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1
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Li BQ, Wang HY, Li L, Jiang B, Ma CL, Yuan CH, Xiu DR. Should Positive Cytology Revealed by Intraoperative Lavage Preclude Radical Resection in Resectable Pancreatic Cancer?: A Systemic Review and Meta-analysis. Pancreas 2022; 51:1263-1276. [PMID: 37099766 DOI: 10.1097/mpa.0000000000002163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
OBJECTIVES The aims of this review were to determine whether positive peritoneal lavage cytology (CY+) precludes radical resection in pancreatic cancer and to propose prospections for future studies. METHODS MEDLINE, Embase, and Cochrane Central were searched for related articles. Dichotomous variables and survival outcomes were analyzed with the estimation of odds ratio and hazards ratio (HR), respectively. RESULTS A total of 4905 patients were included, of which 7.8% were CY+. Positive peritoneal lavage cytology was correlated with poor overall survival (univariate survival analysis [HR, 2.35; P < 0.00001]; multivariate analysis [HR, 1.62; P < 0.00001]), poor recurrence-free survival (univariate survival analysis [HR, 2.50; P < 0.00001]; multivariate analysis [HR, 1.84; P < 0.00001]), and higher initial peritoneal recurrence rate (odds ratio, 5.49; P < 0.00001). CONCLUSIONS Although CY+ predicts poor prognosis and a higher risk of peritoneal metastasis after curative resection, it is not sufficient to preclude curative resection based on the current evidence, and high-quality trials should be conducted to assess the prognostic impact of operation among resectable CY+ patients. In addition, more sensitive and accurate methods to detect peritoneal exfoliated tumor cells and more effective comprehensive treatment for resectable CY+ pancreatic cancer patients are clearly warranted.
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Affiliation(s)
- Bing-Qi Li
- From the Department of General Surgery, Peking University Third Hospital, Beijing, China
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2
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Zhang Y, Qin X, Chen W, Liu D, Luo J, Wang H, Wang H. Risk factors for developing peritoneal metastases after curative surgery for colorectal cancer: A systematic review and meta-analysis. Colorectal Dis 2021; 23:2846-2858. [PMID: 34411399 DOI: 10.1111/codi.15880] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 07/20/2021] [Accepted: 08/16/2021] [Indexed: 01/10/2023]
Abstract
AIM Proactive detection and treatment strategies have achieved encouraging survival outcomes for patients with early peritoneal metastases (PM), but these costly and invasive approaches can only be applied to selected high-risk patients. This meta-analysis aimed to identify the risk factors for metachronous PM after curative surgery for colorectal cancer (CRC). METHOD The study was registered at PROSPERO (CRD42020219187). Databases were searched for studies comparing clinical and histopathological characteristics between patients with metachronous peritoneal metastases from colorectal cancer (pmCRC) and patients without (non-pmCRC). RESULTS Thirty-six studies were included. Metachronous PM were positively associated with perforation (OR 1.920; 95% CI 1.144-3.223; P = 0.014), poor differentiation (OR 2.291; 1.603-3.275; P < 0.001), T4 (OR 2.897; 1.248-6.726; P = 0.013), N1-2 (OR 3.429; 2.684-4.381; P < 0.001), mucinous adenocarcinoma (OR 4.175; 1.798-9.692; P = 0.001), obstruction (OR 4.467; 1.919-10.398; P = 0.001), synchronous ovarian metastases (OR 5.005; 1.140-21.977; P = 0.033), positive peritoneal carcinoembryonic antigen mRNA (OR 9.472; 3.643-24.631; P < 0.001), elevated serum carcinoembryonic antigen (preoperative group, OR 3.545, 1.486-8.459, P = 0.004; postoperative group, OR 13.673, 2.222-84.129, P = 0.005), elevated serum cancer antigen 19-9 (preoperative group, OR 5.281, 2.146-12.994, P < 0.001; postoperative group, OR 18.646, 6.429-54.083, P < 0.001) and positive peritoneal cytology (OR 25.884; 11.372-58.913; P < 0.001). CONCLUSION These evidence-based risk factors are conducive to designing early detection and proactive treatment strategies, enabling precision medicine.
