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Wu Y, He F, Liu L, Jiang W, Deng J, Zhang Y, Cao Z, Xu X, Gong J. The Use of CellCollector Assay to Detect Free Cancer Cells in the Peritoneal Cavity of Colorectal Cancer Patients: An Experimental Study. Cancer Med 2024; 13:e70378. [PMID: 39503055 PMCID: PMC11538901 DOI: 10.1002/cam4.70378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 10/04/2024] [Accepted: 10/16/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is associated with high incidence and mortality rates globally. The presence of intraperitoneal free cancer cells (IFCCs) is recognized as an independent prognostic factor for CRC patients. However, a clinical gold standard for IFCCs detection is lacking. The GILUPI CellCollector has demonstrated high sensitivity and specificity in detecting free cancer cells, yet its application for CRC IFCCs detection remains unreported. METHODS We selected CRC and normal cell lines to evaluate the CellCollector's ability to detect tumor cells. A total of 70 CRC patients and 17 patients with benign disease undergoing laparoscopic procedures were investigated. Peritoneal lavage fluid was collected pre- and post-operation, and both real-time PCR (CEA mRNA) and CellCollector detection were performed. We compared the sensitivity and specificity of these two methods. RESULTS CellCollector can distinguish well between CRC and normal cells in cell line experiments. CellCollector detects IFCCs better than real-time PCR (CEA) in CRC patients in different TNM Stages. The sensitivity of CellCollector was higher than that of real-time PCR (84.6% vs. 48.4%), and the specificity of CellCollector was also higher than real-time PCR (79.1% vs. 60.4%). There was no significant difference in the results of IFCCs detected by CellCollector before and after total mesorectal excision (TME) or complete mesocolic excision (CME) radical colorectomy (p > 0.05), but there was a significant difference in real-time PCR detection (p < 0.05). CONCLUSIONS The CellCollector demonstrates superior sensitivity and specificity compared to real-time PCR for detecting IFCCs in CRC patients, suggesting its potential as a clinical tool for IFCCs detection. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01978444.
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Affiliation(s)
- Yudi Wu
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
- GI Cancer Research InstituteTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Fangxun He
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Liang Liu
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Wei Jiang
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Jiao Deng
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Yujie Zhang
- GI Cancer Research InstituteTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Zhixin Cao
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
- GI Cancer Research InstituteTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Xiangshang Xu
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
- GI Cancer Research InstituteTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
| | - Jianping Gong
- Department of Gastrointestinal SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
- GI Cancer Research InstituteTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
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Wu Y, Liu L, He F, Zhang Y, Jiang W, Cao Z, Xu X, Gong J. Long noncoding RNA small nucleolar RNA host gene 1 as a potential novel biomarker for intraperitoneal free cancer cells in colorectal cancer. iScience 2024; 27:110228. [PMID: 38993673 PMCID: PMC11237925 DOI: 10.1016/j.isci.2024.110228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 05/03/2024] [Accepted: 06/06/2024] [Indexed: 07/13/2024] Open
Abstract
Colorectal cancer (CRC) is a prevalent cancer with intraperitoneal free cancer cells (IFCCs) playing a significant role in prognosis, especially during surgeries. The identification of IFCCs is crucial for determining the stage and treatment of patients with CRC. Existing methods for IFCC detection, such as conventional cytology, immunocytochemistry (ICC), and polymerase chain reaction (PCR), have limitations in sensitivity and specificity. This study investigates the potential of long noncoding RNA (lncRNA) SNHG1 as a biomarker for detecting IFCCs in patients with CRC. Testing on a cohort of 91 patients with CRC and 26 patients with gastrointestinal benign disease showed that SNHG1 outperformed CEA in distinguishing CRC cells and detecting IFCCs across different disease stages. SNHG1 demonstrated higher sensitivity (76.1% vs. 43.1%) and specificity (68.4% vs. 52.3%) than CEA for IFCC detection in patients with CRC, suggesting its promising role as a clinical method for identifying IFCCs in CRC.
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Affiliation(s)
- Yudi Wu
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
- GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Liang Liu
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Fangxun He
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Yujie Zhang
- GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Wei Jiang
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Zhixin Cao
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Xiangshang Xu
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
- GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Jianping Gong
- Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
- GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China
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Takei Y, Hotta T, Takifuji K, Yokoyama S, Matsuda K, Watanabe T, Tamura K, Mitani Y, Ieda J, Iwamoto H, Mizumoto Y, Iwahashi Y, Yamaue H. New diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for patients with colorectal cancer. Surg Endosc 2022; 36:8843-8855. [PMID: 35562509 DOI: 10.1007/s00464-022-09313-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/27/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Accurate tumor stage diagnosis during laparoscopic surgery remains difficult. We clarify the impact of new diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for colorectal cancer compared with other strategies. METHODS We defined angiogenesis (Ag) and fibrosis (Fib) grades using NBI laparoscopy (lap-NBI), and assessed the clinicopathological features associated with these grades for 67 patients with colorectal cancer who underwent surgery. We assessed vessel density and gray scale with computer software. RESULTS NBI-Ag-grade and NBI-Fib-grade of the serosal surface of cancer lesions and peritoneal nodules correlated with vessel density and gray scale of those assessed by Image J computer software. NBI-Fib-grades of liver nodules also correlated with gray scale. NBI-Ag- grade and Fib-grade of the serosal surface of cancer lesions correlated with pathological depth of invasion. These NBI grades of pathological metastatic peritoneal nodules were higher than those of pathologically benign peritoneal nodules. NBI- Fib grades of pathological metastatic liver nodules were higher than those of pathologically benign liver nodules. In multivariate analysis, lap-NBI was associated with different diagnosis for T3, T4 and non-T3, and non-T4. Moreover, lap-NBI was associated with different diagnosis for T4 and non-T4. Predictive value for T4 by lap-NBI showed high sensitivity (85%) specificity (87%), positive predictive value (74%), negative predictive value (93%), and overall accuracy (87%). Sensitivity and overall accuracy of lap-NBI was superior to that of other diagnostic modalities. CONCLUSION We clarified the usefulness of the new diagnostic strategy using lap-NBI during laparoscopic surgery for colorectal cancer in comparison with other strategies.
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Affiliation(s)
- Yoh Takei
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Tsukasa Hotta
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan.
| | - Katsunari Takifuji
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Shozo Yokoyama
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Kenji Matsuda
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Takashi Watanabe
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Koichi Tamura
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Yasuyuki Mitani
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Junji Ieda
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Hiromitsu Iwamoto
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Yuki Mizumoto
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Yoshifumi Iwahashi
- Departments of Human Pathology and Diagnostic Pathology, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8510, Japan
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Mo TW, Zhang ZJ, Chen YL, Huang JH, Su D, Song WL, Hu JC, He XW. Risk factors for metachronous peritoneal carcinomatosis after radical resection for patients with nonmetastatic pT3-4 colon cancer. J Surg Oncol 2022; 126:757-771. [PMID: 35661159 DOI: 10.1002/jso.26975] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 05/02/2022] [Accepted: 05/22/2022] [Indexed: 12/20/2022]
Abstract
BACKGROUND Patients with nonmetastatic pT3-4 colon cancers are prone to develop metachronous peritoneal carcinomatosis (mPC). Risk factors for mPC and the influence of mutant kirsten rat sarcoma viral oncogene (KRAS)/neuroblastoma rat sarcoma (NRAS)/v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and DNA mismatch repair (MMR) status on mPC remain to be described in these patients. METHOD All enrolled patients were identified from the prospectively collected colorectal cancer database of a tertiary referral hospital between 2013 and 2018. Multivariate analysis was used to identify risk factors associated with mPC. RESULTS Of the 1689 patients with nonmetastatic pT3-4 colon carcinoma, 8.4% (142/1689) progressed to mPC. Endoscopic obstruction (HR = 3.044, p < 0.001), elevated CA125 (HR = 1.795, p = 0.009), pT (T4a vs. T3, HR = 2.745, p < 0.001; T4b vs. T3, HR = 3.167, p = 0.001), pN (N1 vs. N0, HR = 2.592, p < 0.001; N2 vs. N0, HR = 4.049, p < 0.001), less than 12 lymph nodes harvested (HR = 2.588, p < 0.001), mucinous or signet ring cell carcinoma (HR = 1.648, p = 0.038), perineural invasion (HR = 1.984, p < 0.001), and adjuvant chemotherapy (HR = 1.522, p = 0.039) were strongly related to mPC but that mutant KRAS/NRAS/BRAF and MMR status was not associated with mPC. CONCLUSION This study identified the high-risk factors for mPC in patients with nonmetastatic pT3-4 colon carcinoma, and these factors should be considered in selective preventive therapy and close follow-up for patients subsequently deemed to have high risk for mPC.
