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International Journal of Clinical and Experimental Medicine logoLink to International Journal of Clinical and Experimental Medicine
. 2015 Nov 15;8(11):19850–19858.

Clinical modalities for management of gastric cancer hepatic metastasis

Feng Tao 1, Jieqing Lv 1, Wei Wang 1, Ketao Jin 1
PMCID: PMC4723740  PMID: 26884895

Abstract

The best treatment for gastric cancer hepatic metastasis is still widely debated. Gastric cancer hepatic metastases has long been justified the indication of palliative chemotherapy. Inspired by the good results of the management of colorectal cancer hepatic metastases, surgeons have focused on the curative or palliative treatment of gastric cancer hepatic metastases. The current clinical modalities used for treatment of gastric cancer hepatic metastasis include liver resection, systemic chemotherapy, radiofrequency ablation (RFA), hepatic arterial infusion (HAI), and palliative gastrectomy. This article presents a review of the literature on hepatic resection, RFA, HAI, palliative gastrectomy, and systemic chemotherapy for the treatment of liver metastases in gastric carcinoma, and discusses the indications and long-term results.

Keywords: Gastric cancer, hepatic metastases, liver resection, radiofrequency ablation (RFA), hepatic arterial infusion (HAI), palliative gastrectomy, systemic chemotherapy

Introduction

The gastric cancer is the third leading cause of cancer death in men and the fifth in women with approximately 723,100 deaths per year worldwide [1]. Poor survival is largely attributed to delayed presentation [2]. At the time of diagnosis, 35% of gastric cancer patients have evidence of distant metastases, 31% with peritoneal disease, 14% with liver metastases, and 16% with lung metastases [3]. Its prognosis is poor with a 5-year survival rate less than 30%. This unfortunate prognosis becomes even more compromised if the gastric tumor was associated with liver metastases since the 5-year survival rate does not exceed in this case the 10% and the median survival without any treatment is about 3 to 5 months [4]. Unfortunately this situation is not uncommon as liver metastases are present in 4%-14% of patients with primary gastric cancer [5-8], which is often associated with extrahepatic disease such as peritoneal dissemination, lymph node metastasis, and direct cancer invasion of other organs [8-11].

Clinical approach to gastric cancer patients displaying hepatic metastases at diagnosis is still debated. Inspired by the good results of the management of colorectal cancer hepatic metastases, surgeons have focused on the curative or palliative treatment of gastric cancer hepatic metastases. The current clinical modalities used for treatment of gastric cancer hepatic metastasis are liver resection [6-9,12-33], systemic chemotherapy [34], radiofrequency ablation (RFA) [34-37], hepatic arterial infusion (HAI) [38-42], and palliative gastrectomy [43-47].

In this article, we review the current state of knowledge of the clinical strategies to manage gastric cancer hepatic metastasis focus on hepatic resection, systemic chemotherapy, RFA, HAI, and palliative gastrectomy.

Liver resection

The efficacy of resection of liver metastases from gastric cancer has not been established. Encouraged by the results of treatment of liver metastases of colorectal cancers [48,49], surgeons have focused on the curative treatment of gastric cancer hepatic metastases via liver resection. Numerous studies have investigated the clinical appropriateness, technical feasibility, safety, and outcomes of liver resection alone or in combination with systemic chemotherapy, HAI and palliative gastrectomy for treatment of gastric cancer hepatic metastasis, these studies are summarized in Table 1 [6-9,12-33]. The vast majority of liver metastases from gastric cancer are multiple, bilobar, and often associated with extrahepatic disease, such as peritoneal dissemination, lymph node metastasis, and direct cancer invasion of other organs. Therefore, most of patients with liver metastases are not suitable candidates for hepatic resection, even if only a solitary hepatic metastasis is involved [7]. Selected patients accounting for one-fifth of all cases with liver metastasis can undergo hepatic resection [8]. The indications for offering liver resection to patients with gastric cancer hepatic metastasis are listed in Table 2 [6,15,18].

Table 1.