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Affiliation(s)
- Yuanxin Zhang
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiusen Qin
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenle Chen
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Duo Liu
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jian Luo
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hui Wang
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Alves LB, Tsukazan MT, Serafim AE, Mendoza R, Padoin AV, Baú PC, Moreira LF. PROGNOSTIC VALUE OF CARCINOEMBRYONIC ANTIGEN LEVELS IN TRANSOPERATIVE PERITONEAL LAVAGE IN PATIENTS WITH GASTRIC CANCER. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2018; 31:e1358. [PMID: 29947692 PMCID: PMC6049989 DOI: 10.1590/0102-672020180001e1358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 02/16/2018] [Indexed: 11/22/2022]
Abstract
Background: The carcinoembryonic antigen level in peritoneal lavage has been showing to be a reliable prognostic factor in gastric cancer. Aim: To identify any association between carcinoembryonic antigen level in peritoneal lavage, in gastric cancer patients, with mortality, peritoneal recurrence, tumor relapse or other prognostic factors. Methods: In total, 30 patients (22 men, 8 women; median age 66 years) with resectable gastric cancer (mainly stage III and IV) were studied. Carcinoembryonic antigen level in peritoneal lavage was detected at operation by immunocytochemical method and a level over 210 ng/g of protein was considered as positive. Results: There were detected 10 positive cases (33.3%) of plCEA levels. These levels were associated with mortality, RR: 2.1 (p=0.018); peritoneal recurrence, OR: 9.0 (p=0.015); and relapse or gastric cancer progression, OR: 27.0 (p=0.001). Conclusion: Increased levels of plCEA fairly predicts mortality, peritoneal recurrence tumor relapse or cancer progression.
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Affiliation(s)
- Letícia Biscaino Alves
- Post-Graduate Program in Surgery, Hospital de Clínicas of Porto Alegre, Federal University of Rio Grande do Sul.,Center for Obesity and Metabolic Syndrome, São Lucas Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
| | | | | | | | - Alexandre Vontobel Padoin
- Center for Obesity and Metabolic Syndrome, São Lucas Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS).,Post-Graduate Program in Medicine and Health Sciences, PUCRS
| | | | - Luis Fernando Moreira
- Post-Graduate Program in Surgery, Hospital de Clínicas of Porto Alegre, Federal University of Rio Grande do Sul
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Li S, Lan X, Gao H, Wang W, Chen L, Song S, Xue Y. Addition of peritonectomy to gastrectomy can predict good prognosis of gastric adenocarcinoma patients with intraoperatively proven single P1/P2 carcinomatosis. Tumour Biol 2017; 39:1010428317697567. [PMID: 28618957 DOI: 10.1177/1010428317697567] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
This study was to evaluate the prognosis of peritonectomy following gastrectomy for gastric adenocarcinoma patients with intraoperatively proven single P1/P2 carcinomatosis and to define the best therapeutic strategy of the patient cohort. The patients with intraoperatively proven single P1/P2 carcinomatosis from a prospectively maintained database were divided into resection group and non-resection group based on complete gross resection of peritoneal carcinomatosis. From 2005 to 2012, there were 103 patients in the resection group and 122 patients in the non-resection group. There was no difference in morbidity and mortality between groups. The patients did not have improved median survival in P1 carcinomatosis compared to P2 carcinomatosis (15.53 vs 14.80 months, p = 0.450). The median survival was significantly improved in the resection group compared to the patients in the non-resection group (21.07 vs 13.37 months, p < 0.001). The patients undergoing complete gross peritonectomy plus postoperative chemotherapy had a significantly longer median survival than patients who had complete gross peritonectomy alone, patients receiving postoperative chemotherapy alone, and patients receiving neither peritonectomy nor postoperative chemotherapy (27.33 vs 12.00 vs 16.00 vs 10.33 months, p < 0.001). In the multivariate analysis, poor performance status ( p = 0.036), absence of complete gross peritonectomy ( p < 0.001), and lack of postoperative chemotherapy ( p < 0.001) were identified as independently associated with poor survival. The data indicate complete gross peritonectomy following gastrectomy confers a survival benefit to gastric cancer patients with intraoperatively proven single P1/P2 carcinomatosis. In addition, postoperative chemotherapy improves survival regardless of resection of peritoneal carcinomatosis and should be recommended.
