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Yin X, Ruan X, Zhu Y, Yin Y, Huang R, Liang C. Prediction of peritoneal free cancer cells in gastric cancer patients by golden-angle radial sampling dynamic contrast-enhanced magnetic resonance imaging. J Zhejiang Univ Sci B 2024; 25:617-627. [PMID: 39011681 PMCID: PMC11254683 DOI: 10.1631/jzus.b2300929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 03/21/2024] [Indexed: 07/13/2024]
Abstract
OBJECTIVES Peritoneal free cancer cells can negatively impact disease progression and patient outcomes in gastric cancer. This study aimed to investigate the feasibility of using golden-angle radial sampling dynamic contrast-enhanced magnetic resonance imaging (GRASP DCE-MRI) to predict the presence of peritoneal free cancer cells in gastric cancer patients. METHODS All enrolled patients were consecutively divided into analysis and validation groups. Preoperative magnetic resonance imaging (MRI) scans and perfusion were performed in patients with gastric cancer undergoing surgery, and peritoneal lavage specimens were collected for examination. Based on the peritoneal lavage cytology (PLC) results, patients were divided into negative and positive lavage fluid groups. The data collected included clinical and MR information. A nomogram prediction model was constructed to predict the positive rate of peritoneal lavage fluid, and the validity of the model was verified based on data from the verification group. RESULTS There was no statistical difference between the proportion of PLC-positive cases predicted by GRASP DCE-MR and the actual PLC test. MR tumor stage, tumor thickness, and perfusion parameter Tofts-Ketty model volume transfer constant (Ktrans) were independent predictors of positive peritoneal lavage fluid. The nomogram model featured a concordance index (C-index) of 0.785 and 0.742 for the modeling and validation groups, respectively. CONCLUSIONS GRASP DCE-MR could effectively predict peritoneal free cancer cells in gastric cancer patients. The nomogram model constructed using these predictors may help clinicians to better predict the risk of peritoneal free cancer cells being present in gastric cancer patients.
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Affiliation(s)
- Xueqing Yin
- The First Affiliated Hospital of Ningbo University, Ningbo 315000, China.
| | - Xinzhong Ruan
- The First Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Yongmeng Zhu
- The First Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Yongfang Yin
- The First Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Rui Huang
- The First Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Chao Liang
- Ningbo Medical Center Lihuili Hospital, Ningbo 315000, China
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Kim S, Lee HH, Song KY, Seo HS. Peritoneal Washing Cytology Positivity in Gastric Cancer: Role of Lymph Node Metastasis as a Risk Factor. J Gastric Cancer 2024; 24:185-198. [PMID: 38575511 PMCID: PMC10995825 DOI: 10.5230/jgc.2024.24.e14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/28/2023] [Accepted: 11/12/2023] [Indexed: 04/06/2024] Open
Abstract
PURPOSE Peritoneal washing cytology (PWC) is a widely used diagnostic tool for detecting peritoneal metastasis of advanced gastric cancer. However, the prognosis of patients with positive PWC remains poor even after gastrectomy, and treatments vary among institutions and eras. In this study, we identified the clinical factors that can help predict cytology-positive (CY(+)) gastric cancer. MATERIALS AND METHODS We retrospectively reviewed the national data of patients with gastric cancer from 2019, as provided by the Information Committee of the Korean Gastric Cancer Association. Of the 13,447 patients with gastric cancer, 3,672 underwent PWC. Based on cytology results, we analyzed the clinicopathological characteristics and assessed the possibility of CY(+) outcomes in relation to T and N stages. RESULTS Of the 3,270 patients who underwent PWC without preoperative chemotherapy, 325 were CY(+), whereas 2,945 were negative. CY(+) was more commonly observed in patients with Borrmann type IV gastric cancer, an undifferentiated histological type, and advanced pathological stages. Multivariate analysis revealed Borrmann type IV (odds ratio [OR], 1.821), tumor invasion to T3-4 (OR, 2.041), and lymph node metastasis (OR, 3.155) as independent predictors of CY(+). Furthermore, for circular tumor location, the N stage emerged as a significant risk factor for CY(+), particularly when the tumor was located on the posterior wall (PW) side. CONCLUSIONS Lymph node metastasis significantly affects CY(+) outcomes, particularly when the tumor is located on the PW side. Therefore, PWC should be considered not only in suspected serosal exposure cases but also in cases of lymph node metastasis.
