polymorphisms is likely to be a reliable marker of response to oxaliplatin therapy. The GSTP1 313A>G homozygous A genotype may have a prognostic value in male patients.
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Fariña Sarasqueta A, van Lijnschoten G, Lemmens VEPP, Rutten HJT, van den Brule AJC. Pharmacogenetics of oxaliplatin as adjuvant treatment in colon carcinoma: are single nucleotide polymorphisms in GSTP1, ERCC1, and ERCC2 good predictive markers? Mol Diagn Ther 2012. [PMID: 21958378 DOI: 10.2165/11592080-000000000-00000] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE Adjuvant chemotherapy improves survival in stage III colon cancer patients. However, a subgroup of patients still develops recurrent disease at some point in time, partly because of the ineffectiveness of the chemotherapy. Predictive markers of response are therefore crucial. Our aim was to study the predictive value of functional polymorphisms in genes involved in the metabolism of oxaliplatin and in DNA repair in stage III colon cancer patients. MATERIALS AND METHODS Normal DNA was isolated from 98 patients diagnosed with stage III colon carcinoma. Single nucleotide polymorphisms (SNPs) in three genes (the excision repair cross-complementing genes ERCC1 [19007T>C] and ERCC2 [2251A>C], and the glutathione S-transferase pi 1 gene [GSTP1 313A>G]) were tested by PCR followed by digestion with restriction enzymes or by direct sequencing. These genes and SNPs were selected on the basis of their reported associations with oxaliplatin response in colorectal cancer. RESULTS The genotype frequencies were in Hardy-Weinberg equilibrium. GSTP1 and ERCC2 polymorphisms were significantly associated with sex. The AA genotype of GSTP1 313A>G was more frequent in men than in women (59% vs 30%, p = 0.02), and the CC genotype of ERCC2 2251A>C was significantly more frequent in women than in men (24% vs 6%, p = 0.02). In univariate and multivariate survival analysis, none of the tested polymorphisms seemed to influence disease-free survival. The GSTP1 AA genotype had different effects on survival between men and women; homozygous A men had significantly worse cancer-specific survival and overall survival than women with the same genotype (log rank p = 0.029 and p = 0.015, respectively). CONCLUSION None of the tested polymorphisms is likely to be a reliable marker of response to oxaliplatin therapy. The GSTP1 313A>G homozygous A genotype may have a prognostic value in male patients.
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Moghimi-Dehkordi B, Safaee A. An overview of colorectal cancer survival rates and prognosis in Asia. World J Gastrointest Oncol 2012; 4:71-5. [PMID: 22532879 PMCID: PMC3334382 DOI: 10.4251/wjgo.v4.i4.71] [Citation(s) in RCA: 129] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 03/03/2012] [Accepted: 03/10/2012] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer is a rapidly rising trend in Asia. The incidence in many Asian countries is on par with the West. Several studies have provided data regarding the survival of patients with colorectal cancer. In Asia, the overall cure rate of colorectal cancer has not improved dramatically in the last decade, 5-year survival remaining at approximately 60%. Colorectal cancer survival time has increased in recent years, but mortality rate remains high. Although studies have determined a number of factors that can predict survival of patients after diagnosis, life expectancy has not been increased dramatically. It seems that among the prognostic factors explored so far, the most important are those that relate to early diagnosis of cancer. Primary detection is feasible since efficient screening modalities are available. Colonoscopic surveillance is needed, especially in subjects at higher risk.
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Affiliation(s)
- Bijan Moghimi-Dehkordi
- Bijan Moghimi-Dehkordi, Azadeh Safaee, Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran 1985711151, Iran
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Gender differences in colorectal cancer during the past 20 years in Taiwan. Int J Colorectal Dis 2012; 27:345-53. [PMID: 22038305 DOI: 10.1007/s00384-011-1318-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/04/2011] [Indexed: 02/04/2023]
Abstract
PURPOSE Gender differences in colorectal cancer (CRC) incidence have been previously reported. We designed this population-based study to determine if this gender difference was restricted to specific patient subgroups. METHODS Using the Taiwan Cancer Registry database, we identified a total of 124,314 CRCs registered from 1988 to 2007. We compared the incidence of CRCs by gender in all CRCs, in colon and rectal cancers considered separately, and in right-sided versus left-sided colon cancers. RESULTS In individuals aged 50 years and older, the incidence of CRCs was lower in females compared with males. For right-sided colon cancers, the incidence in both genders was similar. Because the proportion of right-sided colon cancer accounted for only one fourth of the total CRCs, its influence on the incidence of total CRCs is reduced. CONCLUSIONS Although the incidence of total CRCs is male dominant, the actual gender difference in CRC incidence in Taiwan is limited to the left side of the colon.