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Affiliation(s)
- Sen Li
- 1 Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiuwen Lan
- 1 Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Hongyu Gao
- 1 Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Wenpeng Wang
- 2 Department of Gynecologic Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Chen
- 1 Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shubin Song
- 1 Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yingwei Xue
- 1 Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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5
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Xu Y, Huang Y, Wang H, Liu Y. Inhibition of the peritoneal metastasis of human gastric cancer cells by dextran sulphate in vivo and in vitro. Oncol Lett 2016; 11:2384-2390. [PMID: 27073484 DOI: 10.3892/ol.2016.4234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Accepted: 01/14/2016] [Indexed: 11/06/2022] Open
Abstract
The present study investigated the inhibitory effects of dextran sulphate (DS) on the peritoneal metastasis of gastric cancer by observing the adhesion and implantation of human gastric cancer cells in the omenta of nude mice. DS or PBS was added to the culture medium of gastric cancer MKN1 cells. The adhesion of the cancer cells to the culture dishes, and the morphological changes of fixed and living cancer cells were observed using fluorescence staining and confocal microscopy. In addition, the expression of integrin β1 was measured using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Gastric cancer BGC-823 cells were peritoneally injected into nude mice to develop an animal model. DS and PBS were peritoneally injected into the experimental and control groups, respectively, concurrently with the tumour cells. Haematoxylin and eosin staining was performed, and the number of carcinoma nodules with celiac implantation was counted. Integrin expression was determined by immunohistochemistry and RT-PCR. The results showed that MKN1 cells strongly expressed integrin β1 in the cell membrane and clustered in vitro. DS inhibited the expression of integrin β1 and reduced cluster formation. In addition, the number of pseudopodia formed by the cells decreased, and the cells maintained a rounded shape. The expression of integrin β1 in the adherent and free cells in the experimental group was reduced to 74 and 38% of the levels in the control group, respectively. In the in vivo study, significantly fewer tumour nodules were observed in the experimental group than in the control group (P<0.01). Integrin β1 expression in the experimental group was decreased significantly compared with that in the control group (P<0.01). The present study indicates that DS inhibits the adhesion of human gastric cancer cells, accompanied by a decrease in the expression of integrin β1. DS may inhibit the metastatic celiac implantation of human gastric cancer cells by downregulating integrin β1.
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Affiliation(s)
- Yuanyi Xu
- Department of Pathology, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Yunning Huang
- Department of Gastrointestinal Surgery, Ningxia People's Hospital, Yinchuan, Ningxia 750001, P.R. China
| | - Honghong Wang
- Department of Pathology, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Yong Liu
- Department of Pathology, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
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Yang K, Liu K, Zhang WH, Lu ZH, Chen XZ, Chen XL, Zhou ZG, Hu JK. The Value of Palliative Gastrectomy for Gastric Cancer Patients With Intraoperatively Proven Peritoneal Seeding. Medicine (Baltimore) 2015; 94:e1051. [PMID: 26166075 PMCID: PMC4504616 DOI: 10.1097/md.0000000000001051] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The aim of this study was to evaluate the survival benefit of palliative gastrectomy for gastric cancer patients with peritoneal seeding proven intraoperatively and to identify positive predictive factors for improving survival.The value of palliative resection for gastric cancer patients with peritoneal metastasis is controversial.From 2006 to 2013, 267 gastric cancer patients with intraoperatively identified peritoneal dissemination were retrospectively analyzed. Patients were divided into resection group and nonresection group according to whether a palliative gastrectomy was performed. Clinicopathologic variables and survival were compared. Subgroup analyses stratified by clinicopathologic factors and multivariable analysis for overall survival were also performed.There were 114 patients in the resection group and 153 in nonresection group. The morbidities in the resection and nonresection groups were 14.91% and 5.88%, respectively (P = 0.014). There, however, was no difference in mortality between the 2 groups. The median survival time of patients in the resection group was longer than in nonresection group (14.00 versus 8.57 months, P = 0.000). The median survivals among the patients with different classifications of peritoneal metastasis were statistically significant (P = 0.000). Patients undergoing resection followed by chemotherapy had a significantly longer median survival, compared with that of patients who had chemotherapy alone, those who had resection alone, or those who had not received chemotherapy or resection (P = 0.000). Results of subgroup analyses showed that except for P3 patients and patients with multisite distant metastases, overall survival was significantly better in patients with palliative gastrectomy, compared with the nonresection group. In multivariate analysis, P3 disease (P = 0.000), absence of resection (P = 0.000), and lack of chemotherapy (P = 0.000) were identified as independently associated with poor survival.Palliative gastrectomy might be beneficial to the survival of gastric cancer patients with intraoperatively proven P1/P2 alone, rather than P3. Postoperative palliative chemotherapy could improve survival regardless of operation and should be recommended.
