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Song JH, Lee MS, Cha EY, Lee KH, Kim JY, Kim JS. Apurinic/apyrimidinic endonuclease 1 is associated with poor prognosis after curative resection followed by adjuvant chemotherapy in patients with stage III colon cancer. KOREAN JOURNAL OF CLINICAL ONCOLOGY 2022; 18:1-10. [PMID: 36945334 PMCID: PMC9942767 DOI: 10.14216/kjco.22001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 06/14/2022] [Accepted: 06/15/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE Apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme involved in the base excision repair pathway. It also has redox activity and maintains various transcription factors in an active reduced state. APE1 may be associated with chemoresistance. In the present study, we first investigated the expression level of APE1 protein and its correlation with oncologic outcomes of oxaliplatin-based chemotherapy in patients with stage III colon cancer. Further, we investigated the effects of human APE1 siRNA on the sensitivity of oxaliplatin in SNU-C2A colon cancer cells. METHODS Tissue specimens from tumor and normal colon of 33 patients with stage III colon cancer were obtained from 2006 to 2009. The patients received at least eight cycles of oxaliplatin-based chemotherapy. APE1 expression was analyzed by immunohistochemistry and Western blotting using a cultured SNU-C2A cell line. Cell viability and apoptosis were determined by Cell Counting Kit-8 and caspase-3 cleavage using Western blotting. RESULTS All the colon cancer tissues showed APE1 staining in the nucleus, whereas all the normal colon tissues were negative for APE1 staining in the cytoplasm. The group with a higher expression of APE1 demonstrated poorer prognosis than the group with low expression (P=0.026 for overall survival and P=0.021 for disease-free survival). Treatment with oxaliplatin resulted in a dose-dependent increase in APE1 expression in SNU-C2A cells. APE1 siRNA significantly enhanced oxaliplatin-induced growth inhibition, and also increased oxaliplatin-induced apoptosis in SNU-C2A cells. CONCLUSION APE1 could be considered a prognostic factor in colon cancer patients treated with oxaliplatin-based chemotherapy.
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Affiliation(s)
- Ji Hyeong Song
- Department of Surgery, Chungnam National University Sejong Hospital, Sejong, Korea
| | - Myung Sun Lee
- Surgical Oncology Research Laboratory, Chungnam National University Hospital, Daejeon, Korea
| | - Eun Young Cha
- Surgical Oncology Research Laboratory, Chungnam National University Hospital, Daejeon, Korea
| | - Kyung Ha Lee
- Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Ji Yeon Kim
- Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Jin Soo Kim
- Department of Surgery, Chungnam National University Sejong Hospital, Sejong, Korea
- Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
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Association of Clinical Features of Colorectal Cancer with Circulating Tumor Cells and Systemic Inflammatory Markers. DISEASE MARKERS 2022; 2022:5105599. [PMID: 35493298 PMCID: PMC9050256 DOI: 10.1155/2022/5105599] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 03/16/2022] [Indexed: 12/23/2022]
Abstract
Background. Circulating tumor cells (CTCs) in peripheral blood have been shown to reflect the prognosis of patients with colorectal cancer, and epithelial and mesenchymal markers further predict the likelihood of cancer dissemination. This study was conducted to identify possible association of clinical features of colorectal cancer with CTC counts, their subtypes, and systemic inflammatory markers. Methods. Blood samples of 316 colorectal cancer patients were used for CTC detection and subtyping with EpCAM, CK8/18/19, vimentin, and twist as biomarkers. The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio, lymphocyte/monocyte ratio, and systemic immune-inflammation index (SII) were also measured. The relationship between clinical data and these markers or parameters was analyzed. Results. Total CTC counts were correlated with whether there was lymph node involvement but was not correlated with TNM staging. There was a difference in mesenchymal CTCs between patients with and without lymph node involvement (
). Also, more patients with metastasis tested positive for mesenchymal CTCs (
). Of the systemic inflammatory markers, platelet/lymphocyte ratio was positively correlated with CTC counts (
), and lymphocyte/monocyte ratio was negatively correlated with CTC counts (
). Conclusions. Colorectal cancer patients with the mesenchymal markers on their CTCs are more likely to have lymph node involvement or distant metastasis than those without these markers.
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Soh JE, Abu N, Sagap I, Mazlan L, Yahaya A, Mustangin M, Khoo TS, Saidin S, Ishak M, Ab Mutalib NS, Jamal R. Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer. Immunotherapy 2019; 11:1205-1219. [PMID: 31478431 DOI: 10.2217/imt-2019-0073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Colorectal cancer is the third commonest malignancy in Asia including Malaysia. The immunogenic cancer-testis antigens, which are expressed in a variety of cancers but with limited expression in normal tissues except the testis, represent an attractive approach to improve treatment options for colorectal cancer. We aimed to validate four PASD1 peptides as the immunotherapeutic targets in colorectal cancer. First, PASD1 mRNA and protein expression were determined via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. The PASD1 peptides specific to HLA-A*24:02 were investigated using IFN-y-ELISpot assay, followed by the cytolytic and granzyme-B-ELISpot assays to analyze the cytolytic effects of CD8+ T cells. Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. CD8+ T cells raised against PASD1(4) peptide were able to lyze HLA-A*24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.
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Affiliation(s)
- Joanne Ec Soh
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ismail Sagap
- Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Luqman Mazlan
- Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Azyani Yahaya
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Muaatamarulain Mustangin
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Tze S Khoo
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Sazuita Saidin
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Muhiddin Ishak
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nurul S Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Rahman Jamal
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Kim JH, Baek MJ, Ahn BK, Kim DD, Kim IY, Kim JS, Bae BN, Seo BG, Jung SH, Hong KH, Kim H, Park DG, Lee JH. Clinical Practice in the Use of Adjuvant Chemotherapy for Patients with Colon Cancer in South Korea: a Multi-Center, Prospective, Observational Study. J Cancer 2016; 7:136-43. [PMID: 26819636 PMCID: PMC4716845 DOI: 10.7150/jca.13405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 11/01/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Adjuvant chemotherapy is a crucial part of treatment for patients with locally advanced colon cancer. This study was conducted to investigate the actual practice in the use of adjuvant chemotherapy for patients with high-risk stage II or stage III colon cancer in South Korea. METHODS This was a 24-month open-label, prospective, observational study conducted at 12 centers across South Korea. Patients with high-risk stage II and stage III colon cancer receiving adjuvant chemotherapy after curative surgery were included, and data were collected at baseline, third, and sixth month. RESULTS A total of 246 patients were included in the analyses. Of five available regimens (FOLFOX, CAPOX, 5-FU/LV, capecitabine, and UFT/LV), FOLFOX was most commonly used (82.5%). Investigators indicated the "efficacy" as the major cause for selecting FOLFOX or CAPOX. For 5-FU/LV, capecitabine, or UFT/LV, the "safety" or "patient's characteristics (age, comorbidity, and stage)" was one of the most important selecting factors. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. Hematologic toxicities were the most common cause of dose adjustment and treatment delay. CONCLUSIONS In South Korea, FOLFOX was the most commonly used regimen for adjuvant chemotherapy and its efficacy was the main cause for selecting this regimen. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX.
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Affiliation(s)
- Jung Han Kim
- 1. Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University College of Medicine, Seoul 150-950, Korea
| | - Moo Jun Baek
- 2. Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Byung-Kwon Ahn
- 3. Department of Surgery, Kosin University College of Medicine, Busan, Korea
| | - Dae Dong Kim
- 4. Department of Surgery, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Ik Yong Kim
- 5. Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jin Soo Kim
- 6. Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Byung-Noe Bae
- 7. Department of Surgery, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Bong-Gun Seo
- 8. Department of Hemato-Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
| | - Sang Hun Jung
- 9. Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Kwan Hee Hong
- 10. Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Hungdai Kim
- 11. Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Guk Park
- 12. Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
| | - Ji Hye Lee
- 13. Medical department of sanofi-aventis Korea, Seoul, Korea
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Vogelaar FJ, Reimers MS, van der Linden RLA, van der Linden JC, Smit VTHBM, Lips DJ, van de Velde CJH, Bosscha K. The diagnostic value of one-step nucleic acid amplification (OSNA) for sentinel lymph nodes in colon cancer patients. Ann Surg Oncol 2014; 21:3924-30. [PMID: 24912612 DOI: 10.1245/s10434-014-3820-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Lymph node status in colon cancer is critical for prognosis estimation and treatment allocation. The purpose of this study was to compare the performance of one-step nucleic acid amplification (OSNA) through detection of cytokeratin 19 mRNA levels with routine pathological examination (RP) and multilevel fine pathological examination (FP) in sentinel lymph nodes (SLN), detected using the ex vivo SLN mapping (SLNM) procedure, in presurgically defined nonmetastatic colon cancer patients. METHODS In this prospective study, 325 SLNs of 128 patients from the Jeroen Bosch Hospital in 's-Hertogenbosch and the Leiden University Medical Center were investigated by RP (H&E), FP (H&E and Keratin Pan immunohistochemical staining), and OSNA. The SLNs were harvested by the SLNM procedure, using Patent blue or Indocyanine green. SLNs were divided and separate parts were used for RP, FP, and the OSNA assay. RESULTS The diagnostic value of OSNA was 82.1 and 100 % for both FP and combined method (OSNA and FP) compared with RP. An upstaging rate of 20.2 % was obtained with the use of OSNA only and 36.4 % with the use of FP only. An upstaging rate of 46.5 % was obtained by combining the two methods together. CONCLUSIONS OSNA and FP appeared to be promising tools for the detection of lymph node micro- and macrometastases in SLNs after SLNM. The performances of OSNA and FP in this study were superior to RP. Because OSNA allows analysis of the whole lymph node, sampling bias can be avoided. OSNA therefore may improve tumor staging.