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McDonald JR, Renehan AG, O'Dwyer ST, Haboubi NY. Lymph node harvest in colon and rectal cancer: Current considerations. World J Gastrointest Surg 2012; 4:9-19. [PMID: 22347537 PMCID: PMC3277879 DOI: 10.4240/wjgs.v4.i1.9] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2011] [Revised: 04/18/2011] [Accepted: 04/25/2011] [Indexed: 02/06/2023] Open
Abstract
The prognostic significance of identifying lymph node (LN) metastases following surgical resection for colon and rectal cancer is well recognized and is reflected in accurate staging of the disease. An established body of evidence exists, demonstrating an association between a higher total LN count and improved survival, particularly for node negative colon cancer. In node positive disease, however, the lymph node ratios may represent a better prognostic indicator, although the impact of this on clinical treatment has yet to be universally established. By extension, strategies to increase surgical node harvest and/or laboratory methods to increase LN yield seem logical and might improve cancer staging. However, debate prevails as to whether or not these extrapolations are clinically relevant, particularly when very high LN counts are sought. Current guidelines recommend a minimum of 12 nodes harvested as the standard of care, yet the evidence for such is questionable as it is unclear whether an increasing the LN count results in improved survival. Findings from modern treatments, including down-staging in rectal cancer using pre-operative chemoradiotherapy, paradoxically suggest that lower LN count, or indeed complete absence of LNs, are associated with improved survival; implying that using a specific number of LNs harvested as a measure of surgical quality is not always appropriate. The pursuit of a sufficient LN harvest represents good clinical practice; however, recent evidence shows that the exhaustive searching for very high LN yields may be unnecessary and has little influence on modern approaches to treatment.
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Affiliation(s)
- James R McDonald
- James R McDonald, Andrew G Renehan, Sarah T O'Dwyer, Department of Surgery, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
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Widdison AL, Barnett SW, Betambeau N. The impact of age on outcome after surgery for colorectal adenocarcinoma. Ann R Coll Surg Engl 2011; 93:445-50. [PMID: 21929914 DOI: 10.1308/003588411x587154] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION The incidence of colorectal cancer (CRC) increases with age. The aim of this study was to investigate the impact of age and age-related factors on post-operative mortality and survival following CRC resections. METHODS A prospectively collected database of 459 CRC resections was analysed. RESULTS The mean age of the patients was 70 years (range: 25-95 years) and 54% were male. The relative proportion of female patients increased with age so that for patients aged over 77 more women were treated than men. The probability of undergoing an emergency resection (25%) did not change with age. In older patients the proportion of rectal cancers resected decreased and the proportion of hemicolectomies and Hartmann's operations performed increased. The 30-day mortality rate was 4% after elective and 11% after emergency resections. Most deaths were caused by medical complications, reflecting increased co-morbidity in the elderly. Post-operative mortality was 1% in patients under the age of 59. This increased by 3 percentage points every 10 years after elective resections and by 8 percentage points every 10 years after emergency resections. CRC-specific survival was independent of age whereas overall survival decreased so the likelihood of dying from CRC decreased with age: at age 50 half the deaths were from CRC, at age 70 a third and at age 80 a quarter. CONCLUSIONS CRC stage and the probability of presenting as an emergency did not change with age but older patients were more likely to be female and have colon cancer. Post-operative mortality progressively increased with age. Most deaths were caused by medical complications, reflecting increased co-morbidity. Older patients were less likely to die from CRC.
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Affiliation(s)
- A L Widdison
- Department of Surgical Gastroenterology, Royal Cornwall Hospital, Truro, UK.
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Repici A, de Paula Pessoa Ferreira D. Expandable metal stents for malignant colorectal strictures. Gastrointest Endosc Clin N Am 2011; 21:511-33, ix. [PMID: 21684468 DOI: 10.1016/j.giec.2011.04.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The surgical management of malignant colorectal obstruction is still controversial and has higher associated mortality and complication rates compared with elective surgery. Placement of self-expanding metallic stents (SEMS) has been proposed as an alternative therapeutic approach for colonic decompression of patients with acute malignant obstruction. SEMS placement may be used both as a bridge to surgery in patients who are good candidates for curative resection and for palliation of those patients presenting with advanced stage disease or with severe comorbid medical illnesses.
