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Hugenschmidt H, Labori KJ, Brunborg C, Verbeke CS, Seeberg LT, Bendigtsen Schirmer C, Renolen A, Borgen E, Naume B, Wiedswang G. Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information. BMC Cancer 2020; 20:1107. [PMID: 33198661 PMCID: PMC7667773 DOI: 10.1186/s12885-020-07510-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 10/07/2020] [Indexed: 12/11/2022] Open
Abstract
Background Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). Methods Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. Results Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0–24.1), for those with benign disease OS was 101 months (95% CI: 69.4–132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3–13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). Conclusions The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed. Trial registration clinicaltrials.gov (NCT01919151).
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Affiliation(s)
- Harald Hugenschmidt
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway. .,Department of Transplantation Surgery, Oslo University Hospital, PO.Box 4950, NO-0424, Oslo, Nydalen, Norway. .,Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.
| | - Knut Jørgen Labori
- Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway
| | - Cathrine Brunborg
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Caroline Sophie Verbeke
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Lars Thomas Seeberg
- Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.,Department of Gastrointestinal Surgery, Vestfold Hospital Trust, Tønsberg, Norway
| | | | - Anne Renolen
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Elin Borgen
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Bjørn Naume
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Deparment of Oncology, Oslo University Hospital, Oslo, Norway
| | - Gro Wiedswang
- Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway
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Circulating and disseminated tumor cells in pancreatic cancer and their role in patient prognosis: a systematic review and meta-analysis. Oncotarget 2017; 8:107223-107236. [PMID: 29291024 PMCID: PMC5739809 DOI: 10.18632/oncotarget.19928] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 07/25/2017] [Indexed: 12/22/2022] Open
Abstract
Background Disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) have been postulated to seed metastases and contribute to poorer patient outcomes in many types of solid cancer. To date, no systematic reviews have examined the role of both DTCs and CTCs in pancreatic cancer. We aimed to determine the prognostic value of DTCs/CTCs in pancreatic cancer using a systematic review and meta-analysis. Materials and Methods A comprehensive literature search identified studies examining DTCs and CTCs in the bone marrow and blood of pancreatic cancer patients at diagnosis with follow-up to determine disease-free/progression-free survival (DFS/PFS) and overall survival (OS). Statistical analyses were performed to determine the hazard ratio (HR) of DTCs/CTCs on DFS/PFS and OS. Results The literature search identified 16 articles meeting the inclusion criteria. The meta-analysis demonstrated statistically significant HR differences in DFS/PFS (HR = 1.93, 95% CI 1.19–3.11, P = 0.007) and OS (HR = 1.84, 95% CI 1.37–2.45, P =< 0.0001), indicating patients with detectable DTCs/CTCs at diagnosis have worse prognoses. Subgroup analyses suggested CTCs in the peripheral blood (HR =2.03) were more indicative of poor OS prognosis than DTCs in the bone marrow (HR = 1.91), although the difference between these was not statistically significant. Positivity of the CellSearch detection method for DTC/CTC had the highest correlation with decreased OS (HR = 2.79) while immunodetection (HR = 1.91) and RT-PCR (HR = 1.25) were less effective in determining prognosis. Conclusion The detection of DTCs/CTCs at diagnosis is associated with poorer DFS/PFS and OS in pancreatic cancer.