Liver resection of gastric cancer hepatic metastasis

Refs PY R Na P Pr CT S/M RI OSR MST Be
1-y 2-ys 3-ys 5-ys 10-ys
[12] 1994 R Japan 30 NA NA S/M 30/284 NA NA NA NA NA NA NA
[13] 1997 R Japan 21 CG NA S/M NA NA NA NA NA NA NA NA
[14] 1998 R France 11 NA NA NA NA NA NA <30 <20 NA NA NA
[15] 2001 R Japan 40 NA NA NA NA NA 27 NA 18 11 NA NA
[16] 2001 R Japan 17 NA NA S/M NA 47 22 NA 0 NA NA NA
[6] 2002 R Japan 19 CG/PG NA S/M 19/807 77 NA 34 34 NA NA Y
[17] 2002 R Austria 15 NA NA S/M NA NA NA NA NA NA 8.8 NA
[7] 2003 R Japan 22 NA NA S/M 22/228 73 NA 38 38 NA NA Y
[18] 2005 R Korea 11 NA NA S/M NA NA NA NA NA NA 13.0/74.3a Y
[8] 2007 R Japan 37 NA SC NA NA NA NA NA 11 NA 31 Y
[9] 2007 R Japan 42 CG SC S/M 42/247 76 NA 48 42 NA 34 Y
[19] 2008 R Germany 24 CG/PG NA S/M NA 38 NA 16 10 NA 9 Y
[20] 2009 R Italy 11 CG NA M NA 80.8 30.3 20.2 NA NA NA Y
[21] 2010 R Japan 16 CG SC/HAI S/M 16/63 82.3 NA 46.4 31.7 NA 31.2 Y
[22] 2010 R Japan 17 CG SC/HAI S/M NA NA NA NA 31.5 NA 34 Y
[23] 2010 R Korea 14 CG NA M NA 67.0 NA 38.3 NA NA 11.9 Y
[24] 2012 R China 30 NA CG S NA 43.3 30.0 16.7 16.7 NA 11.0 Y
[25] 2012 R Japan 64 CG NA S/M NA 80 NA 50 37 NA 34 Y
[26] 2012 R Germany 31 CG SC S/M NA NA NA NA 13 NA NA Y
[27] 2012 R Italy 21 CG NA S/M NA 68 NA 31 19 NA NA Y
[28] 2013 R Korea 12 CG SC S/M 13/67 65 NA NA 39 NA 31.0 Y
[29] 2013 R China 20 NA CG/SC/HAI S 20/114 NA NA NA NA NA 22.3 Y
[30] 2013 R China 25 NA CG S 25/526 96.0 NA 70.4 29.4 NA NA Y
[31] 2014 R China 39 NA CG S NA 56.4 25.6 17.9 10.3 NA NA Y
[32] 2014 R Italy 53 NA CG/SC S 53/195 50.4 NA 14.0 9.3 NA NA Y
[33] 2015 R China 35 NA CG S NA NA NA NA 14.3 NA NA Y
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Abbreviations: Refs, references. PY, published year. R, retrospective study. Na, nation. P, patients enrolled. Pr, pre-treated. CT, combined therapy (regimens). SC, systemic chemotherapy (regimens). HAI, hepatic arterial infusion (regimens). CG, curative gastrectomy. PG, palliative gastrectomy. S/M, synchronous or metachronous hepatic metastasis. RI, resection incidence (patients received liver resection/total patients enrolled). OSR, overall survival rates (%). 1-y, one year. 2-ys, two years. 3-ys, three years. 5-ys, five years. 10-ys, ten years. MST, mean survival time (months). Be, benefits (Y, yes; N, not). NA, not available.

a

Median survival times of synchronous and metachronous hepatic metastases were 13.0 and 74.3 months, respectively.

Table 2.

Criteria for offering liver resection to patients with gastric cancer hepatic metastasis

Liver resection criteria
Patients with synchronous metastases who have no peritoneal dissemination or other distant metastases.
Patients with metachronous metastases, but no other recurrent lesion.
Complete resection of hepatic metastases with acceptable postoperative hepatic function.
Regardless of the timing of hepatic resection.
Solitary liver metastasis.
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Liver resection was rarely applied in gastric cancer hepatic metastasis patients due to its generalized metastases. However, inspired by the exciting achievements by liver resection of colorectal cancer, surgeons are to explore what liver resection brings for metastatic gastric cancer. Studies have reported that liver resection did benefit to the survival of gastric cancer hepatic metastasis patients during the past few years (Table 1). Results reported showed that the overall survival rate of gastric cancer hepatic metastasis for 1, 3, and 5-year after macroscopically liver resection (R0 or R1) was 38% to 96%, 14% to 70.4%, and 0% to 42 %, respectively, and the median survival time was 8.8 to 34 months (Table 1). However, most of these studies had no control arm and limited number of long survivors was regarded as the benefit of liver resection. It has to be noticed that in most of these studies, patients who took resection were highly selected and more favorable population than those who received systemic chemotherapy.

Liver resection of gastric cancer hepatic metastasis is reasonable in selected patients [50-52] and the results of liver resection of gastric cancer hepatic metastasis is encouraging (Table 1). These results have been verifying by a prospective study “The GYMSSA trial” which compared gastrectomy with metastasectomy and systemic chemotherapy vs. systemic chemotherapy alone [3].

Systemic chemotherapy

Systemic chemotherapy is the standard therapy recommended for Stage IV or metastatic gastric cancer by both the National Comprehensive Cancer Network (NCCN) Guidelines [53] and the Japanese Guidelines [54]. Systemic chemotherapy is a standard treatment approach for patients with gastric cancer hepatic metastasis [55,56]. Systemic chemotherapy, apart from surgical resection and local control, is an appropriate option with the hope of prolonged survival, though surgical resection has been recently reported to prolong the survival of patients with gastric cancer hepatic metastasis in highly selected subjects [8,10,25].

The standard treatment regimen for patients with gastric cancer hepatic metastasis was a matter of debate for a long time. In recent years, advances in systemic chemotherapy including the introduction of new anticancer agents and the development of multi-agent regimens, has made macroscopic complete resection possible in some patients with gastric cancer hepatic metastasis and led to an increase in overall survival compared to that achieved supportive treatment. As more effective toxic drugs being explored, systemic chemotherapy seems to bring more benefit to patients with gastric cancer hepatic metastasis nowadays [57,58]. And second-line or even third-line chemotherapy can still result in substantial prolongation of survival when compared to best supportive care if physical performance permits [59]. It has been reported that Her-2 positivity rate was significantly higher in gastric cancer hepatic metastasis [60]. The Trastuzumab for Gastric Cancer (ToGA) trial showed that adding trastuzumab to platinum-based chemotherapy [cisplatin (CDDP) plus capecitabine or 5-fluorouracil] significantly improved survival in first-line treatment for advanced gastric cancer with HER2 overexpression or amplification [61]. Trastuzumab in combination with chemotherapy would be as a new standard option for patients with HER-2 positive gastric cancer hepatic metastasis. In the first-line metastatic setting, a phase II study has evaluated cetuximab in combination with oxaliplatin/leucovorin/5-fluorouracil in metastatic gastric cancer, and reported encouraging objective response rate and median overall survival [62]. Drug resistance is wildly regarded as one of the disadvantages of chemotherapy, but new oral targeted drug like Apatinib has brought hope to chemotherapy-refractory patients with gastric cancer hepatic metastasis [63]. More optimistic results were recently reported from a randomized, placebo-controlled study. In a phase III study with ramucirumab, patients with metastatic gastric cancer treated with ramucirumab had significantly longer progress free survival (PFS) and overall survival (OS) times than patients given placebo [64].