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Affiliation(s)
- Alessandro Repici
- Digestive Endoscopy Unit, IRCCS Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milano, Italy.
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Frago R, Kreisler E, Biondo S, Salazar R, Dominguez J, Escalante E. Outcomes in the management of obstructive unresectable stage IV colorectal cancer. Eur J Surg Oncol 2010; 36:1187-94. [PMID: 20864304 DOI: 10.1016/j.ejso.2010.09.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2010] [Revised: 08/18/2010] [Accepted: 09/02/2010] [Indexed: 02/07/2023] Open
Abstract
AIM To analyze short term results and to report survival rates in a series of patients after palliative emergency treatment for obstructive left sided colorectal cancer (CRC) with unresectable synchronous metastases. PATIENTS AND METHODS From 2004 to 2008, 55 patients were included. Palliative management consisted of stenting to recover bowel patency and starting chemotherapy. Indications for surgery were perforation or failure of stenting. Early failure occurred when decompression after insertion was unsuccessful and late failure when obstruction occurred after successful decompression. Morbidity and mortality were analyzed for stenting and surgery and survival for resected and non-resected patients. RESULTS Stenting was scheduled in 49 patients.Morbidity and mortality occurred in 5 and 3 patients respectively. Early failure occurred in 4 patients and late failure in 11 patients. Surgery was indicated in 6 patients for peritonitis at diagnosis and in 11 patients for complications (1 case) or stenting failure (10 cases). Of the 17 operated patients, 12 cases were resected and 5 cases were not. Mortality occurred in 1 case. Resected patients received first-line (12 cases) and second-line (5 cases) systemic chemotherapy based on FOLFIRI or FOLFOX while stented and non-resected patients were similarly treated in 37 cases and 12 cases respectively. Overall survival at 2 years was 39.3% in resected patients and 1% in stented and non-resected patients (p = 0.008). CONCLUSION Stenting in palliative stage IV obstructive CRC patients may be less successful as previously thought. Prospective studies are needed to define the role of palliative resection.
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Affiliation(s)
- R Frago
- Department of Surgery, Colorectal Unit, Bellvitge University Hospital, University of Barcelona, Barcelona, Spain
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Ahmed S, Ahmad I, Zhu T, Arnold FP, Faiz Anan G, Sami A, Yadav SK, Alvi R, Haider K. Early discontinuation but not the timing of adjuvant therapy affects survival of patients with high-risk colorectal cancer: a population-based study. Dis Colon Rectum 2010; 53:1432-8. [PMID: 20847626 DOI: 10.1007/dcr.0b013e3181e78815] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Adjuvant therapy results in significant improvement in survival of patients with high-risk colorectal cancer. Little is known about the significance of timing and early discontinuation of adjuvant treatment in such patients. Our study aims to determine the prognostic impact of timing and completion of adjuvant therapy in patients with high-risk colorectal cancer. METHODS Medical records of patients with stage III colon and stage II/III rectal cancer diagnosed between 1993 and 2000 in the province of Saskatchewan were reviewed. Cox proportional hazards models were used to analyze the impact of timing and completion of adjuvant therapy on survival. RESULTS Six hundred sixty-three eligible patients with a median age of 66 years were identified. Sixty-five percent patients received adjuvant <56 days after surgery and 79% patients completed planned treatment. Median follow-up was 54.6 months. Five-year disease-free survival and overall survival of patients who received adjuvant therapy <56 days after surgery was 54.6% and 59.5%, respectively, compared with 51.9% and 57.1%, respectively, of patients who received therapy ≥56 days after surgery (P = NS). The five-year disease disease-free survival and overall survival of patients who completed planned treatment was 56.7% and 62.3%, respectively, compared with 42.1% and 45%, respectively, of patients who required early treatment discontinuation (P < .0001). On multivariate analysis, age ≥65 years, T4 tumor, grade 3 cancer, node-positive disease, rectal tumor, and early treatment discontinuation were identified as poor prognostic factors. CONCLUSIONS Although time to adjuvant therapy following surgical resection did not impact the outcomes, failure to complete planned therapy was associated with adverse prognosis.
