Abstract

Background: The clinical significance of surgical resection for liver metastases of gastric cancer remains controversial. Herein, we report a case of twice resections for metachronous liver metastases of gastric cancer in combination with perioperative chemotherapy, which resulted in long-term survival.
Case Presentation: The patient was a 66-year-old man who underwent laparoscopic total gastrectomy for gastric cancer (Stage IB) in March 2012, and subsequently underwent right hemi-hepatectomy with partial resection of the vena cava and diaphragm for solitary metastases in segments 7-8 in April 2013. In September 2013, abdominal computed tomography detected a liver metastasis in segment 4. We administered systematic chemotherapy with S-1 plus cis-diamminedichloroplatinum (CDDP). Because the tumor decreased in size after five courses, and curative resection of the tumor was considered possible, hepatic resection of S4+1 was performed in June 2014. The patient has been followed for 26 months, and, after the last hepatectomy, had no evidence of recurrence.
Conclusion: We experienced a case of long-term survival after twice resections for liver metastases from gastric cancer. Surgical resection for liver metastases of gastric cancer, even repeat hepatectomy, may be an effective treatment after careful selection of the optimal candidate.

Introduction

Synchronous or metachronous metastases of the liver are frequently observed in advanced gastric cancer[1]. Because recurrence usually occurs in a combination of patterns, including peritoneal dissemination and lung and lymph node metastasis, hepatic resection has not been widely accepted as an effective treatment strategy for metastatic gastric cancer, in contrast to colorectal cancer [2].

In this paper, we report on a patient who underwent two resections for metachronous liver metastases of gastric cancer in combination with perioperative chemotherapy, which resulted in long-term survival.

Case Presentation

A 66-year-old man who was diagnosed with early gastric cancer at a routine medical check-up for anemia was admitted to our hospital. Routine laboratory and hematologic data showed normal parameters with the exception of hemoglobin, which was 9.0 g/dL. On gastroscopy, a 0-IIb+IIc-type gastric adenocarcinoma was observed in the upper to middle part of the stomach (Figure 1). Abdominal computed tomography (CT) revealed only one enlarged lymph node (#3); no other metastatic lesion was found (Figure 2). The gastric cancer was thus diagnosed as T1bN1M0 stage IB. Laparoscopic total gastrectomy with D2 lymphadenectomy was then performed.(Operation time was 4 hours and 25 minutes)Pathological stage was the same StageIB as clinical stage, then no adjuvant therapy was administered in accordance with Japanese gastric cancer treatment guidelines 2014 [3].

Figure 1: At gastroscopic biopsy, a 0-IIb+IIc-type gastric adenocarcinoma was observed in the upper to middle part of the stomach.

Figure 2: Abdominal computed tomography revealed only one enlarged metastatic lymph node (#3).

One year after gastrectomy, the patient’s serum CA19-9 level was elevated (69.8 ng/mL), and CT revealed a solitary liver tumor at segment 7/8 (12 cm in diameter), which was suspected to be a metastasis of gastric cancer, based on the results of a dynamic study (Figure 3). Right hepatectomy was then performed, and at surgical findings, a part of diaphragm and the vena cava were invaded by the tumor, so partial resection of diaphragm and the vena cava were also performed.

Figure 3: Abdominal computed tomography revealed a solitary liver tumor at segment 7/8.

Pathological examination revealed that the tumor was consistent with metastasis of gastric cancer (Figure 4). At 5 months after hepatectomy, CT revealed a low-density area at segment 4 of the liver, which was also suspected to be a metastasis of gastric cancer (Figure 5). We began treating the patient with systemic chemotherapy with S-1 plus cis-diamminedichloroplatinum. After five courses of chemotherapy, the metastatic lesion became smaller and no other metastatic lesions were evident on CT (Figure 6) or fluorodeoxyglucose-enhanced positron emission tomography. Therefore, we performed a partial hepatectomy of segment 4. The patient received adjuvant chemotherapy with S-1 for 1 year, and he had experienced no recurrence as of 4 years and 6 months after gastrectomy, which was 2 years and 7 months after the last hepatectomy.

Figure 4: Histopathological examination revealed tubular adenocarcinoma.

Figure 5: Abdominal computed tomography revealed a low-density area at segment 4 of the liver.

Figure 6: After chemotherapy, the metastatic lesions became smaller and no other metastatic lesion was evident on computed tomography or fluorodeoxyglucose-enhanced positron emission tomography.

Discussion

It is thought that the benefit of hepatic resection for liver metastasis from gastric cancer has not been sufficiently established, and this is particularly true of repeat hepatectomies[4, 5]. This is because gastric cancer metastases are often multiple and scattered recurrences that usually occur as peritoneal dissemination and/or lymph node metastases. However, the recent reports are in favor of hepatectomy in synchronous or metachronous lesions of liver from gastric cancer. As reported by Lei Chen et. al., the survival time in patients with hepatectomy was longer than in those without hepatectomy [6].