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Affiliation(s)
- F J Vogelaar
- Department of Surgery, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
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Lv S, Yang Y, Kwon S, Han M, Zhao F, Kang H, Dai C, Wang R. The association of CXCR4 expression with prognosis and clinicopathological indicators in colorectal carcinoma patients: a meta-analysis. Histopathology 2014; 64:701-12. [PMID: 24422942 DOI: 10.1111/his.12321] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2013] [Accepted: 11/03/2013] [Indexed: 12/20/2022]
Abstract
AIMS The clinical relevance of expression of chemokine receptor 4 (CXCR4) in colorectal carcinoma (CRC) remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features. METHODS AND RESULTS A meta-analysis was performed. Original data included the hazard ratios (HRs) of recurrence-free survival (RFS), overall survival (OS) and odds ratio (OR) in CRC patients. We pooled HR/OR with 95% confidence intervals (CIs) to estimate the hazard. A total of 20 published studies (including 2253 patients) were eligible. RFS and OS were related significantly to CXCR4 expression, with HRs 1.62 (95% CI 1.24-2.11; P < 0.0001) and 1.68 (95% CI 1.31-2.14; P < 0.0001), respectively. In addition, a significant association was revealed between positive CXCR4 expression and age (less than median age: OR 0.78, 95% CI 0.62-0.98; P = 0.03), stage (I and II: OR 0.46, 95% CI 0.32-0.66; P < 0.0001), grade (well/moderately differentiated: OR 0.74, 95% CI 0.56-0.98; P = 0.04), location (colon: OR: 0.73, 95% CI 0.57-0.95; P = 0.02), lymph node invasion (present: OR2.14, 95% CI 1.36-3.37; P = 0.001),and distant metastasis (present: OR 2.40; 95% CI 1.36-4.23; P = 0.003). Heterogeneity was observed among the included studies with regard to stage (I(2) = 58 %), lymph node invasiveness (I(2) = 74%) and distant metastasis (I(2) = 56%). No publication bias was observed. CONCLUSIONS Chemokine receptor 4 expression indicates poorer prognosis in older patients and advanced stage or poor differentiation in CRC, and also serves as an indicator of lymph node and distal organ metastasis. Surprisingly, high CXCR4 expression may indicate that the location of the tumour is the rectum. Thus, CXCR4 could help to predict outcome and guide clinical therapy.
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Affiliation(s)
- Shunzeng Lv
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Ueda Y, Yasuda K, Inomata M, Shiraishi N, Yokoyama S, Kitano S. Biological predictors of survival in stage II colorectal cancer. Mol Clin Oncol 2013; 1:643-648. [PMID: 24649222 PMCID: PMC3915554 DOI: 10.3892/mco.2013.126] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2012] [Accepted: 04/23/2013] [Indexed: 01/28/2023] Open
Abstract
The routine use of postoperative adjuvant chemotherapy in patients with stage II colorectal cancer is not recommended. However, the incidence of tumor recurrence or distant metastasis in these patients is reported to be 25–35%. The identification of high-risk patients with stage II colorectal cancer remains difficult. Therefore, the aim of this study was to determine the risk factors that may help identify stage II colorectal cancer patients with unfavorable prognosis. Paraffin-embedded tissue samples from 109 patients with stage II colorectal cancer following curative operation were analyzed. Thirteen clinicopathological variables and 5 biological markers were assessed using immunohistochemistry, including p53 (tumor suppressor gene), CD10 (tumor invasion marker), CD34 (angiogenic marker), Ki-67 (cell proliferation index) and CAM 5.2 (marker of lymph node micrometastasis) and investigated for associations with disease-specific survival. Univariate analysis revealed bowel obstruction, lymph node micrometastasis and lymphatic invasion (P<0.01) to be highly significant factors for determining the 5-year disease-specific survival. By contrast, the multivariate analysis revealed lymph node micrometastasis and lymphatic invasion to be independent prognostic factors. Stage II colorectal cancer patients with lymph node micrometastasis and lymphatic invasion may therefore be suitable candidates for adjuvant chemotherapy to improve prognosis.
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Affiliation(s)
- Yoshitake Ueda
- Departments of Gastroenterological Surgery, Oita University, Yufu, Oita 879-5593, Japan
| | - Kazuhiro Yasuda
- Departments of Gastroenterological Surgery, Oita University, Yufu, Oita 879-5593, Japan
| | - Masafumi Inomata
- Departments of Gastroenterological Surgery, Oita University, Yufu, Oita 879-5593, Japan
| | - Norio Shiraishi
- Departments of Gastroenterological Surgery, Oita University, Yufu, Oita 879-5593, Japan
| | - Shigeo Yokoyama
- Pathology, Faculty of Medicine, Oita University, Yufu, Oita 879-5593, Japan
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Onitilo AA, Stankowski RV, Engel JM, Doi SAR. Adequate lymph node recovery improves survival in colorectal cancer patients. J Surg Oncol 2013; 107:828-34. [PMID: 23592545 DOI: 10.1002/jso.23332] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Accepted: 02/11/2013] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Current recommendations suggest recovery of 12 lymph nodes during surgical resection for colorectal cancer (CRC) for proper staging and prognostication. Adequate lymph node recovery has been associated with improved patient survival, with results inconsistent. METHODS We examined factors for association with adequate lymph node recovery and used findings to adjust survival analyses to clarify whether adequate lymph node examination is associated with CRC survival or associated with a subset of characteristics that biases lymph node recovery. RESULTS In 74% of subjects (1,036/1,397) an adequate number of lymph nodes was examined. A stepwise multivariate regression analysis showed procedure year, cancer stage, tumor size, and age at diagnosis were significantly associated with lymph node recovery. These and other factors associated with survival status were adjusted for in further analyses, revealing no difference in unadjusted overall survival by adequacy of lymph node recovery (HR = 0.90, 95% CI: 0.75-1.08, P = 0.239). However, in adjusted Cox proportional hazards analysis, adequate lymph node recovery was associated with reduced risk for death (HR = 0.71, 95% CI: 0.57-0.89, P = 0.002). CONCLUSION The current recommendation for retrieval and examination of at least 12 lymph nodes is appropriate for proper treatment and prognostication in patients undergoing surgical resection for CRC.
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Affiliation(s)
- Adedayo A Onitilo
- Department of Hematology and Oncology, Marshfield Clinic, Weston Center, Weston, Wisconsin 54476, USA.
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Mescoli C, Albertoni L, Pucciarelli S, Giacomelli L, Russo VM, Fassan M, Nitti D, Rugge M. Isolated tumor cells in regional lymph nodes as relapse predictors in stage I and II colorectal cancer. J Clin Oncol 2012; 30:965-971. [PMID: 22355061 DOI: 10.1200/jco.2011.35.9539] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
PURPOSE Lymph node (LN) involvement is the most important prognostic factor in colorectal cancer (CRC), and pN-positive status identifies patients who require adjuvant chemotherapy. Approximately 15% to 20% of patients without nodal metastases (pN0) develop recurrent disease. In this study, we tested the prognostic significance of isolated tumor cells (ITCs) in LNs of patients with pN0 CRC (stages I and II). PATIENTS AND METHODS ITCs in LNs regional to CRC were assessed in 312 consecutive patients with pN0 CRC who were followed up clinically and/or endoscopically for at least 6 months after surgery (mean, 67 months; median, 64 months; range, 8 to 102 months). LNs were dissected from gross surgical specimens according to a standardized protocol (with a mean of 17 LNs per patient; range, five to 107 LNs). In all, 5,313 pN0 LNs were collected and assessed by using cytokeratin immunostaining in two serial histology sections from each LN, which amounting to a total of 10,626 specimens. The correlation between ITC status and cancer recurrence was tested by using univariate and multivariate statistics. RESULTS ITCs were documented in 185 of 312 patients (59%). CRC relapsed in 31 of 312 patients (10%), and 25 of 31 recurrences (81%) were documented among ITC-positive patients. CRC recurrence rates among ITC-positive and ITC-negative patients were 14% (25 of 185 patients) and 4.7% (six of 127 patients), respectively. In both univariate and multivariate analyses, ITC status was the only variable significantly associated with cancer relapse (Cox model; hazard ratio, 3.00; 95% CI, 1.23 to 7.32; P = .013). CONCLUSION In patients with pN0 CRC, cancer relapse was significantly associated with ITCs in regional LNs. ITCs should be considered among the clinicobiologic variables that identify high-risk patients who can benefit from adjuvant chemotherapy.