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Affiliation(s)
- Shahid Ahmed
- Saskatoon Cancer Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
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Buxhofer-Ausch V, Ausch C, Kitzweger E, Mollik M, Reiner-Concin A, Ogris E, Stampfl M, Hamilton G, Schiessel R, Hinterberger W. Spontaneous changes in tumour cell dissemination to bone marrow in colorectal cancer. Colorectal Dis 2010; 12:776-82. [PMID: 19456841 DOI: 10.1111/j.1463-1318.2009.01950.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The study aimed to evaluate the incidence of disseminated tumour cells (DTCs) in bone marrow (BM) preoperatively and during follow up and to correlate these with established risk factors in patients with colorectal cancer. METHOD We prospectively studied BM in 57 patients using the anti-cytokeratin antibody A45-B/B3. RESULTS The overall detection rate of DTCs was 23% with a similar detection rate through all stages of the disease. No significant association was found between the presence of DTCs and clinicopathological parameters. After a median follow up of 35.4 months, no differences were found in relapse and overall survival between patients with and without DTC preoperatively. In 31 of 45 patients with local disease, we performed a follow-up BM examination after 1 year. In 26% of the patients, the BM status had changed as compared with the preoperative finding. CONCLUSION This is the first study to report the follow up of DTC in BM in colorectal cancer using the A45-B/B3 antibody. The presence of tumour cells in the preoperative BM had no impact on outcome. The BM status had changed after 12 months in a quarter of patients.
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Affiliation(s)
- V Buxhofer-Ausch
- 2nd Department of Medicine, Ludwig Boltzmann Society, Donauspital, Langobardenstrasse 122, 1220 Vienna.
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Yamada Y, Arao T, Matsumoto K, Gupta V, Tan W, Fedynyshyn J, Nakajima TE, Shimada Y, Hamaguchi T, Kato K, Taniguchi H, Saito Y, Matsuda T, Moriya Y, Akasu T, Fujita S, Yamamoto S, Nishio K. Plasma concentrations of VCAM-1 and PAI-1: a predictive biomarker for post-operative recurrence in colorectal cancer. Cancer Sci 2010; 101:1886-90. [PMID: 20491774 PMCID: PMC11158901 DOI: 10.1111/j.1349-7006.2010.01595.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
This prospective study used antibody suspension bead arrays to identify biomarkers capable of predicting post-operative recurrence with distal metastasis in patients with colorectal cancer. One hundred colorectal cancer patients who underwent surgery were enrolled in this study. The median follow-up period was 3.9 years. The pre-operative plasma concentrations of 24 angiogenesis-related molecules were analyzed with regard to the TNM stage and the development of post-operative recurrence. The concentrations of half of the examined molecules (13/24) increased significantly according to the TNM stage (P < 0.05). Meanwhile, a multivariate logistic regression analysis revealed that the concentrations of vascular cell adhesion molecule 1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in the post-operative recurrence group. The VCAM-1 and PAI-1 model discriminated post-operative recurrence with an area under the curve of 0.82, a sensitivity of 0.75, and a specificity of 0.73. A leave-one-out cross-validation was applied to the model to assess the prediction performance, and the result indicated that the cross-validated error rate was 12.5% (12/96). In conclusion, our results demonstrate that antibody suspension bead arrays are a powerful tool to screen biomarkers in the clinical setting, and the plasma levels of VCAM-1 and PAI-1 together may be a promising biomarker for predicting post-operative recurrence in patients with colorectal cancer.
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Affiliation(s)
- Yasuhide Yamada
- Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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Desolneux G, Burtin P, Lermite E, Bergamaschi R, Hamy A, Arnaud JP. Prognostic factors in node-negative colorectal cancer: a retrospective study from a prospective database. Int J Colorectal Dis 2010; 25:829-34. [PMID: 20405293 DOI: 10.1007/s00384-010-0934-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/25/2010] [Indexed: 02/06/2023]
Abstract
PURPOSE There is a need to identify a subgroup of high-risk patients with node-negative colorectal cancer who have a poor long-term prognosis and may benefit from adjuvant therapies. The aim of this study was to evaluate the prognostic impact of clinical and pathological parameters in a retrospective study from a prospective, continuous database of homogenously treated patients. METHODS This study included 362 patients operated in a single institution for Dukes A and B (node-negative) colorectal cancer. The median follow-up was 140 months. The prognostic value of 13 clinical and pathological parameters was investigated. RESULTS Multivariate analysis identified six independent prognostic factors: age at time of diagnosis (hazard ratio (HR) = 1.076), number of lymph nodes removed (HR = 0.948), perineural invasion (HR = 2.173), venous invasion (HR = 1.959), lymphatic vessel invasion (HR = 2.126), and T4 stage (HR = 5.876). CONCLUSION These parameters could be useful in identifying patients with high-risk node-negative colorectal cancer who should be presented to adjuvant therapy.
