PDF herunterladen
Z Gastroenterol 2011; 49(2): 225-233
DOI: 10.1055/s-0029-1245849
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Minimale Resterkrankung beim Magenkarzinom – eine Übersicht

Minimal Residual Disease (MRD) in Gastric Carcinoma – an OverviewB. Garlipp1 , R. Steinert2 , H. Lippert1 , F. Meyer1
  • 1Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Magdeburg
  • 2Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Evangelisches Krankenhaus Bielefeld
Weitere Informationen

Publikationsverlauf

Manuskript eingetroffen: 21.8.2010

Manuskript akzeptiert: 19.10.2010

Publikationsdatum:
04. Februar 2011 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Zusammenfassung

Die Prognose des Magenkarzinoms, insbesondere im fortgeschrittenen Stadium, ist trotz der bedeutenden Entwicklungen der letzten Jahre noch immer als schlecht anzusehen. Die Tatsache, dass auch potenziell kurativ behandelte Patienten ohne nachweisbaren Tumorrest in einem erheblichen Teil der Fälle Metastasen entwickeln und adjuvante Therapien dieses Risiko senken können, weist darauf hin, dass bei diesen Patienten Mikrometastasen und isolierte Tumorzellen („minimal residual disease”, MRD) vorliegen, die mit konventionellen Methoden nicht erfassbar sind und zum Ausgangspunkt für Rezidive werden können. Ein Nachweis der MRD in verschiedenen anatomischen Kompartimenten könnte demnach Bedeutung für eine stärkere Individualisierung der Therapie erlangen. Die Untersuchungsmethodik und die Ergebnisbeurteilung sind jedoch bis heute nicht standardisiert und die vorliegenden Studien daher meist nicht vergleichbar, sodass die MRD-Diagnostik zumindest im europäischen und angloamerikanischen Raum bisher für keines der 4 Kompartimente Lymphknoten, Peritonealflüssigkeit, peripheres Blut und Knochenmark Eingang in die klinische Routine gefunden hat. Die besten Daten für den MRD-Nachweis beim Magenkarzinom liegen für die Peritoneallavage vor. Diese Untersuchung ist an einigen japanischen Zentren bereits etabliert und wird für therapeutische Entscheidungen genutzt (z. B. Indikation zur intraperitonealen Chemotherapie). Der MRD-Nachweis in Lymphknoten wird im Zusammenhang mit dem Sentinel-Lymphknoten-Konzept weiter evaluiert werden und hier vor allem bei Patienten mit frühen Tumorstadien, die normalerweise nicht in multimodalen Konzepten behandelt werden, möglicherweise therapeutische Relevanz erlangen. Für Tumorzellen im peripheren Blut und im Knochenmark zeichnet sich ab, dass diese nur unter bestimmten Voraussetzungen zur Metastasenbildung fähig sind. Zukünftige Untersuchungen werden sich daher neben dem reinen Nachweis von Tumorzellen vor allem auf deren molekulare Charakterisierung und auf die Definition von molekularen Prädiktoren für das Metastasierungspotenzial dieser Zellen konzentrieren. Neben Anwendungen in der Diagnostik und der Prognosebeurteilung könnten sich daraus direkte Auswirkungen auf die Entwicklung zielgerichteter Therapien ergeben.

Abstract

Despite recent developments in therapy for gastric cancer, the prognosis of this disease remains poor in advanced stages. In many cases even curatively treated patients without any residual tumour develop metachronous metastases. As in other solid tumours, adjuvant therapies can reduce the metastatic risk, which implies that some of these patients harbour isolated tumour cells or micrometastases (minimal residual disease, MRD) that are undetectable by radiological imaging and conventional histopathology but can still be the cause of tumour recurrence. Therefore, reliable methods for diagnosing MRD would be desirable for individually tailoring therapy for these patients. Unfortunately, testing methods for MRD and interpretation of their results are not standardised and studies published on this topic are difficult to interpret due to methodological differences and small sample sizes. As of now, testing for MRD has not become relevant in clinical routine for any of the anatomic compartments lymph nodes, peritoneal lavage fluid, peripheral blood, and bone marrow in the Western hemisphere. Most reliable data on MRD in gastric cancer patients have been reported for peritoneal lavage fluid. In some centres in Japan, this test is routinely being used for making therapeutic decisions, e. g., on the use of intraperitoneal chemotherapy. MRD in resected lymph nodes will be further evaluated in the context of the sentinel lymph node concept and possibly be employed for designing individualised therapy for patients in early disease stages who are not routinely candidates for multimodal treatment. As for tumour cells in peripheral blood and in bone marrow, studies suggest that these cells are only able to form metastases in the presence of certain molecular factors. Therefore, rather than simply confirming the existence of isolated tumour cells in blood or bone marrow, future studies should concentrate on defining their molecular characteristics and the conditions required for their metastatic potential. This may gain relevance in diagnostics and prognostic evaluation of individual patients as well as in the development of targeted therapies directly interfering with the metastatic process.