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Affiliation(s)
- Sojung Kim
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Han Hong Lee
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyo Young Song
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ho Seok Seo
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Leiting JL, Grotz TE. Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis. World J Gastrointest Oncol 2018; 10:282-289. [PMID: 30364780 PMCID: PMC6198298 DOI: 10.4251/wjgo.v10.i10.282] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 08/07/2018] [Accepted: 08/12/2018] [Indexed: 02/05/2023] Open
Abstract
Peritoneal carcinomatosis (PC) from gastric cancer has traditionally been considered a terminal progression of the disease and is associated with poor survival outcomes. Positive peritoneal cytology similarly worsens the survival of patients with gastric cancer and treatment options for these patients have been limited. Recent advances in multimodality treatment regimens have led to innovative ways to care for and treat patients with this disease burden. One of these advances has been to use neoadjuvant therapy to try and convert patients with positive cytology or low-volume PC to negative cytology with no evidence of active peritoneal disease. These strategies include the use of neoadjuvant systemic chemotherapy alone, using neoadjuvant laparoscopic heated intraperitoneal chemotherapy (NLHIPEC) after systemic chemotherapy, or using neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in a bidirectional manner. For patients with higher volume PC, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been mainstays of treatment. When used together, CRS and HIPEC can improve overall outcomes in properly selected patients, but overall survival outcomes remain unacceptably low. The extent of peritoneal disease, commonly measured by the peritoneal carcinomatosis index (PCI), and the completeness of cytoreduction, has been shown to greatly impact outcomes in patients undergoing CRS and HIPEC. The uses of NLHIPEC and NLHIPEC plus NIPS have both been shown to decrease the PCI and thus increase the opportunity for complete cytoreduction. Newer therapies like pressurized intraperitoneal aerosol chemotherapy and immunotherapy, such as catumaxomab, along with improved systemic chemotherapeutic regimens, are being explored with great interest. There is exciting progress being made in the management of PC from gastric cancer and its' treatment is no longer futile.
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Affiliation(s)
- Jennifer L Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55905, United States
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55905, United States
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Kelly KJ, Wong J, Gönen M, Allen P, Brennan M, Coit D, Fong Y. Human Trial of a Genetically Modified Herpes Simplex Virus for Rapid Detection of Positive Peritoneal Cytology in the Staging of Pancreatic Cancer. EBioMedicine 2016; 7:94-9. [PMID: 27322463 PMCID: PMC4909379 DOI: 10.1016/j.ebiom.2016.03.043] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 02/29/2016] [Accepted: 03/29/2016] [Indexed: 01/16/2023] Open
Abstract
Introduction Patients with peritoneal dissemination of pancreatic adenocarcinoma do not benefit from surgical resection, but radiologic and cytologic detection of peritoneal cancer lack sensitivity. This trial sought to determine if an oncolytic virus may be used as a diagnostic agent to detect peritoneal cancer. Methods Peritoneal washings from patients with pancreatic adenocarcinoma were incubated with the enhanced green fluorescent protein (eGFP)-expressing oncolytic herpes simplex virus (HSV) NV1066. eGFP-positive or negative status was recorded for each specimen and compared to results obtained by conventional cytologic evaluation. These results were correlated with recurrence and survival for patients who underwent R0 resection. Results Of 82 patients entered in this trial, 12 (15%) had positive cytology and 50 (61%) had virally-mediated eGFP positive cells in peritoneal washings. All cytology-positive patients were also eGFP positive. HSV-mediated fluorescence detection had sensitivities of 94% and 100% for detection of any and peritoneal metastatic disease; respectively. Median recurrence free and disease specific survival were 6.5 and 18.3 months for eGFP positive patients, versus 12.2 and 36.2 months for eGFP negative patients (P = 0.01 and 0.19); respectively. Conclusions A genetically modified HSV can be used as a highly sensitive diagnostic agent for detection of micro-metastatic disease in patients with pancreatic adenocarcinoma and may improve patient selection for surgery.
Oncolytic virus-mediated fluorescence is a sensitive assay for detection of cancer cells in peritoneal fluid. Pancreatic cancer patients with eGFP-positive cells in peritoneal washings had a poor prognosis following surgery. Pancreatic cancer is an aggressive disease. Even with complete surgical removal of a pancreatic tumor, recurrence is common. Patients with microscopic spread of cancer cells into the abdomen, or peritoneum, do not benefit from surgery. Current methods of detection of this kind of spread are not very sensitive. This study utilized a virus that specifically infects cancer cells and expresses a green fluorescent protein within them to detect peritoneal disease. Viral fluorescence was more sensitive than standard methods for detecting peritoneal disease and may help to identify which patients with pancreas cancer will benefit from surgery.
