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Overt bone metastasis and bone marrow micrometastasis of early gastric cancer

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Abstract

Recently we encountered two cases of early gastric cancer (EGC) with bone metastasis after surgery. As they were not accompanied by overt liver, lung, or peritoneal metastasis, we examined the clinical significance of bone metastasis in EGC and its mechanisms by a review of the literature. We found only 10 cases of EGC complicated with overt bone metastasis in the English literature, so we also examined the Japanese reports of such cases. The main histologic type of cases of bone metastasis from EGC was the diffuse type, and there were long intervals between surgery and overt bone metastasis. One reason for such long intervals may have been the tumor dormancy. Two types of dormancy, dynamic and static, and two types of postoperative overt metastases, that of micrometastatic origin (normograde metastatic process) and that of bone marrow origin (retrograde metastatic process), were considered. We speculated that there may be specific routes by which the cancer cells infiltrate the bone marrow directly from EGC or lymph node metastasis. The procedures for diagnosing bone micrometastasis using monoclonal antibodies have recently been improved, but their accuracy rates are still not universally accepted. New, more reliable examinations are required to improve the survival rates of EGC.

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References

  1. Japanese Research Society for Gastric Cancer. The general rules for gastric cancer study. (2nd English Edition). Tokyo: Kanehara Shuppan; 2004.

    Google Scholar 

  2. Shiraishi N, Inomata M, Osawa N, Yasuda K, Adachi Y, Kitano S. Early and late recurrence after gastrectomy for gastric carcinoma. Cancer 2000;89:255–261.

    Article  CAS  PubMed  Google Scholar 

  3. Ohdaira H, Nimura H, Takahashi N, Mitsumori N, Kashiwagi H, Narimiya N, et al. The possibility of performing a limited resection and a lymphadenectomy for proximal gastric carcinoma based on sentinel node navigation. Surg Today 2009;39:1026–1031.

    Article  PubMed  Google Scholar 

  4. Nakajima T. Gastric cancer treatment guidelines in Japan. Gastric Cancer 2002;5:1–5.

    Article  PubMed  Google Scholar 

  5. Nakata Y, Watanabe Y, Nakata T, Kimura K, Sato M, Kawachi K. Early gastric cancer with synchronous liver metastasis and portal timorous embolism: report of a case. Surg Today 1998;28:752–757.

    Google Scholar 

  6. Nomura T, Yoshikawa T, Kato H, Nikkuni K, Sasaki K, Shiray, Y et al. Early gastric cancer manifested as brain metastasis: report of a case. Surg Today 1997;27:334–336.

    Article  CAS  PubMed  Google Scholar 

  7. Shiomi M, Kamishako T, Yutani I, Kudo M, Shigeoka H, Tanaka A, et al. Two cases of histopathologically advanced (Stage IV) early gastric cancer. Tumori 2001;87:191–195.

    CAS  PubMed  Google Scholar 

  8. Tsurumachi T, Yamamoto H, Watanabe K, Honda I, Watanabe S, Yamada S, et al. Resection of liver metastasis from alpha-fetoprotein-producing early gastric cancer: report of a case. Surg Today 1997;27:563–566.

    Article  CAS  PubMed  Google Scholar 

  9. Yasuda O, Hayashi S. Factors influencing the postoperative course 113 patients with early gastric cancer. Jpn J Clin Oncol 1986;16:325–334.

    Google Scholar 

  10. Noda N, Sano T, Shirao K, Ono H, Katai H, Sasako M, et al. A case of bone marrow recurrence from gastric carcinoma after a nine-year disease-free interval. Jpn J Clin Oncol 1996;26:472–475.

    CAS  PubMed  Google Scholar 

  11. Kobayashi M, Araki K, Matsuura K, Kawai S, Moriki T. Early gastric cancer giving rise to bone and brain metastasis — a review of the Japanese literature. Hepato-Gastroenterology 2002;49:1751–1754.

    PubMed  Google Scholar 

  12. Omi R, Hatori M, Sano H, Watanabe K, Watamabe M, Kokubun S. Super bone scan due to bone marrow metastasis appearing 19 years after surgery for early gastric cancer — a case report. Uppsala J Med Sci 2004;109:49–56.

    Article  Google Scholar 

  13. Kikuchi S, Katada N, Sakuramoto S, Kobayashi N, Shimao H, Watanabe M, et al. Survival after surgical treatment of early gastric cancer: surgical techniques and long-term survival. Langenbecks Arch Surg 2004;389:69–74.