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Evaluation of laparoscopic resection of colorectal carcinoma from the viewpoint of molecular biology. Wideochir Inne Tech Maloinwazyjne 2011; 7:19-26. [PMID: 23255996 PMCID: PMC3516955 DOI: 10.5114/wiitm.2011.25664] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Revised: 10/10/2011] [Accepted: 10/22/2011] [Indexed: 11/17/2022] Open
Abstract
AIM Detection of the possible impact of surgical management on the occurrence of minimal residual disease (MRD) in patients with colorectal carcinoma (CRC) in bone marrow samples, portal and peripheral blood samples. Comparison of MRD prevalence in patients with laparoscopic resection of CRC and those with open colorectal resection. Assessment of the potential impact of MRD on the relapse of the disease and overall survival of patients. MATERIAL AND METHODS The study included 124 patients with primary CRC without proven distant metastases indicated for elective laparoscopic resection and operated on between September 21, 2006 and December 31, 2008 at the Department of Surgery, Hospital and J.G. Mendel Oncological Centre Novy Jicin. 6 samples were collected from each patient to determine MRD (system venous blood and bone marrow at the beginning of surgery, venous blood from mesenteric bloodstream, system venous blood after the resection, system venous blood and bone marrow 1 month after the surgery). Detection of MRD on the basis of CEA expression was performed by real-time RT-PCR technique. The results were compared with those obtained within the similar research using the same methodology at the 2(nd) Department of Surgery, University Hospital in Olomouc (the group included 230 patients treated with open resection of CRC). RESULTS In the group of patients treated with laparoscopic resection, a correlation between positive MRD in the sample of bone marrow collected before the surgery and the stage of the disease was found (p < 0.035). We also recorded the impact of surgical management on MRD occurrence in system venous blood in primary negative patients (p < 0.025). However, in the course of the short period of time we have not found a statistically significant correlation between the finding in patients with stage I-III, and the period prior to the relapse of the disease (p < 0.59). With regard to the results obtained, we can expect a potential direct correlation between a positive MRD finding in system venous blood taken prior to surgery in patients with stage I-III CRC and shorter time of survival (p < 0.075). In the group of patients treated with open resection of CRC, no statistically significant relationship between the stage of the disease and MRD occurrence was found. Incidence of circulating tumour cells (CTC) in the samples of venous blood taken prior to surgery is a prognostically important factor (p < 0.05) from the viewpoint of disease-free survival (DFS). Another prognostically important factor with regard to DFS seems to be the occurrence of disseminated tumour cells (DTC) in the bone marrow taken 1 month after the surgery. CONCLUSIONS The data recorded suggest a relationship between MRD finding and the disease prognosis. Collection of samples as well as evaluation of results continue as we strive to include more patients in our study and to obtain more data within 5-10 years of the follow-up. The comparison between the data obtained in the laparoscopic approach and the data obtained in open resection performed from the viewpoint of molecular biology did not show a significant difference in MRD detection in the samples collected after the surgery.
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Abstract
Lymph node metastasis predicts survival and recurrence in colon cancer (CC), so decisions regarding adjuvant therapy are largely based on nodal status. Chemotherapy is not a routine treatment for node-negative CC because its toxicity and expense exceed its limited benefit in patients without evidence of nodal involvement. The sentinel lymph node (SLN) procedure is a selective sampling technique that can be used to ultrastage regional nodes. The real problem of SLN biopsy in CC is the procedure sensitivity rate. In future, studies concerning SLNs will have to consider issues such as the role of laparoscopy in colorectal resection (which cause technical difficulties in identification of SLNs) and the risk of overstaging of illness as well as the need to exclude T4 CC and, probably, rectal cancer from the studies. Is this the future of correct staging of colorectal cancer? Lymphadenectomy is at the present an integral part of colorectal surgery and surgeons must perform it correctly to improve their results. Nevertheless, for the future another "staging system" is necessary in colorectal cancer which takes into account biologic aspects of the tumor to identify patients with aggresive illness in order to treat them with more effective and less toxic therapies.
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Affiliation(s)
- Stefano Scabini
- Stefano Scabini, Oncologic Surgical Unit, AOU San Martino Hospital, 16132 Genoa, Italy
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Zhao ZS, Li L, Wang HJ, Wang YY. Expression and prognostic significance of CEACAM6, ITGB1, and CYR61 in peripheral blood of patients with gastric cancer. J Surg Oncol 2011; 104:525-9. [PMID: 21618249 DOI: 10.1002/jso.21984] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2010] [Accepted: 05/04/2011] [Indexed: 11/08/2022]
Abstract
BACKGROUND We examined CEACAM6, ITGB1, and cyr61 concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. METHODS Real-time reverse transcription-polymerase chain reaction was used to detect the expressions of CEA, CEACAM6, ITGB1, IGF1R, CK20, cyr61, and S100A4 in peripheral blood karyocyte from 82 patients with GC, 24 patients with recurrence, and 37 healthy volunteers. Receiver operating characteristics (ROC) curves were constructed. RESULTS There were significant association between these CEACAM6, ITGB1, and cyr61 and TNM Stages and distant metastasis. The AUC of CEACAM6 was 0.884 ± 0.044 (P = 0.0001), the AUC of cyr61 was 0.833 ± 0.047 (P = 0.0001), and the AUC of ITGB1 was 0.838 ± 0.042 (P = 0.0001) by differentiating preoperative GC patients from healthy volunteers from ROC curve analysis. The AUC of CEACAM6 was 0.761 ± 0.066 (P = 0.001), the AUC of CYR61 was 0.762 ± 0.063 (P = 0.001), and the AUC of ITGB1 was 0.824 ± 0.051 (P = 0.0001), by differentiating recurrence of GC from healthy volunteers from ROC curve analysis. CONCLUSION The method of detecting the expression of CEACAM6, ITGB1, and CYR61 in peripheral blood of GC patients was more sensitive than CEA, IGF1R, CK20, and S100A4 for the early diagnosis of metastasis and recurrence.
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Affiliation(s)
- Zhong-Sheng Zhao
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, PR China.
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Yamamoto H, Sekimoto M, Oya M, Yamamoto N, Konishi F, Sasaki J, Yamada S, Taniyama K, Tominaga H, Tsujimoto M, Akamatsu H, Yanagisawa A, Sakakura C, Kato Y, Matsuura N. OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan. Ann Surg Oncol 2011; 18:1891-8. [PMID: 21290195 DOI: 10.1245/s10434-010-1539-5] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2010] [Indexed: 01/11/2023]
Abstract
BACKGROUND Lymph node (LN) metastasis in colorectal cancer (CRC) is a critical factor in making accurate prognoses and therapeutic decisions. This study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay in accurately diagnosing LN metastases in CRC patients through the specific detection of cytokeratin 19 mRNA levels in LNs. METHODS The OSNA assay was performed on 121 LNs dissected from early-stage CRC patients (pStage 0 or I) or from patients with benign colorectal disease (study 1). Separately, 385 LNs were dissected from 85 CRC patients (any stage); the OSNA assay was performed on half of each LN, and the results were compared with histopathological examination in 2-mm intervals of the other LN half (study 2). RESULTS In study 1, all 121 histopathologically negative LNs were also negative by the OSNA assay (concordance rate for metastasis negative: 1.0, 95% confidence interval [95% CI]: 0.976-1.0). In study 2, the concordance rate between the OSNA assay and the 2-mm-interval histopathological examination was 0.971 (95% CI: 0.950-0.984), with a sensitivity of 0.952 (95% CI: 0.881-0.987) and a specificity of 0.977 (95% CI: 0.953-0.991). CONCLUSIONS The OSNA assay provided a judgment performance equivalent to a 2-mm-interval histopathological examination, a more detailed assay than the common pathological examination. Therefore, the OSNA assay is considered a new molecular examination method for the diagnosis of LN metastases in CRC patients in clinical settings.
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14
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Stanniocalcin-1 detection of peripheral blood in patients with colorectal cancer. Chin J Cancer Res 2010. [DOI: 10.1007/s11670-010-0274-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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15
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Buxhofer-Ausch V, Ausch C, Kitzweger E, Mollik M, Reiner-Concin A, Ogris E, Stampfl M, Hamilton G, Schiessel R, Hinterberger W. Spontaneous changes in tumour cell dissemination to bone marrow in colorectal cancer. Colorectal Dis 2010; 12:776-82. [PMID: 19456841 DOI: 10.1111/j.1463-1318.2009.01950.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The study aimed to evaluate the incidence of disseminated tumour cells (DTCs) in bone marrow (BM) preoperatively and during follow up and to correlate these with established risk factors in patients with colorectal cancer. METHOD We prospectively studied BM in 57 patients using the anti-cytokeratin antibody A45-B/B3. RESULTS The overall detection rate of DTCs was 23% with a similar detection rate through all stages of the disease. No significant association was found between the presence of DTCs and clinicopathological parameters. After a median follow up of 35.4 months, no differences were found in relapse and overall survival between patients with and without DTC preoperatively. In 31 of 45 patients with local disease, we performed a follow-up BM examination after 1 year. In 26% of the patients, the BM status had changed as compared with the preoperative finding. CONCLUSION This is the first study to report the follow up of DTC in BM in colorectal cancer using the A45-B/B3 antibody. The presence of tumour cells in the preoperative BM had no impact on outcome. The BM status had changed after 12 months in a quarter of patients.
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Affiliation(s)
- V Buxhofer-Ausch
- 2nd Department of Medicine, Ludwig Boltzmann Society, Donauspital, Langobardenstrasse 122, 1220 Vienna.
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Scabini S. Sentinel node biopsy in colorectal cancer: Must we believe it? World J Gastrointest Surg 2010; 2:6-8. [PMID: 21160827 PMCID: PMC2999193 DOI: 10.4240/wjgs.v2.i1.6] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2009] [Revised: 11/18/2009] [Accepted: 11/25/2009] [Indexed: 02/06/2023] Open
Abstract
April 22, 2013
As Editor-in-Chief of the World Journal of Gastrointestinal Surgery, it has come to my attention that two articles that have published in our journal are very similar to the content of previously published papers.
Specifically, the two articles:
Scabini S, Rimini E, Massobrio A, Romairone E, Linari C, Scordamaglia R, Marini LD, Ferrando V. Primary omental torsion: A case report. World J Gastrointest Surg 2011 Oct 27; 3(10): 153-5. DOI: 10.4240/wjgs.v3.i10.153. PubMed PMID: 22110847; PMCID: PMC3220728 has a number of very common features to the previously published paper Efthimiou M, Kouritas VK, Fafoulakis F, Fotakakis K, Chatzitheofilou K. Primary omental torsion: report of two cases. Surg Today 2009; 39(1): 64-7. DOI: 10.1007/s00595-008-3794-7. Epub 2009 Jan 8. PMID: 19132472.