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Affiliation(s)
- Kun Yang
- Department of Gastrointestinal Surgery (KY, KL, W-HZ, Z-HL, X-ZC, X-LC, Z-GZ, J-KH); Laboratory of Gastric cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China (KY, KL, W-HZ, Z-HL, X-ZC, X-LC, J-KH)
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7
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De Vlieghere E, Gremonprez F, Verset L, Mariën L, Jones CJ, De Craene B, Berx G, Descamps B, Vanhove C, Remon JP, Ceelen W, Demetter P, Bracke M, De Geest BG, De Wever O. Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells. Biomaterials 2015; 54:148-57. [PMID: 25907048 DOI: 10.1016/j.biomaterials.2015.03.012] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 02/27/2015] [Accepted: 03/04/2015] [Indexed: 12/22/2022]
Abstract
Peritoneal metastasis is life threatening and is the result of an extensive communication between disseminated cancer cells, mesothelial cells and cancer-associated fibroblasts (CAF). CAFs secrete extracellular matrix (ECM) proteins creating a receptive environment for peritoneal implantation. Considering cancer as an ecosystem may provide opportunities to exploit CAFs to create biomimetic traps to deceive and redirect cancer cells. We have designed microparticles (MP) containing a CAF-derived ECM-surface that is intended to compete with natural niches. CAFs were encapsulated in alginate/gelatine beads (500-750 μm in diameter) functionalised with a polyelectrolyte coating (MP[CAF]). The encapsulated CAFs remain viable and metabolically active (≥35 days), when permanently encapsulated. CAF-derived ECM proteins are retained by the non-biodegradable coating. Adhesion experiments mimicking the environment of the peritoneal cavity show the selective capture of floating cancer cells from different tumor origins by MP[CAF] compared to control MP. MP[CAF] are distributed throughout the abdominal cavity without attachment to intestinal organs and without signs of inflammatory reaction. Intraperitoneal delivery of MP[CAF] and sequential removal redirects cancer cell adhesion from the surgical wound to the MP[CAF], delays peritoneal metastasis formation and prolongs animal survival. Our experiments suggest the use of a biomimetic trap based on tumor-environment interactions to delay peritoneal metastasis.
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Affiliation(s)
- Elly De Vlieghere
- Laboratory of Experimental Cancer Research, Ghent University, Belgium
| | | | - Laurine Verset
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Belgium
| | - Lore Mariën
- Laboratory of Experimental Cancer Research, Ghent University, Belgium
| | | | - Bram De Craene
- Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium
| | - Geert Berx
- Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium
| | - Benedicte Descamps
- Department of Electronics and Information Systems, IBiTech, MEDISIP, INFINITY, Ghent University, Belgium
| | - Christian Vanhove
- Department of Electronics and Information Systems, IBiTech, MEDISIP, INFINITY, Ghent University, Belgium
| | - Jean-Paul Remon
- Laboratory of Pharmaceutical Technology, Ghent University, Belgium
| | - Wim Ceelen
- Department of Surgery, Ghent University Hospital, Belgium
| | - Pieter Demetter
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Belgium
| | - Marc Bracke
- Laboratory of Experimental Cancer Research, Ghent University, Belgium
| | - Bruno G De Geest
- Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
| | - Olivier De Wever
- Laboratory of Experimental Cancer Research, Ghent University, Belgium.
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Nakamura J, Tanaka T, Kitajima Y, Noshiro H, Miyazaki K. Methylation-mediated gene silencing as biomarkers of gastric cancer: A review. World J Gastroenterol 2014; 20:11991-12006. [PMID: 25232236 PMCID: PMC4161787 DOI: 10.3748/wjg.v20.i34.11991] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 01/29/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Despite a decline in the overall incidence of gastric cancer (GC), the disease remains the second most common cause of cancer-related death worldwide and is thus a significant global health problem. The best means of improving the survival of GC patients is to screen for and treat early lesions. However, GC is often diagnosed at an advanced stage and is associated with a poor prognosis. Current diagnostic and therapeutic strategies have not been successful in decreasing the global burden of the disease; therefore, the identification of reliable biomarkers for an early diagnosis, predictive markers of recurrence and survival and markers of drug sensitivity and/or resistance is urgently needed. The initiation and progression of GC depends not only on genetic alterations but also epigenetic changes, such as DNA methylation and histone modification. Aberrant DNA methylation is the most well-defined epigenetic change in human cancers and is associated with inappropriate gene silencing. Therefore, an increasing number of genes methylated at the promoter region have been targeted as possible biomarkers for different purposes, including early detection, classification, the assessment of the tumor prognosis, the development of therapeutic strategies and patient follow-up. This review article summarizes the current understanding and recent evidence regarding DNA methylation markers in GC with a focus on the clinical potential of these markers.
