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Liver Metastases from Stomach Cancer

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Noncolorectal, Nonneuroendocrine Liver Metastases

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Abstract

Gastric carcinoma is a malignant epithelial tumor of the stomach mucosa. Adenocarcinoma of the esophagogastric junction is another clinical entity and is difficult to distinguish from gastric carcinoma. Gastric cancer is estimated to be the fifth most common type of cancer with 952,000 cases worldwide (6.8 % of the total) and is the third leading cause of cancer death (723,000 deaths, 8.8 % of the total) worldwide, according to a report in GLOBOCAN 2012 by the World Health Organization. The incidence of gastric cancer varies with geographic regions, with half of the cases worldwide occurring in Eastern Asia. The highest estimated mortality rates are in Eastern Asia (24 per 100,000 in men, 9.8 per 100,000 in women) and the lowest in Northern America (2.8 and 1.5 per 100,000, respectively) (Fig. 11.1). High mortality rates are also present in both sexes in Central and Eastern Europe and in Central and South America. Age-standardized incidence rates are about twice as high in men as in women, ranging from 3.3 per 100,000 in Western Africa to 35.4 per 100,000 in Eastern Asia for men and from 2.6 per 100,000 in Western Africa to 13.8 per 100,000 in Eastern Asia for women. However, there has been a rapid decline in the incidence of gastric cancer and a steady decline in gastric cancer mortality worldwide. In some Western countries, rates have decreased by more than one third within just one generation. There is about a 20-fold difference in the incidence rates when comparing the rates in Japan with those of some white populations from the USA and of some African countries. The intestinal type of adenocarcinoma is more common in high-risk areas, while the diffuse type is more common in low-risk areas.

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References

  1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2013) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [internet]. International Agency for Research on Cancer, Lyon, Available from: http://globocan.iarc.fr, accessed on 10 April 2014

    Google Scholar 

  2. Munoz N, Correa P, Cuello C, Duque E (1968) Histologic types of gastric carcinoma in high- and low-risk areas. Int J Cancer 3(6):809–818

    Article  CAS  PubMed  Google Scholar 

  3. Gaddy JA, Radin JN, Loh JT, Zhang F, Washington MK, Peek RM Jr, Algood HM, Cover TL (2013) High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. Infect Immun 81(6):2258–2267

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Peek RM Jr, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2(1):28–37

    Article  CAS  PubMed  Google Scholar 

  5. Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G (2006) A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg 93(4):465–474

    Article  CAS  PubMed  Google Scholar 

  6. Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, Kameoka S, Saito Y, Takahashi K, Hase K, Oya M, Maeda K, Hirai T, Kameyama M, Shirouzu K, Muto T (2007) Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery 141(1):67–75

    Article  PubMed  Google Scholar 

  7. Koga S, Kawaguchi H, Kishimoto H, Tanaka K, Miyano Y, Kimura O, Takeda R, Nishidoi H (1980) Therapeutic significance of noncurative gastrectomy for gastric cancer with liver metastasis. Am J Surg 140(3):356–359

    Article  CAS  PubMed  Google Scholar 

  8. Okuyama K, Isono K, Juan IK, Onoda S, Ochiai T, Yamamoto Y, Koide Y, Satoh H (1985) Evaluation of treatment for gastric cancer with liver metastasis. Cancer 55(10):2498–2505

    Article  CAS  PubMed  Google Scholar 

  9. Ueda K, Iwahashi M, Nakamori M, Nakamura M, Naka T, Ishida K, Ojima T, Yamaue H (2009) Analysis of the prognostic factors and evaluation of surgical treatment for synchronous liver metastases from gastric cancer. Langenbeck’s Arch Surg Deutsche Gesellschaft fur Chirurgie 394(4):647–653

    Article  Google Scholar 

  10. Shitara K, Ikeda J, Kondo C, Takahari D, Ura T, Muro K, Matsuo K (2012) Reporting patient characteristics and stratification factors in randomized trials of systemic chemotherapy for advanced gastric cancer. Gastric Cancer 15(2):137–143