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Affiliation(s)
- Kaitlyn J Kelly
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Joyce Wong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Mithat Gönen
- Department of Epidemiology and Statistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Peter Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Murray Brennan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Daniel Coit
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Yuman Fong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States.
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Nakabayashi K, Uraoka T, Shibuya M, Matsuura N, Tsujimoto M. Rapid detection of CEA mRNA in peritoneal washes using One-Step Nucleic acid Amplification (OSNA®) for gastric cancer patients. Clin Chim Acta 2015; 439:137-42. [DOI: 10.1016/j.cca.2014.10.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Revised: 09/29/2014] [Accepted: 10/10/2014] [Indexed: 01/12/2023]
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Kang KK, Hur H, Byun CS, Kim YB, Han SU, Cho YK. Conventional cytology is not beneficial for predicting peritoneal recurrence after curative surgery for gastric cancer: results of a prospective clinical study. J Gastric Cancer 2014; 14:23-31. [PMID: 24765534 PMCID: PMC3996246 DOI: 10.5230/jgc.2014.14.1.23] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 03/04/2014] [Accepted: 03/05/2014] [Indexed: 12/19/2022] Open
Abstract
PURPOSE The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery. MATERIALS AND METHODS We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates. RESULTS Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081). CONCLUSIONS Peritoneal washing cytology using samples harvested from two different sites in the abdominal cavity was not able to predict peritoneal recurrence or survival in gastric cancer patients. Further studies will be required to determine whether peritoneal washing cytology during gastric cancer surgery is a meaningful procedure.
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Affiliation(s)
- Ki-Kwan Kang
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hoon Hur
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Cheul Su Byun
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Young Bae Kim
- Department of Pathology, Ajou University School of Medicine, Suwon, Korea
| | - Sang-Uk Han
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Yong Kwan Cho
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
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Xiao Y, Zhang J, He X, Ji J, Wang G. Diagnostic values of carcinoembryonic antigen in predicting peritoneal recurrence after curative resection of gastric cancer: a meta-analysis. Ir J Med Sci 2013; 183:557-64. [PMID: 24378872 DOI: 10.1007/s11845-013-1051-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 12/03/2013] [Indexed: 01/15/2023]
Abstract
AIM A meta-analysis was performed to assess the diagnostic values of carcinoembryonic antigen (CEA) in predicting the peritoneal recurrence after curative resection of gastric cancer. METHODS The Medline, Embase, Web of Science, Ovid and Cochrane databases, Google Scholar and Vivisimo engines were searched to identify studies reporting on the accuracy of CEA protein or CEA mRNA in predicting the postoperative peritoneal recurrence of gastric cancer. Publication bias was demonstrated by Funnel plots and Egger test. The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated and summary receiver operating characteristic curves were generated. RESULTS Seven and eight studies fulfilled the inclusion criteria for CEA protein and mRNA determination, including 635 and 849 patients, respectively. The pooled sensitivity, specificity and DOR of CEA protein for predicting the peritoneal recurrence were 0.77 (95 % CI 0.69-0.84), 0.89 (95 % CI 0.86-0.92), 29.71 (95 % CI 10.27-85.92), respectively. Similarly, the values for CEA mRNA were 0.82 (95 % CI 0.75-0.88), 0.82 (95 % CI 0.79-0.85) and 22.97 (95 % CI 10.90-48.41). Meanwhile, the sensitivity and DOR of CEA protein or mRNA were higher than those of cytology, while higher specificity was noted in cytology assay. CONCLUSION CEA protein and mRNA levels in peritoneal lavage show a high diagnostic accuracy and may help accurately predict the peritoneal recurrence after curative resection of gastric cancer.
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Affiliation(s)
- Y Xiao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Jiefang Ave 1277#, Wuhan, 430022, Hubei, China
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8
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Qiu MZ, Li ZH, Zhou ZW, Li YH, Wang ZQ, Wang FH, Huang P, Aziz F, Wang DY, Xu RH. Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma. J Transl Med 2010; 8:107. [PMID: 21040522 PMCID: PMC2989934 DOI: 10.1186/1479-5876-8-107] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2009] [Accepted: 10/31/2010] [Indexed: 12/27/2022] Open
Abstract
Background The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Methods Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. Results The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. Conclusions CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients.