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9
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Kikuchi H, Kamiya K, Hiramatsu Y, Miyazaki S, Yamamoto M, Ohta M, Baba S, Konno H. Laparoscopic narrow-band imaging for the diagnosis of peritoneal metastasis in gastric cancer. Ann Surg Oncol 2014; 21:3954-62. [PMID: 24859934 DOI: 10.1245/s10434-014-3781-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Staging laparoscopy (SL) is often used to diagnose peritoneal metastasis in patients with advanced gastric cancer, but accurate detection of metastasis can be difficult. We evaluated the usefulness of laparoscopic narrow-band imaging (NBI) versus conventional laparoscopic white-light imaging (WLI) for the diagnosis of peritoneal metastasis. METHODS We excised 37 white nodules from the parietal peritoneum of 26 patients with gastric cancer and suspected peritoneal metastasis. The WLI and NBI findings were compared with the pathological findings. All the peritoneal lesions examined were observed as white nodules on WLI. Intranodular vessels were evaluated by WLI and NBI for (1) vessel dilatation, (2) vessel tortuousness, (3) vessel heterogeneity, and (4) brown spots. RESULTS Each individual abnormal finding had a diagnostic accuracy of less than 79 % with or without NBI. Detection of any one abnormal finding had a sensitivity, specificity, and accuracy of 47.8, 85.7, and 62.2 %, respectively, on WLI and 91.3, 71.4, and 83.8 %, respectively, on NBI, for detection of peritoneal metastasis. Detection of any one abnormal finding on NBI plus clear demarcation of the nodule on WLI had a sensitivity of 91.3 %, specificity of 92.9 %, and accuracy of 91.9 % for detection of peritoneal metastasis. Pathological examination showed that a brown spot detected on NBI correlated with dilated vessels around cancer cells. Vascular endothelial growth factor was expressed in 76.2 % of peritoneal metastases. CONCLUSIONS NBI was more sensitive for the detection of dilated vessels than WLI. NBI could be a useful tool for the diagnosis of peritoneal metastasis during SL.
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Affiliation(s)
- Hirotoshi Kikuchi
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan,
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10
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Havlik R, Srovnal J, Klos D, Benedikova A, Lovecek M, Ghothim M, Cahova D, Neoral C, Hajduch M. Occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 157:233-8. [DOI: 10.5507/bp.2012.061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Indexed: 11/23/2022] Open
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Bosanquet DC, Harris DA, Evans MD, Beynon J. Systematic review and meta-analysis of intraoperative peritoneal lavage for colorectal cancer staging. Br J Surg 2013; 100:853-62. [PMID: 23536330 DOI: 10.1002/bjs.9118] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Intraperitoneal cancer cells are detectable at the time of colorectal cancer resection in some patients. The significance of this, particularly in patients with no other adverse prognostic features, is poorly defined. Consequently peritoneal lavage is not part of routine practice during colorectal cancer resection, in contrast with other abdominal malignancies. The aim of this systematic review was to determine the effect of positive intraoperative peritoneal cytology on cancer-specific outcomes in colorectal cancer. METHODS A systematic review of key electronic journal databases was undertaken using the search terms 'peritoneal cytology' and 'colorectal' from 1980 to 2012. Studies including patients with frank peritoneal metastasis were excluded. Meta-analysis for overall survival, local/peritoneal recurrence and overall recurrence was performed. RESULTS Twelve cohort studies (2580 patients) met the inclusion criteria. The weighted mean yield was 11·6 (range 2·2-41) per cent. Yield rates were dependent on timing of sampling (before resection, 11·8 per cent; after resection, 13·2 per cent) and detection methods used (cytopathology, 8·4 per cent; immunocytochemistry, 28·3 per cent; polymerase chain reaction, 14·5 per cent). Meta-analysis showed that positive peritoneal lavage predicted worse overall survival (odds ratio (OR) 4·26, 95 per cent confidence interval 2·86 to 6·36; P < 0·001), local/peritoneal recurrence (OR 6·57, 2·30 to 18·79; P < 0·001) and overall recurrence (OR 4·02, 2·24 to 7·22; P < 0·001). CONCLUSION Evidence of intraoperative peritoneal tumour cells at colorectal cancer resection is predictive of adverse cancer outcomes.