    Article  PubMed  Google Scholar 

  11. Japanese classification of gastric carcinoma: 3rd English edition (2011) Gastric Cancer 14(2): 101–112

    Google Scholar 

  12. Washington K (2010) 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 17(12):3077–3079

    Article  PubMed  Google Scholar 

  13. Nakajima T, Nishi M, Kajitani T (1991) Improvement in treatment results of gastric cancer with surgery and chemotherapy: experience of 9,700 cases in the Cancer Institute Hospital, Tokyo. Semin Surg Oncol 7(6):365–372

    Article  CAS  PubMed  Google Scholar 

  14. Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M (1993) Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72(1):37–41

    Article  CAS  PubMed  Google Scholar 

  15. Glimelius B, Hoffman K, Haglund U, Nyren O, Sjoden PO (1994) Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5(2):189–190

    CAS  PubMed  Google Scholar 

  16. Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M (1995) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71(3):587–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Prolla JC, Kobayashi S, Kirsner JB (1969) Gastric cancer. Some recent improvements in diagnosis based upon the Japanese experience. Arch Intern Med 124(2):238–246

    Article  CAS  PubMed  Google Scholar 

  18. Koga R, Yamamoto J, Ohyama S, Saiura A, Seki M, Seto Y, Yamaguchi T (2007) Liver resection for metastatic gastric cancer: experience with 42 patients including eight long-term survivors. Jpn J Clin Oncol 37(11):836–842

    Article  PubMed  Google Scholar 

  19. Garancini M, Uggeri F, Degrate L, Nespoli L, Gianotti L, Nespoli A, Uggeri F, Romano F (2012) Surgical treatment of liver metastases of gastric cancer: is local treatment in a systemic disease worthwhile? HPB (Oxford) 14(3):209–215

    Article  Google Scholar 

  20. Qiu JL, Deng MG, Li W, Zou RH, Li BK, Zheng Y, Lao XM, Zhou K, Yuan YF (2013) Hepatic resection for synchronous hepatic metastasis from gastric cancer. Eur J Surg Oncol 39(7):694–700

    Article  PubMed  Google Scholar 

  21. Kim SJ, Kim HH, Kim YH, Hwang SH, Lee HS, do Park J, Kim SY, Lee KH (2009) Peritoneal metastasis: detection with 16- or 64-detector row CT in patients undergoing surgery for gastric cancer. Radiology 253(2):407–415

    Article  PubMed  Google Scholar 

  22. Karanicolas PJ, Elkin EB, Jacks LM, Atoria CL, Strong VE, Brennan MF, Coit DG (2011) Staging laparoscopy in the management of gastric cancer: a population-based analysis. J Am Coll Surg 213(5):644–651, 651 e641

    Article  PubMed  Google Scholar 

  23. Mukai K, Ishida Y, Okajima K, Isozaki H, Morimoto T, Nishiyama S (2006) Usefulness of preoperative FDG-PET for detection of gastric cancer. Gastric Cancer 9(3):192–196

    Article  PubMed  Google Scholar 

  24. Smyth E, Schoder H, Strong VE, Capanu M, Kelsen DP, Coit DG, Shah MA (2012) A prospective evaluation of the utility of 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. Cancer 118(22):5481–5488

    Article  PubMed  Google Scholar 

  25. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345(10):725–730

    Article  CAS  PubMed  Google Scholar 

  26. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20

    Article  CAS  PubMed  Google Scholar 

  27. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357(18):1810–1820

    Article  CAS  PubMed  Google Scholar 

  28. Shirabe K, Shimada M, Matsumata T, Higashi H, Yakeishi Y, Wakiyama S, Ikeda Y, Ezaki T, Fukuzawa S, Takenaka K, Kishikawa K, Ikeda T, Taguchi K, Maehara Y, Sugimachi K (2003) Analysis of the prognostic factors for liver metastasis of gastric cancer after hepatic resection: a multi-institutional study of the indications for resection. Hepatogastroenterology 50(53):1560–1563

    PubMed  Google Scholar 

  29. Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom H, Heuman R (1997) Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8(2):163–168

    Article  CAS  PubMed  Google Scholar 

  30. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE (2006) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24(18):2903–2909

    Article  CAS  PubMed  Google Scholar 

  31. Wils JA, Klein HO, Wagener DJ, Bleiberg H, Reis H, Korsten F, Conroy T, Fickers M, Leyvraz S, Buyse M et al (1991) Sequential high-dose methotrexate and fluorouracil combined with doxorubicin–a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol 9(5):827–831