Radiofrequency ablation (RFA)

Radiofrequency ablation (RFA) is a popular alternative to surgery for tumor ablation due to its safety, availability, and wide applicability to primary or secondary hepatic malignancies [65]. RFA of liver malignancies has been widely accepted as a safe and effective modality for those tumors that cannot be resected because of their number, location, or size relative to liver volume. The complementary role of the RFA is recommended in the palliative treatment of the hepatic metastases of advanced gastric cancer that are difficult to treat surgically [65,66]. Some surgeons and oncologists evaluated the efficacy of RFA alone or in combination with chemotherapy and curative gastrectomy for the treatment of liver metastasis of gastric cancer, these clinical data are summarized in Table 3 [34-37].

Table 3.

Radiofrequency ablation of gastric cancer hepatic metastasis

Refs PY P/R Na P Pr CT S/M OSR OS PFS MST Be RR
1-y 2-ys 3-ys 5-ys
[35] 2009 R Korea 7 CG SC M NA NA NA NA NA NA 10.0 Y 14.3
[36] 2010 R Korea 20 CG NA NA 66.8 NA 40.1 16.1 NA 6.8 30.7 Y 70
[37] 2013 R China 21 NA NA S/M 70 11 5 3 NA NA 14 Y 19
[34] 2014 P Korea 44 SC SC M NA NA NA NA 20.9 9.8 NA Y NA
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Abbreviations: Refs, references. PY, published year. P/R, prospective or retrospective study. Na, nation. P, patients enrolled. Pr, pre-treated. CT, combined therapy (regimens). SC, systemic chemotherapy (regimens). CG, curative gastrectomy. S/M, synchronous or metachronous hepatic metastasis. OSR, overall survival rates (%). 1-y, one year. 2-ys, two years. 3-ys, three years. 5-ys, five years. OS, overall survival (months). PFS, progress-free survival (months). MST, mean survival time (months). Be, benefits (Y, yes; N, not). RR, recurrence rate (%). NA, not available.

RFA provides a minimally invasive treatment for liver metastasis and offers patients a short-term survival benefit. RFA has several benefits including both safety and easy accessibility. RFA is less invasive and can be easily repeated when applied in a percutaneous manner. With appropriate selection of patients (excluding large tumor size, certain locations, cases with bile duct obstruction, etc.), RFA is a safe and feasible treatment option, even when multiple RFA treatments are required. Combination of RFA and systemic chemotherapy may be effective treatment modalities for patients with a single, unilobar metachronous gastric cancer hepatic metastasis without extrahepatic metastatic disease [34].

Hepatic arterial infusion (HAI)

Advances in vascular interventional radiology have made it easier to insert a catheter percutaneously. Connecting a catheter indwelling in the hepatic artery with a subcutaneously implanted port system facilitates repeated hepatic arterial infusion (HAI) on an outpatient basis. With regard to HAI of chemotherapy, this method takes advantage of the first-pass effects of cytotoxic agents, delivering higher local drug concentration to unresectable liver tumors with minimal systemic side effects [67]. HAI therapy for the local control of hepatic metastatic lesions has commonly been performed in patients with colorectal cancer [68]. However, there have been few studies reporting on the use of HAI to treat a large number of cases of gastric cancer with hepatic metastases. Clinical studies of HAI alone or in combination with chemotherapy and palliative gastrectomy for the treatment of gastric cancer hepatic metastasis is limited, these limited clinical data are summarized in Table 4 [38-42]. HAI is not a systemic treatment but is an effective treatment for local organ providing a higher concentration to the tumor tissue and a lower one in the rest of the body.

Table 4.

Hepatic arterial infusion of gastric cancer hepatic metastasis

Refs PY P/R Na P Pr HAI CT S/M 1-y OSR MST Be Rs Ph
[38] 1992 R Japan 93 PG or SC ① No S NA 11.5 Y NA NA
[39] 1992 R Japan 34 NA ② No NA NA 15 Y 73 NA
[40] 1999 P Japan 88 NA ③ No S/M 38.1 10.6 Y 55.6 II
[41] 2005 P Japan 7 NA ④ RFA S/M NA 16.5 Y 71 NA
[42] 2007 R Japan 18 PG ⑤ No S/M NA 19.2 Y 83 NA
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Abbreviations: Refs, references. PY, published year. P/R, prospective or retrospective study. Na, nation. P, patients enrolled. Pr, pre-treated. HAI, hepatic arterial infusion (regimens). CT, combined therapy (regimens). SC, systemic chemotherapy (regimens). RFA, radiofrequency ablation. PG, palliative gastrectomy. S/M, synchronous or metachronous hepatic metastasis. OSR, overall survival rates (%). 1-y, one year. MST, mean survival time (months). Be, benefits (Y, yes; N, not). Rs, response rate (%). Ph, phase of clinical trial. NA, not available. ① mitomycin + cisplatin. ② Adriamycin + mitomycin C. ③ 5-fluorouracil + epirubicin + mitomycin C. ④ cisplatin + 5-fluorouracil. ⑤ 5-fluorouracil.

