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 Table of Contents  
Year : 2019  |  Volume : 52  |  Issue : 3  |  Page : 103-106

Long-term survival of a patient with advanced hepatoid type adenocarcinoma of stomach and liver metastasis

1 Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
2 Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung; Department of Nursing, Meiho University, Pingtung, Taiwan

Date of Submission12-May-2018
Date of Decision04-Jul-2018
Date of Acceptance21-Mar-2019
Date of Web Publication17-Jun-2019

Correspondence Address:
Dr. I-Shu Chen
Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung 81362
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/fjs.fjs_50_18

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Hepatoid adenocarcinoma is a rare variant of gastric cancer, and exhibits most of the characteristics of alpha-fetoprotein-secreting cancer; it has been reported to have poor outcomes irrespective of the treatment used. Here, we report a case wherein a relatively favorable outcome was obtained following surgical treatment of metastatic hepatoid adenocarcinoma originated in the stomach, and discuss the treatment of the disease. Metastatic gastric cancer is considered a systemic disease; however, even with a worse prognosis of the hepatic variant type, we achieved long term survival following surgical resection of primary and metastatic tumor. This experience highlights the importance of using aggressive surgical treatments for potentially resectable metastatic gastric cancer, irrespective of the tumor variant.

Keywords: Adenocarcinoma, alpha-fetoprotein, liver neoplasm metastasis, stomach

How to cite this article:
Hung CC, Liang TJ, Lee HP, Chen IS. Long-term survival of a patient with advanced hepatoid type adenocarcinoma of stomach and liver metastasis. Formos J Surg 2019;52:103-6

How to cite this URL:
Hung CC, Liang TJ, Lee HP, Chen IS. Long-term survival of a patient with advanced hepatoid type adenocarcinoma of stomach and liver metastasis. Formos J Surg [serial online] 2019 [cited 2021 Mar 8];52:103-6. Available from: https://www.e-fjs.org/text.asp?2019/52/3/103/260440

  Introduction Top

Hepatoid cancer has been described in a wide variety of tumors that secret alpha-fetoprotein (AFP), and have an extrahepatic origin. This specific tumor type has variable tissue origin, including the stomach, pancreas, ovaries, uterus, lungs, and gastrointestinal tract, with the most common origin being the stomach.[1] Hepatoid adenocarcinoma of the stomach (HAS) was first termed by Ishikura et al. in 1985 as a specific subtype of gastric cancer.[2] Owing to the rare incidence of the disease of <1%[3],[4],[5] among all gastric cancer cases, only few large-scale clinical trial and systematic studies have been conducted regarding this disease. However, according to the reported case series to date, the cases of this disease show a clinical presentation similar to that of ordinary adenocarcinomas, albeit showing an association high potential lymph node and liver metastasis and a significantly poor clinical outcome.[3] Early diagnosis and radical surgical treatment remain the gold standard for the treatment of this disease, although early detection has been achieved in only a few patients. However, in the present case, the patient experienced long-term disease-free survival despite the initial advanced disease presentation and distant metastasis.