    CAS  PubMed  Google Scholar 

  32. Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267

    Article  CAS  PubMed  Google Scholar 

  33. Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E, Planker M, Santos JG, Piedbois P, Paillot B, Bodenstein H, Schmoll HJ, Bleiberg H, Nordlinger B, Couvreur ML, Baron B, Wils JA (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18(14):2648–2657

    CAS  PubMed  Google Scholar 

  34. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24(31):4991–4997

    Article  PubMed  Google Scholar 

  35. Allum WH, Blazeby JM, Griffin SM, Cunningham D, Jankowski JA, Wong R (2011) Guidelines for the management of oesophageal and gastric cancer. Gut 60(11):1449–1472

    Article  CAS  PubMed  Google Scholar 

  36. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9(3):215–221

    Article  CAS  PubMed  Google Scholar 

  37. Okines AF, Norman AR, McCloud P, Kang YK, Cunningham D (2009) Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 20(9):1529–1534

    Article  CAS  PubMed  Google Scholar 

  38. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697

    Article  CAS  PubMed  Google Scholar 

  39. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29(30):3968–3976

    Article  CAS  PubMed  Google Scholar 

  40. Onsum MD, Geretti E, Paragas V, Kudla AJ, Moulis SP, Luus L, Wickham TJ, McDonagh CF, Macbeath G, Hendriks BS (2013) Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients. Am J Pathol 183(5):1446–1460

    Article  CAS  PubMed  Google Scholar 

  41. Ochiai T, Sasako M, Mizuno S, Kinoshita T, Takayama T, Kosuge T, Yamazaki S, Maruyama K (1994) Hepatic resection for metastatic tumours from gastric cancer: analysis of prognostic factors. Br J Surg 81(8):1175–1178

    Article  CAS  PubMed  Google Scholar 

  42. Adam R, Chiche L, Aloia T, Elias D, Salmon R, Rivoire M, Jaeck D, Saric J, Le Treut YP, Belghiti J, Mantion G, Mentha G (2006) Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model. Ann Surg 244(4):524–535

    PubMed Central  PubMed  Google Scholar 

  43. Elias D, Cavalcanti de Albuquerque A, Eggenspieler P, Plaud B, Ducreux M, Spielmann M, Theodore C, Bonvalot S, Lasser P (1998) Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients. J Am Coll Surg 187(5):487–493

    Article  CAS  PubMed  Google Scholar 

  44. Romano F, Garancini M, Uggeri F, Degrate L, Nespoli L, Gianotti L, Nespoli A, Uggeri F (2012) Surgical treatment of liver metastases of gastric cancer: state of the art. World J Surg Oncol 10:157

    Article  PubMed Central  PubMed  Google Scholar 

  45. Okano K, Maeba T, Ishimura K, Karasawa Y, Goda F, Wakabayashi H, Usuki H, Maeta H (2002) Hepatic resection for metastatic tumors from gastric cancer. Ann Surg 235(1):86–91

    Article  PubMed Central  PubMed  Google Scholar 

  46. Saiura A, Umekita N, Inoue S, Maeshiro T, Miyamoto S, Matsui Y, Asakage M, Kitamura M (2002) Clinicopathological features and outcome of hepatic resection for liver metastasis from gastric cancer. Hepatogastroenterology 49(46):1062–1065

    PubMed  Google Scholar 

  47. Takemura N, Saiura A, Koga R, Arita J, Yoshioka R, Ono Y, Hiki N, Sano T, Yamamoto J, Kokudo N, Yamaguchi T (2012) Long-term outcomes after surgical resection for gastric cancer liver metastasis: an analysis of 64 macroscopically complete resections. Langenbeck’s Arch Surg Deutsche Gesellschaft fur Chirurgie 397(6):951–957

    Article  Google Scholar 

  48. Miyazaki M, Itoh H, Nakagawa K, Ambiru S, Shimizu H, Togawa A, Shiobara M, Ohtsuka M, Sasada K, Shimizu Y, Yoshioka S, Nakajima N, Suwa T, Kimura F (1997) Hepatic resection of liver metastases from gastric carcinoma. Am J Gastroenterol 92(3):490–493