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Affiliation(s)
- Tai-Wei Mo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zong-Jin Zhang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yong-Le Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jun-Hua Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dan Su
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Coloproctology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wen-Li Song
- Department of Endoscopic Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Jian-Cong Hu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Endoscopic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Wen He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Dahdaleh FS, Sherman SK, Witmer HD, Dhiman A, Rajeev R, Poli EC, Johnston FM, Turaga KK. Potential evidence of peritoneal recurrence in Stage-II colon cancer from the control arm of CALGB9581. Am J Surg 2022; 224:459-464. [DOI: 10.1016/j.amjsurg.2022.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 01/11/2022] [Accepted: 01/19/2022] [Indexed: 11/01/2022]
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Sun T, Zhang G, Ning T, Chen Q, Chu Y, Luo Y, You H, Su B, Li C, Guo Q, Jiang C. A Versatile Theranostic Platform for Colorectal Cancer Peritoneal Metastases: Real-Time Tumor-Tracking and Photothermal-Enhanced Chemotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:e2102256. [PMID: 34398516 PMCID: PMC8529449 DOI: 10.1002/advs.202102256] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/30/2021] [Indexed: 06/13/2023]
Abstract
A versatile tumor-targeting stimuli-responsive theranostic platform for peritoneal metastases of colorectal cancer is proposed in this work for tumor tracking and photothermal-enhanced chemotherapy. A quenched photosensitizer ("off" state) is developed and escorted into a tumor-targeting oxaliplatin-embedded micelle. Once reaching the tumor cell, the micelle is clasped to release free oxaliplatin, as well as the "off" photosensitizer, which is further activated ("turned-on") in the tumor reducing microenvironment to provide optical imaging and photothermal effect. The combined results from hyperthermia-enhanced chemotherapy, deep penetration, perfused O2 , and the leveraged GSH-ROS imbalance in tumor cells are achieved for improved antitumor efficacy and reduced systematic toxicity.
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Affiliation(s)
- Tao Sun
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Guangping Zhang
- Shandong Province Key Laboratory of Medical Physics and Image Processing TechnologySchool of Physics and Electronics and Institute of Materials and Clean EnergyShandong Normal University1 University RoadJinan250358P. R. China
| | - Tingting Ning
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Qinjun Chen
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Yongchao Chu
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Yifan Luo
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Haoyu You
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Boyu Su
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Chao Li
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Qin Guo
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
| | - Chen Jiang
- Key Laboratory of Smart Drug Delivery (Ministry of Education)Minhang HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceDepartment of PharmaceuticsSchool of PharmacyFudan University826 Zhangheng RoadShanghai201203China
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Xiao Y, Huang G, Xiang Y. Research on Anti-Tumor Nano-Particle with New Type 5-Fluorouracil on the Peritoneal Metastasis of Breast Cancer. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The 5-fluorouracil (5-FU) was a classical chemotherapy drug. The administrational carrier of nano-particle provides enhancement effect prior to target and reduce side effect. But the specific function of nano-particle on the peritoneal metastasis of breast cancer was poorly understood.
Our study was designed to discover the biological function of anti-tumor nano-particle with new type 5-FU on breast cancer. The nano-particle of 5-fluorouracil (5-FU-NPs) was prepared by multiple emulsion method. The distribution of particle size was analyzed by electron microscope. The proliferation
and apoptosis of cell in breast cancer was interfered by 5-FU solution (control group) or 5-FU-NPs. Cell cycle was assessed by flow cytometry and proliferation was detected by MTT and cell clone technology. The rat was injected with 5-FU solution (control group) or 5-FU-NPs intraperitoneally
followed by analysis of tumor volume and size. The average tumor diameter was 200±10.84 nm. The encapsulation rate and loading rate was 81.6±5.7% and 7.29±0.14% respectively. The apoptosis of MCF-7 cell treated by 5-FU-NPs was increased significantly with abundant rounded
and floating apoptotic cellular morphology as well as reduced quantity of surviving cells. The number of bacterial colony induced by 5-FU-NPs, which could interdict cell cycle. The 5-FU-NPs could restrain tumor cell growth in peritoneal metastasis of breast cancer. The new-type nano-particle
of 5-FU loaded with PEG-PLGA could retard breast cancer cell proliferation and peritoneal metastasis of breast cancer in rats.
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Affiliation(s)
- Yujie Xiao
- Thyroid and Breast Surgery, The First People’s Hospital of Yichang, Yichang, Hubei, 434000, China
| | - Guilin Huang
- General Surgery Department II, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang, 832003, China
| | - Yibo Xiang
- Department of Otolaryngology, Xiantao First People’s Hospital Affiliated to Changjiang University, Xiantao City, Hubei Province, 433000, China
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Yang Z, Li Y, Qin X, Lv Z, Wang H, Wu D, Yuan Z, Wang H. Development and Validation of a Prognostic Nomogram for Colorectal Cancer Patients With Synchronous Peritoneal Metastasis. Front Oncol 2021; 11:615321. [PMID: 34277396 PMCID: PMC8281961 DOI: 10.3389/fonc.2021.615321] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 05/17/2021] [Indexed: 12/19/2022] Open
Abstract
PURPOSE Synchronous peritoneal metastasis (S-PM) is considered a poor prognostic factor for colorectal cancer (CRC) and there is no nomogram to predict the survival of these patients. In this study, we aimed to use a multicenter data to identify the factors associated with S-PM of CRC to construct a nomogram for predicting the overall survival (OS) of these patients. METHODS CRC patients with S-PM from two medical centers were enrolled between September 2007 and June 2017. Multivariate analysis was used to identify independent factors associated with OS for the nomogram to predict the 1-, 2-, and 3-year OS rates in the development group. The concordance index (C-index), calibration plot, relative operating characteristic (ROC) curve with area under the curve (AUC) were calculated to evaluate the performance of the nomogram in both the development and an external validation group. RESULTS 277 CRC patients with S-PM in the development group and 68 patients in the validation group were eligible for this study. In multivariate analysis of development group, age, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and chemotherapy were independent variables for OS, based on which the nomogram was built. The C-index of the nomogram in the development and validation group was 0.701 (95% Cl, 0.666-0.736) and 0.716 (95% Cl, 0.622-0.810); demonstrating good discriminative ability. The calibration plots showed satisfactory consistency between actual observation and nomogram-predicted OS probabilities in the development and external validation group. The nomogram showed good predictive accuracy for 1-, 2-, and 3-year OS rates in both groups with AUC >0.70. An online dynamic webserver was also developed for increasing the ease of the nomogram. CONCLUSIONS We developed and validated a predictive nomogram with good discriminative and high accuracy to predict the OS in CRC patients with S-PM.
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Affiliation(s)
- Zifeng Yang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yong Li
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xiusen Qin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zejian Lv
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Deqing Wu
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zixu Yuan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hui Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Sato K, Imaizumi K, Kasajima H, Kurushima M, Umehara M, Tsuruga Y, Yamana D, Obuchi K, Sato A, Nakanishi K. Comparison of prognostic impact between positive intraoperative peritoneal and lavage cytologies in colorectal cancer. Int J Clin Oncol 2021; 26:1272-1284. [PMID: 33844111 DOI: 10.1007/s10147-021-01918-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 04/02/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The prognostic value of positive intraoperative peritoneal cytology and lavage cytology, including the differences in their prognostic impact, in colorectal cancer is controversial. We aimed to investigate the prognostic values of positive peritoneal cytology and lavage cytology findings for colorectal cancer and compare their prognostic impact. METHODS We retrospectively evaluated 592 clinical stage II-IV colorectal cancer patients who underwent peritoneal cytology (n = 225) or lavage cytology (n = 367) between November 1993 and December 2018. The prognostic factors for cancer-specific survival were identified, and the differences in cancer-specific survival were examined between the patients. RESULTS The cytology-positive rate was 10.8% (64/592), 17.8% (40/225), and 6.5% (24/367) in the overall, peritoneal cytology, and lavage cytology groups, respectively. Both positive peritoneal cytology (hazard ratio: 2.196) and lavage cytology (hazard ratio: 2.319) were independent prognostic factors. The peritoneal cytology-positive group showed significantly poorer cancer-specific survival than the cytology-negative group (5-year: 3.5% vs. 59.5%; 10-year: 3.5% vs. 46.1%, p < 0.001). Similar results were obtained for lavage cytology (5-year: 14.1% vs. 73.9%; 10-year: 4.7% vs. 63.5%, p < 0.001). The cancer-specific survival was not significantly different between the peritoneal cytology-positive and lavage cytology-positive groups (p = 0.058). Both positive peritoneal and lavage cytology were associated with poorer cancer-specific survival across all colorectal cancer stages. CONCLUSIONS Positive peritoneal and lavage cytology are associated with worse cancer-specific survival in colorectal cancer. The prognostic impact was comparable between positive lavage and peritoneal cytology. Thus, cytology should be a standard assessment modality for colorectal cancer.