Scabini S. Sentinel node biopsy in colorectal cancer: Must we believe it World J Gastrointest Surg 2010 Jan 27; 2(1): 6-8. DOI: 10.4240/wjgs.v2.i1.6 PMID: 21160827; PMCID: PMC2999193 has copied entire paragraphs from two papers by Nicholl M, Bilchik AJ. Is routine use of sentinel node biopsy justified in colon cancer Ann Surg Oncol 2008 Jan; 15(1): 1-3. Epub 2007 Oct 11. PubMed PMID: 17929100 and Bilchik AJ, Compton C. Close collaboration between surgeon and pathologist is essential for accurate staging of early colon cancer. Ann Surg. 2007 Jun; 245(6): 864-6. PMID: 17522510; PMCID: PMC1876950.
Based on my review of the aforementioned articles, these two articles are being retracted.
I have also asked the office of the World Journal of Gastrointestinal Surgery to make it a matter of policy to use routinely anti-plagiarism software to screen all submissions to the journal in the future.
Sincerely,
Timothy M. Pawlik, MD, MPH, PhD
Editor-in-Chief World Journal of Gastrointestinal Surgery
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Affiliation(s)
- Stefano Scabini
- Stefano Scabini, Oncologic Surgical Unit, AOU San Martino Hospital, 16132 Genoa, Italy
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17
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Martínez-Fernandez A, García-Albeniz X, Pineda E, Visa L, Gallego R, Codony-Servat J, Augé JM, Longarón R, Gascón P, Lacy A, Castells A, Maurel J. Serum matrilysin levels predict outcome in curatively resected colorectal cancer patients. Ann Surg Oncol 2009; 16:1412-20. [PMID: 19259740 DOI: 10.1245/s10434-009-0405-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2009] [Revised: 02/08/2009] [Accepted: 02/08/2009] [Indexed: 11/18/2022]
Abstract
BACKGROUND Matrix metalloproteinase 7 (MMP-7) is involved in invasion, metastasis, growth, and angiogenesis. The aim of this study is to assess the prognostic role of serum MMP-7 in curatively resected colorectal cancer (CRC). MATERIALS AND METHODS Patients undergoing resection for CRC (n = 175) were recruited from July 2003 to December 2004. MMP-7 was determined using a quantitative solid phase sandwich ELISA. Cox analysis was used to assess the role of MMP-7 in predicting overall survival (OS) and disease-free survival (DFS). RESULTS The median length of follow-up was 45 months (range 1 to 59). Levels of MMP-7 are predictors of DFS (hazard ratio [HR] 1.119, 95% confidence interval [95% CI] 1.038-1.207) and of OS (HR 1.113, 95% CI 1.025-1.209). Patients with MMP-7 higher than the median (4.3 ng/ml) are more likely to relapse (29.5% vs 18.4%, P = .084); median time to progression in relapsed patients is 8 months if MMP-7 is > or =4.3 ng/ml and 18 months if MMP-7 is <4.3 ng/ml. Node-negative patients with low MMP-7 have a predicted probability of relapse-free survival at 4 years of 88% (95% CI 83-92%); if the MMP-7 is higher than the median value; this probability is 77% (95% CI 73-81%). CONCLUSION MMP-7 predicts recurrence in curatively resected CRC patients.
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Affiliation(s)
- Alejandro Martínez-Fernandez
- Department of Medical Oncology, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Médica de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Catalonia, Spain
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18
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Thalheimer A, Otto C, Bueter M, Illert B, Gattenlohner S, Gasser M, Meyer D, Fein M, Germer CT, Waaga-Gasser AM. The intraportal injection model: a practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer. BMC Cancer 2009; 9:29. [PMID: 19166621 PMCID: PMC2648996 DOI: 10.1186/1471-2407-9-29] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2008] [Accepted: 01/24/2009] [Indexed: 12/18/2022] Open
Abstract
Background The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. Methods We injected immunoincompetent nude mice intraportally with different numbers (1 × 105, 1 × 106 and 5 × 106 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Results Only the injection of 1 × 106 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 106 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. Conclusion The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD.
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Affiliation(s)
- Andreas Thalheimer
- Department of Surgery, University of Wuerzburg Hospital, Wuerzburg, Germany.
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19
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Pancione M, Forte N, Sabatino L, Tomaselli E, Parente D, Febbraro A, Colantuoni V. Reduced beta-catenin and peroxisome proliferator-activated receptor-gamma expression levels are associated with colorectal cancer metastatic progression: correlation with tumor-associated macrophages, cyclooxygenase 2, and patient outcome. Hum Pathol 2009; 40:714-25. [PMID: 19121846 DOI: 10.1016/j.humpath.2008.08.019] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2008] [Revised: 07/31/2008] [Accepted: 08/19/2008] [Indexed: 12/14/2022]
Abstract
Recent studies have reported cross talk between beta-catenin, peroxisome proliferator-activated receptor-gamma, and cyclooxygenase 2 signaling pathways. We examined whether molecular changes of these pathways could be related to colorectal cancer metastatic progression. Seventy-two sporadic colorectal cancers and the distant nonneoplastic mucosa were analyzed for beta-catenin, peroxisome proliferator-activated receptor-gamma, cyclooxygenase 2, and nuclear factor kappaB levels by immunohistochemistry and Western blot. The expression profiles were correlated with patient outcome and 5-year survival. Nuclear beta-catenin staining was detected in only 18.1% of tumors and correlated with poor survival as compared with cases showing cytosolic/membrane accumulation (59.7%, P < .05). This latter group and tumor samples showing cytosolic/nuclear peroxisome proliferator-activated receptor-gamma expression (70.8%) were significantly associated with a favorable prognosis (P < .001). Remarkably, reduction or loss of beta-catenin (22.2%) and peroxisome proliferator-activated receptor-gamma (29.2%) expression was strongly correlated with marked infiltration of tumor-associated macrophages (P < .01), presence of liver metastases, and very short survival (P = .0001). Moreover, beta-catenin and peroxisome proliferator-activated receptor-gamma levels were inversely correlated with cyclooxygenase 2 (P < .01) and nuclear factor kappaB expression (P < .05). Our results suggest that reduced expression of beta-catenin and peroxisome proliferator-activated receptor-gamma could play a key role in aggressive colorectal cancer behavior. This finding may provide a relevant prognostic tool and contribute to early identification of patients at high risk of mortality.
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Affiliation(s)
- Massimo Pancione
- Department of Biological and Environmental Sciences, University of Sannio, 82100 Benevento, Italy
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20
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Pagès F, Berger A, Zinzindohoué F, Kirilovsky A, Galon J, Fridman WH. [Not Available]. JOURNAL DE CHIRURGIE 2008; 145:12S6-12S12. [PMID: 22794075 DOI: 10.1016/s0021-7697(08)45002-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
F. Pagès, A. Berger, F. Zinzindohoué, A. Kirilovsky, J. Galon, W.-H. Fridman Lymph node dissection is an integral part of the surgical resection of colon cancers; it completes the wide regional resection of tumor and it allows prognostic evaluation through accurate staging. Studies have demonstrated an immune reaction to the tumoral site which attests to an ongoing dialog between the tumor and systemic defenses. The regional lymph nodes constitute an important first line of immune defense where initial host response is initiated or, inversely, they may participate in a local state of immunosuppression. This article reviews current knowledge on intra-tumoral and nodal immune status in colorectal cancers and attempts to evaluate the potential immunologic implications of lymph node dissection.
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Affiliation(s)
- F Pagès
- Laboratoire d'immunologie, hôpital européen Georges-Pompidou, AP-HP- Paris.; Centre de recherche des Cordeliers, UMRS 872 - Paris
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21
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Pagès F, Berger A, Zinzindohoué F, Kirilovsky A, Galon J, Fridman WH. [Not Available]. JOURNAL DE CHIRURGIE 2008; 145S4:12S6-12S12. [PMID: 22793988 DOI: 10.1016/s0021-7697(08)74715-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
F. Pagès, A. Berger, F. Zinzindohoué, A. Kirilovsky, J. Galon, W.-H. Fridman Lymph node dissection is an integral part of the surgical resection of colon cancers; it completes the wide regional resection of tumor and it allows prognostic evaluation through accurate staging. Studies have demonstrated an immune reaction to the tumoral site which attests to an ongoing dialog between the tumor and systemic defenses. The regional lymph nodes constitute an important first line of immune defense where initial host response is initiated or, inversely, they may participate in a local state of immunosuppression. This article reviews current knowledge on intra-tumoral and nodal immune status in colorectal cancers and attempts to evaluate the potential immunologic implications of lymph node dissection.