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Affiliation(s)
- Miao-Zhen Qiu
- State Key Laboratory of Oncology in South China, Guangzhou 510060, China
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La Torre M, Ferri M, Giovagnoli MR, Sforza N, Cosenza G, Giarnieri E, Ziparo V. Peritoneal wash cytology in gastric carcinoma. Prognostic significance and therapeutic consequences. Eur J Surg Oncol 2010; 36:982-6. [PMID: 20591604 DOI: 10.1016/j.ejso.2010.06.007] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Accepted: 06/07/2010] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS The prognosis of patients with gastric cancer is poor, even following curative resection, and is related primarily to the extent of disease at presentation. In locally advanced gastric tumors, peritoneal lavage cytology (PLC) is a relevant prognostic factor. The Authors present their results of peritoneal washing cytology, evaluating the prognostic value of this technique, and discussing the clinical impact. PATIENTS AND METHODS From July 2003 to May 2008, results of PLC in 64 patients with histologically proven primary gastric adenocarcinomas were analyzed. At laparotomy the abdomen was irrigated with 200 ml of normal saline, and ≥50 ml were aspirated and examined by means of cytology and immunocytopathology. RESULTS PLC was positive in 7 cases (11%). Overall, 86% of patients with a positive PLC had a pT3/pT4 tumor and 100% with a positive PLC had an N-positive tumor (p < 0.001); 71% of patients with a positive PLC had a grade G3/G4 tumor (p = 0.001). At a median follow-up of 32 months, the cumulative 5-year survival was 28%. The median survival of patients presenting positive PLC (19 months) was significantly lower than that of patients with negative peritoneal cytology (38 months) (p = 0.0001). Multivariate analysis identified cytology as a significant predictor of outcome (p = 0.018). CONCLUSIONS Results in the present series demonstrated that patients with a positive peritoneal cytology had advanced disease and poor prognosis, thus indicating that patients with locally advanced gastric cancer should undergo staging laparoscopy and PLC examination in order to select those requiring more aggressive treatment. Future therapeutic strategies should include PLC examination in preoperative staging, in order to select patients for more aggressive treatment.
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Affiliation(s)
- M La Torre
- Department of Surgery, S. Andrea Hospital, Sapienza University of Rome, Rome, Italy.
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10
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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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Li G, Passebosc-Faure K, Feng G, Lambert C, Cottier M, Gentil-Perret A, Fournel P, Pérol M, Genin C. MN/CA9: a potential gene marker for detection of malignant cells in effusions. Biomarkers 2007; 12:214-20. [PMID: 17536770 DOI: 10.1080/13547500601068192] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Many cancers cause malignant effusions. The presence of malignant cells in effusions has implications in diagnosis, tumour staging and prognosis. The detection of malignant cells currently presents a challenge for cytopathologists. New adjunctive methods are needed. Although the effusions provide excellent materials for molecular assay, the available molecular markers are extremely limited, which hinders its clinical application. MN/CA9 has proved to be a valuable marker in many cancers such as lung, breast, colon, kidney, etc. The present study was to evaluate MN/CA9 as a new molecular marker for the detection of cancer cells in pleural effusions. Seventy-one pleural effusions including 59 malignant effusions from patients with cancer, and 12 patients with benign diseases as a control, were subjected to RT-PCR for detection of MN/CA9 gene expression. MN/CA9 gene expression was detected in 53/59 (89.8%) pleural effusions from cancer patients (15/16 for breast cancers, 10/11 for lung cancers, 4/4 for ovary cancers, 2/3 for colon-rectal cancers, 5/6 for cancers of unknown site, 7/8 for mesothelioma and 10/11 for other cancers). Furthermore, MN/CA9 was positive in 13/18 (72.2%) of cytologically negative effusions of cancer patients. MN/CA9 was detected in only 1/12 (8.3%) effusions from the control patients (p < 0.01). The sensitivity and specificity of MN/CA9 gene expression were, respectively, 89.8% and 91.7%. Our preliminary results suggest that MN/CA9 could be a potential marker for the detection of malignant cells in effusions. A large-scale study is needed to confirm these results.
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Affiliation(s)
- G Li
- Laboratory of Clinical Immunology, North Hospital, CHU of Saint-Etienne, France.