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Effenberger KE, Schroeder C, Eulenburg C, Reeh M, Tachezy M, Riethdorf S, Vashist YK, Izbicki JR, Pantel K, Bockhorn M. Disseminated tumor cells in pancreatic cancer-an independent prognosticator of disease progression and survival. Int J Cancer 2011; 131:E475-83. [PMID: 21932421 DOI: 10.1002/ijc.26439] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2011] [Accepted: 08/31/2011] [Indexed: 12/23/2022]
Abstract
Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 3-5%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of disseminated tumor cells (DTC) in bone marrow, a reservoir for early DTC potentially contributing to metastatic progression, of pancreatic cancer patients. After exclusion of patients with different postsurgery diagnosis or missing DTC status (n = 40) a total of 175 patients remained for final analyses. One-hundred and nineteen patients were male and 96 female with a median age of 67 years, 96 patients underwent complete resection. Bone marrow aspirates taken at primary surgery were analyzed for DTC by an immunocytochemical cytokeratin assay and correlated to survival data. Overall 13.7% of patient samples (24/175) harbored DTC in their bone marrow. Histopathological parameters did not correlate significantly. Univariate survival analysis revealed a borderline significant correlation between DTC and decreased progression-free survival (p = 0.069), and was significant for overall survival (p = 0.036). Regarding patients with resected tumors, the respective p-values were 0.058 for progression-free and 0.016 for overall survival. Importantly, the prognostic influence was independent from other risk factors as shown by multivariate analyses for progression-free (p = 0.030, HR: 2.057; CI (95%): 1.073-3.943) and overall survival (p = 0.006, HR: 2.283; CI (95%): 1.260-4.135). The presence of DTC in bone marrow is a strong and independent prognostic factor of survival in patients with pancreatic cancer. Thus, bone-targeting may be a new future therapeutic option for DTC-positive patients.
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Affiliation(s)
- Katharina E Effenberger
- Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Germany.
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Athanassiadou P, Grapsa D. Bone marrow micrometastases in different solid tumors: Pathogenesis and importance. Surg Oncol 2008; 17:153-64. [PMID: 18511264 DOI: 10.1016/j.suronc.2008.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
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Occult disseminated tumor cells in lymph nodes of patients with gastric carcinoma. A critical appraisal of assessment and relevance. Langenbecks Arch Surg 2008; 394:105-13. [DOI: 10.1007/s00423-008-0369-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2008] [Accepted: 06/10/2008] [Indexed: 12/22/2022]
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Athanassiadou P, Grapsa D. Recent advances in the detection of bone marrow micrometastases: A promising area for research or just another false hope? A review of the literature. Cancer Metastasis Rev 2007; 25:507-19. [PMID: 17160555 DOI: 10.1007/s10555-006-9030-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The presence of early disseminated tumor cells (DTC), otherwise termed micrometastases or minimal residual disease, in the bone marrow (BM), or other secondary compartments, such as the blood and the lymph nodes, is the main reason for recurrence of patients with early stage epithelial cancers after "curative" resection of the primary tumor. There is increasing evidence, that the detection of DTC in BM aspirates may provide additional and independent prognostic information and aid in the stratification of these patients for adjuvant clinical treatment. However, the clinical relevance of micrometastases has not yet been firmly established. In addition, the molecular events and interactions that prevail in early metastatic disease and determine the formation or not of overt metastases remain poorly understood. The methods currently used for the detection of micrometastatic cells include extremely sensitive immunocytochemical and molecular assays, often in conjunction with enrichment techniques for the purification of tumor cells and additional increase of their sensitivity. Nevertheless, the specificity of these methods is mostly inadequate. After the impressive advances of molecular cytogenetics, a highly accurate and global assessment of the genetic status of tumors is now possible. Therefore, the greatest challenge of our time is the application of these novel technologies for the clarification of the key molecular events that initiate metastatic spread. This will further enable us to identify the highly specific and sensitive diagnostic and prognostic markers as well as the therapeutic targets which are so urgently needed.
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Affiliation(s)
- Pauline Athanassiadou
- Pathology Laboratory-Cytology Department, Medical School, Athens University, 75 Mikras Asias Str., 11527, Athens, Greece
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Hoffmann K, Kerner C, Wilfert W, Mueller M, Thiery J, Hauss J, Witzigmann H. Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood, bone marrow and peritoneal lavage of pancreatic carcinoma patients. World J Gastroenterol 2007; 13:257-63. [PMID: 17226905 PMCID: PMC4065954 DOI: 10.3748/wjg.v13.i2.257] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [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 evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas.