Palliative gastrectomy

Regarding palliative gastrectomy, its defenders argue that this procedure may be beneficial for survival, reducing symptoms, and enhancing the quality of life for patients with advanced stage IV gastric cancer [69-71]. On the other hand, the reduction in tumor mass decreases both metabolic consumption and the secretion of tumor-induced immunosuppressive cytokines [72]. Studies investigated the clinical value of palliative gastrectomy alone or in combination with chemotherapy and liver resection for treatment of gastric cancer hepatic metastasis are summarized in Table 5 [43-47]. The Criteria for offering palliative gastrectomy to patients with gastric cancer hepatic metastasis are listed in Table 6 [72-74].

Table 5.

Palliative gastrectomy of gastric cancer hepatic metastasis

Refs PY P/R Na P Pr CT S/M OSR OS PFS MST Be
1-y 2-ys
[43] 2010 R China 101 NA NA S NA NA NA NA NA N
[44] 2012 R Korea 25 No NA NA NA NA 15 NA NA Y
[45] 2012 R China 54 Yes LR NA NA NA NA NA 19.5a/36.8b/19.6c Y
[46] 2014 R Korea 14 NA SC NA NA NA NA NA NA NA
[47] 2015 P China 24 SC SCd/LR S 72 32 20.5 13.0 NA Y
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Abbreviations: Refs, references. PY, published year. P/R, prospective or retrospective study. Na, nation. P, patients enrolled. Pr, pre-treated. CT, combined therapy (regimens). LR, liver resection. SC, systemic chemotherapy (regimens). S/M, synchronous or metachronous hepatic metastasis. OSR, overall survival rates (%). 1-y, one year. 2-ys, two years. OS, overall survival (months). PFS, progress-free survival (months). MST, mean survival time (months). Be, benefits (Y, yes; N, not). NA, not available.

a

Tumor located in gastric cardia.

b

Tumor located in middle stomach.

c

Tumor located in antrum.

d

Paclitaxel plus capecitabine (PX).

Table 6.

Criteria for offering palliative gastrectomy to patients with gastric cancer hepatic metastasis

Palliative gastrectomy criteria
Patients with potential life-threatening symptoms such as obstruction, perforation, or bleeding can be eliminated by removing a bulky symptomatic tumor.
Decreasing the tumor load makes the residual tumor more responsive to adjuvant treatment.
Volume and tumor burden reduction diminishes the metabolic demands made on the patient by the tumor.
As the tumor can produce immunosuppressive cytokines, reducing the tumor burden may also have some immunologic benefits.
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Studies that find a benefit in terms of survival after palliative gastrectomy, are almost all retrospective and include selection bias in favor of surgical patients (Table 5). Only one prospective study evaluating the usefulness of palliative gastrectomy for treatment of gastric cancer hepatic metastasis is reported [47]. For late-stage gastric cancer patients, palliative gastrectomy should be considered for local late-stage, distant lymph node metastasis, and resectable liver metastasis patients. Especially for the patients with liver metastasis, transfer medicine is essential to allow the potentially curable patients to undergo radical surgery to improve the prognosis. With the improvement of perioperative chemotherapy and surgical skills, the significance of palliative gastrectomy may increase further.

Conclusion

The optimal treatment of gastric cancer with liver metastases without peritoneal dissemination or other distant metastases remains a matter for debate. Surgery for liver metastases arising from gastric cancer is reasonable if a complete resection seems feasible after careful preoperative staging. A hepatic resection should always be considered as an option for gastric cancer patients with hepatic metastases. Systemic chemotherapy remains one of the best hopes for a longer survival and an improved quality of life. HAI offers an alternative to surgery in inoperable patients and can be proposed as neoadjuvant treatment to surgery. The interest of RFA and palliative gastrectomy remains unproven. To date a large number of treatment modalities for gastric cancer hepatic metastasis are available, but no current regimes can be regarded as a standard therapy, thus new therapeutic strategies are required to achieve a better clinical efficacy. A randomized study comparing therapeutic outcomes among patients receiving liver resection, systemic chemotherapy alone or in combination with RFA and HAI should be conducted.

Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant No. 81374014) and Zhejiang Provincial Medical and Healthy Science and Technology Projects (Grant No. 2013KYA228).

Disclosure of conflict of interest

None.