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Affiliation(s)
- Gregoire Desolneux
- Service de Chirurgie Viscérale et Digestive CHU Angers, Angers Cedex 9, France
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Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken JB. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist 2010; 15:699-731. [PMID: 20584808 PMCID: PMC3228001 DOI: 10.1634/theoncologist.2010-0025] [Citation(s) in RCA: 116] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2010] [Accepted: 05/01/2010] [Indexed: 02/06/2023] Open
Abstract
Rapidly growing insights into the molecular biology of colorectal cancer (CRC) and recent developments in gene sequencing and molecular diagnostics have led to high expectations for the identification of molecular markers to be used in optimized and tailored treatment regimens. However, many of the published data on molecular biomarkers are contradictory in their findings and the current reality is that no molecular marker, other than the KRAS gene in the case of epidermal growth factor receptor (EGFR)- targeted therapy for metastatic disease, has made it into clinical practice. Many markers investigated suffer from technical shortcomings, resulting from lack of quantitative techniques to capture the impact of the molecular alteration. This understanding has recently led to the more comprehensive approaches of global gene expression profiling or genome-wide analysis to determine prognostic and predictive signatures in tumors. In this review, an update of the most recent data on promising biological prognostic and/or predictive markers, including microsatellite instability, epidermal growth factor receptor, KRAS, BRAF, CpG island methylator phenotype, cytotoxic T lymphocytes, forkhead box P3-positive T cells, receptor for hyaluronic acid-mediated motility, phosphatase and tensin homolog, and T-cell originated protein kinase, in patients with CRC is provided.
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Affiliation(s)
- Vanessa Deschoolmeester
- Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
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Likui W, Hong W, Shuwen Z. Clinical significance of the upregulated osteopontin mRNA expression in human colorectal cancer. J Gastrointest Surg 2010; 14:74-81. [PMID: 19763701 DOI: 10.1007/s11605-009-1035-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2009] [Accepted: 09/02/2009] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Osteopontin (OPN) is a phosphorylated glycoprotein which is associated with tumor progression, development, and metastasis. Recently, it has been reported that OPN is highly upregulated in a variety of human malignancies. The aim of this study is to investigate the clinical significance of OPN mRNA expression in colorectal cancer (CRC). MATERIAL AND METHODS Conventional reverse transcription polymerase chain reaction (RT-PCR) and Western blot assays were performed to detect the expression of OPN mRNA and protein in human CRC cell lines and normal cell line. Real-time quantitative RT-PCR assay was performed to analyze the expression of OPN mRNA in 82 CRC tissue samples and corresponding non-tumor tissues. Immunohistochemistry was also performed to detect the expression of OPN protein in above tissues. Finally, the correlation between the status of OPN mRNA expression and clinicopathological factors and clinical outcome was evaluated. RESULTS Compared with normal human intestinal epithelial cell line, human CRC cell lines showed high level of OPN gene expression at both transcriptional and translational levels. Moreover, the results of real-time quantitative RT-PCR and immunohistochemistry showed that the expression levels of OPN mRNA and protein in tumor tissues were significantly higher than those in the corresponding non-tumor tissues (P < 0.001). The expression level of OPN mRNA was significantly correlated with lymph node metastasis, lymphatic or venous invasion, and TNM stage (P = 0.0033, 0.0061, 0.0008, and 0.0012, respectively). Moreover, we also observed that the disease-free and overall survival rates in patients with high OPN mRNA expression were significantly shorter than those in patients with low OPN mRNA expression (P = 0.0047 and 0.0125). Additionally, the status of OPN mRNA expression was an independent prognostic factor for the prognosis of CRC patients (P = 0.008; RR, 2.775; 95% confidence interval, 2.334-3.811). CONCLUSION OPN might play an important role in CRC progression and the status of OPN mRNA expression could be a novel prognostic molecular marker for CRC patients.