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Affiliation(s)
- F Pagès
- Laboratoire d'immunologie, hôpital européen Georges-Pompidou, AP-HP- Paris.; Centre de recherche des Cordeliers, UMRS 872 - Paris
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22
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Cahill RA, Leroy J, Marescaux J. Could lymphatic mapping and sentinel node biopsy provide oncological providence for local resectional techniques for colon cancer? A review of the literature. BMC Surg 2008; 8:17. [PMID: 18816403 PMCID: PMC2565653 DOI: 10.1186/1471-2482-8-17] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2008] [Accepted: 09/24/2008] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Endoscopic resectional techniques for colon cancer are undermined by their inability to determine lymph node status. This limits their application to only those lesions at the most minimal risk of lymphatic dissemination whereas their technical capacity could allow intraluminal or even transluminal address of larger lesions. Sentinel node biopsy may theoretically address this breach although the variability of its reported results for this disease is worrisome. METHODS Medline, EMBASE and Cochrane databases were interrogated back to 1999 to identify all publications concerning lymphatic mapping for colon cancer with reference cross-checking for completeness. All reports were examined from the perspective of in vivo technique accuracy selectively in early stage disease (i.e. lesions potentially within the technical capacity of endoscopic resection). RESULTS Fifty-two studies detailing the experiences of 3390 patients were identified. Considerable variation in patient characteristics as well as in surgical and histological quality assurances were however evident among the studies identified. In addition, considerable contamination of the studies by inclusion of rectal cancer without subgroup separation was frequent. Indeed such is the heterogeneity of the publications to date, formal meta-analysis to pool patient cohorts in order to definitively ascertain technique accuracy in those with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early stage neoplasia alone has rarely been specifically studied, those studies that included examination of false negative rates identified high T3/4 patient proportions and larger tumor size as being important confounders. Under selected circumstances however the technique seems to perform sufficiently reliably to allow it prompt consideration of its use to tailor operative extent. CONCLUSION The specific question of whether sentinel node biopsy can augment the oncological propriety for endoscopic resective techniques (including Natural Orifice Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at present. Study heterogeneity may account for the variability evident in the results from different centers. Enhanced capacity (perhaps to the level necessary to consider selective avoidance of en bloc mesenteric resection) by its confinement to only early stage disease is plausible although not proven. Specific study of the technique in early stage tumors is clearly essential before proffering this approach.
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Affiliation(s)
| | - Joel Leroy
- Department of Surgery, IRCAD/EITS, Strasbourg, France
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23
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Athanassiadou P, Grapsa D. Bone marrow micrometastases in different solid tumors: Pathogenesis and importance. Surg Oncol 2008; 17:153-64. [PMID: 18511264 DOI: 10.1016/j.suronc.2008.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
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Yie SM, Lou B, Ye SR, Cao M, He X, Li P, Hu K, Rao L, Wu SM, Xiao HB, Gao E. Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse. Ann Surg Oncol 2008; 15:3073-82. [PMID: 18670822 DOI: 10.1245/s10434-008-0069-x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2008] [Accepted: 06/18/2008] [Indexed: 12/16/2022]
Abstract
BACKGROUND We previously demonstrated that the detection of circulating cancer cells (CCCs) expressing survivin mRNA could provide valuable information for predicting metastasis and recurrence in breast cancer. The objective of this study was to investigate whether or not the detection of survivin expression in the peripheral blood could also have significant effects on the clinical outcomes of patients with gastric and colorectal cancer. METHODS Survivin-expressing CCCs in peripheral blood samples obtained from 55 gastric cancer patients, 86 colorectal cancer patients, and 87 healthy volunteers were quantitatively examined by using a RT-PCR ELISA. Its clinical significance was statistically evaluated. RESULTS The CCCs in the peripheral blood samples were detected in 45.4% and 44.0% of gastric and colorectal cancer patients, respectively. The presence of survivin-expressing CCCs was found to be significantly associated with the degree of tumor penetration, nodal status, and disease stages for both types of cancers. During a follow-up period of 36 months, patients who had a positive detection at the time of the initial assay test had a higher relapse rate than those who had a negative detection. As well, survivin-expressing CCCs were statistically shown to be a significant and independent predictor for cancer recurrence. The detection of survivin-expressing CCCs was also demonstrated to be more accurate in terms of predicting recurrence than traditional detection methods such as plasma carcinoembryonic antigen (CEA) measurements. CONCLUSION The detection of CCCs expressing survivin mRNA could be used to accurately identify gastric and colorectal cancer patients with high risks of relapse.
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Affiliation(s)
- Shang-mian Yie
- Core Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, 32 Yi Huan Lu Xi Er Duan 610078, Chengdu, Sichuan, People's Republic of China.
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25
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Bilchik AJ. Current and emerging trends in the treatment of early-stage colorectal cancer: importance of a multidisciplinary approach. Hematol Oncol Clin North Am 2007; 21 Suppl 1:8-18. [PMID: 17916494 DOI: 10.1016/s0889-8588(07)80012-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Anton J Bilchik
- Department of Gastrointestinal Surgery, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California 90404, USA.
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Matter M, Winckler M, Aellen S, Bouzourene H. Detection of metastatic disease with sentinel lymph node dissection in colorectal carcinoma patients. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2007; 33:1183-90. [PMID: 17490848 DOI: 10.1016/j.ejso.2007.03.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2006] [Accepted: 03/20/2007] [Indexed: 11/25/2022]
Abstract
BACKGROUND In curative colorectal cancer surgery, radical lymph node dissection is essential for staging and decision-making for adjuvant treatment. PURPOSE The aims of the study were to analyse to what extent sentinel lymph node dissection (SLND) in colorectal cancer could upstage N0 patients and how lymphatic mapping could demonstrate micrometastatic disease. PATIENTS AND METHODS In a prospective study, patients were selected by CT scanning, avoiding bulky disease and distant metastasis. When standard staining (HE) was negative, micrometastases were searched for by immunohistochemistry (cytokeratin 11, CEA and Ca19-9 antibodies). Micrometastatic lymph nodes were classified N+(i). RESULTS Detection of sentinel lymph nodes was successful in 48 out of 52 colorectal cancer patients. Among the 44 M0 patients, 22 were N0 (i-) and 22 were N+ (13 with standard HE procedure, three were N+ (macrometastasis) with the SN as the only positive node and six patients had 1-4 micrometastatic SN (N+(i)). An overall potential upstaging of 9/44 could be considered after SLND. With a mean follow-up of 48 months survival, analysis showed that disease-specific survival of the group of six N+(i) patients was intermediate between the group of 22 N0 (i-) patients and the group of 16 N+ patients. CONCLUSION SLND may improve the detection of metastasis in conventionally bivalved nodes. Further studies could assess if micrometastatic disease detected in SN could be integrated into the risk factors for stage II patients in order to consider adjuvant chemotherapy.
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Affiliation(s)
- M Matter
- Visceral Surgery, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
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Rekhraj S, Aziz O, Prabhudesai S, Zacharakis E, Mohr F, Athanasiou T, Darzi A, Ziprin P. Can intra-operative intraperitoneal free cancer cell detection techniques identify patients at higher recurrence risk following curative colorectal cancer resection: a meta-analysis. Ann Surg Oncol 2007; 15:60-8. [PMID: 17909914 DOI: 10.1245/s10434-007-9591-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2007] [Revised: 08/06/2007] [Accepted: 08/06/2007] [Indexed: 12/17/2022]
Abstract
BACKGROUND Accurate staging of colorectal cancer is important for predicting prognosis and guiding treatment. This study uses meta-analysis to investigate if the pre- or post-resection detection of intraperitoneal free cancer cells can predict recurrence in patients undergoing curative colorectal cancer surgery. METHODS A literature search was performed on all studies between January 1990 and July 2007 comparing the detection of intraperitoneal free cancer cells either pre- or post-resection with prognosis in colorectal cancer. The following prognostic outcomes were meta-analyzed: overall recurrence rate and local recurrence rate. A random-effect model was used and heterogeneity was assessed. RESULTS Nine studies reporting on a total of 1182 subjects matched the selection criteria. Free cancer cells were detected prior to tumor resection in 125/822 (15.2%) of patients and following resection in 64/533 (12%) of patients. Preresection, the absence of tumor cells was associated with a lower overall recurrence (25.2%) compared to the presence of tumor cells [46.4%, odds ratio (OR) = 0.41, confidence interval (CI) 0.19-0.88]; as well as a significantly lower local recurrence (12.2% versus 21.1%, OR = 0.42, CI 0.21-0.82). Postresection, the absence of tumor cells also resulted in significantly lower overall recurrence (17.3%) when compared to the presence of tumor cells (52.6%, OR = 0.07, CI 0.03-0.18). CONCLUSIONS The detection of intraperitoneal free cancer cells is associated with higher recurrence and poorer prognosis. Use of these techniques can identify patients at higher recurrence risk. This could be particularly valuable in stage II disease to identify patients who may benefit from adjuvant chemotherapy.
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Affiliation(s)
- Sushil Rekhraj
- Department of Biosurgery and Surgical Technology, Imperial College London, St Mary's Hospital, London, W2 1NY, United Kingdom.
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Cianchi F, Messerini L, Comin CE, Boddi V, Perna F, Perigli G, Cortesini C. Pathologic determinants of survival after resection of T3N0 (Stage IIA) colorectal cancer: proposal for a new prognostic model. Dis Colon Rectum 2007; 50:1332-41. [PMID: 17429709 DOI: 10.1007/s10350-007-0222-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE There is an increasing need for accurate prognostic stratification of patients with Stage II colorectal cancer to identify a subgroup of high-risk patients who may benefit from adjuvant therapies. This study was designed to evaluate the prognostic impact of a wide spectrum of pathologic parameters in a consecutive series of homogenously treated and well-characterized patients with Stage IIA (T3N0M0) colorectal cancer. METHODS The study included 238 patients operated on by a single surgeon for Stage IIA colorectal tumors. The median postoperative follow-up was 110 (range, 96-120) months. At least 12 lymph nodes were harvested and examined in all the resection specimens. The prognostic value of 13 pathologic parameters, including lymph node occult disease (micrometastases) detected by immunohistochemistry, was investigated. RESULTS Multivariate analysis identified tumor growth pattern (expanding or infiltrating; P = 0.01) and extent of tumor spread beyond muscularis propria (< or =5 mm or >5 mm; P = 0.04) as the only factors having independent prognostic value. The combination of these two easily determined parameters allowed us to identify two groups of patients at low risk or high risk of tumor recurrence. The eight-year survival rates were 83.3 and 53.4 percent for the two groups, respectively. The high-risk group comprised those patients with infiltrating tumors and extramural tumor spread > 5 mm. CONCLUSIONS We propose a new and simple prognostic model to identify patients with high-risk Stage IIA colorectal cancer for whom adjuvant therapies may be justified and effective.