References

  • 1.Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. doi: 10.3322/caac.21262. [DOI] [PubMed] [Google Scholar]
  • 2.Shah MA, Kelsen DP. Gastric cancer: a primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease. J Natl Compr Canc Netw. 2010;8:437–447. doi: 10.6004/jnccn.2010.0033. [DOI] [PubMed] [Google Scholar]
  • 3.Kerkar SP, Kemp CD, Duffy A, Kammula US, Schrump DS, Kwong KF, Quezado M, Goldspiel BR, Venkatesan A, Berger A, Walker M, Toomey MA, Steinberg SM, Giaccone G, Rosenberg SA, Avital I. The GYMSSA trial: a prospective randomized trial comparing gastrectomy, metastasectomy plus systemic therapy versus systemic therapy alone. Trials. 2009;10:121. doi: 10.1186/1745-6215-10-121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Leong T. Chemotherapy and radiotherapy in the management of gastric cancer. Curr Opin Gastroenterol. 2005;21:673–678. doi: 10.1097/01.mog.0000179833.28158.b7. [DOI] [PubMed] [Google Scholar]
  • 5.Marrelli D, Roviello F, De Stefano A, Fotia G, Giliberto C, Garosi L, Pinto E. Risk factors for liver metastases after curative surgical procedures for gastric cancer: a prospective study of 208 patients treated with surgical resection. J Am Coll Surg. 2004;198:51–58. doi: 10.1016/j.jamcollsurg.2003.08.013. [DOI] [PubMed] [Google Scholar]
  • 6.Okano K, Maeba T, Ishimura K, Karasawa Y, Goda F, Wakabayashi H, Usuki H, Maeta H. Hepatic resection for metastatic tumors from gastric cancer. Ann Surg. 2002;235:86–91. doi: 10.1097/00000658-200201000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Sakamoto Y, Ohyama S, Yamamoto J, Yamada K, Seki M, Ohta K, Kokudo N, Yamaguchi T, Muto T, Makuuchi M. Surgical resection of liver metastases of gastric cancer: an analysis of a 17-year experience with 22 patients. Surgery. 2003;133:507–511. doi: 10.1067/msy.2003.147. [DOI] [PubMed] [Google Scholar]
  • 8.Sakamoto Y, Sano T, Shimada K, Esaki M, Saka M, Fukagawa T, Katai H, Kosuge T, Sasako M. Favorable indications for hepatectomy in patients with liver metastasis from gastric cancer. J Surg Oncol. 2007;95:534–539. doi: 10.1002/jso.20739. [DOI] [PubMed] [Google Scholar]
  • 9.Koga R, Yamamoto J, Ohyama S, Saiura A, Seki M, Seto Y, Yamaguchi T. Liver resection for metastatic gastric cancer: experience with 42 patients including eight long-term survivors. Jpn J Clin Oncol. 2007;37:836–842. doi: 10.1093/jjco/hym113. [DOI] [PubMed] [Google Scholar]
  • 10.Cheon SH, Rha SY, Jeung HC, Im CK, Kim SH, Kim HR, Ahn JB, Roh JK, Noh SH, Chung HC. Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases. Ann Oncol. 2008;19:1146–1153. doi: 10.1093/annonc/mdn026. [DOI] [PubMed] [Google Scholar]
  • 11.Ueda K, Iwahashi M, Nakamori M, Nakamura M, Naka T, Ishida K, Ojima T, Yamaue H. Analysis of the prognostic factors and evaluation of surgical treatment for synchronous liver metastases from gastric cancer. Langenbecks Arch Surg. 2009;394:647–653. doi: 10.1007/s00423-008-0311-9. [DOI] [PubMed] [Google Scholar]
  • 12.Ochiai T, Sasako M, Mizuno S, Kinoshita T, Takayama T, Kosuge T, Yamazaki S, Maruyama K. Hepatic resection for metastatic tumours from gastric cancer: analysis of prognostic factors. Br J Surg. 1994;81:1175–1178. doi: 10.1002/bjs.1800810832. [DOI] [PubMed] [Google Scholar]
  • 13.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. Hepatic resection of liver metastases from gastric carcinoma. Am J Gastroenterol. 1997;92:490–493. [PubMed] [Google Scholar]
  • 14.Elias D, Cavalcanti de Albuquerque A, Eggenspieler P, Plaud B, Ducreux M, Spielmann M, Theodore C, Bonvalot S, Lasser P. Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients. J Am Coll Surg. 1998;187:487–493. doi: 10.1016/s1072-7515(98)00225-7. [DOI] [PubMed] [Google Scholar]
  • 15.Ambiru S, Miyazaki M, Ito H, Nakagawa K, Shimizu H, Yoshidome H, Shimizu Y, Nakajima N. Benefits and limits of hepatic resection for gastric metastases. Am J Surg. 2001;181:279–283. doi: 10.1016/s0002-9610(01)00567-0. [DOI] [PubMed] [Google Scholar]
  • 16.Imamura H, Matsuyama Y, Shimada R, Kubota M, Nakayama A, Kobayashi A, Kitamura H, Ikegami T, Miyagawa SI, Kawasaki S. A study of factors influencing prognosis after resection of hepatic metastases from colorectal and gastric carcinoma. Am J Gastroenterol. 2001;96:3178–3184. doi: 10.1111/j.1572-0241.2001.05278.x. [DOI] [PubMed] [Google Scholar]
  • 17.Zacherl J, Zacherl M, Scheuba C, Steininger R, Wenzl E, Muhlbacher F, Jakesz R, Langle F. Analysis of hepatic resection of metastasis originating from gastric adenocarcinoma. J Gastrointest Surg. 2002;6:682–689. doi: 10.1016/s1091-255x(01)00075-0. [DOI] [PubMed] [Google Scholar]
  • 18.Roh HR, Suh KS, Lee HJ, Yang HK, Choe KJ, Lee KU. Outcome of hepatic resection for metastatic gastric cancer. Am Surg. 2005;71:95–99. [PubMed] [Google Scholar]