Schlüsselwörter

minimale Resterkrankung - Magenkarzinom - Mikrometastasen - isolierte Tumorzellen

Key words

minimal residual disease - gastric carcinoma - micrometastasis - isolated tumor cells

Literatur

  • 1 Cunningham D, Allum W H, Stenning S P et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.  N Engl J Med. 2006;  355 11-20
    Suche in Google Scholar
  • 2 Boige V, Pignon J, Saint-Aubert B et al. Final results of a randomized trial comparing preoperative 5-fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial. J Clin Oncol, ASCO Annual Meeting Proceedings Part I. Vol. 25, No. 18S (June 20 Supplement), 2007: 4510
    Suche in Google Scholar
  • 3 Songun I, Putter H, Kranenbarg E M et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D 1D2 trial.  Lancet Oncol. 2010;  11 439-449
    Suche in Google Scholar
  • 4 Yuasa N, Nimura Y. Survival after surgical treatment of early gastric cancer, surgical techniques, and long-term survival.  Langenbecks Arch Surg. 2005;  390 286-293
    Suche in Google Scholar
  • 5 Marrelli D, Roviello F, Manzoni G de et al. Different patterns of recurrence in gastric cancer depending on Lauren’s histological type: longitudinal study.  World J Surg. 2002;  26 1160-1165
    Suche in Google Scholar
  • 6 Knebel Doeberitz von M, Koch M, Weitz J et al. Diagnosis and significance of minimal residual disease in patients with colorectal carcinoma.  Zentralbl Chir. 2000;  125 (Suppl 1) 15-19
    Suche in Google Scholar
  • 7 Bonadonna G, Gasparini M, Rossi A. Adjuvant therapies of postsurgical minimal residual disease.  Recent Results Cancer Res. 1980;  74 8-25
    Suche in Google Scholar
  • 8 Piñiero A, Giménez J, Vidal-Sicart S et al. Selective sentinel lymph node biopsy and primary systemic therapy in breast cancer.  Tumori. 2010;  96 17-23
    Suche in Google Scholar
  • 9 Maughan K L, Lutterbie M A, Ham P S. Treatment of breast cancer.  Am Fam Physician. 2010;  81 1339-1346
    Suche in Google Scholar
  • 10 Giuliano A E, Dale P S, Turner R R et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy.  Ann Surg. 1995;  222 394-399 ; discussion 399 – 401
    Suche in Google Scholar
  • 11 Moroi Y. Significance of sentinel lymph node biopsy in malignant melanoma: overview of international data.  Int J Clin Oncol. 2009;  14 485-489
    Suche in Google Scholar
  • 12 Gretschel S, Bembenek A, Schulze T et al. Minimal residual tumor in gastrointestinal carcinoma. Relevance to prognosis and oncologic surgical consequences.  Chirurg. 2006;  77 1104-1117
    Suche in Google Scholar
  • 13 Nicastri D G, Doucette J T, Godfrey T E et al. Is occult lymph node disease in colorectal cancer patients clinically significant? A review of the relevant literature.  J Mol Diagn. 2007;  9 563-571
    Suche in Google Scholar
  • 14 Edge S B, Byrd D R, Compton C C et al. AJCC Cancer Staging Manual. Springer-Verlag. Berlin; 2010
    Suche in Google Scholar
  • 15 Jiang W G, Puntis M C, Hallett M B. Molecular and cellular basis of cancer invasion and metastasis: implications for treatment.  Br J Surg. 1994;  81 1576-1590
    Suche in Google Scholar
  • 16 Hermanek P. Disseminated tumor cells versus micrometastasis: definitions and problems.  Anticancer Res. 1999;  19 2771-2774
    Suche in Google Scholar
  • 17 Hermanek P, Hutter R V, Sobin L H et al. International Union Against Cancer. Classification of isolated tumor cells and micrometastasis.  Cancer. 1999;  86 2668-2673
    Suche in Google Scholar
  • 18 Galus R, Wlodarski K. Cytokeratin detection as a diagnostic tool in oncology.  Pol Merkur Lekarski (Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego). 2007;  23 209-211
    Suche in Google Scholar
  • 19 Pantel K, Knebel Doeberitz von M. Detection and clinical relevance of micrometastatic cancer cells.  Curr Opin Oncol. 2000;  12 95-101
    Suche in Google Scholar