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Affiliation(s)
- Kentaro Sato
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Ken Imaizumi
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan.
| | - Hiroyuki Kasajima
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Michihiro Kurushima
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Minoru Umehara
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Yosuke Tsuruga
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Daisuke Yamana
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Keisuke Obuchi
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Aya Sato
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
| | - Kazuaki Nakanishi
- Department of Gastroenterological Surgery, Hakodate Municipal Hospital, 1-10-1 Minatocho, Hakodate, Hokkaido, 041-8680, Japan
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10
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Shalaby M, El Baradie TS, Salama M, Shaaban HAM, Allam RM, Hafiz EOA, Abdelhamed MA, Attia A. Conventional peritoneal cytology lacks the prognostic significance of detecting local or peritoneal recurrence in colorectal cancer: An Egyptian experience. JGH OPEN 2020; 5:264-272. [PMID: 33553666 PMCID: PMC7857300 DOI: 10.1002/jgh3.12482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/10/2020] [Accepted: 12/11/2020] [Indexed: 11/10/2022]
Abstract
Background and Aim Colorectal cancer (CRC) accounts for over 8% of all deaths each year, with 1.2 million new cases diagnosed annually worldwide. It represents the seventh most common cancer in Egypt. Early detection of peritoneal metastasis is a major challenge in such cases. It helps with the decision of the immediate application of intraperitoneal chemotherapy after resection. Meta-analysis studies reported contrast evidence for a possible prognostic role of intraperitoneal free cancer cells (IPCCs) in peritoneal recurrence and survival after curative resection. In this work, we aim to evaluate the prevalence and impact of detecting free malignant cells in peritoneal fluid on survival and local recurrence and to estimate the incidence of peritoneal carcinomatosis (PC) during follow up. Methods Design: This was a prospective cohort study. Settings: From June 2016 to December 2018, samples were collected from 104 patients who underwent abdominal surgery for colorectal cancer in the Egyptian National Cancer Institute. A total of 96 Egyptian CRC patients who underwent curative resection were enrolled. Intraoperative peritoneal lavage was performed to detect IPCC by conventional cytology. Patients with no residual tumor after surgery and no evidence of PC were followed up for a median 14 months. The cumulative 12-month overall survival rate for patients with IPCC was 100% versus 86% for patients with negative cytology. Results Our results demonstrated that the prevalence of IPCC in the peritoneal lavage was 11.5%. Peritoneal and local recurrence occurred at a higher rate in patients with cytology positive lavage (9.1% vs 6.3% and 9.1% vs 3.8%, respectively), although this was statistically insignificant. Distant metastasis occurred significantly in patients with positive cytology (45.5% vs 8.9%) with P-value <0.001.The conventional cytology technique has a high specificity but less sensitivity. Conclusions The presence of IPCC using conventional cytology was not an independent prognostic factor for the development of PC or survival.
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Affiliation(s)
- Mohamed Shalaby
- Surgery Department National Cancer Institute, Cairo University Cairo Egypt
| | - Tarek S El Baradie
- Surgery Department National Cancer Institute, Cairo University Cairo Egypt
| | - Mohamed Salama
- Surgery Department National Cancer Institute, Cairo University Cairo Egypt
| | - Hebat A M Shaaban
- Department of Pathology National Cancer Institute, Cairo University Cairo Egypt
| | - Rasha M Allam
- Biostatistics and Cancer Epidemiology Department National Cancer Institute, Cairo University Cairo Egypt
| | - Ehab O A Hafiz
- Clinical Laboratory Research Department Theodor Bilharz Research Institute (TBRI) Giza Egypt
| | | | - Amr Attia
- Surgery Department National Cancer Institute, Cairo University Cairo Egypt
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11
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Li T, Yu J, Chen Y, Liu R, Li Y, Wang YX, Wang JJ, Zhu P. Preventive intraperitoneal hyperthermic perfusion chemotherapy for patients with T4 stage colon adenocarcinoma. Tech Coloproctol 2020; 25:683-691. [PMID: 32572664 DOI: 10.1007/s10151-020-02270-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 06/14/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be an effective treatment for peritoneal tumors; whether preventive HIPEC after radical resection for T4 stage colon adenocarcinoma could decrease peritoneal recurrence remains unknown. The aim of the present study was to compare peritoneal recurrence and short-term survival in patients with T4 stage colon adenocarcinoma undergoing HIPEC plus adjuvant chemotherapy or adjuvant chemotherapy alone following surgery. METHODS We retrospectively reviewed T4 stage colon adenocarcinoma patients who had radical tumor resection at our institution between January 2014 and January 2019. Clinical data were extracted from the database at our institution, and patient survival and long-term complications were assessed through repeated outpatient examinations and telephone interviews. RESULTS A total of 352 patients were included in this study; 157 patients received postoperative HIPEC plus adjuvant chemotherapy (HIPEC group), 195 patients received adjuvant chemotherapy alone (conventional chemotherapy group). Forty-one (26.1%) patients in the HIPEC group had a peritoneal recurrence and the peritoneum was the first site of tumor recurrence in 6 (14.6%) of them. However, 73 (37.4%) patients experienced peritoneal recurrence in the conventional group, and the peritoneum was the first site of tumor recurrence in 25 (34.2%) (p = 0.019). Disease-free survival in the HIPEC group at 1 and 3 years was 93.3% and 61.1%, respectively, versus 89.3% and 51.7% in the conventional chemotherapy group (p = 0.038). Overall survival in the HIPEC group at 1 and 3 years was 100.0% and 82.7%, respectively, versus 100.0% and 76.9% in the conventional chemotherapy group (p = 0.420). The two groups did not differ with respect to severe complications. CONCLUSIONS Preventive HIPEC after radical surgery may decrease peritoneal recurrence and promote disease-free survival for T4 stage colon adenocarcinoma. Large-scale randomized controlled studies are needed to confirm the results of our study.
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Affiliation(s)
- T Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - J Yu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - Y Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - R Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - Y Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - Y X Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - J J Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China
| | - P Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China.
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12
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Takada M, Okuyama T, Yoshioka R, Noie T, Takeshita E, Sameshima S, Oya M. A case with mesenteric desmoid tumor after laparoscopic resection of stage I sigmoid colon cancer. Surg Case Rep 2019; 5:38. [PMID: 30820780 PMCID: PMC6395456 DOI: 10.1186/s40792-019-0587-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 02/10/2019] [Indexed: 12/11/2022] Open
Abstract
Background Intra-abdominal desmoid tumors are rare and generally occur in some patients with familial adenomatous polyposis or secondary to an external stimulus such as surgical trauma. We report herein a case of intra-abdominal desmoid tumor in the jejunal mesentery after laparoscopic colectomy for sigmoid colon cancer. Case presentation A 74-year-old woman underwent laparoscopic sigmoid colectomy for colon cancer with pathological stage I. Follow-up computed tomography (CT) 18 months after primary surgery showed a nodular and enhanced soft tissue density mass, 20 mm in size, in the mesentery at the left side of the abdomen. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range. Fluorodeoxyglucose positron emission tomography did not suggest cancer recurrence. Another CT scan, done 1 month later, revealed that the tumor had enlarged to 25 mm in size. Although the pathological diagnosis was not obtained, we suspected recurrence of the sigmoid colon cancer and applied chemotherapy using capecitabine, oxaliplatin, and bevacizumab. After 3 cycles of chemotherapy, however, the tumor had enlarged further. Therefore, the surgical resection of the tumor was performed to determine the diagnosis and to achieve possible curative resection of the tumor. The tumor existed in the mesentery of the jejunum, 100 cm from the ligament of Treitz, and showed invasive growth. We resected 40 cm of the jejunal segment together with the tumor. Microscopically, the tumor was composed of fibroblast, myofibroblast, and infiltrating the inflammatory cell and diagnosed as desmoid tumor by immunostaining (desmin+/−, β-catenin+, CD117−, vimentin+). At 33 months after the resection of the desmoid tumor, neither the sigmoid colon cancer nor desmoid tumor has had a recurrence. Conclusions After surgery for gastrointestinal cancer, it is difficult to differentiate between intra-abdominal desmoid tumor and recurrence. The possibility of intra-abdominal desmoid should be considered along with tumor recurrence during postoperative surveillance after resection of gastrointestinal cancer, especially when the risk of recurrence is low.
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Affiliation(s)
- Musashi Takada
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan
| | - Takashi Okuyama
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan.
| | - Ryuji Yoshioka
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan
| | - Tamaki Noie
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan
| | - Emiko Takeshita
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan
| | - Shinichi Sameshima
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan
| | - Masatoshi Oya
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan
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13
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Nozawa H, Kawai K, Hata K, Tanaka T, Nishikawa T, Otani K, Sasaki K, Kaneko M, Emoto S, Murono K. High-risk Stage II Colorectal Cancers Carry an Equivalent Risk of Peritoneal Recurrence to Stage III. In Vivo 2018; 32:1235-1240. [PMID: 30150450 PMCID: PMC6199616 DOI: 10.21873/invivo.11370] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Revised: 05/30/2018] [Accepted: 06/04/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND/AIM Several risk factors for recurrence have been identified in stage II colorectal cancer. However, in contrast to stage III, the benefits of adjuvant chemotherapy for these patients remain controversial. We hypothesized that the different impacts of chemotherapy may be due to different patterns of recurrence between these stages. The aim of this study was to characterize recurrence in high-risk stage II colorectal cancer (CRC) in comparison with stage III. PATIENTS AND METHODS A total of 442 patients with curatively resected stage III and high-risk stage II CRCs were evaluated. The recurrence site and frequency were compared between these stages. The risk factors of recurrence by site were identified using multivariate analyses. RESULTS During the follow-up (median: 6.4 years), 31% of stage III and 13% of high-risk stage II patients manifested recurrence. Recurrence in the liver, lung, and distant lymph nodes was significantly more frequent in stage III (18%, 12%, 11%) than in high-risk stage II (7%, 6%, 3%). Stage III was independently associated with recurrence in these organs. In contrast, the rate of peritoneal recurrence was 5% in both stages. CONCLUSION Clinicians should be aware that high-risk stage II CRC has a similar risk of postoperative recurrence in the peritoneum to Stage III CRC.