METHODS: Sixty-eight patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non-pancreatic benign surgical diseases (n = 15, control group) were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR.
RESULTS: CK-19 mRNA expression was increased in 24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the patients with pancreatic cancer. In 15 (40%) of the patients with pancreatic cancer, disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3). Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancer patients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis.
CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocar-cinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.
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MESH Headings
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/blood
- Bone Marrow/pathology
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/pathology
- Humans
- Keratin-19/genetics
- Neoplastic Cells, Circulating/chemistry
- Neoplastic Cells, Circulating/pathology
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/pathology
- Peritoneal Lavage
- RNA, Messenger/analysis
- RNA, Messenger/blood
- RNA, Neoplasm/analysis
- RNA, Neoplasm/blood
- Reverse Transcriptase Polymerase Chain Reaction/methods
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Affiliation(s)
- Katrin Hoffmann
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Germany.
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Schmitz-Winnenthal FH, Volk C, Z'graggen K, Galindo L, Nummer D, Ziouta Y, Bucur M, Weitz J, Schirrmacher V, Büchler MW, Beckhove P. High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients. Cancer Res 2005; 65:10079-87. [PMID: 16267034 DOI: 10.1158/0008-5472.can-05-1098] [Citation(s) in RCA: 122] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Pancreatic cancer is characterized by aggressive growth and treatment resistance. New approaches include immunotherapeutic strategies but the type and extent of spontaneous immune responses against tumor antigens remains unclear. A dominance of TH2 cytokines in patients' sera reported previously suggests systemic tumor-induced immunosuppression, potentially inhibiting the induction of tumor-reactive T cells. We characterized the localization, frequencies, and functional potential of spontaneously induced memory T cells specific for individual tumor antigens or the tumor-associated antigen mucin-1 in the peripheral blood and bone marrow of 41 pancreatic cancer patients. We found high numbers of tumor-reactive T cells in all bone marrow samples and in 50% of the blood samples. These cells secreted the TH1 cytokine IFN-gamma rather than TH2 cytokines upon stimulation with tumor antigens. Although consistently induced during pancreatic cancer, T cells specific for pancreatic antigens were not detected during chronic pancreatitis, suggesting that their evaluation may be of diagnostic use in both diseases. Freshly isolated T cells from cancer patients recognized autologous tumor cells and rejected them in vitro and in a xenotransplant model in vivo, suggesting their therapeutic potential. Thus, tumor antigen-specific T cell responses occur regularly during pancreatic cancer disease and lead to enrichment of tumor cell-reactive memory T cells in the bone marrow. The bone marrow can therefore be considered an important organ for antitumor immune responses in pancreatic cancer.
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Soeth E, Grigoleit U, Moellmann B, Röder C, Schniewind B, Kremer B, Kalthoff H, Vogel I. Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival. J Cancer Res Clin Oncol 2005; 131:669-76. [PMID: 16136352 DOI: 10.1007/s00432-005-0008-1] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2005] [Accepted: 05/09/2005] [Indexed: 12/27/2022]
Abstract
PURPOSE This prospective study evaluates the diagnostic potential of Cytokeratin 20 (CK 20) RT-PCR for the detection of disseminated tumor cells in bone marrow and blood of a large cohort of patients with ductal adenocarcinoma of the pancreas and the prognostic value on overall survival prediction. METHODS Between 1994 and 2003, 172 patients (83 male, 89 female; 13-82 years) with pancreatic ductal adenocarcinoma underwent surgery. Bone marrow samples and venous blood were taken preoperatively and analyzed for disseminated tumor cells by nested CK 20 RT-PCR. RESULTS Disseminated tumor cells were detected in 81 (47.1%) of the 172 patients in the bone marrow and/or the venous blood. Overall, in 45 of the 135 (33.3%) bone marrow samples and in 52 of the 154 (33.8%) blood samples, CK 20 positive cells were detected. Detection rates increased with the UICC-tumor stage. According to Kaplan-Meier, univariate survival analysis of all 172 patients (n = 78 R0-; n = 18 R1- and n = 5 R2-resected; n = 71 palliative surgery) showed a statistically significant relationship of overall survival to radicality of the operation (P < 0.0001), the UICC-stage of the tumors (P = 0.0011) and the detection of disseminated tumor cells in bone marrow and/or venous blood (P = 0.05). Patients with well- and moderately- differentiated tumors (G1 and G2) had a significantly longer survival (P = 0.045) than patients suffering from poorly differentiated tumors (G3). A positive CK 20 status in the bone marrow and/or blood within the group of patients with G1 and G2 tumors had a significantly negative prognostic impact on their survival (P = 0.046). CONCLUSIONS Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK 20 RT-PCR. Detection rates are stage dependent, and survival analysis demonstrated statistically relevant data. From a clinical point of view, this finding is especially noteworthy for the group of well- and moderately-differentiated tumors.