  • 20 Pantel K, Schlimok G, Angstwurm M et al. Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow.  J Hematother. 1994;  3 165-173
    Suche in Google Scholar
  • 21 Winter M J, Nagtegaal I D, Krieken J HJM et al. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology.  Am J Pathol. 2003;  163 2139-2148
    Suche in Google Scholar
  • 22 Bauer K D, La Torre-Bueno van J, Diel de I J et al. Reliable and sensitive analysis of occult bone marrow metastases using automated cellular imaging.  Clin Cancer Res. 2000;  6 3552-3559
    Suche in Google Scholar
  • 23 Zach O, Lutz D. Tumor cell detection in peripheral blood and bone marrow.  Curr Opin Oncol. 2006;  18 48-56
    Suche in Google Scholar
  • 24 Paterlini-Brechot P, Benali N L. Circulating tumor cells (CTC) detection: clinical impact and future directions.  Cancer Lett. 2007;  253 180-204
    Suche in Google Scholar
  • 25 Pinzani P, Salvadori B, Simi L et al. Isolation by size of epithelial tumor cells in peripheral blood of patients with breast cancer: correlation with real-time reverse transcriptase-polymerase chain reaction results and feasibility of molecular analysis by laser microdissection.  Hum Pathol. 2006;  37 711-718
    Suche in Google Scholar
  • 26 Wong N S, Kahn H J, Zhang L et al. Prognostic significance of circulating tumour cells enumerated after filtration enrichment in early and metastatic breast cancer patients.  Breast Cancer Res Treat. 2006;  99 63-69
    Suche in Google Scholar
  • 27 Allard W J, Matera J, Miller M C et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.  Clin Cancer Res. 2004;  10 6897-6904
    Suche in Google Scholar
  • 28 Lee M S, Chang K S, Cabanillas F et al. Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification.  Science. 1987;  237 175-178
    Suche in Google Scholar
  • 29 Gribben J G, Freedman A S, Neuberg D et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma.  N Engl J Med. 1991;  325 1525-1533
    Suche in Google Scholar
  • 30 Roth M S, Antin J H, Ash R et al. Prognostic significance of Philadelphia chromosome-positive cells detected by the polymerase chain reaction after allogeneic bone marrow transplant for chronic myelogenous leukemia.  Blood. 1992;  79 276-282
    Suche in Google Scholar
  • 31 Datta Y H, Adams P T, Drobyski W R et al. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction.  J Clin Oncol. 1994;  12 475-482
    Suche in Google Scholar
  • 32 Hibi K, Robinson C R, Booker S et al. Molecular detection of genetic alterations in the serum of colorectal cancer patients.  Cancer Res. 1998;  58 1405-1407
    Suche in Google Scholar
  • 33 Hsieh J, Lin S, Chang M et al. APC, K-ras, and p53 gene mutations in colorectal cancer patients: correlation to clinicopathologic features and postoperative surveillance.  Am Surg. 2005;  71 336-343
    Suche in Google Scholar
  • 34 Kobayashi Y, Yoshinouchi M, Tianqi G et al. Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes.  Clin Cancer Res. 1998;  4 979-983
    Suche in Google Scholar
  • 35 Müller P, Schlimok G. Bone marrow „micrometastases” of epithelial tumors: detection and clinical relevance.  J Cancer Res Clin Oncol. 2000;  126 607-618
    Suche in Google Scholar
  • 36 Ghossein R A, Bhattacharya S, Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors.  Clin Cancer Res. 1999;  5 1950-1960
    Suche in Google Scholar
  • 37 Mitelman F, Johansson B, Mertens F. The impact of translocations and gene fusions on cancer causation.  Nat Rev Cancer. 2007;  7 233-245
    Suche in Google Scholar
  • 38 Willeke F, Ridder R, Mechtersheimer G et al. Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications.  Clin Cancer Res. 1998;  4 1779-1784
    Suche in Google Scholar
  • 39 Khair G, Monson J RT, Greenman J. Epithelial molecular markers in the peripheral blood of patients with colorectal cancer.  Dis Colon Rectum. 2007;  50 1188-1203