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Affiliation(s)
- Fabio Cianchi
- Department of General Surgery, University of Florence, Florence, Italy.
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Ausch C, Dandachi N, Buxhofer-Ausch V, Balic M, Huber K, Bauernhofer T, Ogris E, Hinterberger W, Braun S, Schiessel R. Immunomagnetic CD45 depletion does not improve cytokeratin 20 RT-PCR in colorectal cancer. Clin Chem Lab Med 2007; 45:351-6. [PMID: 17378731 DOI: 10.1515/cclm.2007.059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Cytokeratin 20 reverse transcriptase polymerase chain reaction (CK20 RT-PCR) of blood and bone marrow specimens has been suggested for assessment of hematogenously disseminated tumor cell (DTC) spread in colorectal cancer (CRC) patients. Considerable discrepancies among the studies reported indicate a need for better evaluation procedures. We investigated whether mononucleated cell (MNC) enrichment by Ficoll density gradient centrifugation followed by immunomagnetic depletion of CD45-positive cells (extended enrichment) allows better detection of DTC-associated CK20 mRNA compared to MNC enrichment by Ficoll density gradient centrifugation alone (Ficoll enrichment). METHODS We analyzed 53 samples [38 peripheral blood (PB), 15 bone marrow (BM)] from 38 CRC patients. Extended enrichment was performed for 30 specimens (PB and BM, n=15 each), and Ficoll enrichment for 23 blood specimens. Total RNA was extracted, reverse-transcribed and analyzed by real-time RT-PCR using a LightCycler instrument. RESULTS Despite extended enrichment, 10 PB and 8 BM samples could not be analyzed because of low cellular yield. The depletion efficiency of CD45 separation was 2 log. RT-PCR of the housekeeping gene PBGD resulted in high and varied crossing point values (mean 37.1+3.0) for five PB and seven BM specimens. Ficoll enrichment yielded 23 analyzable blood specimens for which the mean crossing point value was 26.7+0.5 in PBGD RT-PCR. CK20 RT-PCR of 23 blood samples (all from Dukes D patients) revealed CK20 transcripts in four cases (17%). CONCLUSIONS Extended enrichment was not superior to Ficoll enrichment; in fact, the sensitivity was lower. Improvement of the reported CK20 RT-PCR assay of Ficoll-enriched MNC populations is warranted.
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Affiliation(s)
- Christoph Ausch
- Department of Surgery, Ludwig Boltzmann Research Institute of Surgical Oncology, Danube Hospital SMZ Ost, Vienna, Austria.
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Bilchik AJ, Compton C. Close collaboration between surgeon and pathologist is essential for accurate staging of early colon cancer. Ann Surg 2007; 245:864-6. [PMID: 17522510 PMCID: PMC1876950 DOI: 10.1097/sla.0b013e31805d07e3] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Athanassiadou P, Grapsa D. Recent advances in the detection of bone marrow micrometastases: A promising area for research or just another false hope? A review of the literature. Cancer Metastasis Rev 2007; 25:507-19. [PMID: 17160555 DOI: 10.1007/s10555-006-9030-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The presence of early disseminated tumor cells (DTC), otherwise termed micrometastases or minimal residual disease, in the bone marrow (BM), or other secondary compartments, such as the blood and the lymph nodes, is the main reason for recurrence of patients with early stage epithelial cancers after "curative" resection of the primary tumor. There is increasing evidence, that the detection of DTC in BM aspirates may provide additional and independent prognostic information and aid in the stratification of these patients for adjuvant clinical treatment. However, the clinical relevance of micrometastases has not yet been firmly established. In addition, the molecular events and interactions that prevail in early metastatic disease and determine the formation or not of overt metastases remain poorly understood. The methods currently used for the detection of micrometastatic cells include extremely sensitive immunocytochemical and molecular assays, often in conjunction with enrichment techniques for the purification of tumor cells and additional increase of their sensitivity. Nevertheless, the specificity of these methods is mostly inadequate. After the impressive advances of molecular cytogenetics, a highly accurate and global assessment of the genetic status of tumors is now possible. Therefore, the greatest challenge of our time is the application of these novel technologies for the clarification of the key molecular events that initiate metastatic spread. This will further enable us to identify the highly specific and sensitive diagnostic and prognostic markers as well as the therapeutic targets which are so urgently needed.
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Affiliation(s)
- Pauline Athanassiadou
- Pathology Laboratory-Cytology Department, Medical School, Athens University, 75 Mikras Asias Str., 11527, Athens, Greece
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Yagci G, Unlu A, Kurt B, Can MF, Kaymakcioglu N, Cetiner S, Tufan T, Sen D. Detection of micrometastases and skip metastases with ex vivo sentinel node mapping in carcinoma of the colon and rectum. Int J Colorectal Dis 2007; 22:167-73. [PMID: 16721490 DOI: 10.1007/s00384-006-0132-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/05/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND The debate over sentinel lymph node mapping (SLNM) and focused pathologic examination to detect micrometastases in patients with colorectal cancer (CRC) continues. We present in this paper our experience with SLNM for CRCs to improve staging. In addition, we have detailed the mapping procedure on an anatomical basis to define skip metastasis. MATERIALS AND METHODS Forty-seven patients underwent ex vivo SLNM. Immediately after resection, 1 ml of patent blue VF was injected submucosally around the tumor. Lymph nodes harvested from the first 15 patients were mapped in a standard fashion as the blue-stained nodes (SLNs), and the others (non-SLNs) were dissected away. In the remaining 32 patients, the lymph nodes were also mapped separately in relation to their anatomic location and described as epicolic-paracolic, intermediate, and principal. The blue-stained nodes (SLNs) and non-SLNs, negative by hematoxylin and eosin stain, were further stained with cytokeratin immunohistochemical analysis and carcinoembryonic antigen. RESULTS A total of 873 histologically confirmed LNs were examined with a mean of 18.6+/-8.1 nodes per patient. In 46 of 47 patients (97.8%), SLNs were identified. Immunohistochemical staining revealed micrometastases in the lymph nodes of four patients, which were negative by conventional methods. Anatomical skip metastases were noted in 4 of 32 patients studied (12.5%). CONCLUSION Ex vivo SLNM in CRCs is a feasible technique with a high SLN identification rate. Results of anatomical mapping of lymph nodes correlates with the limited literature, suggesting that occult skip metastases can occur in the apical lymph node group and may occur outside the resected area.
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Affiliation(s)
- Gokhan Yagci
- Department of Surgery, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey.
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Madbouly KM, Senagore AJ, Mukerjee A, Delaney CP, Connor J, Fazio VW. Does immunostaining effectively upstage colorectal cancer by identifying micrometastatic nodal disease? Int J Colorectal Dis 2007; 22:39-48. [PMID: 16528541 DOI: 10.1007/s00384-006-0098-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/23/2005] [Indexed: 02/04/2023]
Abstract
PURPOSE Measure the association between the incidence of primary tumor staining and the identification of mediastinal lymph node (MLN) using cytokeratins, NM23, DCC-positive tumors, and vascular endothelial growth factor (VEGF) expression in T(2) and T(3)/N(0) colorectal cancers. The impact of MLN on both recurrence and survival was assessed. MATERIALS AND METHODS There were 153 CORC patients (T(2), T(3)/N(0)) selected from a prospectively accrued database. All patients had been staged by routine histopathology after a curative resection and no patients received adjuvant chemotherapy. The primary tumors (PT) were assessed with a panel of immunohistochemical stains (cytokeratin, DCC, Nm23, and VEGF). If the PT was positive, the regional nodes were assessed with that marker(s). For any positive tumor marker, all lymph nodes (LNs, mean of 12.6+/-4.2) were stained for this marker. RESULTS Patient age ranged from 38 to 86 years with a mean age of 61.56+/-25.56 years. Mean follow-up was 72.1+/-32.4 months. Recurrence rate of the whole group was 19/153 (12.4%) and the mean time to recurrence was 37.6+/-23.6 months (15 to 77 months). Crude mortality was 39.9%, while the cancer specific mortality was 11.2% after the whole follow-up period. The relationship between PT staining and MLNs was: cytokeratin-PT 143 (93.5%)/MLN 9 (6.3%); NM23-PT 51 (33.3%)/MLN 3 (5.9%); DCC-PT 79 (53%)/MLN 3 (3.8%); and VEGF-PT 72 (47%)/MLN 4 (5.6%). Nineteen (12.4%) patients experienced tumor recurrence. No correlation exist between PT and/or MLN staining and either recurrence or survival. No patient with MLN with any stain experienced a recurrence. There was no advantage to using an individual stain or all four stains. CONCLUSION Immunohistochemical stains for PT and focused analysis of regional nodes did not improve prediction of survival or recurrence. Sentinel LN evaluation and the provision of adjuvant chemotherapy in node-negative patients should be questioned and not be utilized outside of a research protocol.