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Affiliation(s)
- D C Bosanquet
- Department of Colorectal Surgery, Abertawe Bro Morgannwg University Trust, Singleton Hospital, Sketty Lane, Swansea, SA2 8QA, UK
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12
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Hiraki M, Kitajima Y, Kai K, Nakamura J, Hashiguchi K, Noshiro H, Miyazaki K. Knockdown of hypoxia-inducible factor-1α accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines. Exp Ther Med 2012. [PMID: 23181099 PMCID: PMC3503539 DOI: 10.3892/etm.2012.600] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
This study was performed to clarify the role of hypoxia-inducible factor-1 α (HIF-1α) in the development of peritoneal dissemination in a xenograft mouse model of gastric cancer. HIF-1α knockdown (KD) and control (SC) gastric cancer cells, which were established using the MKN45 and MKN74 cell lines, were studied. The two paired cell lines were directly inoculated into the peritoneal cavity of nude mice. The number and the weight of disseminated nodules were compared between tumors generated from the KD and SC cells. In addition, the molecular mechanism was addressed through analysis of the expression levels of metastasis-related genes. The MKN45-KD cell line demonstrated significantly greater numbers of disseminated nodules and formed a larger tumor mass than the MKN45-SC cell line (p<0.05). MKN74-KD cells also tended to induce a greater number of nodules and to produce those with a heavier weight than the SC cells. An in vitro adhesion assay revealed differing results regarding the adhesion activity to extracellular matrix and monolayer mesothelium cells of the gastric cancer cells derived from the various parental cells. However, the expression of MMP-1 mRNA in the disseminated nodules was significantly increased in the KD cells compared to the SC cells derived from the two parental cell lines (p<0.01). An immunohisto-chemical study further demonstrated that there was stronger staining for MMP-1 in the MKN74-KD in comparison to MKN74-SC cells. Loss of HIF-1α may contribute to the development of aggressive peritoneal dissemination via the upregulation of MMP-1 in gastric cancer cells.
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13
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Chen S, Li YF, Feng XY, Zhou ZW, Yuan XH, Chen YB. Significance of palliative gastrectomy for late-stage gastric cancer patients. J Surg Oncol 2012; 106:862-71. [PMID: 22648960 DOI: 10.1002/jso.23158] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Accepted: 04/24/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE To investigate the significance of palliative gastrectomy for different types of metastatic gastric cancer patients displaying peritoneal dissemination, hepatic metastasis, distant lymph node metastasis occurring locally during late-stage disease, and multi-organ metastases. METHODS We performed a retrospective study of 862 patients who were histologically diagnosed as late-stage gastric cancer who could not undergo radical surgery at the Sun Yat-sen University Cancer Center between January 1993 and December 2008. The follow-up lasted until December 2010. Chi-square tests and Kaplan-Meier methods were employed to compare the adverse events and prognoses. RESULTS In the peritoneal dissemination and multi-organ metastases groups, palliative gastrectomy has no survival benefit (P = 0.705, 0.331, respectively). In the patients with distant lymph-node metastases, liver metastasis and locally late-stage gastric cancer patients, palliative gastrectomy was a prognostic factor (P < 0.001, P < 0.001, P = 0.010, respectively). Multivariable analysis demonstrated that palliative gastrectomy was an independent prognostic factor for distant lymph-node metastases, liver metastasis, and local late-stage gastric cancer patients. Palliative gastrectomy combined with hepatectomy proved to be an independent prognostic factor to improve the overall survival of patients with liver metastases who underwent palliative gastrectomy (P = 0.008). CONCLUSION For late-stage gastric cancer patients, palliative gastrectomy should be considered for locally late-stage, distant lymph node metastasis, and resectable liver metastasis patients. Especially among patients with liver metastasis, transfer medicine is essential for potentially curable patients to obtain access to radical surgery to improve the prognosis.