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Affiliation(s)
- Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Takeshi Nishikawa
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Kensuke Otani
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Kazuhito Sasaki
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Manabu Kaneko
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Shigenobu Emoto
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
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14
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Shin JK, Kim HC, Lee WY, Yun SH, Cho YB, Huh JW, Park YA, Chun HK. High preoperative serum CA 19-9 levels can predict poor oncologic outcomes in colorectal cancer patients on propensity score analysis. Ann Surg Treat Res 2018; 96:107-115. [PMID: 30838182 PMCID: PMC6393410 DOI: 10.4174/astr.2019.96.3.107] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/27/2018] [Accepted: 10/16/2018] [Indexed: 01/21/2023] Open
Abstract
Purpose The purpose of this study is to evaluate the prognostic value of preoperative serum CA 19-9 levels in colorectal cancer patients. Methods Between 2008 and 2011, 4,794 consecutive patients who underwent curative resection for colorectal cancer were analyzed. These patients were classified into 2 groups according to preoperative CA 19-9 (high CA 19-9: ≥37 ng/mL, n = 440; normal CA 19-9: <37 ng/mL, n = 4,354). We used 1:20 propensity score matching to adjust for potential baseline confounders between groups. Results After matching, 424 patients (10.5%) among 4,021 patients with colorectal cancer showed a high pre-CA 19-9 level (≥37 ng/mL). There were no significant differences between these 2 groups in age, sex, preoperative CEA level, or T, N, and M stage after matching. Of the 424 patients with high pre-CA 19-9, 141 (33.3%) exhibited cancer recurrence more frequently than patients with normal preoperative CA 19-9 (18.5%). Patients with an elevated preoperative CA 19-9 level showed significantly poorer survival than those with normal levels. The 5-year overall survival rate was 79.7% in the high preoperative CA 19-9 group and 91.9% in the normal preoperative CA 19-9 group (P < 0.001). The 5-year disease-free survival rate was 70.2% in the high preoperative CA 19-9 group and 82.7% in the normal preoperative CA 19-9 group (P < 0.001). Conclusion Patients with an elevated preoperative CA 19-9 level in colorectal cancer have a significantly poorer prognosis than those with normal levels of CA 19-9. We therefore suggest preoperative CA 19-9 level can be used as an additional prognostic indicator of poor outcomes in colorectal cancer.
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Affiliation(s)
- Jung Kyong Shin
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Cheol Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Yong Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seong Hyeon Yun
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Beom Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Wook Huh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Ah Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ho-Kyung Chun
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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15
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Van der Speeten K, Lemoine L. HIPEC Methodology, Comparison of Techniques, and Drug Regimens: Is There a Need for Standardization? MANAGEMENT OF PERITONEAL METASTASES- CYTOREDUCTIVE SURGERY, HIPEC AND BEYOND 2018:79-102. [DOI: 10.1007/978-981-10-7053-2_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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16
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Klaver CEL, van Huijgevoort NCM, de Buck van Overstraeten A, Wolthuis AM, Tanis PJ, van der Bilt JDW, Sagaert X, D'Hoore A. Locally Advanced Colorectal Cancer: True Peritoneal Tumor Penetration is Associated with Peritoneal Metastases. Ann Surg Oncol 2018; 25:212-220. [PMID: 29076043 PMCID: PMC5740196 DOI: 10.1245/s10434-017-6037-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Findings show T4 colorectal cancer (CRC) to be a risk factor for the development of peritoneal metastases (PM). Heterogeneity regarding peritoneal involvement of T4 tumors might explain the wide range of reported PM incidences (8-50%). Hyperplastic and mesothelial inflammatory reactions complicate evaluation of the exact primary tumor involvement of the peritoneal layer. This retrospective cohort study aimed to assess the association between either inflammatory peritoneal reaction or peritoneal involvement of the primary tumor and the risk of PM. METHODS Since 2010, pathologists at UZ Leuven have systematically categorized peritoneal involvement in peritoneal reaction with tumor less than 1 mm from the peritoneal surface or true peritoneal penetration. All patients undergoing resection of CRC between January 2010 and July 2013 who fulfilled either of these pathologic criteria were included in this study. RESULTS The study enrolled 159 CRC patients. Peritoneal reaction with tumor less than 1 mm from the peritoneal surface was present in 43 patients and true peritoneal penetration in 116 patients. Overall, 29 patients (18%) had synchronous PM, and 30 patients (23%) had metachronous PM. In the multivariable analysis, true peritoneal penetration, in contrast to peritoneal reaction with tumor less than 1 mm from the peritoneum, was associated with greater risk of PM (odds ratio [OR], 2.518; range, 1.038-6.111; p = 0.041) and lymph node involvement (N1: OR, 1.572; range, 0.651-3.797 vs N2: OR, 4.046; range, 1.549-10.569; p = 0.014). CONCLUSION Histologically confirmed true peritoneal penetration by CRC, rather than inflammatory peritoneal reaction constitutes a high risk for PM. With evolving treatment strategies that aim to treat PM in an earlier phase, identification of high-risk patients becomes highly important clinically.
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Affiliation(s)
- Charlotte E L Klaver
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
| | | | | | - Albert M Wolthuis
- Department of Abdominal Surgery, UZ Leuven, KU Leuven, Louvain, Belgium
| | - Pieter J Tanis
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Jarmila D W van der Bilt
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- Department of Abdominal Surgery, UZ Leuven, KU Leuven, Louvain, Belgium
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands
| | | | - André D'Hoore
- Department of Abdominal Surgery, UZ Leuven, KU Leuven, Louvain, Belgium
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17
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Hornung M, Werner JM, Schlitt HJ. Applications of hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer. Expert Rev Anticancer Ther 2017; 17:841-850. [PMID: 28715968 DOI: 10.1080/14737140.2017.1357470] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) plays a pivotal role in the current treatment of peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Since the first demonstration, benefits for patients and especially an increase in survival have been described. In recent years, feasibility, efficacy and safety of HIPEC have been improved and progress has been made in understanding its oncological mechanism. Areas covered: In this article, leading publications have been reviewed including clinical trials to describe the clinical presentation of PC due to CRC and present recent evidence of the CRS/HIPEC procedure. The surgical approach including evaluation of the extent of PC is described and, in addition, the article reports about different HIPEC techniques as well as several protocols. Furthermore, the development and prognostic benefit of the combination of intraperitoneal and intravenous chemotherapy are outlined. Consideration has been given in particular to patient selection and the use of HIPEC if complete cytoreduction is not feasible. Expert commentary: The CRS/HIPEC procedure represents a curative approach to treat patients with PC from CRC. However, surgical skills and the HIPEC technique still require specialized oncological centers.
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Affiliation(s)
- Matthias Hornung
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| | - Jens M Werner
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| | - Hans J Schlitt
- a Department of Surgery , University of Regensburg , Regensburg , Germany
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18
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Klaver CEL, Stam R, Sloothaak DAM, Crezee J, Bemelman WA, Punt CJA, Tanis PJ. Colorectal cancer at high risk of peritoneal metastases: long term outcomes of a pilot study on adjuvant laparoscopic HIPEC and future perspectives. Oncotarget 2017; 8:51200-51209. [PMID: 28881641 PMCID: PMC5584242 DOI: 10.18632/oncotarget.17158] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 03/10/2017] [Indexed: 12/12/2022] Open
Abstract
Objective Early detection of peritoneal metastases (PM) of colorectal cancer (CRC) is difficult and treatment options at a clinically overt stage are limited. Potentially, adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) is of value. The aim of this study was to present long term oncological outcomes of a pilot study on adjuvant HIPEC to reduce development of PMCRC, with systematic review of literature. Methods Long term oncological outcomes of ten patients who underwent laparoscopic HIPEC within eight weeks after resection of primary CRC in the pilot study were retrospectively collected. A systematic search of literature was performed on studies describing the use of HIPEC in patients with CRC at high risk of developing PM. Results The median follow-up was 54 months (range 49-63). All patients were alive at the last follow-up moment and none of them had developed PM. Two patients had developed pulmonary metastases. Systematic review revealed five small cohort studies, including two matched comparisons. Peritoneal recurrences were found in 0% to 9% after adjuvant HIPEC, which was 28% and 43% in the two control groups, respectively. Disease free and overall survival were significantly higher in favour of HIPEC. Conclusion Long term follow-up of ten patients included in a pilot study on adjuvant HIPEC revealed no peritoneal recurrences. This result is in line with other published pilot studies, a promising observation. However, the outcomes of the Dutch randomized COLOPEC trial and similar trials worldwide should be awaited for definitive conclusions on the effectiveness of adjuvant HIPEC.