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Messerini L, Cianchi F, Cortesini C, Comin CE. Incidence and prognostic significance of occult tumor cells in lymph nodes from patients with stage IIA colorectal carcinoma. Hum Pathol 2006; 37:1259-67. [PMID: 16949928 DOI: 10.1016/j.humpath.2006.04.023] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2006] [Revised: 04/05/2006] [Accepted: 04/25/2006] [Indexed: 12/26/2022]
Abstract
Approximately 30% of patients with lymph node (LN)-negative colorectal carcinoma (CRC) die of tumor recurrence, which can be related to the presence of tumor cells in LNs not detected by conventional histopathologic analysis. However, the prognostic significance of occult cancer cells still remains uncertain. We evaluated the incidence and the prognostic significance of occult cancer cells in LNs from 395 consecutive patients with curatively resected stage IIA CRC using immunohistochemistry for cytokeratin 20. Immunostained tumor cells were categorized as micrometastases (MCMs) or isolated tumor cells (ITCs) according to the American Joint Committee on Cancer criteria. The detection rates were compared with the clinicopathologic characteristics of the patients and with cancer-specific survival. The median follow-up time was 128 months. Micrometastases were detected in 39 patients (9.9%), whereas ITCs were found in 112 (28.4%), for an overall frequency of 38.2%. None of the clinicopathologic parameters examined was correlated with the presence of occult cancer cells. Patients with ITCs and those with negative LNs showed a similar survival rate (77.7% and 78.3%, respectively), whereas patients with MCMs had a lower survival rate (64.1%). At the univariate analysis, MCMs, tumor growth pattern, extent of tumor spread, and Crohn's-like lymphoid reaction influenced the survival rate significantly. Nevertheless, at the multivariate analysis, only the pattern of tumor growth and the extent of tumor spread were independent prognostic factors. The detection of immunostained tumor cells in the LNs of patients with stage IIA CRC occurs relatively frequently but has no significant effect on prognosis.
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Affiliation(s)
- Luca Messerini
- Department of Human Pathology and Oncology, University of Florence Medical School, Florence 50134, Italy.
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Viehl CT, Guller U, Hamel CT, Riehle HM, Plaass C, Marti WR, Oertli D, Zuber M. Carbon dye staining of sentinel lymph nodes facilitates microstaging of colon cancer patients. World J Surg 2006; 30:453-6. [PMID: 16479343 DOI: 10.1007/s00268-005-0336-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND Carbon dye, when peritumourally injected, permanently marks the drainage site of sentinel lymph nodes (SLN). The objective of the current study was to evaluate whether the use of carbon dye facilitated the detection of small nodal tumour infiltrates in colon cancer patients. METHODS In a prospective trial, 19 patients underwent open, oncological resections of localized colon cancer and SLN procedure according to a standardized protocol. Isosulfan blue 1% and sterile filtered carbon dye (mixed 1:1) were injected into the subserosa circumferentially around the tumour. Lymph nodes staining blue were marked as SLN. Serial sections of each SLN were stained with hematoxylin and eosin (H&E) and with the pancytokeratin marker AE1/AE3. The intranodal presence and site of carbon particles were noted and compared with the location of possible tumour infiltrates. RESULTS Identification of at least one SLN was successful in 18 patients (identification rate 95%). Four patients (22%) were pN+, 11 (61%) were pN0(i-). Three patients (17%) were upstaged from pN0(i-) to pN0(i+) as isolated tumour cells were detected in their SLN: in two (11%) of the three patients, carbon dye and isolated tumour cells were found in the same nodal compartment, hence facilitating the recognition of isolated tumour cells by the pathologist. CONCLUSION The use of carbon dye in the SLN procedure for colon cancer may facilitate the detection of small nodal tumour infiltrates.
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Affiliation(s)
- Carsten T Viehl
- Department of Surgery, University Hospital Basel, Spitalstrasse 21, Basel, 4031, Switzerland
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Hladík P, Vizd'a J, Hadzi Nikolov D, Dvorák J, Voboril Z. Radio-guided sentinel node detection during the surgical treatment of rectal cancer. Nucl Med Commun 2005; 26:977-82. [PMID: 16208175 DOI: 10.1097/01.mnm.0000184997.35461.b8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE The detection of sentinel nodes is performed in various types of malignant disease. The aim of this study was to evaluate the results of the radiodetection of sentinel nodes, based on the use of Tc-colloid, during the surgical treatment of rectal cancer. METHODS In 2003-2004, 42 patients (24 males and 18 females; average ages of 62.4 and 67 years, respectively) were examined during rectal carcinoma surgical procedures. Miles abdominoperineal rectal resection was performed in nine cases; 33 patients underwent low anterior rectum resection by total mesorectal excision. On the day of the operation, a transanal submucosal infiltration of colloid labelled with radioactive 99mTc was performed; infiltration was performed strictly peritumorally. After the operation, radiodetection of the surgical specimens (using a hand-held gamma probe) was performed. The areas of higher radioactivity were marked. The specimens were then examined by a histopathologist. The nodes found closest to the marked areas were considered to be 'sentinel nodes'. The results of scintigraphy and postoperative radiodetection were checked by histological examination. All the discovered lymph nodes were examined by haematoxylin and eosin staining; when this was negative, immunohistochemical examination with cytokeratin was used for the sentinel nodes. RESULTS In 36 of the 42 patients, the data obtained by scintigraphy and radiodetection were in agreement with histopathological proof of a sentinel node. The sensitivity of the method in this group of patients was 86% (95% confidence limits: 70.75-94.05). CONCLUSIONS The scintigraphic method of detection of sentinel nodes in total mesorectal excision is not therapeutic, but diagnostic, and demonstrates a high level of reliability. It can be used to indicate the nodes that should be examined to detect the presence of possible micrometastases immunohistochemically. However, this method cannot be used for all detected nodes as it is very demanding. In the evaluated group of patients, there were no intraoperative or postoperative complications caused by this diagnostic method.
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Affiliation(s)
- Pavel Hladík
- University Hospital Hradec Králové, Faculty of Medicine in Hradec Králové and Charles University, Prague, Czech Republic.
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Martinez SR, Bilchik AJ. Quality control issues in the management of colon cancer patients. Eur J Surg Oncol 2005; 31:616-29. [PMID: 15927443 DOI: 10.1016/j.ejso.2005.02.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2004] [Revised: 10/26/2004] [Accepted: 02/10/2005] [Indexed: 11/17/2022] Open
Abstract
Quality assurance in colon cancer demands a multidisciplinary effort involving general practitioners, surgeons, radiologists, gastroenterologists, medical oncologists, and pathologists, among others. Maximal improvements in survival will result when colon cancer screening, diagnosis, staging, treatment and surveillance are optimized. We seek to identify those issues most relevant to the quality of care we provide our colon cancer patients.
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Affiliation(s)
- S R Martinez
- Department of Gastrointestinal Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, USA
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Martinez SR, Bilchik AJ. Lymphatic mapping and sentinel node analysis in colon cancer. Clin Colorectal Cancer 2005; 4:320-4. [PMID: 15663835 DOI: 10.3816/ccc.2005.n.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Accurate staging of colon cancer is prognostically and therapeutically important. By identifying those patients who would most benefit from adjuvant chemotherapy, accurate staging should decrease recurrence rates and improve overall survival. Lymphatic mapping and sentinel node analysis allow for a focused review of the lymph nodes, which are most likely to harbor a metastasis and may make ultrastaging techniques, such as immunohistochemistry and reverse-transcriptase polymerase chain reaction, more practical. The prognostic significance of micrometastatic disease detected via ultrastaging techniques remains controversial.
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Dahl K, Westlin J, Kraaz W, Winqvist O, Bergkvist L, Thörn M. Identification of sentinel nodes in patients with colon cancer. Eur J Surg Oncol 2005; 31:381-5. [PMID: 15837044 DOI: 10.1016/j.ejso.2004.12.015] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2004] [Revised: 11/29/2004] [Accepted: 12/15/2004] [Indexed: 01/22/2023] Open
Abstract
AIMS Lymphatic mapping and sentinel node biopsy entails better staging in malignant melanoma and breast cancer and we used this technique in patients with colon cancer to possibly improve detection of lymphatic spread. METHODS Thirty patients with invasive adenocarcinomas were investigated. The tumour status in identified sentinel node(s) was compared with the status in all other harvested regional nodes for each patient. Patients were followed at regular visits for more than 30 months. RESULTS Sentinel nodes were identified in all cases, either per-operatively (28 cases) or at dissection of the formalin-fixed specimen (2 cases). The sentinel nodes were diagnostic for the entire lymphatic field in 28 patients and the false negative rate was 2/12. In four cases, the sentinel nodes were the only metastatic nodes. After at minimum 30 months, three patients had died of colon cancer metastases. CONCLUSION This method improved the identification of patients with lymph-node metastases, especially those with only few metastatic nodes. Patients dying from metastatic disease had lymph-node metastases at diagnosis.
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Affiliation(s)
- K Dahl
- Department of Surgery, Karolinska Institutet, South Stockholm General Hospital, 118 83 Stockholm, Sweden.
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Abstract
Every year, more than 945000 people develop colorectal cancer worldwide, and around 492000 patients die. This form of cancer develops sporadically, in the setting of hereditary cancer syndromes, or on the basis of inflammatory bowel diseases. Screening and prevention programmes are available for all these causes and should be more widely publicised. The adenoma-carcinoma sequence is the basis for development of colorectal cancer, and the underlying molecular changes have largely been identified. Prognosis depends on factors related to the patient, treatment, and tumour, and the expertise of the treatment team is one of the major determinants of outcome. New information on the molecular basis of this cancer have led to the development of targeted therapeutic options, which are being tested in clinical trials. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.