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12
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Li JK, Zheng M, Miao CW, Zhang JH, Ding GH, Wu WS. Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer. World J Gastroenterol 2006; 11:7374-7. [PMID: 16437646 PMCID: PMC4725135 DOI: 10.3748/wjg.v11.i46.7374] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer. METHODS PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases. RESULTS The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05). The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer. CONCLUSION Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.
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Affiliation(s)
- Ji-Kun Li
- Department of General Surgery, First Affiliated People's Hospital of Shanghai Jiaotong University, Shanghai 200080, China.
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Zhang YS, Xu J, Luo GH, Wang RC, Zhu J, Zhang XY, Nilsson-Ehle P, Xu N. Detection of carcinoembryonic antigen mRNA in peritoneal washes from gastric cancer patients and its clinical significance. World J Gastroenterol 2006; 12:1408-1411. [PMID: 16552810 PMCID: PMC4124319 DOI: 10.3748/wjg.v12.i9.1408] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2005] [Revised: 08/01/2005] [Accepted: 10/09/2005] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a more sensitive method for detection of free cancer cells in peritoneal washes from gastric cancer patients during surgery and to evaluate its clinical significance. METHODS The carcinoembryonic antigen (CEA) mRNA levels in peritoneal washes from 65 cases of gastric cancer were detected by real-time RT-PCR. Peritoneal lavage cytology (PLC) was applied simultaneously to detection of free cancer cells.Negative controls included peritoneal washes from 5 cases of benign gastric disease and blood samples from 5 adult healthy volunteers. RESULTS There was no CEA mRNA in peritoneal washes from benign gastric disease patients and in blood of adult healthy volunteers. The positive percentage of free cancer cells detected by real-time RT-PCR was 47.7% and only 12.3% by PLC. The positive rate of CEA mRNA was significantly related with serosa invasion between peritoneal metastasis and stage of gastric cancer. CONCLUSION Real-time RT-PCR is a sensitive and rapid method for the detection of free cancer cells in peritoneal washes. The presence of free cancer cells in peritoneal washes is related to the pathologic stage of gastric cancer.
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Affiliation(s)
- Yan-Song Zhang
- Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Suzhou University, China
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Wang JY, Lin SR, Lu CY, Chen CC, Wu DC, Chai CY, Chen FM, Hsieh JS, Huang TJ. Gastric cancer cell detection in peritoneal lavage: RT-PCR for carcinoembryonic antigen transcripts versus the combined cytology with peritoneal carcinoembryonic antigen levels. Cancer Lett 2004; 223:129-35. [PMID: 15890245 DOI: 10.1016/j.canlet.2004.09.031] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2004] [Revised: 09/16/2004] [Accepted: 09/20/2004] [Indexed: 12/11/2022]
Abstract
Free cancer cells exfoliated from the serosal surfaces of primary cancers are considered to be responsible for peritoneal dissemination, which are both the most frequent pattern of treatment failure and the most important cause of death in gastric cancer patients. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is thought to be of great value in predicting peritoneal recurrence and accordingly the prognosis of gastric cancer patients. This study was designed to determine whether free cancer cells in peritoneal lavage fluid from gastric cancer patients could be identified by a reverse-transcriptase polymerase chain reaction (RT-PCR) method specific to carcinoembryonic antigen (CEA) mRNA. Simultaneously, the results from conventional cytological examination were evaluated and the levels of CEA in peritoneal lavage were determined. Of the 40 gastric cancer patients enrolling in this investigation, 11 (27.5%) were positive for CEA mRNA in their peritoneal lavage, whereas only 6 (15%) and 8 (20%) were shown to be positive by cytological examination and peritoneal CEA (pCEA) assay, respectively. Furthermore, RT-PCR positive for CEA mRNA was correlated with the depth of tumor invasion (P<0.001), lymph node metastases (P=0.004), the TNM stage (P<0.001) and peritoneal recurrence (P<0.001). The technique of RT-PCR was more sensitive than conventional cytological examination and pCEA levels in the detection of peritoneal free cancer cells as well as in the prediction of peritoneal recurrence. In addition, CEA RT-PCR had a high concordance rate (82.5%) with the combination of cytology with pCEA levels. These observations suggest that it is feasible to identify free cancer cells in peritoneal lavage by using a CEA mRNA-specific RT-PCR method, and this assay can be a promising diagnostic modality for evaluating the risk of peritoneal dissemination in gastric cancer patients following operations.
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Affiliation(s)
- Jaw-Yuan Wang
- Department of Surgery, Kaohsiung Medical University and Hospital, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan, ROC
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