    Suche in Google Scholar
  • 40 Castells A, Boix L, Bessa X et al. Detection of colonic cells in peripheral blood of colorectal cancer patients by means of reverse transcriptase and polymerase chain reaction.  Br J Cancer. 1998;  78 1368-1372
    Suche in Google Scholar
  • 41 Kim J J, Song K Y, Hur H et al. Lymph node micrometastasis in node negative early gastric cancer.  Eur J Surg Oncol. 2009;  35 409-414
    Suche in Google Scholar
  • 42 Kim J, Park J, Jung C et al. The significances of lymph node micrometastasis and its correlation with E-cadherin expression in pT1-T3N0 gastric adenocarcinoma.  J Surg Oncol. 2008;  97 125-130
    Suche in Google Scholar
  • 43 Yun H Y, Bandou E, Kawamura T et al. Influence of micrometastasis on N stage in gastric cancer and clinical application.  J Exp Clin Cancer Res. 2005;  24 531-539
    Suche in Google Scholar
  • 44 Sonoda H, Yamamoto K, Kushima R et al. Detection of lymph node micrometastasis in pN0 early gastric cancer: efficacy of duplex RT-PCR with MUC2 and TFF1 in mucosal cancer.  Oncol Rep. 2006;  16 411-416
    Suche in Google Scholar
  • 45 Yonemura Y, Endo Y, Hayashi I et al. Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer.  Br J Surg. 2007;  94 731-736
    Suche in Google Scholar
  • 46 Fukagawa T, Sasako M, Shimoda T et al. The prognostic impact of isolated tumor cells in lymph nodes of T 2N0 gastric cancer: comparison of American and Japanese gastric cancer patients.  Ann Surg Oncol. 2009;  16 609-613
    Suche in Google Scholar
  • 47 Yanagita S, Natsugoe S, Uenosono Y et al. Sentinel node micrometastases have high proliferative potential in gastric cancer.  J Surg Res. 2008;  145 238-243
    Suche in Google Scholar
  • 48 Arigami T, Natsugoe S, Uenosono Y et al. Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction.  Ann Surg. 2006;  243 341-347
    Suche in Google Scholar
  • 49 Uenosono Y, Natsugoe S, Ehi K et al. Detection of sentinel nodes and micrometastases using radioisotope navigation and immunohistochemistry in patients with gastric cancer.  Br J Surg. 2005;  92 886-889
    Suche in Google Scholar
  • 50 Fujiwara Y, Doki Y, Taniguchi H et al. Genetic detection of free cancer cells in the peritoneal cavity of the patient with gastric cancer: present status and future perspectives.  Gastric Cancer. 2007;  10 197-204
    Suche in Google Scholar
  • 51 Bando E, Yonemura Y, Takeshita Y et al. Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma.  Am J Surg. 1999;  178 256-262
    Suche in Google Scholar
  • 52 Rosenberg R, Nekarda H, Bauer P et al. Free peritoneal tumour cells are an independent prognostic factor in curatively resected stage IB gastric carcinoma.  Br J Surg. 2006;  93 325-331
    Suche in Google Scholar
  • 53 Bonenkamp J J, Songun I, Hermans J et al. Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer.  Br J Surg. 1996;  83 672-674
    Suche in Google Scholar
  • 54 Bentrem D, Wilton A, Mazumdar M et al. The value of peritoneal cytology as a preoperative predictor in patients with gastric carcinoma undergoing a curative resection.  Ann Surg Oncol. 2005;  12 347-353
    Suche in Google Scholar
  • 55 Ribeiro U, Safatle-Ribeiro A V, Zilberstein B et al. Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection?.  J Gastrointest Surg. 2006;  10 170-176, discussion 176 – 177
    Suche in Google Scholar
  • 56 Ishii T, Fujiwara Y, Ohnaka S et al. Rapid genetic diagnosis with the transcription-reverse transcription concerted reaction system for cancer micrometastasis.  Ann Surg Oncol. 2004;  11 778-785
    Suche in Google Scholar
  • 57 Kodera Y, Nakanishi H, Ito S et al. Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigen.  Gastric Cancer. 2005;  8 142-148
    Suche in Google Scholar
  • 58 Bessa X, Piñol V, Castellví-Bel S et al. Prognostic value of postoperative detection of blood circulating tumor cells in patients with colorectal cancer operated on for cure.  Ann Surg. 2003;  237 368-375