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Affiliation(s)
- Edlyn Soeth
- Section Molecular Oncology, Department for General Surgery and Thoracic Surgery, University Clinic Schleswig-Holstein, Campus Kiel, Germany
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Andersson R, Vagianos CE, Williamson RCN. Preoperative staging and evaluation of resectability in pancreatic ductal adenocarcinoma. HPB (Oxford) 2004; 6:5-12. [PMID: 18333037 PMCID: PMC2020655 DOI: 10.1080/13651820310017093] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cancer of the pancreas is a common disease, but the large majority of patients have tumours that are irresectable at the time of diagnosis. Moreover, patients whose tumours are clearly beyond surgical cure are best treated non-operatively, if possible, by relief of biliary obstruction and percutaneous biopsy to confirm the diagnosis and then consideration of oncological treatment, notably chemotherapy. These facts underline the importance of a standard protocol for the preoperative determination of operability (is it worth operating?) and resectability (is there a chance that the tumour can be removed?). Recent years have seen the advent of many new techniques, both radiological and endoscopic, for the diagnosis and staging of pancreatic cancer. It would be impracticable in time and cost to submit every patient to every test. This review will evaluate the available techniques and offer a possible algorithm for use in routine clinical practice. DISCUSSION In deciding whether to operate with a view to resecting a pancreatic cancer, the surgeon must take into account factors related to the patient, the tumour and the institution and team entrusted with the patient's care. Patient-related factors include age, general health, pain and the presence or absence of malnutrition and an acute phase inflammatory response. Tumour-related factors include tumour size and evidence of spread, whether to adjacent organs (notably major blood vessels) or further afield. Hospital-related factors chiefly concern the volume of pancreatic cancer treated and thus the experience of the whole team. Determination of resectability is heavily dependent upon detailed imaging. Nowadays conventional ultrasonography can be supplemented by endoscopic, laparoscopic and intra-operative techniques. Computed tomography (CT) remains the single most useful staging modality, but MRI continues to improve. PET scanning may demonstrate unsuspected metastases and likewise laparoscopy. Diagnostic cholangiography can be performed more easily by MR techniques than by endoscopy, but ERCP is still valuable for preoperative biliary decompression in appropriate patients. The role of angiography has declined. Percutaneous biopsy and peritoneal cytology are not usually required in patients with an apparently resectable tumour. The prognostic value of tumour marker levels and bone marrow biopsy is yet to be established. Preoperative chemotherapy or chemoradiation may have a role in down-staging an irresectable tumour sufficiently to render it resectable. Selective use of diagnostic laparoscopy staging is potentially helpful in determination of resectability. Laparotomy remains the definitive method for determining the resectability of pancreatic cancer, with or without portal vein resection, and should be undertaken in suitable patients without clear-cut evidence of irresectability.