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Affiliation(s)
- Shi Chen
- Department of Gastropancreatic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, PR China
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Kowalewska M, Nowak R, Chechlinska M. Implications of cancer-associated systemic inflammation for biomarker studies. Biochim Biophys Acta Rev Cancer 2010; 1806:163-71. [PMID: 20600631 DOI: 10.1016/j.bbcan.2010.06.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2010] [Revised: 06/16/2010] [Accepted: 06/17/2010] [Indexed: 12/19/2022]
Abstract
Highly sensitive molecular technologies provide new capacities for cancer biomarker research, but with sensitivity improvements marker specificity is significantly decreased, and too many false-positive results should disqualify the measurement from clinical use. Hence, of the thousands of potential cancer biomarkers only a few have found their way to clinical application. Differentiating false-positive results from true-positive (cancer-specific) results can indeed be difficult, if validation of a marker is performed against inadequate controls. We present examples of accumulating evidence that not only local but also systemic inflammatory reactions are implicated in cancer development and progression and interfere with the molecular image of cancer disease. We analyze several modern strategies of tumor marker discovery, namely, proteomics, metabonomics, studies on circulating tumor cells and circulating free nucleic acids, or their methylation degree, and provide examples of scarce, methodologically correct biomarker studies as opposed to numerous methodologically flawed biomarker studies, that examine cancer patients' samples against those of healthy, inflammation-free persons and present many inflammation-related biomarker alterations in cancer patients as cancer-specific. Inflammation as a cancer-associated condition should always be considered in cancer biomarker studies, and biomarkers should be validated against their expression in inflammatory conditions.
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Affiliation(s)
- Magdalena Kowalewska
- Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
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Hiraki M, Kitajima Y, Sato S, Nakamura J, Hashiguchi K, Noshiro H, Miyazaki K. Aberrant gene methylation in the peritoneal fluid is a risk factor predicting peritoneal recurrence in gastric cancer. World J Gastroenterol 2010; 16:330-8. [PMID: 20082478 PMCID: PMC2807953 DOI: 10.3748/wjg.v16.i3.330] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether gene methylation in the peritoneal fluid (PF) predicts peritoneal recurrence in gastric cancer patients.
METHODS: The gene methylation of CHFR (checkpoint with forkhead and ring finger domains), p16, RUNX3 (runt-related transcription factor 3), E-cadherin, hMLH1 (mutL homolog 1), ABCG2 (ATP-binding cassette, sub-family G, member 2) and BNIP3 (BCL2/adenovirus E1B 19 kDa interacting protein 3) were analyzed in 80 specimens of PF by quantitative methylation-specific polymerase chain reaction (PCR). Eighty patients were divided into 3 groups; Group A (n = 35): the depth of cancer invasion was less than the muscularis propria; Group B (n = 31): the depth of cancer invasion was beyond the muscularis propria. Both group A and B were diagnosed as no cancer cells in peritoneal cytology and histology; Group C (n = 14): disseminated nodule was histologically diagnosed or cancer cells were cytologically defined in the peritoneal cavity.
RESULTS: The positive rates of methylation in CHFR, E-cadherin and BNIP3 were significantly different among the 3 groups and increased in order of group A, B and C (0%, 0% and 21% in CHFR, P < 0.05; 20%, 45% and 50% in E-cadherin, P < 0.05; 26%, 35% and 71% in BNIP3, P < 0.05). In addition, the multigene methylation rate among CHFR, E-cadherin and BNIP3 was correlated with group A, B and C (9%, 19% and 57%, P < 0.001). Moreover, the prognosis was analyzed in group B, excluding 3 patients who underwent a non-curative resection. Two of the 5 patients with multigene methylation showed peritoneal recurrence after surgery, while those without or with a single gene methylation did not experience recurrence (P < 0.05).
CONCLUSION: This study suggested that gene methylation in the PF could detect occult neoplastic cells in the peritoneum and might be a risk factor for peritoneal metastasis.
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Carcinoembryonic antigen and cytokeratin 20 in peritoneal cells of cancer patients: are we aware of what we are detecting by mRNA examination? Br J Cancer 2008; 98:512-3; author reply 514. [PMID: 18195708 PMCID: PMC2361435 DOI: 10.1038/sj.bjc.6604189] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Da MX, Wu XT, Guo TK, Zhao ZG, Luo T, Qian K, Zhang MM, Wang J. Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation. World J Gastroenterol 2007; 13:3122-7. [PMID: 17589931 PMCID: PMC4172622 DOI: 10.3748/wjg.v13.i22.3122] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [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 efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.
METHODS: Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined.
RESULTS: The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% (25/60), and 25.0% (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group of pT4 (15/16 vs 9/16, P < 0.05), P1-3 (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05). The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index (PI), (55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ± 10.18 vs 29.15 ± 8.31, and 49.82 ± 6.74 vs 24.65 ± 7.33, respectively, P < 0.05).
CONCLUSION: The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.