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Affiliation(s)
- Charlotte E L Klaver
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Roos Stam
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Didi A M Sloothaak
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Johannes Crezee
- Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Willem A Bemelman
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Cornelis J A Punt
- Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Pieter J Tanis
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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Lee CL, Huang CJ, Yang SH, Chang CC, Huang CC, Chien CC, Yang RN. Discovery of genes from feces correlated with colorectal cancer progression. Oncol Lett 2016; 12:3378-3384. [PMID: 27900008 DOI: 10.3892/ol.2016.5069] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 07/20/2016] [Indexed: 12/17/2022] Open
Abstract
Colorectal cancer (CRC) is considered to develop slowly via a progressive accumulation of genetic mutations. Markers of CRC may serve to provide the basis for decision-making, and may assist in cancer prevention, detection and prognostic prediction. DNA and messenger (m)RNA molecules that are present in human feces faithfully represent CRC manifestations. In the present study, exogenous mouse cells verified the feasibility of total fecal RNA as a marker of CRC. Furthermore, five significant genes encoding solute carrier family 15, member 4 (SLC15A4), cluster of differentiation (CD)44, 3-oxoacid CoA-transferase 1 (OXCT1), placenta-specific 8 (PLAC8) and growth arrest-specific 2 (GAS2), which are differentially expressed in the feces of CRC patients, were verified in different CRC cell lines using quantitative polymerase chain reaction. The present study demonstrated that the mRNA level of SLC15A4 was increased in the majority of CRC cell lines evaluated (SW1116, LS123, Caco-2 and T84). An increased level of CD44 mRNA was only detected in an early-stage CRC cell line, SW1116, whereas OXCT1 was expressed at higher levels in the metastatic CRC cell line CC-M3. In addition, two genes, PLAC8 and GAS2, were highly expressed in the recurrent CRC cell line SW620. Genes identified in the feces of CRC patients differed according to their clinical characteristics, and this differential expression was also detected in the corresponding CRC cell lines. In conclusion, feces represent a good marker of CRC and can be interpreted through the appropriate CRC cell lines.
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Affiliation(s)
- Chia-Long Lee
- School of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; Department of Internal Medicine, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.; Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Shung-Haur Yang
- Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.; School of Medicine, National Yang Ming University, Taipei 11221, Taiwan, R.O.C
| | - Chun-Chao Chang
- School of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taipei Medical University Hospital, Taipei 11031, Taiwan, R.O.C
| | - Chi-Cheng Huang
- School of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, R.O.C.; Department of General Surgery, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Chih-Cheng Chien
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.; Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Ruey-Neng Yang
- Department of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, Taiwan, R.O.C.; Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
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Abe S, Kawai K, Ishihara S, Nozawa H, Hata K, Kiyomatsu T, Tanaka T, Watanabe T. Prognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection. J Surg Res 2016; 205:384-392. [PMID: 27664887 DOI: 10.1016/j.jss.2016.06.078] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 06/08/2016] [Accepted: 06/27/2016] [Indexed: 01/04/2023]
Abstract
BACKGROUND Although preoperative carcinoembryonic antigen (pre-CEA) and carbohydrate antigen 19-9 (pre-CA 19-9) are reportedly prognostic indicators for colorectal cancer (CRC), the prognostic roles of postoperative CEA (post-CEA) and CA 19-9 (post-CA 19-9) shortly after surgery have not been clarified in patients with curatively resected stage IV CRC. The aim of this study was to evaluate the predictive abilities of post-CEA and post-CA 19-9. METHODS A total of 129 consecutive patients who had stage IV CRC and underwent R0 resection were retrospectively analyzed. Pre-CEA and post-CEA and CA 19-9 levels were measured within 1 mo before and 3 mo after surgery, respectively. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazards model. RESULTS Pre-CEA was elevated (≥5.0 ng/mL) in 73.6% of the patients and remained elevated after surgery in 32.7% of the patients. Elevated post-CA 19-9 (≥50 U/mL) was observed in 9.5% of the patients. Neither elevated pre-CEA nor elevated pre-CA 19-9 was significantly associated with RFS but both elevated post-CEA and elevated post-CA 19-9 were associated with markedly reduced RFS (P = 0.0002 and P = 0.0004, respectively). When considered in combination, post-CEA and post-CA 19-9 significantly stratified RFS and was an independent predictive factor for recurrence (P = 0.0035), as was lymphatic invasion (P = 0.0015). Post-CA 19-9 was the only evident independent predictive factor for overall survival (P = 0.0336). CONCLUSIONS In patients with stage IV CRC who underwent curative resection, the combination of post-CEA and post-CA 19-9 at 3 mo after surgery was a potent prognostic indicator for recurrence.
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Affiliation(s)
- Shinya Abe
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Kazushige Kawai
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
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21
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Ozawa T, Ishihara S, Kawai K, Nozawa H, Yamaguchi H, Kitayama J, Watanabe T. Prognostic Significance of Preoperative Serum Carbohydrate Antigen 19-9 in Patients With Stage IV Colorectal Cancer. Clin Colorectal Cancer 2016; 15:e157-e163. [PMID: 27245559 DOI: 10.1016/j.clcc.2016.04.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Revised: 03/22/2016] [Accepted: 04/27/2016] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Carbohydrate antigen (CA) 19-9 is a widely used tumor marker in colorectal cancer (CRC). However, its prognostic impact in patients with stage IV CRC who have undergone curative resection is not clear. We evaluated the prognostic power of preoperative serum CA 19-9 in these patients. PATIENTS AND METHODS We performed a retrospective review of 173 patients with stage IV CRC who had undergone curative resection at our institution. Patients were categorized into normal and high CA 19-9 groups, and relapse-free survival and overall survival were compared using Kaplan-Meier curves. Multivariate analyses were performed using a Cox proportional hazard model. RESULTS The preoperative serum CA 19-9 level was elevated in 80 patients (46%). The 3-year relapse-free survival of the high CA 19-9 group was significantly worse than that of the normal CA 19-9 group (18% vs. 28%, respectively; P = .026). The 3-year overall survival of the high CA 19-9 group was significantly lower than that of the normal CA 19-9 group (75% vs. 82%; P = .047). Multivariate analyses indicated that elevated preoperative serum CA 19-9 level was an independent prognostic factor for poor relapse-free survival and overall survival, with a hazard ratio of 1.46 (95% confidence interval, 1.03-2.06; P = .035) and 1.90 (95% confidence interval, 1.10-3.29; P = .023), respectively. CONCLUSION The preoperative serum CA 19-9 level is a good predictive marker of tumor recurrence and prognosis in patients with stage IV CRC who have undergone curative resection.
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Affiliation(s)
- Tsuyoshi Ozawa
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hironori Yamaguchi
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Joji Kitayama
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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22
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Sluiter N, de Cuba E, Kwakman R, Kazemier G, Meijer G, Te Velde EA. Adhesion molecules in peritoneal dissemination: function, prognostic relevance and therapeutic options. Clin Exp Metastasis 2016; 33:401-16. [PMID: 27074785 PMCID: PMC4884568 DOI: 10.1007/s10585-016-9791-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 04/07/2016] [Indexed: 12/14/2022]
Abstract
Peritoneal dissemination is diagnosed in 10–25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2β1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLex and Lex, chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLea and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete.
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Affiliation(s)
- Nina Sluiter
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Erienne de Cuba
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.,Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Riom Kwakman
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Gerrit Meijer
- Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.,Department of Pathology, Antoni van Leeuwenhoek Hospital (NKI-AVL), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Elisabeth Atie Te Velde
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. .,Department of Surgical Oncology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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23
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Klaver CEL, Musters GD, Bemelman WA, Punt CJA, Verwaal VJ, Dijkgraaf MGW, Aalbers AGJ, van der Bilt JDW, Boerma D, Bremers AJA, Burger JWA, Buskens CJ, Evers P, van Ginkel RJ, van Grevenstein WMU, Hemmer PHJ, de Hingh IHJT, Lammers LA, van Leeuwen BL, Meijerink WJHJ, Nienhuijs SW, Pon J, Radema SA, van Ramshorst B, Snaebjornsson P, Tuynman JB, Te Velde EA, Wiezer MJ, de Wilt JHW, Tanis PJ. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial. BMC Cancer 2015; 15:428. [PMID: 26003804 PMCID: PMC4492087 DOI: 10.1186/s12885-015-1430-7] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 05/13/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. METHODS/DESIGN The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. DISCUSSION Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival. TRIAL REGISTRATION NUMBER NCT02231086 (Clinicaltrials.gov).