    Suche in Google Scholar
  • 59 Ikeguchi M, Kaibara N. Detection of circulating cancer cells after a gastrectomy for gastric cancer.  Surg Today. 2005;  35 436-441
    Suche in Google Scholar
  • 60 Smith H W, Marshall C J. Regulation of cell signalling by uPAR.  Nat Rev Mol Cell Biol. 2010;  11 23-36
    Suche in Google Scholar
  • 61 Kita Y, Fukagawa T, Mimori K et al. Expression of uPAR mRNA in peripheral blood is a favourite marker for metastasis in gastric cancer cases.  Br J Cancer. 2009;  100 153-159
    Suche in Google Scholar
  • 62 Kaplan R N, Riba R D, Zacharoulis S et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche.  Nature. 2005;  438 820-827
    Suche in Google Scholar
  • 63 Mimori K, Fukagawa T, Kosaka Y et al. Hematogenous metastasis in gastric cancer requires isolated tumor cells and expression of vascular endothelial growth factor receptor-1.  Clin Cancer Res. 2008;  14 2609-2616
    Suche in Google Scholar
  • 64 Mimori K, Fukagawa T, Kosaka Y et al. A large-scale study of MT 1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases.  Ann Surg Oncol. 2008;  15 2934-2942
    Suche in Google Scholar
  • 65 Hildenbrand R, Allgayer H, Marx A et al. Modulators of the urokinase-type plasminogen activation system for cancer.  Expert Opin Investig Drugs. 2010;  19 641-652
    Suche in Google Scholar
  • 66 Mekkawy A H, Morris D L, Pourgholami M H. Urokinase plasminogen activator system as a potential target for cancer therapy.  Future Oncol. 2009;  5 1487-1499
    Suche in Google Scholar
  • 67 Lindemann F, Schlimok G, Dirschedl P et al. Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients.  Lancet. 1992;  340 685-689
    Suche in Google Scholar
  • 68 Jauch K W, Heiss M M, Gruetzner U et al. Prognostic significance of bone marrow micrometastases in patients with gastric cancer.  J Clin Oncol. 1996;  14 1810-1817
    Suche in Google Scholar
  • 69 Thorban S, Roder J D, Nekarda H et al. Immunocytochemical detection of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma.  J Natl Cancer Inst. 1996;  88 1222-1227
    Suche in Google Scholar
  • 70 Schlimok G, Funke I, Pantel K et al. Micrometastatic tumour cells in bone marrow of patients with gastric cancer: methodological aspects of detection and prognostic significance.  Eur J Cancer. 1991;  27 1461-1465
    Suche in Google Scholar
  • 71 Putz E, Witter K, Offner S et al. Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases.  Cancer Res. 1999;  59 241-248
    Suche in Google Scholar
  • 72 Wang G, Li Y, Yu Y et al. Detection of disseminated tumor cells in bone marrow of gastric cancer using magnetic activated cell sorting and fluorescent activated cell sorting.  J Gastroenterol Hepatol. 2009;  24 299-306
    Suche in Google Scholar
  • 73 Wang G, Wang S, Li Y et al. Detecting bone marrow micrometastasis of gastric cancer by magnetic activated cell sorting combined with fluorescent activated cell sorting.  Ai Zheng. 2005;  24 605-610
    Suche in Google Scholar
  • 74 Iwatsuki M, Mimori K, Fukagawa T et al. The Clinical Significance of Vimentin-Expressing Gastric Cancer Cells in Bone Marrow.  Ann Surg Oncol. 2010;  17 (9) 2526-2533
    Suche in Google Scholar
  • 75 Iwatsuki M, Fukagawa T, Mimori K et al. Bone marrow and peripheral blood expression of ID 1 in human gastric carcinoma patients is a bona fide indicator of lymph node and peritoneal metastasis.  Br J Cancer. 2009;  100 1937-1942
    Suche in Google Scholar
  • 76 Kolodziejczyk P, Pituch-Noworolska A, Drabik G et al. The effects of preoperative chemotherapy on isolated tumour cells in the blood and bone marrow of gastric cancer patients.  Br J Cancer. 2007;  97 589-592
    Suche in Google Scholar
  • 77 Ryan P, McCarthy S, Kelly J et al. Prevalence of bone marrow micrometastases in esophagogastric cancer patients with and without neoadjuvant chemoradiotherapy.  J Surg Res. 2004;  117 121-126