  Case Report Top

An 84 year-old man with hypertension as the underlying disease of hypertension, benign prostatic hyperplasia, left renal stone following left nephrectomy in 2005, and bilateral inguinal hernia following Lichtenstein hernioplasty presented to our hospital. He reported intermittent epigastric, dull epigastric pain for 3 months before this presentation, in addition to abdominal bloating and acid regurgitation. However, he did not have nausea, vomiting, diarrhea, or tarry stool, and his body weight showed no substantial change at the initial clinical presentation. Accordingly, the patient underwent esophagogastroscopy that revealed a 4-cm Borrmann type III lesion over the lesser curvature side of the lower gastric body [Figure 1]. Abdominal computed tomography (CT) revealed regional lymphadenopathy, but intra-abdominally did not reveal any other suspicious metastatic lesion. His diagnosis was confirmed by endoscopic biopsy, which was pathologically confirmed to be poorly differentiated gastric adenocarcinoma. Accordingly, radical distal gastrectomy with D2 lymph node dissection was performed in November 2010. While surgical pathology revealed a T3N2, stage IIIA tumor, histology demonstrated the tumor to be a tubular adenocarcinoma [Figure 2]. Further, immunostaining demonstrated positive results for the MOC-31 antibody, focal-scattered positive results for hepatocyte antigen, and focal positive results for AFP. The patient received adjuvant oral Xeloda treatment following recovery and was followed up at our outpatient department. However, abdominal sonography performed in February 2011 revealed a 7-cm hypoechoic tumor lesion at the liver S7, whereas CT showed a hypoenhancement and hypodense tumor in the arterial and venous phases, in favor of a metastatic tumor [Figure 3]. The tumor exhibited rapid growth, with an approximate doubling in size from 7.40 to 12.71 cm in 2 months [Figure 4]. In June 2011, liver S7-8 segmental resection with concurrent cholecystectomy was performed. During the operation, a small nodule approximately 1.1 cm × 1.5 cm × 0.4 cm was observed on the diaphragm and was completely resected. Both specimens were pathologically found to be metastatic hepatoid-variant adenocarcinomas with gastric origin [Figure 5]. Notably, the surgery was smoothly performed without any complication, and the patient was postoperatively maintained on adjuvant oral Xeloda therapy until the 2-year treatment was completed. The AFP level dropped from the preoperative value of 474.9 to <3.0 ng/mL after 3 months of the surgery and showed no elevation thereafter. A recently performed abdominal sonogram and chest X-ray did not reveal any evidence of a metastatic tumor lesion, and the patient is currently disease free and living a fair quality of life.
Figure 1: Esophagogastroduodenoscopy on November 10, 2010, revealed a Bormann Type III lesion over lesser curvature side of gastric lower body

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Figure 2: Stomach, poorly differentiated adenocarcinoma, with solid growth pattern (H and E, ×200)

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Figure 3: Contrasted abdominal computed tomography on March 23, 2011 revealed a hypoenhance and early wash-out well-margined tumor over segment 7–8 of liver

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Figure 4: Computed tomography on June 7, 2011, the tumor expressed rapid growth and nearly doubled the diameter in a 3-month period

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Figure 5: Liver, metastatic poorly differentiated adenocarcinoma, with polygonal neoplastic cells with abundant cytoplasm, partly similar to previous gastric adenocarcinoma morphologically (H and E, ×200)

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  Discussion Top

In some previous studies, HAS has been described as a highly malignant tumor with an aggressive behavior, and patients diagnosed with HAS reportedly have a poor prognosis, with a reported 3-year survival of 7%–13%.[5],[6] Its most common site of metastasis is liver, with an incidence of 46.3%–75.6%.[5],[7]

The Japanese Gastric Cancer Treatment Guidelines (version 4) announced an algorithm that did not suggest curative treatment for M1 gastric cancer due to the absence of a prospective trial demonstrated a benefit of hepatectomy. However, it also suggested that curative treatment in highly selected patients, such as those with solitary or few metastatic tumors, may present favorable outcomes. In our case, although the patient was older (operated at the age of 84-year-old and he is 90-year-old now), he did not have any marked underlying disease with a fairly controlled hypertension and Grade 0 on the Eastern Co-operative of Oncology Group index. Although a solitary tumor seeding on the diaphragm was incidentally noted during the surgery, the patient's clinical outcome following curative surgical resection seemed to be favorable.

Previous studies presented an aggressive tumor behavior and a high rate of concurrent gastric and liver lesions at the time of diagnosis. However, in our case, abdominal CT revealed no detectable tumor before the surgery.

We further retrospectively reviewed the pathology data of our hospital and discovered that our patient was the only patient diagnosed with HAS among 586 patients who underwent gastrectomy in the past 10 years, accounting for 0.17%. This incidence is lower than that reported in previous studies, i.e., 0.3%–1%, and it may be severely underestimated because we do not consider AFP level in the routine gastric cancer survey and the pathological examination performed at hospital does not regularly involve AFP staining for primary adenocarcinomas.