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Affiliation(s)
- Charlotte E L Klaver
- Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Gijsbert D Musters
- Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Willem A Bemelman
- Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Cornelis J A Punt
- Department of oncology, Academic Medical Centre, University of Amsterdam, Post box 22660, Amsterdam, The Netherlands.
| | - Victor J Verwaal
- Department of Surgery, Antoni van Leeuwenhoek hospital/the Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Marcel G W Dijkgraaf
- Clinical Research Unit, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Arend G J Aalbers
- Department of Surgery, Antoni van Leeuwenhoek hospital/the Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Jarmila D W van der Bilt
- Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Djamila Boerma
- Department of surgery, St. Antonius Hospital, Post box 2500, 3430 EM, Nieuwegein, The Netherlands.
| | - Andre J A Bremers
- Department of surgery, Radboud University Medical Centre, Geert Grooteplein-Zuid 22, 6525 GA, Nijmegen, The Netherlands.
| | - Jacobus W A Burger
- Department of surgery, Erasmus Medical Centre/Daniel den Hoed, Post box 2040, 3000 CA, Rotterdam, The Netherlands.
| | - Christianne J Buskens
- Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Pauline Evers
- Dutch Cancer Patient Organization 'Leven met Kanker', Utrecht, the Netherlands.
| | - Robert J van Ginkel
- Department of surgery, University Medical Centre, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
| | | | - Patrick H J Hemmer
- Department of surgery, University Medical Centre, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
| | - Ignace H J T de Hingh
- Department of surgery, Catharina Ziekenhuis, Post box 1350, 5602 ZA, Eindhoven, The Netherlands.
| | - Laureen A Lammers
- Department of pharmacy, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
| | - Barbara L van Leeuwen
- Department of surgery, University Medical Centre, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
| | - Wilhelmus J H J Meijerink
- Departement of surgery, Vrije University Medical Center, Post box 7057, 1007 MB, Amsterdam, The Netherlands.
| | - Simon W Nienhuijs
- Department of surgery, Catharina Ziekenhuis, Post box 1350, 5602 ZA, Eindhoven, The Netherlands.
| | - Jolien Pon
- Society of patients with cancer of the gastrointestinal tract (SPKS), Darmkanker Nederland, Utrecht, the Netherlands.
| | - Sandra A Radema
- Department of oncology, Radboud University Medical Centre, Geert Grooteplein-Zuid 22, 6525 GA, Nijmegen, The Netherlands.
| | - Bert van Ramshorst
- Department of surgery, St. Antonius Hospital, Post box 2500, 3430 EM, Nieuwegein, The Netherlands.
| | - Petur Snaebjornsson
- Department of pathology, Antoni van Leeuwenhoek hospital/the Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Jurriaan B Tuynman
- Departement of surgery, Vrije University Medical Center, Post box 7057, 1007 MB, Amsterdam, The Netherlands.
| | - Elisabeth A Te Velde
- Departement of surgery, Vrije University Medical Center, Post box 7057, 1007 MB, Amsterdam, The Netherlands.
| | - Marinus J Wiezer
- Department of surgery, St. Antonius Hospital, Post box 2500, 3430 EM, Nieuwegein, The Netherlands.
| | - Johannes H W de Wilt
- Department of surgery, Radboud University Medical Centre, Geert Grooteplein-Zuid 22, 6525 GA, Nijmegen, The Netherlands.
| | - Pieter J Tanis
- Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands.
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Takakura Y, Ikeda S, Imaoka Y, Urushihara T, Itamoto T. An elevated preoperative serum carbohydrate antigen 19-9 level is a significant predictor for peritoneal dissemination and poor survival in colorectal cancer. Colorectal Dis 2015; 17:417-25. [PMID: 25512077 DOI: 10.1111/codi.12865] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Accepted: 10/02/2014] [Indexed: 01/02/2023]
Abstract
AIM Many studies support the role of carcinoembryonic antigen (CEA) as a strong indicator of the status of colorectal cancer patients, but evidence for carbohydrate antigen 19-9 (CA19-9) is poor. For this reason the study aimed to evaluate the prognostic value of preoperative serum CA19-9 levels in colorectal cancer patients. METHOD In all, 1190 colorectal cancer patients were included in this study, of whom 955 underwent a potentially curative resection. These were analysed for recurrence and survival. The 255 patients with Stage IV disease were analysed for metastatic status. RESULTS Patients with an elevated preoperative CEA with Stage II and III disease showed a significantly poorer survival than those with normal levels. In contrast patients with elevated preoperative CA19-9 levels were associated with a significantly poorer survival irrespective of disease stage. Of the 255 patients with Stage IV disease, 92 (39.1%) had peritoneal dissemination at laparotomy observed more frequently in patients with an elevated CA19-9 (47.9%). Of the 955 patients having a curative resection, 18 (1.9%) developed peritoneal dissemination. In multivariate analysis, an elevated preoperative CA19-9 level was a significant risk factor for postoperative peritoneal recurrence. CONCLUSION After curative surgery for colorectal cancer the preoperative CA19-9 level is a strong prognostic indicator of higher risk of peritoneal dissemination.
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Affiliation(s)
- Y Takakura
- Department of Gastrointestinal Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
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De Divitiis C, Nasti G, Montano M, Fisichella R, Iaffaioli RV, Berretta M. Prognostic and predictive response factors in colorectal cancer patients: Between hope and reality. World J Gastroenterol 2014; 20:15049-15059. [PMID: 25386053 PMCID: PMC4223238 DOI: 10.3748/wjg.v20.i41.15049] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Revised: 03/13/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e., bevacizumab, cetuximab and panitumab), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy. Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings, and a greater emphasis on early detection, the outlook still remains poor for most patients. Molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of prognostic factors and predictive factors according to the recently published English literature.
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26
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Intraperitoneal chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal cancer origin: a systematic review. Br J Cancer 2014; 111:1112-21. [PMID: 25025964 PMCID: PMC4453838 DOI: 10.1038/bjc.2014.369] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 05/20/2014] [Accepted: 06/09/2014] [Indexed: 01/05/2023] Open
Abstract
Background: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC. Methods: A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC. Results: Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed. Conclusions: The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.
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27
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Tang Q, Wang Y, Huang R, You Q, Wang G, Chen Y, Jiang Z, Liu Z, Yu L, Muhammad S, Wang X. Preparation of anti-tumor nanoparticle and its inhibition to peritoneal dissemination of colon cancer. PLoS One 2014; 9:e98455. [PMID: 24896096 PMCID: PMC4045714 DOI: 10.1371/journal.pone.0098455] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2014] [Accepted: 05/04/2014] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND 5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs. Nanoparticle drug delivery vehicles offer superiority over target effect enhancement and abatement of side effects. Little is known however as to the specific effect of nanoparticle on peritoneal dissemination of colon cancer. The aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and investigate the characteristic of NPs and the role of it in peritoneal metastasis nodules formation of human colon cancer. METHODOLOGY/PRINCIPAL FINDINGS Prepared the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the method of double emulsion. Then evaluate the characteristics of the NPs by scanning electron microscopy, analyzing the particle diameter distribution and determining the loading efficiency. Detect the release features of NPs in vitro and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and mesenterium and survey the size of them. We got NPs with average-diameter of 310 nm. In vitro release test shows NPs can release equably for 5 days with release rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU longer than it in solution group. The number of peritoneal dissemination nodule below 1 mm in 5-FU-sol group(17.3 ± 3.5) and 5-FU-NP group(15.2 ± 3.2) is less than control group(27.2 ± 4.7)(P<0.05). The total number of nodules in 5-FU-NP group(28.7 ± 4.2) is significantly smaller than in 5-FU-sol group(37.7 ± 6.3) (P<0.05). CONCLUSIONS/SIGNIFICANCE The novel anti-tumor nanoparticles loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory action to peritoneal dissemination of colon cancer in mice.
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Affiliation(s)
- Qingchao Tang
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yihui Wang
- Department of Colorectal Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Rui Huang
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Qi You
- Department of Colorectal Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Guiyu Wang
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yinggang Chen
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Zheng Jiang
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Zheng Liu
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Lei Yu
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Shan Muhammad
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Xishan Wang
- Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
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Passot G, Mohkam K, Cotte E, Glehen O. Intra-operative peritoneal lavage for colorectal cancer. World J Gastroenterol 2014; 20:1935-9. [PMID: 24616569 PMCID: PMC3934463 DOI: 10.3748/wjg.v20.i8.1935] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/28/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies.
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Allard M, Adam R, Ruiz A, Vibert E, Paule B, Levi F, Sebagh M, Guettier C, Azoulay D, Castaing D. Is unexpected peritoneal carcinomatosis still a contraindication for resection of colorectal liver metastases? Eur J Surg Oncol 2013; 39:981-7. [DOI: 10.1016/j.ejso.2013.06.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 05/08/2013] [Accepted: 06/06/2013] [Indexed: 01/29/2023] Open
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Homma Y, Hamano T, Akazawa Y, Otsuki Y, Shimizu S, Kobayashi H, Kameoka S, Kobayashi Y. Positive peritoneal washing cytology is a potential risk factor for the recurrence of curatively resected colorectal cancer. Surg Today 2013; 44:1084-9. [PMID: 23942820 DOI: 10.1007/s00595-013-0689-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Accepted: 05/13/2013] [Indexed: 12/29/2022]
Abstract
PURPOSES Whether free peritoneal cancer cells should be considered peritoneal dissemination in colorectal cancer patients remains controversial. The aim of this study was to investigate the clinical significance of positive peritoneal washing cytology (PWC) in patients with colorectal cancer. METHODS We retrospectively analyzed the records of 771 sequential patients diagnosed with stage 0-III colorectal cancer who underwent R0 resection and had no distant metastases or peritoneal dissemination. RESULTS PWC was performed on all 771 patients. Sixty-eight patients experienced metastasis recurrence, 10 of whom experienced peritoneal recurrence. Of the 10 patients with peritoneal recurrence, 6 had positive PWC. Out of the 771 patients, 21 had positive PWC. Of these 21 patients, 6 had peritoneal recurrence, while 4 had distant metastasis and no peritoneal recurrence during the observation period. The 5-year disease-free survival was 89.0 % in the patients with negative PWC vs. 46.8 % in the patients with positive PWC (p < 0.0001, log-rank test). A Cox proportional hazards model revealed that positive PWC was the strongest independent risk factor for cancer-specific recurrence. CONCLUSIONS Our study highlights PWC as a useful prognostic tool in patients undergoing curative surgery for colorectal cancer, since positive PWC was shown to be a potential risk factor for recurrence.