  • 19.Thelen A, Jonas S, Benckert C, Lopez-Hanninen E, Neumann U, Rudolph B, Schumacher G, Neuhaus P. Liver resection for metastatic gastric cancer. Eur J Surg Oncol. 2008;34:1328–1334. doi: 10.1016/j.ejso.2008.01.022. [DOI] [PubMed] [Google Scholar]
  • 20.Tiberio GA, Coniglio A, Marchet A, Marrelli D, Giacopuzzi S, Baiocchi L, Roviello F, de Manzoni G, Nitti D, Giulini SM. Metachronous hepatic metastases from gastric carcinoma: a multicentric survey. Eur J Surg Oncol. 2009;35:486–491. doi: 10.1016/j.ejso.2008.12.017. [DOI] [PubMed] [Google Scholar]
  • 21.Makino H, Kunisaki C, Izumisawa Y, Tokuhisa M, Oshima T, Nagano Y, Fujii S, Kimura J, Takagawa R, Kosaka T, Ono HA, Akiyama H, Tanaka K, Endo I. Indication for hepatic resection in the treatment of liver metastasis from gastric cancer. Anticancer Res. 2010;30:2367–2376. [PubMed] [Google Scholar]
  • 22.Tsujimoto H, Ichikura T, Ono S, Sugasawa H, Hiraki S, Sakamoto N, Yaguchi Y, Hatsuse K, Yamamoto J, Hase K. Outcomes for patients following hepatic resection of metastatic tumors from gastric cancer. Hepatol Int. 2010;4:406–413. doi: 10.1007/s12072-009-9161-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Choi SB, Song J, Kang CM, Hyung WJ, Kim KS, Choi JS, Lee WJ, Noh SH, Kim CB. Surgical outcome of metachronous hepatic metastases secondary to gastric cancer. Hepatogastroenterology. 2010;57:29–34. [PubMed] [Google Scholar]
  • 24.Wang YN, Shen KT, Ling JQ, Gao XD, Hou YY, Wang XF, Qin J, Sun YH, Qin XY. Prognostic analysis of combined curative resection of the stomach and liver lesions in 30 gastric cancer patients with synchronous liver metastases. BMC Surg. 2012;12:20. doi: 10.1186/1471-2482-12-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Takemura N, Saiura A, Koga R, Arita J, Yoshioka R, Ono Y, Hiki N, Sano T, Yamamoto J, Kokudo N, Yamaguchi T. Long-term outcomes after surgical resection for gastric cancer liver metastasis: an analysis of 64 macroscopically complete resections. Langenbecks Arch Surg. 2012;397:951–957. doi: 10.1007/s00423-012-0959-z. [DOI] [PubMed] [Google Scholar]
  • 26.Schildberg CW, Croner R, Merkel S, Schellerer V, Muller V, Yedibela S, Hohenberger W, Peros G, Perrakis A. Outcome of operative therapy of hepatic metastatic stomach carcinoma: a retrospective analysis. World J Surg. 2012;36:872–878. doi: 10.1007/s00268-012-1492-5. [DOI] [PubMed] [Google Scholar]
  • 27.Garancini M, Uggeri F, Degrate L, Nespoli L, Gianotti L, Nespoli A, Uggeri F, Romano F. Surgical treatment of liver metastases of gastric cancer: is local treatment in a systemic disease worthwhile? HPB (Oxford) 2012;14:209–215. doi: 10.1111/j.1477-2574.2011.00428.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Baek HU, Kim SB, Cho EH, Jin SH, Yu HJ, Lee JI, Bang HY, Lim CS. Hepatic resection for hepatic metastases from gastric adenocarcinoma. J Gastric Cancer. 2013;13:86–92. doi: 10.5230/jgc.2013.13.2.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Chen L, Song MQ, Lin HZ, Hao LH, Jiang XJ, Li ZY, Chen YX. Chemotherapy and resection for gastric cancer with synchronous liver metastases. World J Gastroenterol. 2013;19:2097–2103. doi: 10.3748/wjg.v19.i13.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Qiu JL, Deng MG, Li W, Zou RH, Li BK, Zheng Y, Lao XM, Zhou K, Yuan YF. Hepatic resection for synchronous hepatic metastasis from gastric cancer. Eur J Surg Oncol. 2013;39:694–700. doi: 10.1016/j.ejso.2013.03.006. [DOI] [PubMed] [Google Scholar]
  • 31.Wang W, Liang H, Zhang H, Wang X, Xue Q, Zhang R. Prognostic significance of radical surgical treatment for gastric cancer patients with synchronous liver metastases. Med Oncol. 2014;31:258. doi: 10.1007/s12032-014-0258-3. [DOI] [PubMed] [Google Scholar]
  • 32.Tiberio GA, Baiocchi GL, Morgagni P, Marrelli D, Marchet A, Cipollari C, Graziosi L, Ministrini S, Vittimberga G, Donini A, Nitti D, Roviello F, Coniglio A, de Manzoni G. Gastric cancer and synchronous hepatic metastases: is it possible to recognize candidates to R0 resection? Ann Surg Oncol. 2015;22:589–596. doi: 10.1245/s10434-014-4018-6. [DOI] [PubMed] [Google Scholar]
  • 33.Liu Q, Bi JJ, Tian YT, Feng Q, Zheng ZX, Wang Z. Outcome after simultaneous resection of gastric primary tumour and synchronous liver metastases: survival analysis of a single-center experience in China. Asian Pac J Cancer Prev. 2015;16:1665–1669. doi: 10.7314/apjcp.2015.16.4.1665. [DOI] [PubMed] [Google Scholar]
  • 34.Hwang JE, Kim SH, Jin J, Hong JY, Kim MJ, Jung SH, Shim HJ, Bae WK, Hwang EC, Kim JW, Shin SS, Jeong O, Park YK, Cho SH, Chung IJ. Combination of percutaneous radiofrequency ablation and systemic chemotherapy are effective treatment modalities for metachronous liver metastases from gastric cancer. Clin Exp Metastasis. 2014;31:25–32. doi: 10.1007/s10585-013-9606-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Kim HO, Hwang SI, Hong HP, Yoo CH. Radiofrequency ablation for metachronous hepatic metastases from gastric cancer. Surg Laparosc Endosc Percutan Tech. 2009;19:208–212. doi: 10.1097/SLE.0b013e3181a033d7. [DOI] [PubMed] [Google Scholar]