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Affiliation(s)
- Wang Likui
- Department of Infection, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
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Koo JH, Leong RWL. Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer. J Gastroenterol Hepatol 2010; 25:33-42. [PMID: 19874446 DOI: 10.1111/j.1440-1746.2009.05992.x] [Citation(s) in RCA: 94] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Sex significantly influences the clinical and pathological characteristics of colorectal cancer (CRC). These include differences in incidence and mortality rates, clinical presentations including age, emergency surgery for complications from CRC, screening participation rates, site, stage and treatment utilization, histopathology and survival. Environmental, behavioral and biological factors contribute to the differential risk. Recent advances in the molecular biology of CRC, specifically in microsatellite status, estrogen hormone and estrogen receptor beta, have led to greater understanding of the effect of estrogen in colorectal carcinogenesis. Estrogen may preferentially protect against microsatellite unstable cancers through its effect on selected molecular targets; however, the exact pathways have not been elucidated. Recognition of important sex disparities in these areas may lead to the implementation of specific measures to diminish these differences and facilitate equitable distribution of health resources. Identifying specific molecular targets on CRC that interact with estrogen may stimulate research to improve the overall outcomes of all patients with CRC.
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Affiliation(s)
- Jenn Hian Koo
- Gastroenterology and Liver Services, Sydney South West Area Health Service, and Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.
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Abstract
BACKGROUND It has been observed that survival after colorectal cancer resection is longer in women than men. The majority of these studies are in non-U.S. populations and few use appropriate multivariate adjustment. We used the Surveillance, Epidemiology and End Results- Medicare database to examine disease-specific survival in women and men undergoing colorectal cancer resection in the United States, adjusting for patient, cancer, and hospital characteristics in an effort to identify disparities, not only in survival, but also in patterns of presentation, surgical resection, and treatment. METHODS With use of the Surveillance, Epidemiology and End Results-Medicare-linked database, we performed a retrospective cohort study of 30,975 patients with colon cancer and 8,350 patients with rectal cancer who underwent surgical resection from 1996 to 2003. Kaplan-Meier curves, the log-rank test, and Cox regression compared survival between genders. Multivariate adjustment was performed by use of patient demographics; cancer variables including stage, medical treatment, and adequacy of nodal harvest; and hospital characteristics. RESULTS In both cancers, women presented at an older age and more emergently than men. They also underwent less aggressive medical therapy for advanced disease; in particular, in the octogenarian population. In unadjusted analysis, there was no gender difference in survival (colon hazard ratio, 0.98; P = 0.74; rectal hazard ratio, 0.95; P =0.10). After full adjustment, however, women had significantly longer survival, in particular, after rectal resection (colon hazard ratio, 0.91; P< 0.001; rectal hazard ratio, 0.82; P< 0.001). CONCLUSIONS Women in this cohort have longer adjusted survival compared with men; however, they present more emergently and at an older age, and they receive less aggressive medical treatment. These are noticeable disparities that could serve as targets for continued improvement.
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ErbB family immunohistochemical expression in colorectal cancer patients with higher risk of recurrence after radical surgery. Int J Colorectal Dis 2009; 24:1059-68. [PMID: 19390858 DOI: 10.1007/s00384-009-0702-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/01/2009] [Indexed: 02/04/2023]
Abstract
PURPOSE Investigate ErbB family expression in colorectal cancer patients with higher risk of recurrence after surgical treatment. METHODS We studied 109 individuals with high risk stage II and stage III patients submitted to radical surgery. ErbB expression was assessed by tissue microarray technique. RESULTS The immunohistochemical expression was considered positive for EGFR, ErbB2, ErbB3, ErbB4 membrane, and ErbB4 cytoplasmic in respectively 57.8%, 8.3%, 69.7%, 11%, and 19.3% of patients. ErbB3 negative expression was associated with lymphovascular invasion. EGFR, ErbB2, and cytoplasmic ErbB4 expression was not associated with prognosis. Membranous positive ErbB4 expression was an independent prognostic factor for recurrence. ErbB3 negative expression was an independent prognostic factor for recurrence and survival in the multivariate analysis. CONCLUSIONS The immunohistochemical expression of ErbB3 and ErbB4 may identify a subgroup with stage II and III colorectal cancer at higher risk of recurrence.