Furthermore, two systematic review by Di Long et al. [7] and Ying-Yang Liao. [8] provide comprehensive evidence that hepatectomy is associated with longer median overall survival than palliative treatments for selected patients with liver metastases from gastric cancer [7,8].

Details of patients who survived more than 2 years after hepatectomy were summarized in Table 1 [1,9-13].

Table 1: Details of patients who survived more than 2 years after hepatectomy.

Author Ref No. Age Gender Histology No. of metastasis Size of metastatic lesion (cm) Temporal relationship Operation Survival (months) Good prognostic factors
Tsujimoto 1 52 NR NR 1 2.5 synchronous S 130 Gastric tumor size <6cm D2 lymphadenectomy
53 NR NR 1 4.5 metachronous LR 99
71 NR NR 1 4.5 metachronous S 61
66 NR NR 1 5 metachronous H 65
53 NR NR 1 4.8 synchronous H 85
Ochiai 5 55 M pap 1 NR synchronous S 218 Metachronous metastasis No serosal invasion of primary tumor
59 M tub1 1 NR synchronous LR 219
52 F pap 1 NR metachronous LR 77
49 M tub1 6 NR synchronous S 86
Miyazaki 6 54 M pap 1 NR metachronous S 39 1. T stage of primary tumor
55 M por 1 NR synchronous S 85
68 M tub2 2 NR metachronous H 32
Okano 7 59 M NR 1 2 synchronous LR 42 Peritumoral fibrous pseudocapsule Well-differentiated histologic type of metastatic tumor
61 M NR 1 5 metachronous S 138
75 F NR 1 7 metachronous LR 96
69 M NR 1 3 metachronous LR 81
Koga 8 61 F tub2 1 NR synchronous H 71 1. Solitary hepatic metastasis
75 F por 1 NR metachronous LR 85
56 M por 1 NR metachronous LR 84
65 M tub1 1 NR metachronous H 86
61 M tub2 1 NR synchronous LR 77
52 M tub1 1 NR synchronous LR 78
52 F muc 1 NR synchronous LR 65
67 F tub2 1 NR metachronous LR 61
Ogawa 9 60 M pap 2 1.9 metachronous LR 32 1. Neoadjuvant chemotherapy
Our case 66 M tub2 1 3.5 metachronous LR 26

NR, not referred

In these studies, the median survival time ranged from 9 months to 38 months. One-year survival rates have ranged from 38% to 96%, and 5-year survival rates from 10% to 42%. The previously reported poor prognostic factors for hepatectomy for liver metastasis from gastric cancer are serosal invasion [9,12], lymph node metastasis of primary gastric cancer[10,14], maximum diameter of the liver metastasis[15,16], and synchronous metastasis[11,17].

Repeat hepatectomy has been well established as a radical treatment for hepatocellular carcinoma and liver metastasis from colorectal cancer[18-20]. However, there have been a limited number of reports regarding repeat hepatectomy for metastasis from gastric cancer (Table 2) [11,16].

Table 2: Reports of repeat hepatectomy for liver metastases from gastric cancer.

Author Year No. of patient Interval between 1sprimary hepatectomy and appearance of intrahepatic recurrence (months) Survival time after (month)
Okano 2002 1 26 138 (from 1st hepatectomy)
Saiura 2002 2 NR NR
Shirabe 2003 3 NR NR
Sakamoto 2003 4 10 (median) NR
Koga 2007 6 NR NR
Takemura 2012 14 9.5 (median) 31 (median) (from 2nd hepatectomy)
Komeda 2014 3 NR >96 (from 1st hepatectomy)
Our case 1 4 31 (from 1st hepatectomy)

NR, not referred

Takemura et al. reported that 14 patients (21.9%) out of 64 patients who had undergone curative hepatectomy for liver metastasis from gastric cancer successfully underwent repeat hepatectomy[16]. According to this analysis, a long interval between the primary hepatectomy and the appearance of intra hepatic recurrence was the only independent significant factor predicting better survival. These findings suggested that the malignant potential and controllability of tumor growth by chemotherapy of the recurrent tumor have the greatest impact on survival.

In our case, primary hepatectomy but not chemotherapy was performed 1 year after gastrectomy, because the hepatic tumor was solitary and no other reason was found on the results of a dynamic study. After the recurrence of a hepatic tumor, chemotherapy with S-1 plus CDDP was administered, which decreased the liver metastasis, with no appearance of any other remote metastases for 6 months. Thus, we believe that patients whose hepatic tumors are controllable by chemotherapy for long periods should be optimal candidates for repeat hepatectomy for liver metastasis from gastric cancer.

In conclusion, repeat hepatectomy for gastric cancer liver metastasis should be considered as one of the treatment options for the recurrence of gastric cancer liver metastasis to improve to the survival of these patients, although this does require careful selection of the optimal candidate.

Acknowledgements

The authors have no conflicts of interest to disclose and received no financial support for this study. All authors certify that they have no commercial associations that might pose a conflict of interest in connection with submitted article.

Authors’ contributions: YI, HT, SN, HH, YY and SH helped to draft the manuscript. JY and HU have revised manuscript critically. All authors read and approved the final manuscript.