  • 36.Kim HR, Cheon SH, Lee KH, Ahn JR, Jeung HC, Lee SS, Chung HC, Noh SH, Rha SY. Efficacy and feasibility of radiofrequency ablation for liver metastases from gastric adenocarcinoma. Int J Hyperthermia. 2010;26:305–315. doi: 10.3109/02656730903555696. [DOI] [PubMed] [Google Scholar]
  • 37.Chen J, Tang Z, Dong X, Gao S, Fang H, Wu D, Xiang D, Zhang S. Radiofrequency ablation for liver metastasis from gastric cancer. Eur J Surg Oncol. 2013;39:701–706. doi: 10.1016/j.ejso.2013.03.023. [DOI] [PubMed] [Google Scholar]
  • 38.Yonemura Y, Matuki N, Sakuma H, Katayama K, Sawa T, Fujimura T, Ohyama S, Miwa K, Miyazaki I, Tanaka M, et al. Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer patients with liver metastases. Surg Today. 1992;22:253–259. doi: 10.1007/BF00308831. [DOI] [PubMed] [Google Scholar]
  • 39.Arai Y, Endo T, Sone Y, Tohyama N, Inaba Y, Kohno S, Ariyoshi Y, Kido C. Management of patients with unresectable liver metastases from colorectal and gastric cancer employing an implantable port system. Cancer Chemother Pharmacol. 1992;31(Suppl):S99–102. doi: 10.1007/BF00687116. [DOI] [PubMed] [Google Scholar]
  • 40.Kumada T, Arai Y, Itoh K, Takayasu Y, Nakamura K, Ariyoshi Y, Tajima K. Phase II study of combined administration of 5-fluorouracil, epirubicin and mitomycin-C by hepatic artery infusion in patients with liver metastases of gastric cancer. Oncology. 1999;57:216–223. doi: 10.1159/000012034. [DOI] [PubMed] [Google Scholar]
  • 41.Yamakado K, Nakatsuka A, Takaki H, Mori Y, Tonouchi H, Kusunoki M, Kida H, Takeda K. Prospective study of arterial infusion chemotherapy followed by radiofrequency ablation for the treatment of liver metastasis of gastric cancer. J Vasc Interv Radiol. 2005;16:1747–1751. doi: 10.1097/01.RVI.0000188738.84911.3B. [DOI] [PubMed] [Google Scholar]
  • 42.Ojima H, Ootake S, Yokobori T, Mochida Y, Hosouchi Y, Nishida Y, Kuwano H. Treatment of multiple liver metastasis from gastric carcinoma. World J Surg Oncol. 2007;5:70. doi: 10.1186/1477-7819-5-70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Li C, Yan M, Chen J, Xiang M, Zhu ZG, Yin HR, Lin YZ. Survival benefit of non-curative gastrectomy for gastric cancer patients with synchronous distant metastasis. J Gastrointest Surg. 2010;14:282–288. doi: 10.1007/s11605-009-1095-0. [DOI] [PubMed] [Google Scholar]
  • 44.Chang YR, Han DS, Kong SH, Lee HJ, Kim SH, Kim WH, Yang HK. The value of palliative gastrectomy in gastric cancer with distant metastasis. Ann Surg Oncol. 2012;19:1231–1239. doi: 10.1245/s10434-011-2056-x. [DOI] [PubMed] [Google Scholar]
  • 45.Chen S, Li YF, Feng XY, Zhou ZW, Yuan XH, Chen YB. Significance of palliative gastrectomy for late-stage gastric cancer patients. J Surg Oncol. 2012;106:862–871. doi: 10.1002/jso.23158. [DOI] [PubMed] [Google Scholar]
  • 46.Jeong O, Park YK, Choi WY, Ryu SY. Prognostic significance of non-curative gastrectomy for incurable gastric carcinoma. Ann Surg Oncol. 2014;21:2587–2593. doi: 10.1245/s10434-014-3638-1. [DOI] [PubMed] [Google Scholar]
  • 47.Li Z, Fan B, Shan F, Tang L, Bu Z, Wu A, Zhang L, Wu X, Zong X, Li S, Ren H, Ji J. Gastrectomy in comprehensive treatment of advanced gastric cancer with synchronous liver metastasis: a prospectively comparative study. World J Surg Oncol. 2015;13:212. doi: 10.1186/s12957-015-0627-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Bentrem DJ, Dematteo RP, Blumgart LH. Surgical therapy for metastatic disease to the liver. Annu Rev Med. 2005;56:139–156. doi: 10.1146/annurev.med.56.082103.104630. [DOI] [PubMed] [Google Scholar]
  • 49.Liu LX, Zhang WH, Jiang HC. Current treatment for liver metastases from colorectal cancer. World J Gastroenterol. 2003;9:193–200. doi: 10.3748/wjg.v9.i2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Shirabe K, Wakiyama S, Gion T, Watanabe M, Miyazaki M, Yoshinaga K, Tokunaga M, Nagaie T. Hepatic resection for the treatment of liver metastases in gastric carcinoma: review of the literature. HPB (Oxford) 2006;8:89–92. doi: 10.1080/13651820500472168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Kakeji Y, Morita M, Maehara Y. Strategies for treating liver metastasis from gastric cancer. Surg Today. 2010;40:287–294. doi: 10.1007/s00595-009-4152-0. [DOI] [PubMed] [Google Scholar]
  • 52.Liu J, Chen L. Current status and progress in gastric cancer with liver metastasis. Chin Med J (Engl) 2011;124:445–456. [PubMed] [Google Scholar]