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Affiliation(s)
- Yoichiro Homma
- Department of Colorectal Surgery, Seirei Hamamatsu General Hospital, Naka-ku, Sumiyoshi 2-12-12, Hamamatsu, Shizuoka, 430-8558, Japan,
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Lee JH. Clinical Usefulness of Serum CYFRA 21-1 in Patients with Colorectal Cancer. Nucl Med Mol Imaging 2013; 47:181-7. [PMID: 24900105 DOI: 10.1007/s13139-013-0218-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Revised: 06/25/2013] [Accepted: 07/16/2013] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Among diverse tumor markers, pretreatment evaluation and follow-up detection of recurrence in colorectal cancer are generally evaluated by serum carcinoembryonic antigen (CEA) levels. However, there have been some reports about the low accuracy and high false-positive results of CEA in colorectal cancer. We investigated the clinical utilities of CYFRA 21-1 by comparing CEA and cancer antigen 19-9 (CA 19-9) in pretreatment and recurrent colorectal cancer. METHODS Using a solid-phase immunoradiometric assay, serum levels of CYFRA 21-1, CEA and CA 19-9 were analyzed in 132 patients with primary colorectal cancer, 124 healthy controls, 104 patients with benign colorectal disease and 19 patients with recurrent colorectal cancer. We determined three different cutoff values to evaluate the sensitivity of diagnostic performance in pretreatment and recurrent colorectal cancer. RESULTS CYFRA 21-1 (≥ 1.13 ng/ml) had a sensitivity of 47 %, compared with 37 % for CEA (≥ 3.05 ng/ml) and 32.6 % for CA 19-9 (≥ 23.1 ng/ml) in the initial staging of primary colorectal cancer. Using different cutoff values, CYFRA 21-1 showed higher sensitivity for pretreatment colorectal cancer than CEA and CA 19-9 in adenocarcinoma and adenosquamous carcinoma of this study. A mildly significant correlative relationship was noted between Dukes' stages and three tumor markers (p < 0.01). The areas under the receiver operating characteristic curves of CYFRA 21-1, CEA and CA 19-9 were 0.81 ± 0.03, 0.74 ± 0.03 and 0.62 ± 0.04, respectively, for discriminating colorectal cancer patients from patients with benign colorectal disease. In addition, CYFRA 21-1 was determined as the most sensitive tumor marker for evaluating recurrent colorectal cancer for all cutoff values. CONCLUSION This study showed that CYFRA 21-1 could be a useful and dependable tumor marker for pretreatment and recurrent colorectal cancer. Further prospective studies on its usefulness with respect to the prognosis and utility of combined tumor markers are needed.
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Affiliation(s)
- Jai Hyuen Lee
- Department of Nuclear Medicine, Dankook University Medical College, Dongnam-ku, Anseo-dong, Cheonan, 330-715 Republic of Korea
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Huang CJ, Yang SH, Lee CL, Cheng YC, Tai SY, Chien CC. Ribosomal protein S27-like in colorectal cancer: a candidate for predicting prognoses. PLoS One 2013; 8:e67043. [PMID: 23826192 PMCID: PMC3691124 DOI: 10.1371/journal.pone.0067043] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Accepted: 05/13/2013] [Indexed: 01/25/2023] Open
Abstract
Background The development and progression of colorectal cancer (CRC) involve a complex process of multiple genetic changes. Tumor suppressor p53 is capable of determining the fate of CRC cells. However, the role of a p53-inducible modulator, ribosomal protein S27-like (RPS27L), in CRC is unknown. Methods Here, the differential expression of RPS27L was examined in the feces and colonic tissues of CRC patients, to explore its possible correlation with patient survival and to investigate the cellular mechanisms underlying their clinical outcomes. Eighty intermediate-stage CRC patients (42 at stage II and 38 at stage III) were divided into two groups according to their fecal RPS27L mRNA levels. The survival probabilities of the groups were estimated using the Kaplan–Meier method. The RPS27L protein in the colonic tissues of stage III patients with different prognoses was further examined immunohistochemically. RPS27L expression in LoVo cells was manipulated to examine the possible cellular responses in vitro. Results Elevated RPS27L expression, in either feces or tissues, was related to a better prognosis. In vitro, RPS27L-expressing LoVo cells ceased DNA synthesis and apoptotic activity while the expression of their DNA repair molecules was upregulated. Conclusions Elevated RPS27L may improve the prognoses of certain CRC patients by enhancing the DNA repair capacity of their colonic cells, and can be determined in feces. By integrating clinical, molecular, and cellular data, our study demonstrates that fecal RPS27L may be a useful index for predicting prognoses and guiding personalized therapeutic strategies, especially in patients with intermediate-stage CRC.
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Affiliation(s)
- Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
- Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan
| | - Shung-Haur Yang
- Department of Surgery, Taipei-Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming University, Taipei, Taiwan
| | - Chia-Long Lee
- Department of Internal Medicine, Hsinchu Cathay General Hospital, Hsinchu, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu-Che Cheng
- Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
| | - Szu-Yun Tai
- Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
| | - Chih-Cheng Chien
- Department of Medical Research, Cathay General Hospital, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
- Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei, Taiwan
- * E-mail:
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Yu H, Son GM, Joh YG. The clinical significance of preoperative serum levels of carbohydrate antigen 19-9 in colorectal cancer. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2013; 84:231-7. [PMID: 23577318 PMCID: PMC3616277 DOI: 10.4174/jkss.2013.84.4.231] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Revised: 02/06/2013] [Accepted: 02/12/2013] [Indexed: 02/06/2023]
Abstract
Purpose Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most frequently used tumor markers in the clinical setting of colorectal cancer (CRC). This study was designed to investigate the correlation between preoperative serum levels of CA 19-9 (pre-CA 19-9) and the clinicopathologic factors of patients with CRC. Methods A study was performed on 333 patients with histologically diagnosed colorectal adenocarcinoma between December 2008 and November 2011, based on prospective collected data. The clinical data such as age, sex, location of tumor, size of tumor, differentiation, depth of tumor (T), lymph node metastasis (N), distant metastasis (M), lymphatic invasion, venous invasion, perineural invasion, stage, and preoperative serum levels of CEA (pre-CEA) and pre-CA 19-9 were obtained. These patients were classified into two groups according to pre-CA 19-9 (CA 19-9 high: >39 U/mL, n = 61 [18.3%]; CA 19-9 normal: <39 U/mL, n = 272 [81.7%]). Results Sixty-one patients among 333 patients (18.3%) with CRC showed a high pre-CA 19-9. The elevation of pre-CA 19-9 was significantly associated with size of tumor (4.8 ± 0.1 cm vs. 6.1 ± 0.3 cm, P < 0.001), right colon cancer (P < 0.001), depth of tumor (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001), perineural invasion (P = 0.008), peritoneal seeding (P < 0.001), and stage (P < 0.001). On multivariate analysis, high pre-CA 19-9 was shown to be independently associated with high pre-CEA, lymph node metastasis, right colon cancer, large tumor size, and peritoneal seeding. There were twelve patients confirmed for peritoneal seeding among 333 patients (3.6%). Conclusion High pre-CA 19-9 in advanced colorectal cancer might provide important information to predict the possibility of peritoneal seeding.
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Affiliation(s)
- Hyeon Yu
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
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Dong H, Tang J, Li LH, Ge J, Chen X, Ding J, Men HT, Luo WX, Du Y, Li C, Zhao F, Chen Y, Cheng K, Liu JY. Serum carbohydrate antigen 19-9 as an indicator of liver metastasis in colorectal carcinoma cases. Asian Pac J Cancer Prev 2013; 14:909-913. [PMID: 23621260 DOI: 10.7314/apjcp.2013.14.2.909] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
PURPOSE The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. METHODS Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC- NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. RESULTS A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, γ-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. CONCLUSION Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.
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Affiliation(s)
- Hang Dong
- Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
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Honoré C, Goéré D, Souadka A, Dumont F, Elias D. Definition of Patients Presenting a High Risk of Developing Peritoneal Carcinomatosis After Curative Surgery for Colorectal Cancer: A Systematic Review. Ann Surg Oncol 2012; 20:183-92. [DOI: 10.1245/s10434-012-2473-5] [Citation(s) in RCA: 122] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Indexed: 12/17/2022]
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Abstract
Peritoneal carcinomatosis occurs in patients with advanced gastrointestinal and gynecological malignancies and also in patients who experience recurrence after treatment failure of the primary tumor. Malignant disease in the peritoneal cavity is a morbid and significant predictor of a diminished survival in a cancer patient. Systemic chemotherapy alone will not be adequate to palliate or treat patients with peritoneal carcinomatosis. Cytoreductive surgery is a new surgical technique that is performed using peritonectomy procedures to allow total eradication of peritoneal tumors. Intraperitoneal chemotherapy regimens such as intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) are effective adjuvant treatment to treat the minimal residual disease after cytoreductive surgery to reduce the risk of locoregional recurrence. A substantial body of evidence available in the current literature has documented the survival benefits of combining cytoreductive surgery and intraperitoneal chemotherapy to treat a previously fatal phase of malignancy. This review provides a summary of the developments in the understanding and treatment of peritoneal surface malignancy from colorectal cancer.