    Suche in Google Scholar
  • 78 Arigami T, Natsugoe S, Uenosono Y et al. CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer.  Int J Oncol. 2009;  35 19-24
    Suche in Google Scholar
  • 79 Ishii K, Kinami S, Funaki K et al. Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer.  J Exp Clin Cancer Res. 2008;  27 7-13
    Suche in Google Scholar
  • 80 Morita D, Tsuda H, Ichikura T et al. Analysis of sentinel node involvement in gastric cancer.  Clin Gastroenterol Hepatol. 2007;  5 1046-1052
    Suche in Google Scholar
  • 81 Miyake K, Seshimo A, Kameoka S. Assessment of lymph node micrometastasis in early gastric cancer in relation to sentinel nodes.  Gastric Cancer. 2006;  9 197-202
    Suche in Google Scholar
  • 82 Wu Z, Zhan W, Li J et al. [Value of lymph node micrometastasis detected by RT-PCR assay in determining the stage of gastric carcinoma].  Zhonghua Wei Chang Wai Ke Za Zhi. 2006;  9 217-220
    Suche in Google Scholar
  • 83 Katsuragi K, Yashiro M, Sawada T et al. Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R 0 resection.  Br J Cancer. 2007;  97 550-556
    Suche in Google Scholar
  • 84 Da M X, Wu X T, Guo T K et al. 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 3122-3127
    Suche in Google Scholar
  • 85 Kodera Y, Nakanishi H, Ito S et al. Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: analysis of real time reverse transcriptase-polymerase chain reaction after 5 years of followup.  J Am Coll Surg. 2006;  202 231-236
    Suche in Google Scholar
  • 86 Wang Z, Zhang X, Xu H et al. Detection of peritoneal micrometastasis by reverse transcriptase-polymerase chain reaction for heparanase mRNA and cytology in peritoneal wash samples.  J Surg Oncol. 2005;  90 59-65
    Suche in Google Scholar
  • 87 Wang Z, Xu H, Jiang L et al. Expression of survivin mRNA in peritoneal lavage fluid from patients with gastric carcinoma.  Chin Med J. 2004;  117 1210-1217
    Suche in Google Scholar
  • 88 Koga T, Tokunaga E, Sumiyoshi Y et al. Detection of circulating gastric cancer cells in peripheral blood using real time quantitative RT-PCR.  Hepatogastroenterology. 2008;  55 1131-1135
    Suche in Google Scholar
  • 89 Wu C H, Lin S R, Hsieh J S et al. Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance.  Dis Markers. 2006;  22 103-109
    Suche in Google Scholar
  • 90 Chen X, Chen G, Wang Z et al. Detection of micrometastasis of gastric carcinoma in peripheral blood circulation.  World J Gastroenterol. 2004;  10 804-808
    Suche in Google Scholar
  • 91 Zhang X, Fan P, Yang H et al. Significance of detecting disseminated tumor cells in peripheral blood of gastric and colorectal cancer patients.  Zhonghua Zhong Liu Za Zhi. 2003;  25 66-69
    Suche in Google Scholar
  • 92 Oki E, Kakeji Y, Baba H et al. Clinical significance of cytokeratin positive cells in bone marrow of gastric cancer patients.  J Cancer Res Clin Oncol. 2007;  133 995-1000
    Suche in Google Scholar
  • 93 Gretschel S, Schick C, Schneider U et al. Prognostic value of cytokeratin-positive bone marrow cells of gastric cancer patients.  Ann Surg Oncol. 2007;  14 373-380
    Suche in Google Scholar
  • 94 Fujita Y, Terashima M, Hoshino Y et al. Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK 19, and CK 20 mRNA in patients with gastric cancer.  Gastric Cancer. 2006;  9 308-314
    Suche in Google Scholar
  • 95 Matsunami K, Nakamura T, Oguma H et al. Detection of bone marrow micrometastasis in gastric cancer patients by immunomagnetic separation.  Ann Surg Oncol. 2003;  10 171-175
    Suche in Google Scholar

Dr. Benjamin Garlipp

Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Magdeburg

Leipziger Straße 44

39120 Magdeburg

Telefon: ++ 49/3 91/6 71 55 00

Fax: ++ 49/3 91/6 71 55 70

eMail: benjamin.garlipp@med.ovgu.de