    CAS  PubMed  Google Scholar 

  49. Imamura H, Matsuyama Y, Shimada R, Kubota M, Nakayama A, Kobayashi A, Kitamura H, Ikegami T, Miyagawa SI, Kawasaki S (2001) A study of factors influencing prognosis after resection of hepatic metastases from colorectal and gastric carcinoma. Am J Gastroenterol 96(11):3178–3184

    Article  CAS  PubMed  Google Scholar 

  50. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ (2010) Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 11(5):439–449

    Article  PubMed  Google Scholar 

  51. Yamakado K, Nakatsuka A, Takaki H, Mori Y, Tonouchi H, Kusunoki M, Kida H, Takeda K (2005) Prospective study of arterial infusion chemotherapy followed by radiofrequency ablation for the treatment of liver metastasis of gastric cancer. J Vasc Interv Radiol 16(12):1747–1751

    Article  PubMed  Google Scholar 

  52. Bines SD, England G, Deziel DJ, Witt TR, Doolas A, Roseman DL (1993) Synchronous, metachronous, and multiple hepatic resections of liver tumors originating from primary gastric tumors. Surgery 114(4):799–805; discussion 804–795

    CAS  PubMed  Google Scholar 

  53. Ambiru S, Miyazaki M, Ito H, Nakagawa K, Shimizu H, Yoshidome H, Shimizu Y, Nakajima N (2001) Benefits and limits of hepatic resection for gastric metastases. Am J Surg 181(3):279–283

    Article  CAS  PubMed  Google Scholar 

  54. Roh HR, Suh KS, Lee HJ, Yang HK, Choe KJ, Lee KU (2005) Outcome of hepatic resection for metastatic gastric cancer. Am Surg 71(2):95–99

    PubMed  Google Scholar 

  55. Fujii K, Fujioka S, Kato K, Machiki Y, Kutsuna Y, Ishikawa A, Takamizawa J, Ko K, Yoshida K, Nimura Y (2001) Resection of liver metastasis from gastric adenocarcinoma. Hepatogastroenterology 48(38):368–371

    CAS  PubMed  Google Scholar 

  56. Sakamoto Y, Ohyama S, Yamamoto J, Yamada K, Seki M, Ohta K, Kokudo N, Yamaguchi T, Muto T, Makuuchi M (2003) Surgical resection of liver metastases of gastric cancer: an analysis of a 17-year experience with 22 patients. Surgery 133(5):507–511

    Article  PubMed  Google Scholar 

  57. Cheon SH, Rha SY, Jeung HC, Im CK, Kim SH, Kim HR, Ahn JB, Roh JK, Noh SH, Chung HC (2008) Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases. Ann Oncol 19(6):1146–1153

    Article  CAS  PubMed  Google Scholar 

  58. Takemura N, Saiura A, Koga R, Yoshioka R, Yamamoto J, Kokudo N (2013) Repeat hepatectomy for recurrent liver metastasis from gastric carcinoma. World J Surg 37(11):2664–2670

    Article  PubMed  Google Scholar 

  59. Chen J, Tang Z, Dong X, Gao S, Fang H, Wu D, Xiang D, Zhang S (2013) Radiofrequency ablation for liver metastasis from gastric cancer. Eur J Surg Oncol 39(7):701–706

    Article  CAS  PubMed  Google Scholar 

  60. Edge SB, Byrd DR, Compton CC Fritz AG, Greene FL, Trotti A AJCC: Stomach (2010) In: Edge SB, Byrd DR, Compton CC, et al (eds) AJCC cancer staging manual. 7th edn. Springer, New York, pp 117-126

    Google Scholar 

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  1. Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Akio Saiura

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  1. Department of Surgical Sciences Organ Transplantation and Advanced Technologies, University of Catania, Cannizzaro Hospital, Catania, Catania, Italy

    Isidoro Di Carlo

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Saiura, A. (2015). Liver Metastases from Stomach Cancer. In: Di Carlo, I. (eds) Noncolorectal, Nonneuroendocrine Liver Metastases. Springer, Cham. https://doi.org/10.1007/978-3-319-09293-5_11

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