    Article  PubMed  Google Scholar 

  14. Soufleris K, Phipilidis I, Tzilves J, Gatopoulou A, Patakiouta F, Tarpagos A, et al. A case of early gastric cancer with bone metastasis: are bone marrow micrometastases significant? Acta Gastro-Ent Belg 2007;70:231–234.

    CAS  Google Scholar 

  15. Anagnostopoulos G, Sakorafa GH, Kostopoulos P, Margantinis G, Tsiakos S, Pavlakis G. Early (mucosa) gastric cancer with synchronous osteosclerotic bone metastases: a case report. Eur J Cancer Care 2009;1–4.

  16. Kobayashi M, Okabayashi T, Sano T, Araki K. Metastatic bone cancer as a recurrence of early gastric cancer-characteristics and possible mechanisms. World J Gastroenterol 2005;11:5587–5591.

    PubMed  Google Scholar 

  17. Choi CW, Lee DS, Chung JK, Lee MC, Kim NK, Choi KW, et al. Evaluation of bone metastases by Tc-99m MDP imaging in patients with stomach cancer. Clin Nucl Med 1995;20:310–314.

    Article  CAS  PubMed  Google Scholar 

  18. Bross IDJ, Blumenson LE. Metastatic sites that produce generalized cancer: identification and kinetics of generalized sites. In: Weiss L, editor. Fundamental aspects of metastasis. Amsterdam: North-Holland; 1976. p. 359–375.

    Google Scholar 

  19. Viadana E, Bross IDJ, Pickren JW. The metastatic spread of cancers of the digestive system in man. Oncology 1978;35:114–126.

    Article  CAS  PubMed  Google Scholar 

  20. Yoshikawa K, Kitaoka H. Bone metastasis of gastric cancer. Jpn J Surg 1983;13:173–176.

    Article  CAS  PubMed  Google Scholar 

  21. Yamamura Y, Kito K, Yamada E. Clinical evaluation of bone and bone marrow metastasis of gastric carcinoma. Jpn J Gastroenterol Surg 1985;18:2288–2293.

    Google Scholar 

  22. Mori W, Adachi Y, Okabe H, Ohta K. An analysis of 755 autopsied cases of malignant tumors. A statistical study of their metastasis (in Japanese with English abstract). Gan No Rinsho 1963;9:351–374.

    Google Scholar 

  23. Murakami G, Abe M, Abe T. Last-intercalated node and direct lymphatic drainage into the thoracic duct from the thoracoabdominal viscera. Jpn J Thorac Cardiovasc Surg 2002;50:93–103.

    Article  PubMed  Google Scholar 

  24. Crivellari D, Carbone A, Sigon R, Buonadonna A, Cannizzaro R, Sorio R, et al. Gastric cancer with bone marrow invasion at presentation: case-report and review of the literature. Tumori 1995;81:74–76.

    CAS  PubMed  Google Scholar 

  25. Schlimok G, Funke I, Pantel K, Strobel F, Lindemann F, Witte J, 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.

    Article  CAS  PubMed  Google Scholar 

  26. Meltzer A. Dormancy and breast cancer. J Surg Oncol 1990;43:181–188.

    Article  CAS  PubMed  Google Scholar 

  27. Demicheli R, Terenziani M, Valagussa P, Moliterni A, Zambetti M, Bonadonna G. Local recurrence following mastectomy: Support for the concept of tumor dormancy. J Natl Cancer I 1994;86:45–48.

    CAS  Google Scholar 

  28. Braun S, Pantel K. Micrometastatic bone marrow involvement: detection and prognostic significance. Med Oncol 1999;16:154–165.

    Article  CAS  PubMed  Google Scholar 

  29. Crowley NJ, Seigler HF. Relationship between disease-free interval and survival in patients with recurrent melanoma. Arch Surg 1992;127:1303–1308.

    CAS  PubMed  Google Scholar 

  30. Macadam R, Sarela A, Wilson J, MacLennan K, Guillou P. Bone marrow micrometastases predict early postoperative recurrence following surgical resection of oesophageal and gastric carcinoma. Eur J Surg Oncol 2003;29:450–454.

    Article  PubMed  Google Scholar 

  31. Vogel I, Kalthoff H. Disseminated tumour cells. Their detection and significance for prognosis of gastrointestinal and pancreatic carcinomas. Virchows Arch 2001;439:109–117.