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Affiliation(s)
- R Andersson
- Department of Surgery, Lund University Hospital, Lund, Sweden.
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Velanovich V. The effects of staging laparoscopy on trocar site and peritoneal recurrence of pancreatic cancer. Surg Endosc 2003; 18:310-3. [PMID: 14691701 DOI: 10.1007/s00464-003-8909-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2003] [Accepted: 08/26/2003] [Indexed: 10/26/2022]
Abstract
BACKGROUND Staging laparoscopy (SL) has been used to assess resectability of patients with pancreatic cancer. It has lead to increased resectability rates and decreased morbidity. However, experimental data suggests that laparoscopy and peritoneal insufflation can promote tumor growth and potential recurrence. Few clinical data exist to allow assessment of whether these theoretical concerns translate into clinical problems. The purpose of this study was to determine if SL increases the incidence of trocar-site and peritoneal recurrence of pancreatic cancer. METHODS A retrospective review of all patients evaluated for pancreatic cancer from 1996 to 2001, inclusive, was included in this study. Patients were divided into five groups: nonoperative management (NM), SL followed by resection (SL-R), SL without resection (SL-NR), exploratory laparotomy with resection (EL-R), and exploratory laparotomy without resection (EL-NR). Patient records were assessed for postoperative occurrence of carcinomatosis and/or malignant ascites, trocar- or incisional-site recurrence, use of postoperative chemotherapy or radiation therapy, and survival. RESULTS A total of 235 patients were included. Peritoneal progression of disease: NM 15.9%, SL 24.2%, EL 31.6% ( p = 0.03). Trocar/incisional recurrence: SL 3.0%, EL 3.9% ( p = NS). Use of chemotherapy/radiotherapy: NM 29.4%, SL-R 76.5%, SL-NR 62.5%, EL-R 69.6%, EL-NR 41.5%. Median survival (months): NM 3; SL-R 15, EL-R 10 ( p = NS); SL-NR 6, EL-NR 5 ( p = NS). CONCLUSION SL does not increase the occurrence of trocar-site disease or peritoneal disease progression of pancreatic cancer. Patients who are found not to be resectable by SL are more likely to receive postoperative treatment. However, this does not appear to affect survival greatly. Nevertheless, avoidance of nontherapeutic laparotomy is worthwhile in these patients.
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Affiliation(s)
- V Velanovich
- Division of General Surgery, Henry Ford Hospital, 2799 West Grand Boulevard., Detroit, MI 48202, USA.
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Vlems FA, Ruers TJM, Punt CJA, Wobbes T, van Muijen GNP. Relevance of disseminated tumour cells in blood and bone marrow of patients with solid epithelial tumours in perspective. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2003; 29:289-302. [PMID: 12711279 DOI: 10.1053/ejso.2002.1394] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Currently-used systems to predict prognosis in patients with solid epithelial tumours after surgical resection of the tumour do not give any guarantees for the individual patient. In this respect the clinical relevance of the presence of disseminated tumour cells in blood and bone marrow has been frequently studied. Because of growing awareness that information on merely the presence of disseminated tumour cells is not sufficient for prognostic and therapeutic purposes, attention for characterization of disseminated tumour cells has increased. Numerous reviews have already been published on the detection and clinical relevance of disseminated tumour cells. Therefore, this paper will mainly focus on the biological significance of these cells and discusses the (in)efficiency of the metastatic process, the genotypic and phenotypic characteristics of disseminated tumour cells, and their structure of appearance. Despite the fact that information gained on the several individual aspects is substantial, it did not render any solid solutions for individual patient management yet. Hence, a combined approach of several aspects of disseminated tumour cells together with characteristics and behaviour of the primary tumour is needed to substantially improve our knowledge on the role of disseminated tumour cells in the complex process of tumour metastasis.
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Affiliation(s)
- F A Vlems
- Department of Surgery, University Medical Centre Nijmegen, 6500 HB, Nijmegen, The Netherlands.
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