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Affiliation(s)
- Ming-Xu Da
- Department of General Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, Guangdong Province, China
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Hara M, Nakanishi H, Jun Q, Kanemitsu Y, Ito S, Mochizuki Y, Yamamura Y, Kodera Y, Tatematsu M, Hirai T, Kato T. Comparative analysis of intraperitoneal minimal free cancer cells between colorectal and gastric cancer patients using quantitative RT-PCR: possible reason for rare peritoneal recurrence in colorectal cancer. Clin Exp Metastasis 2007; 24:179-89. [PMID: 17487561 DOI: 10.1007/s10585-007-9067-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2006] [Accepted: 03/09/2007] [Indexed: 01/16/2023]
Abstract
Peritoneal recurrence has a much lower incidence in colorectal cancer (CRC) patients than gastric cancer (GC) patients. The aim of this study is to clarify the reason for the rare peritoneal recurrence in CRC as compared with GC. The incidence and the abundance of free tumor cells in the peritoneal lavages from 102 CRC and 126 GC patients who underwent curative surgery were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) with carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) as genetic markers. Prognostic significance of CEA and CK20 mRNA was also compared between CRC and GC after 2 years of follow-up by Kaplan-Meyer method with overall and peritoneal recurrence-free survival as endpoints. Positivity rate and average values of CEA and CK20 mRNA in peritoneal lavages of CRC patients, which are correlated to the depth of tumor invasion (pT category), were essentially the same as those of GC cases. Overall survival was significantly (marginally) worse in CEA mRNA (CK20 mRNA)-positive CRC patients than negatives like GC. However, peritoneal recurrence-free survival was not different between CEA (CK20) mRNA-positive and -negative CRC patients, in quite contrast to GC cases. Multivariate analysis showed that CEA mRNA was an independent prognostic factor for overall survival in GC patients, but not in CRC patients. These results suggest that the rare peritoneal recurrence in CRC patients is not due to the low incidence or the small number of intraperitoneal free cancer cells, but more likely reflects due to the low-peritoneal metastatic potential of CRC cells.
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Affiliation(s)
- Masayasu Hara
- Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
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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; 12:1408-11. [PMID: 16552810 PMCID: PMC4124319 DOI: 10.3748/wjg.v12.i9.1408] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [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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Wolfrum F, Vogel I, Fändrich F, Kalthoff H. Detection and clinical implications of minimal residual disease in gastro-intestinal cancer. Langenbecks Arch Surg 2005; 390:430-41. [PMID: 15991048 DOI: 10.1007/s00423-005-0558-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2005] [Accepted: 03/23/2005] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Metastatic dissemination is an important factor for the prognosis of patients with gastro-intestinal cancer. Exact staging is crucial to determine appropriate multimodal therapeutic strategies. At present, the sensitivity of routinely performed diagnostic techniques is suboptimal for the detection of minimal residual disease (MRD) and occult metastases since the number of disseminated tumour cells (DTCs) is mostly marginal. To amend the verification of DTCs, immunohistochemical and molecular methods were applied to retrieve epithelial cell-specific proteins in non-epithelial tissue of different body compartments or fluids. Many groups have eagerly focussed on the identification of new markers and novel tests, yet specificity and sensitivity of these methods as well as robustness in the clinical setting are frequently missing. MATERIALS AND METHODS This review critically evaluates the prognostic impact of MRD in patients with pancreatic, colorectal and gastric cancer by outlining those studies showing diagnostic results of DTC detection in lymph nodes, bone marrow, venous blood and peritoneal lavage, some of which present novel strategies. CONCLUSION The analysed data concerning MRD in gastro-intestinal cancers reveal that results are undesirably heterogeneous. From a critical point of view, many clinical studies missed their chance because of small cohort size; moreover, methodological standardisation is generally lacking. On the other hand, the very encouraging results achieved so far, together with the comprehensive analyses of a few research groups, foster the prediction that DTC/MRD issues will soon expand the standard TNM classification.
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Affiliation(s)
- Fabian Wolfrum
- Department of General and Thoracic Surgery, University Hospital of Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 7, 24105, Kiel, Germany
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Nakanishi H, Kodera Y, Tatematsu M. Molecular method to quantitatively detect micrometastases and its clinical significance in gastrointestinal malignancies. Adv Clin Chem 2004; 38:87-110. [PMID: 15521189 DOI: 10.1016/s0065-2423(04)38003-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- H Nakanishi
- Division of Oncological Pathology, Aichi Cancer Center Research Institute, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
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