    Article  CAS  PubMed  Google Scholar 

  32. Kosaka Y, Mimori K, Fukagawa T, Ishikawa K, Etoh T, Katai H, et al. Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood. Br J Cancer 2007;96:1723–1728.

    Article  CAS  PubMed  Google Scholar 

  33. Mimori K, Fukagawa T, Kosaka Y, Kita Y, Ishikawa K, Etoh T, 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.

    Article  CAS  PubMed  Google Scholar 

  34. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995;1:149–153.

    Article  CAS  PubMed  Google Scholar 

  35. Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M, et al. Haematogenous metastatic patterns in colonic carcinoma: An analysis of 1541 necropsies. J Pathol 1986;150:195–203.

    Article  CAS  PubMed  Google Scholar 

  36. Houghton J, Wang TC. Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterol 2005;128:1567–1578.

    Article  CAS  Google Scholar 

  37. Rabin I, Chikman B, Lavy R, Poluksht N, Halpern Z, Wasermann I, et al. The accuracy of sentinel node mapping according to T stage in patients with gastric cancer. Gastric Cancer 2010;13:30–35.

    Article  PubMed  Google Scholar 

  38. Hayashi H, Ochiai T, Mori M, Karube T, Suzuki T, Gunji Y, et al. Sentinel lymph node mapping for gastric cancer using a dual procedure with dye- and gamma probe-guided techniques. Am Surg 2003;196:68–74.

    Article  Google Scholar 

  39. Kitagawa Y, Fujii H, Mukai M, Kubota T, Ando N, Watanabe M, et al. The role of the sentinel lymph node in gastrointestinal cancer. Surg Clin North Am 2000;80:1799–1809.

    Article  CAS  PubMed  Google Scholar 

  40. Davis MA, Jones AL. Comparison of 99mTc-labeled phosphate and phosphonate agents for skeletal imaging. Semin Nucl Med 1976;6:19–31.

    Article  CAS  PubMed  Google Scholar 

  41. Nakai T, Okuyama C, Kubota T, Ushijima Y, Nishimura T. FDG-PET in a case of multiple bone metastases of gastric cancer. Ann Nucl Med 2005;19:51–54.

    Article  PubMed  Google Scholar 

  42. Nakamoto Y, Cohade C, Tatsumi M, Hammoud D, Wahl RL. CT appearance of bone metastases detected with FDG-PET as part of the same PET/CT examination. Radiology 2005;237:627–634.

    Article  PubMed  Google Scholar 

  43. Wang L, Yao Q, Wang J, Wei G, Li G, Li D, et al. MRI and hybrid PET/CT for monitoring tumour metastasis in a metastatic breast cancer model in rabbit. Nucl Med Commun 2008;29:137–143.

    Article  PubMed  Google Scholar 

  44. Schlimok G, Funke I, Holzmann B, Göttlinger G, Schmidt G, Häuser H, et al. Micrometastatic cancer cells in bone marrow: In vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc Natl Acad Sci USA 1987;84:8672–8676.

    Article  CAS  PubMed  Google Scholar 

  45. Jauch KW, Heiss MM, Gruetzner U, Funke I, Pantel K, Babic R, et al. Prognostic significance of bone marrow micrometastases in patients with gastric cancer. J Clin Oncol 1996;14:1810–1817.

    CAS  PubMed  Google Scholar 

  46. Schlimok G, Funke I, Bock B, Schweiberer B, Witte J, Riethmüller G. Epithelial tumor cells in bone marrow of patients with colorectal cancer: Immunocytochemical detection, phenotypic characterization, and prognostic significance. J Clin Oncol 1990;8:831–837.

    CAS  PubMed  Google Scholar 

  47. Pantel K. Detection of minimal disease in patients with solid tumors. J Hematother 1996;5:359–367.

    Article  CAS  PubMed  Google Scholar 

  48. Maehara Y, Hasuda S, Abe T, Oki E, Kakeji Y, Ohno S, et al. Tumor angiogenesis and micrometastasis in bone marrow of patients with early gastric cancer. Clin Cancer Res 1998;4:2129–2134.

    CAS  PubMed  Google Scholar 

  49. UICC (International Union Against Cancer). TNM classification of malignant tumors. 7th ed. UK: Blackwell Publishing; 2010.

    Google Scholar 

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Ubukata, H., Motohashi, G., Tabuchi, T. et al. Overt bone metastasis and bone marrow micrometastasis of early gastric cancer. Surg Today 41, 169–174 (2011). https://doi.org/10.1007/s00595-010-4389-7

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