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Affiliation(s)
- Jürgen Weitz
- Department of Surgery, University of Heidelberg, Heidelberg, Germany
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Soroush AR, zadeh HM, Moemeni M, Shakiba B, Elmi S. Plasma prolactin in patients with colorectal cancer. BMC Cancer 2004; 4:97. [PMID: 15617576 PMCID: PMC545065 DOI: 10.1186/1471-2407-4-97] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2004] [Accepted: 12/23/2004] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Colorectal cancer is a common malignancy of the gastrointestinal tract. It is the second cancer cause of death in females and third in males. Production of prolactin has been reported with several tumours. However, elevated prolactin plasma levels in colorectal cancer patients remained unclear. METHODS In this cross sectional study serum prolactin and carcinoembryonic antigen (CEA) concentrations were assayed using immunoradiometric assay kits, preoperatively in 47 patients, and the results were compared with 51 age and sex matched controls. RESULTS Prolactin and CEA concentration in patients were significantly more as compared with controls. Hyperprolactinemia was found in 36 (76.6%) patients, while 28 (59.6%) had high level of CEA. CONCLUSIONS Prolactin may be a better tumour marker than CEA in patients with colorectal malignancy.
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Affiliation(s)
- Ahmad Reza Soroush
- Department of surgery, Tehran University of Medical Sciences, Shariati hospital, kargar shomali st, Tehran 14114, Iran
- Research Development Centre, Tehran University of Medical Sciences, Shariati hospital, kargar shomali st, Tehran 14114, Iran
| | - Hosein Mahmood zadeh
- Department of surgery, Tehran University of Medical Sciences, Shariati hospital, kargar shomali st, Tehran 14114, Iran
| | - Mehrnush Moemeni
- Research Development Centre, Tehran University of Medical Sciences, Shariati hospital, kargar shomali st, Tehran 14114, Iran
| | - Behnam Shakiba
- Students' Scientific Research Centre (SSRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Elmi
- Students' Scientific Research Centre (SSRC), Tehran University of Medical Sciences, Tehran, Iran
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Zheng YC, Tang YY, Zhou ZG, Li L, Wang TC, Deng YL, Chen DY, Liu WP. Tumor micrometastases in mesorectal lymph nodes and their clinical significance in patients with rectal caner. World J Gastroenterol 2004; 10:3369-73. [PMID: 15484321 PMCID: PMC4572316 DOI: 10.3748/wjg.v10.i22.3369] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigate the number, size, and status of lymph nodes within the mesorectum and to explore the prognostic significance of lymph node micrometastases in patients with rectal cancer.
METHODS: Thirty-one patients with rectal cancer undergone total mesorectal excision between October 2001 and October 2002 were included. Mesorectal nodes retrieved from the resected specimens were detected with a combination of haematoxylin and eosin (HE) staining and immunohistoch-emistry (IHC). The relations between lymph node metastases, micrometastases and postoperative recurrence were analyzed.
RESULTS: A total of 548 lymph nodes were harvested, with 17.7 ± 8.2 nodes per case. The average number of metastatic nodes in HE-positive patients and micrometastatic nodes in IHC-positive patients was 5.2 ± 5.1 per case and 2.2 ± 1.3 per case, respectively. The mean size of all nodes and metastatic nodes was 4.1 ± 1.8 mm and 5.2 ± 1.7 mm in diameter, respectively. The mean size of micrometastatic nodes was 3.9 ± 1.4 mm in diameter. The size of the majority of mesorectal nodes (66.8%), metastatic nodes (52.6%), and micrometastatic nodes (79.5%) was less than 5 mm in diameter. During a median follow-up period of 24.6 ± 4.7 mo, 5 patients (16.7%) had recurrence, of them 2 died and 3 survived. Another case died of tumor unrelated cause and was excluded. All 5 recurrent cases had 3 or more nodes involved, and one of them developed only lymph node micrometastases. The mean number of both metastatic and micrometastatic nodes per case differed significantly between the recurrent and non-recurrent groups (P < 0.01 and P = 0.01, respectively).
CONCLUSION: The majority of lymph nodes, metastatic, and micrometastatic lymph nodes within the mesorectum are smaller than 5 mm in diameter. The nodal status and the number of lymph nodes involved with tumor metastases and micrometastases are related to the rapid postoperative recurrence.
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Affiliation(s)
- Yang-Chun Zheng
- Department of Gastroenterological Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China
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Tuech JJ, Pessaux P, Regenet N, Bergamaschi R, Colson A. Sentinel lymph node mapping in colon cancer. Surg Endosc 2004; 18:1721-9. [PMID: 15643527 DOI: 10.1007/s00464-004-9031-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2004] [Accepted: 06/17/2004] [Indexed: 02/08/2023]
Abstract
BACKGROUND By systematically reviewing the literature on sentinel lymph node mapping of colon cancers, this study aimed to evaluate this technique as it applies to colon cancers. METHODS Human studies on lymphatic mapping for colon cancers were reviewed. Multiple publications of the same studies, abstracts, and case reports were excluded. Current Contents, MEDLINE, EMBASE, and Cochrane Library databases were investigated. RESULTS Lymphatic mapping appears to be readily applicable to colon cancers, identifying lymph nodes most likely to harbor metastases. Identification of sentinel lymph nodes varied from 58% to 100% and carried a false-negative rate of approximately 10% in larger studies, but potentially rose 4% to 25% among patients representing a range from node-negative to node-positive (micrometastases) conditions. The prognostic implication of these micrometastases requires further evaluation. Lymphatic mapping in 6% to 29% of cases identified aberrant lymphatic drainage that altered the extent of the lymphadenectomy. CONCLUSIONS Further follow-up evaluation to assess the prognostic significance of micrometastases for colon cancers is required before the staging benefits of sentinel node mapping can have therapeutic implications. Lymphatic mapping offers the possibility of improving staging by identifying patients with early disseminated disease who should be considered for adjuvant treatment or included in trials of adjuvant treatment to speed up the breakthrough of more effective adjuvant regimens. Large studies are needed to determine whether the sentinel node concept is as valid for colon cancers as studies so far have shown it is for malignant melanoma and breast cancer.
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Affiliation(s)
- J-J Tuech
- Department of Digestive Surgery, Hôpital E. Muller, 20 r Docteur René Laennec, 68070, Mulhouse Cedex 1, France.
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Mocellin S, Del Fiore P, Guarnieri L, Scalerta R, Foletto M, Chiarion V, Pilati P, Nitti D, Lise M, Rossi CR. Molecular detection of circulating tumor cells is an independent prognostic factor in patients with high-risk cutaneous melanoma. Int J Cancer 2004; 111:741-5. [PMID: 15252844 DOI: 10.1002/ijc.20347] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifying a subgroup of patients with minimal residual disease and thus a higher risk of disease recurrence. Forty patients with > or =2-mm-thick cutaneous melanoma with or without lymph node metastasis were enrolled. After standard radical surgery and adjuvant therapy in case of lymph node metastasis, patients were followed up with routine physical and radiologic assessments as well as serial PCR-based analysis of CTCs using 2 melanoma markers (tyrosinase and Melan-A/Mart-1). After a median follow-up of 30 months, 18 patients had disease recurrence and 28 were PCR-positive before the disease became clinically evident. The sensitivity of the molecular test was 83%. Median time to PCR positivity and median PCR-to-relapse time were 12 and 8 months, respectively. At multivariate analysis, PCR positivity was an independent predictor of disease recurrence (hazard ratio=2.06, 95% CI 1.07-3.35; p=0.03). Among high-risk melanoma patients, serial PCR-based analysis of CTCs can identify a subgroup at higher risk of disease recurrence, with clinically significant advance. Therefore, CTC detection might be employed for the selection of patients for adjuvant treatment and during follow-up for early indication of therapeutic failure.
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Affiliation(s)
- Simone Mocellin
- Department of Oncologic and Surgical Sciences, University of Padua, Padua, Italy
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Wang Y, Jatkoe T, Zhang Y, Mutch MG, Talantov D, Jiang J, McLeod HL, Atkins D. Gene Expression Profiles and Molecular Markers To Predict Recurrence of Dukes' B Colon Cancer. J Clin Oncol 2004; 22:1564-71. [PMID: 15051756 DOI: 10.1200/jco.2004.08.186] [Citation(s) in RCA: 325] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PurposeThe 5-year survival rate of patients with Dukes' B colon cancer is approximately 75%. Identification of the patients at high risk of recurrence in this group would allow better staging and more informed use of adjuvant chemotherapy. In this study, we used DNA chip technology to systematically identify new prognostic markers for tumor relapse in Dukes' B patients.Patients and MethodsUsing Affymetrix U133a GeneChip containing approximately 22,000 transcripts (Affymetrix, Santa Clara, CA), RNA samples from 74 patients with Dukes' B colon cancer were analyzed. Thirty-one patients developed tumor relapse in less than 3 years, whereas 43 patients remained disease-free for more than 3 years after surgery. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. A multivariate Cox model was built to predict recurrence.ResultsGene expression profiling identified a 23-gene signature that predicts recurrence in Dukes'B patients. This signature was validated in 36 independent patients. The overall performance accuracy was 78%. Thirteen of 18 relapse patients and 15 of 18 disease-free patients were predicted correctly, giving an odds ratio of 13 (95% CI, 2.6 to 65; P = .003). The log-rank test indicated a significant difference in disease-free time between the predicted relapse and disease-free patients (P = .0001).ConclusionThe clinical value of these markers is that the patients at a high predicted risk of relapse (13-fold risk) could be upstaged to receive adjuvant therapy, similar to Dukes' C patients. Our data highlight the feasibility of a prognostic assay that could focus more intensive treatment for localized colon cancer.
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Affiliation(s)
- Yixin Wang
- Veridex, LLC, a Johnson & Johnson Company, 3210 Merryfield Row, San Diego, CA 92121, USA.
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