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Affiliation(s)
- Terence C Chua
- UNSW Department of Surgery, Hepatobiliary and Surgical Oncology Unit, St George Hospital, Sydney, Australia
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37
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Results of Systematic Second-look Surgery Plus HIPEC in Asymptomatic Patients Presenting a High Risk of Developing Colorectal Peritoneal Carcinomatosis. Ann Surg 2011; 254:289-93. [DOI: 10.1097/sla.0b013e31822638f6] [Citation(s) in RCA: 186] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Lin BR, Chang CC, Chen RJC, Jeng YM, Liang JT, Lee PH, Chang KJ, Kuo ML. Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer. Clin Cancer Res 2011; 17:3077-88. [PMID: 21558398 DOI: 10.1158/1078-0432.ccr-09-3256] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
PURPOSE Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. EXPERIMENTAL DESIGN A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. RESULTS The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. CONCLUSIONS CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients.
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Affiliation(s)
- Been-Ren Lin
- Institute of Toxicology, College of Medicine, School of Dentistry, andAngiogenesis Research Center, National Taiwan University, Taipei, Taiwan
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Yang RN, Yang SH, Chang CC, Chien CC, Pan S, Huang CJ. Upregulation of Fecal Cytokeratin 19 Is Associated with Prognosis in Older Colorectal Cancer Patients. Genet Test Mol Biomarkers 2010; 14:703-8. [DOI: 10.1089/gtmb.2010.0047] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Ruey-Neng Yang
- Department of Internal Medicine, Sijhih Cathay General Hospital, Sijhih City, Taipei, Taiwan
- Ching Kuo Institute of Management and Health, Keelung, Taiwan
| | - Shung-Haur Yang
- Department of Surgery, Taipei-Veterans General Hospital and School of Medicine, National Yang Ming University, Taipei, Taiwan
| | - Chun-Chao Chang
- Digestive Disease Research Center, Taipei Medical University, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chih-Cheng Chien
- Department of Anesthesiology, Sijhih Cathay General Hospital, Sijhih City, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
| | - Shiann Pan
- Digestive Disease Research Center, Taipei Medical University, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chi-Jung Huang
- School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
- Department of Medical Research, Cathay Medical Research Institute, Cathay General Hospital, Taipei, Taiwan
- Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan
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Kang BM, Choi GS, Lim KH, Park IJ, Jun SH. Risk Factors of Peritoneal Recurrence after Curative Resection of Colorectal Cancer. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2010. [DOI: 10.4174/jkss.2010.79.5.355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Byung Mo Kang
- Division of Colorectal Surgery, Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - Gyu Seog Choi
- Division of Colorectal Surgery, Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - Kyoung Hoon Lim
- Division of Colorectal Surgery, Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - In Ja Park
- Division of Colorectal Surgery, Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - Soo Han Jun
- Division of Colorectal Surgery, Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
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Prognostic value of peritoneal cytology and the combination of peritoneal cytology and peritoneal dissemination in colorectal cancer. Dis Colon Rectum 2009; 52:2016-21. [PMID: 19934924 DOI: 10.1007/dcr.0b013e3181b4c46e] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE The value of positive peritoneal cytology in colorectal cancer has been controversial. In this study, we aimed to clarify the prognostic significance of peritoneal cytology and the impact of the combination of peritoneal dissemination and peritoneal cytology on the prognostic evaluation of colorectal cancer. METHODS From January 1997 to December 2005, intraoperative peritoneal cytology was performed on 410 patients who had at least serosal invasion. RESULTS Thirty-one patients (7.6%) had positive peritoneal cytology. Patients with negative cytology showed a significantly better survival rate at five years than those with positive cytology (negative cytology, 68.0%; positive cytology, 20.6%; P < 0.0001). Multivariate analysis revealed that peritoneal cytology is one of the significant prognostic factors. Sixty percent of patients with positive cytology and 30.4% of patients with negative cytology recurred (P = 0.08). Regarding the recurrence site, patients with positive cytology showed a significantly higher recurrence rate of peritoneal dissemination than those with negative cytology (P = 0.0038). Some patients with positive cytology but without evident peritoneal dissemination achieved long-term survival. Additionally, some patients with macroscopic peritoneal dissemination and negative peritoneal cytology also achieved long-term survival. But for those patients with both positive cytology and evident macroscopic peritoneal dissemination, the five-year survival rate was zero. CONCLUSIONS Patients with negative peritoneal cytology had a significantly better five-year survival rate than those with positive peritoneal cytology. In some cases in which either peritoneal cytology or peritoneal dissemination was negative, long-term survival could be achieved.
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Evaluation of intraperitoneal lavage cytology before colorectal cancer resection. Int J Colorectal Dis 2009; 24:907-14. [PMID: 19475411 DOI: 10.1007/s00384-009-0733-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/13/2009] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this study was to assess the usefulness of intraperitoneal lavage cytology (lavage Cy) status before the resection of colorectal cancer as a predictive factor of peritoneal recurrence. MATERIALS AND METHODS The lavage Cy-positive [lavage Cy (+)] rate, peritoneal recurrence rate, and 5-year survival rate were examined in 298 cases of colorectal cancer in relation to various clinicopathological factors. RESULTS The overall lavage Cy (+) rate was 6.0%. The lavage Cy (+) rate within the group with peritoneal and hepatic metastases was significantly higher than that in the group without metastases (46.7% vs. 3.9% and 26.9% vs. 4.0%, respectively). The lavage Cy (+) rate was not significantly associated with any of the clinicopathological factors examined. The peritoneal recurrence rate was higher in the lavage Cy (+) group than in the lavage Cy-negative [lavage Cy (-)] group, although the difference was not statistically significant. There was no significant difference in survival, regardless of the lavage Cy status, among the 263 patients who underwent curative resection. CONCLUSION The lavage Cy status before resection was not a useful predictive factor of peritoneal recurrence in cases of colorectal cancer.
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Cytoreductive surgery plus intraperitoneal chemohyperthermia in patients with colorectal cancer at high risk for local-regional recurrence. Cancer J 2009; 15:200-3. [PMID: 19556905 DOI: 10.1097/ppo.0b013e3181a58f1d] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
This article was written to define the situations in which early second-look surgery with a combined treatment should be indicated in patients at high risk of developing peritoneal carcinomatosis (PC). Through a review of the literature, this is a definition of the second-look concept and of the different groups of patients at risk, in different situations (after resection of the primary, after initial cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy, and after the discovery of isolated carcinoembryonic antigen elevation or isolated peritoneal uptake on positron emission tomography scan). Systematic second-look surgery for early treatment of asymptomatic PC is probably beneficial in patients presenting a high risk of developing PC after resection of their primary. The benefit seems considerably lower for the other groups of high-risk patients.
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Koppe MJ, Boerman OC, Oyen WJG, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 2006; 243:212-22. [PMID: 16432354 PMCID: PMC1448921 DOI: 10.1097/01.sla.0000197702.46394.16] [Citation(s) in RCA: 400] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC). SUMMARY BACKGROUND DATA Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC. METHODS The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC. RESULTS The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment. CONCLUSIONS Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.
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Affiliation(s)
- Manuel J Koppe
- Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
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Arao T, Yanagihara K, Takigahira M, Takeda M, Koizumi F, Shiratori Y, Nishio K. ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model. Int J Cancer 2006; 118:483-9. [PMID: 16052530 DOI: 10.1002/ijc.21340] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Angiogenesis inhibitors have been used to treat some cancers, but the therapeutic potential of these agents for gastric cancer has remained unclear. To investigate their therapeutic potential, we examined the effect of ZD6474, an agent that selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2; KDR) tyrosine kinase and epidermal growth factor receptor (EGFR) tyrosine kinase, in a highly metastatic orthotopic model using an undifferentiated gastric cancer cell line, 58As1. ZD6474 (100 mg/kg/day, p.o., 2 weeks) significantly inhibited tumor growth (p < 0.05 vs. control) and reduced tumor dissemination into the peritoneal cavity (p < 0.05 vs. control). In addition, to identify putative tumor biomarkers that would reflect the effects of ZD6474 treatment in clinical settings, we examined the gene expression profiles of implanted gastric tumors treated with ZD6474 in vivo. Twenty-eight candidate genes were identified, including IGFBP-3, ADM, ANGPTL4, PLOD2, DSIPI, NDRG1, ENO2, HIG2 and BNIP3L, which are known to be hypoxia-inducible genes. These genes and gene products may be useful biomarkers for monitoring the effects of ZD6474 treatment. ZD6474 also improved the survival of mice with implanted another undifferentiated gastric cancer cell line, 44As3. In conclusion, our results suggest that ZD6474 may have clinical activity against gastric cancer, particularly undifferentiated gastric cancer with peritoneal dissemination. We also identified putative biomarkers for monitoring the pharmacodynamic effects of ZD6474 by gene expression profiling.
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Affiliation(s)
- Tokuzo Arao
- Shien Lab, Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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