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Lin CC, Lin JK, Chang SC, Wang HS, Yang SH, Jiang JK, Chen WS, Lin TC. Is adjuvant chemotherapy beneficial to high risk stage II colon cancer? Analysis in a single institute. Int J Colorectal Dis 2009; 24:665-76. [PMID: 19238405 DOI: 10.1007/s00384-009-0634-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2009] [Indexed: 02/04/2023]
Abstract
BACKGROUND Colorectal carcinoma is the most common malignancy of the gastrointestinal tract. It remains controversial for adjuvant chemotherapy in patients with stage II colon cancer. This study was designed to identify the risk factors of tumor recurrence in stage II colon cancer. Furthermore, the benefit of adjuvant chemotherapy for high-risk stage II colorectal cancer will be investigated. MATERIALS AND METHODS From May 1998 until August 2004, 375 patients with stage II (T3N0M0, T4N0M0) colon cancer received curative operation in a single hospital. The clinical data were extracted from the prospectively collected colorectal cancer database. The disease-free survival curves were calculated with Kaplan-Meier's analysis, and the survival difference was determined by log-rank test. The p value less than 0.05 was considered to be significant. RESULTS Of 375 stage II colon cancer, 66 patients received 5-FU-based adjuvant chemotherapy, either oral or intravenous (IV) form. Within the median of 48.5 months of follow-up, recurrence developed in 35 patients (9.3%). T4 lesion (p=0.024), lymphovascular invasion (p=0.022), obstruction at presentation (p=0.008), and mucinous component more than 50% (p=0.032) were associated with significantly decreased disease-free survival. High-risk patients (n=102), but not other patients with stage II colon cancer, benefited from adjuvant therapy (3-year disease-free survival: 96.4% vs. 84.7%, p=0.045; 5-year overall survival: 100% vs. 86.4%, p=0.015). CONCLUSION Adjuvant therapy for high-risk stage II colon cancer may be beneficial, and we suggest adjuvant therapy should be considered in high-risk stage II colon cancer patients.
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Affiliation(s)
- Chun-Chi Lin
- Taipei Veterans General Hospital, Surgery, Taipei, Taiwan
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Moreira LR, Schenka AA, Filho PL, Lima CSP, Trevisan MAS, Vassallo J. Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer. ACTA ACUST UNITED AC 2009; 42:593-8. [PMID: 19466284 DOI: 10.1590/s0100-879x2009005000004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2008] [Accepted: 04/13/2009] [Indexed: 11/21/2022]
Abstract
Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 microm(2); P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.
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Affiliation(s)
- L R Moreira
- Laboratório de Patologia Investigativa e Molecular, CIPED, Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brasil
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Gender differences in the treatment of rectal cancer: A population based study. Eur J Surg Oncol 2009; 35:427-33. [DOI: 10.1016/j.ejso.2008.03.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2007] [Accepted: 03/11/2008] [Indexed: 12/18/2022] Open
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The Importance of Tumor Stage and Relative Survival Analysis for the Association Between Sex and Survival After Resection of Colorectal Cancer. Ann Surg 2009; 249:402-8. [DOI: 10.1097/sla.0b013e31819a0469] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Chang YS, Kim SR, Choi SI, Joo SH, Lee SH. Short-term Oncologic Outcome of Curative Resection for Obstructive Colorectal Cancer Followed by Stent Insertion: Comparative Study with Non-abstructive Colorectal Cancer. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2009; 25:41. [DOI: 10.3393/jksc.2009.25.1.41] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Yeon Soo Chang
- Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea
| | - Seong Rae Kim
- Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea
| | - Sung Il Choi
- Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea
| | - Sun Hyung Joo
- Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea
| | - Suk-Hwan Lee
- Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea
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Wong SKC, Jalaludin BB, Henderson CJA, Morgan MJ, Berthelsen AS, Issac MM, Kneebone A. Direct tumor invasion in colon cancer: correlation with tumor spread and survival. Dis Colon Rectum 2008; 51:1331-8. [PMID: 18551346 DOI: 10.1007/s10350-008-9274-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2007] [Revised: 01/04/2008] [Accepted: 01/21/2008] [Indexed: 02/08/2023]
Abstract
PURPOSE This study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival. METHODS A cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied. RESULTS The depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation. CONCLUSION Two types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion.
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Affiliation(s)
- Siu Kin C Wong
- South Western Sydney Colorectal Tumor Group, Sydney South West Area Health Service, Sydney, Australia.
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