  • 53.Ajani JA, Barthel JS, Bekaii-Saab T, Bentrem DJ, D’Amico TA, Das P, Denlinger C, Fuchs CS, Gerdes H, Hayman JA, Hazard L, Hofstetter WL, Ilson DH, Keswani RN, Kleinberg LR, Korn M, Meredith K, Mulcahy MF, Orringer MB, Osarogiagbon RU, Posey JA, Sasson AR, Scott WJ, Shibata S, Strong VE, Washington MK, Willett C, Wood DE, Wright CD, Yang G, Panel NGC. Gastric cancer. J Natl Compr Canc Netw. 2010;8:378–409. doi: 10.6004/jnccn.2010.0030. [DOI] [PubMed] [Google Scholar]
  • 54.Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3) Gastric Cancer. 2011;14:113–123. doi: 10.1007/s10120-011-0042-4. [DOI] [PubMed] [Google Scholar]
  • 55.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. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–221. doi: 10.1016/S1470-2045(08)70035-4. [DOI] [PubMed] [Google Scholar]
  • 56.Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–1069. doi: 10.1016/S1470-2045(09)70259-1. [DOI] [PubMed] [Google Scholar]
  • 57.Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46. doi: 10.1056/NEJMoa073149. [DOI] [PubMed] [Google Scholar]
  • 58.Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START) J Cancer Res Clin Oncol. 2014;140:319–328. doi: 10.1007/s00432-013-1563-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J. Clin. Oncol. 2012;30:1513–1518. doi: 10.1200/JCO.2011.39.4585. [DOI] [PubMed] [Google Scholar]
  • 60.Yokoyama H, Ikehara Y, Kodera Y, Ikehara S, Yatabe Y, Mochizuki Y, Koike M, Fujiwara M, Nakao A, Tatematsu M, Nakanishi H. Molecular basis for sensitivity and acquired resistance to gefitinib in HER2-overexpressing human gastric cancer cell lines derived from liver metastasis. Br J Cancer. 2006;95:1504–1513. doi: 10.1038/sj.bjc.6603459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.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, Rüschoff J, Kang YK ToGA Trial Investigators. 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. 2010;376:687–697. doi: 10.1016/S0140-6736(10)61121-X. [DOI] [PubMed] [Google Scholar]
  • 62.Lordick F, Luber B, Lorenzen S, Hegewisch-Becker S, Folprecht G, Woll E, Decker T, Endlicher E, Rothling N, Schuster T, Keller G, Fend F, Peschel C. Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) Br J Cancer. 2010;102:500–505. doi: 10.1038/sj.bjc.6605521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J. Clin. Oncol. 2013;31:3219–3225. doi: 10.1200/JCO.2013.48.8585. [DOI] [PubMed] [Google Scholar]
  • 64.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J, Investigators RT. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–39. doi: 10.1016/S0140-6736(13)61719-5. [DOI] [PubMed] [Google Scholar]
  • 65.Chen MH, Yang W, Yan K, Gao W, Dai Y, Wang YB, Zhang XP, Yin SS. Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications. World J Gastroenterol. 2005;11:6395–6401. doi: 10.3748/wjg.v11.i40.6395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Iannitti DA, Dupuy DE, Mayo-Smith WW, Murphy B. Hepatic radiofrequency ablation. Arch Surg. 2002;137:422–426. doi: 10.1001/archsurg.137.4.422. discussion 427. [DOI] [PubMed] [Google Scholar]
  • 67.Ganeshan A, Upponi S, Hon LQ, Warakaulle D, Uberoi R. Hepatic arterial infusion of chemotherapy: the role of diagnostic and interventional radiology. Ann Oncol. 2008;19:847–851. doi: 10.1093/annonc/mdm528. [DOI] [PubMed] [Google Scholar]
  • 68.Geoffroy F, Grem JL. Chemotherapy of advanced gastrointestinal cancer. Curr Opin Oncol. 1994;6:427–434. doi: 10.1097/00001622-199407000-00016. [DOI] [PubMed] [Google Scholar]
  • 69.Medina-Franco H, Contreras-Saldivar A, Ramos-De La Medina A, Palacios-Sanchez P, Cortes-Gonzalez R, Ugarte JA. Surgery for stage IV gastric cancer. Am J Surg. 2004;187:543–546. doi: 10.1016/j.amjsurg.2003.12.045. [DOI] [PubMed] [Google Scholar]
  • 70.Samarasam I, Chandran BS, Sitaram V, Perakath B, Nair A, Mathew G. Palliative gastrectomy in advanced gastric cancer: is it worthwhile? ANZ J Surg. 2006;76:60–63. doi: 10.1111/j.1445-2197.2006.03649.x. [DOI] [PubMed] [Google Scholar]
  • 71.Hartgrink HH, Putter H, Klein Kranenbarg E, Bonenkamp JJ, van de Velde CJ Dutch Gastric Cancer Group. Value of palliative resection in gastric cancer. Br J Surg. 2002;89:1438–1443. doi: 10.1046/j.1365-2168.2002.02220.x. [DOI] [PubMed] [Google Scholar]
  • 72.McCarter MD, Fong Y. Role for surgical cytoreduction in multimodality treatments for cancer. Ann Surg Oncol. 2001;8:38–43. doi: 10.1007/s10434-001-0038-0. [DOI] [PubMed] [Google Scholar]
  • 73.Saidi RF, ReMine SG, Dudrick PS, Hanna NN. Is there a role for palliative gastrectomy in patients with stage IV gastric cancer? World J Surg. 2006;30:21–27. doi: 10.1007/s00268-005-0129-3. [DOI] [PubMed] [Google Scholar]
  • 74.Pollock RE, Roth JA. Cancer-induced immunosuppression: implications for therapy? Semin Surg Oncol. 1989;5:414–419. doi: 10.1002/ssu.2980050607. [DOI] [PubMed] [Google Scholar]

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