Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival

Soeth, Edlyn; Grigoleit, U.; Moellmann, Barbara; Röder, Christian; Schniewind, Bodo; Kremer, Bernd; Kalthoff, Holger; Vogel, Ilka

doi:10.1007/s00432-005-0008-1

Cited by 90 publications

(87 citation statements)

References 25 publications

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“…Khoja et al (2012) compared CellSearch and ISET in terms of CTC detection in 54 patients with pancreatic cancer, and found that ISET detects a higher number of CTCs than the CellSearch System. Polymerase chain reaction (PCR)‐based methods are also commonly used; CTCs were detected in 33.8–84% of patients by using Nested PCR with CK20 mRNA as a CTC marker in different studies (Soeth et al, 2005; Zhou et al, 2011). The method of combined immunostaining for CD45, DAPI, and CEP8‐FISH has shown great potential for CTC detection; this method yielded sensitivities of 83.33% and 76.25% for detecting CTCs in lung and ovarian cancers, respectively (Ning et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…CTCs identified based on FISH‐CEP8 were associated with a curative effect following paclitaxel and cisplatin treatment in patients with advanced gastric cancer (Li et al, 2014). Patients with colon cancer who had CTCs detected by CK20 using real‐time PCR had substantially worse OS rates compared to those without detectable CTCs (Soeth et al, 2005). At the same time, several groups have shown that CTCs are not a prognostic factor for OS in several cancers.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

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Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4′,6‐diamidino‐2‐phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45‐/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2–5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7–7.3, p < 0.001) were both associated with shorter disease‐free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2–6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8–8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

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“…Little is known about the precise mechanisms of PDAC recurrence, but it occurs especially at the site of primary resection or in the liver (3,5). This implies that at the time of diagnosis, subclinical metastases or disseminated tumor cells are already present in many patients with no evidence of advanced disease (6) and might change their biological behavior upon surgical manipulation. In accordance with the latter, we recently observed a 3-fold increase in the number of liver and spleen metastases in an orthotopic xenotransplant animal model in mice after pancreatic tumor resection (7,8).…”

Section: Introductionmentioning

confidence: 99%

Anti–Tumor Necrosis Factor Therapy Inhibits Pancreatic Tumor Growth and Metastasis

et al. 2008

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Chronic inflammation has been implicated in the pathogenesis of many severe autoimmune disorders, as well as in diabetes, pulmonary diseases, and cancer. Inflammation accompanies most solid cancers including pancreatic ductal adenocarcinoma (PDAC), one of the most fatal cancers with surgery being the only curative therapeutic approach currently available. In the present work, we investigated the role of the major proinflammatory cytokine tumor necrosis factor A (TNFA) in the malignancy of PDAC cells in vitro and in vivo. In vitro, TNFA strongly increased invasiveness of Colo357, BxPc3, and PancTuI cells and showed only moderate antiproliferative effect. TNFA treatment of mice bearing orthotopically growing PDAC tumors led to dramatically enhanced tumor growth and metastasis. Notably, we found that PDAC cells themselves secrete TNFA. Although inhibition of TNFA with infliximab or etanercept only marginally affected proliferation and invasiveness of PDAC cells in vitro, both reagents exerted strong antitumoral effects in vivo. In severe combined immunodeficient mice with orthotopically growing Colo357, BxPc3, or PancTuI tumors, human-specific anti-TNF antibody infliximab reduced tumor growth and metastasis by about 30% and 50%, respectively. Importantly, in a PDAC resection model performed with PancTuI cells, we found an even stronger therapeutic effect for both anti-TNF compounds. Infliximab and etanercept reduced the number of liver metastases by 69% and 42%, respectively, as well as volumes of recurrent tumors by 73% and 51%. Thus, tumor cell-derived TNFA plays a profound role in malignancy of PDAC, and inhibition of TNFA represents a promising therapeutic option particularly in adjuvant therapy after subtotal pancreatectomy.

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“…2. The investigators conducted the Newcastle-Ottawa Scale (NOS) criteria to assess the methodological quality of the included studies [2][3][4][5][6][7][8][9][10]. They included the study by Uchikura K et al [10], which NOS scale was just 5.…”

Section: Dear Editormentioning

confidence: 99%

Comment on Han L et al.: Prognostic value of circulating tumor cells in patients with pancreatic cancer: a meta-analysis

Zhao

Liu

2014

Tumor Biol.

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Dear EditorWe read with great interests on the recent paper by Han L et al. "Prognostic value of circulating tumor cells in patients with pancreatic cancer: a meta-analysis" published online in Tumor Biology [1]. The investigators (Han L et al.) performed a metaanalysis of nine cohort studies to assess the prognostic value of circulating tumor cells (CTC) in patients with pancreatic cancer. They concluded that CTC-positive pancreatic cancer patients may have worser progression free survival (PFS) and overall survival (OS) than CTC-negative patients. Detection of CTC in peripheral blood may be a promising biomarker for the detection and prognosis of pancreatic cancer. It is the first comprehensive meta-analysis of all eligible studies concerning the prognostic role of CTC in patients with pancreatic cancer. Nevertheless, we have several queries which we would like to communicate with the investigators.1. We think that there are some deficiencies in the literature search. The investigators just provided us some keywords and MeSH terms, while did not describe the search strategy report for databases in details, which played important roles in the meta-analysis. Manual searches were also not expressed clearly. The lack of a manual search protocol may be regarded as a drawback of this meta-analysis. If possible, we suggest that the investigators provide us a complete search protocol to strengthen the credibility of the meta-analysis. 2. The investigators conducted the Newcastle-Ottawa Scale (NOS) criteria to assess the methodological quality of the included studies [2][3][4][5][6][7][8][9][10]. They included the study by Uchikura K et al.[10], which NOS scale was just 5. Based on the NOS criteria, we are wondering whether this study could be included or not. 3. The investigators just extracted data to calculate hazard ratios (HR) for OS and PFS comparing CTC-positive to CTC-negative patients. However, they did not extract data to calculate odds ratios (OR) for objective response ratio (ORR) comparing CTC-positive to CTC-negative patients. To make the meta-analysis better, these correlations should be added in the meta-analysis. 4. The investigators clarified that "The random effect model (the DerSimonian Laird method) was conducted when there was a significant Q test with P<0.10 or I 2 >30 %." Frequently, the heterogeneity was considered by P<0.10 or I 2 >50 %. We hope that the investigators could make some explanations for the discrepancy. 5. The investigators showed forest plots for the difference in OS and PFS between CTC-positive and CTC-negative pancreatic cancer patients just in one figure. If possible, we suggest that the forest plots for OS and PFS should be showed in two single figures. 6. The investigators did not strictly follow the meta-analysis of observational studies in epidemiology (MOOSE). As a minor suggestion, adding MOOSE checklist might make this meta-analysis better.Thanks go to the investigators for their contributions to supplying us with an assessment of prognostic value of CTC in patients w...

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Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival

Cited by 90 publications

References 25 publications

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Anti–Tumor Necrosis Factor Therapy Inhibits Pancreatic Tumor Growth and Metastasis

Comment on Han L et al.: Prognostic value of circulating tumor cells in patients with pancreatic cancer: a meta-analysis

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