In the present case, the patient seemed to benefit from the radical surgery, although chemotherapy alone with capecitabine failed to prevent metastasis and disease progression. Hirashima et al.[8] also reported a case in which AFP-producing gastric cancer seemed to be resistant to chemotherapy regimen with 5-fluoronucleotide prodrugs such as TS-1, and the tumor was much more sensitive to paclitaxel-based chemotherapy. This conclusion was based on the theory of the 5-fluorouracil prodrug that needed to be converted inside a tumor cell, where the inhibition protein was expressed within an AFP-producing tumor. However, recent case reports have demonstrated that the tumor also shows the response to TS-1 either alone [9] or in combination with other chemotherapies,[10],[11],[12] indicating that AFP-producing adenocarcinoma of the stomach can be further classified into different subtypes according to the response to chemotherapy.

Clinical reports and analyses have shown different results for survival and tumor behavior among the subgroups of AFP-producing adenocarcinomas.[13] Recent studies have revealed that HAS is associated with AFP-producing tumor, but HAS is not necessarily the same as AFP-producing tumor, because some HAS do not secrete AFP, and the prognosis of AFP-secreting gastric cancer substantially differs from that of HAS. Further, AFP-secreting gastric cancer and HAS showed marked poor prognoses compared with common gastric cancer.

The clinical importance of differentiating hepatoid-type gastric cancer from common gastric adenocarcinoma is that patients with the former cancer require extended radical lymph node dissection during the initial operation considering the high rate of lymph node extension. The diagnosis also indicates a closer postoperative follow-up for liver metastasis, chemotherapy regimen choice. Furthermore, our patient successfully demonstrated that surgical treatment remains a treatment option when solitary metastasis is detected. Remarkably, the patient postoperatively had a preserved physical condition.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Metzgeroth G, Ströbel P, Baumbusch T, Reiter A, Hastka J. Hepatoid adenocarcinoma-review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie 2010;33:263-9.  Back to cited text no. 1
Ishikura H, Kirimoto K, Shamoto M, Miyamoto Y, Yamagiwa H, Itoh T, et al. Hepatoid adenocarcinomas of the stomach. An analysis of seven cases. Cancer 1986;58:119-26.  Back to cited text no. 2
Qu BG, Bi WM, Qu BT, Qu T, Han XH, Wang H, et al. PRISMA-compliant article: Clinical characteristics and factors influencing prognosis of patients with hepatoid adenocarcinoma of the stomach in China. Medicine (Baltimore) 2016;95:e3399.  Back to cited text no. 3
Kumashiro Y, Yao T, Aishima S, Hirahashi M, Nishiyama K, Yamada T, et al. Hepatoid adenocarcinoma of the stomach: Histogenesis and progression in association with intestinal phenotype. Hum Pathol 2007;38:857-63.  Back to cited text no. 4
Liu X, Cheng Y, Sheng W, Lu H, Xu X, Xu Y, et al. Analysis of clinicopathologic features and prognostic factors in hepatoid adenocarcinoma of the stomach. Am J Surg Pathol 2010;34:1465-71.  Back to cited text no. 5
Chang YC, Nagasue N, Abe S, Taniura H, Kumar DD, Nakamura T. Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers. Am J Gastroenterol 1992;87:321-5.  Back to cited text no. 6
Su JS, Chen YT, Wang RC, Wu CY, Lee SW, Lee TY, et al. Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: A literature review. World J Gastroenterol 2013;19:321-7.  Back to cited text no. 7
Hirashima Y, Kitajima K, Sugi S, Kagawa K, Kumamoto T, Murakami K, et al. Successful bi-weekly paclitaxel treatment of an AFP-producing gastric cancer patient with peritoneal dissemination and multiple liver metastasis. Gan To Kagaku Ryoho 2006;33:517-9.  Back to cited text no. 8
Sano T, Usuki H, Takebayashi R, Akamoto S, Inoue T, Kakinoki K, et al. A case of stage IV AFP producing gastric cancer with long-term survival treated by adjuvant chemotherapy with S-1. Gan To Kagaku Ryoho 2010;37:521-6.  Back to cited text no. 9
Bozkaya Y, Doǧan M, Yazıcı O, Erdem GU, Demirci NS, Zengin N. The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma. Bosn J Basic Med Sci 2017;17:138-43.  Back to cited text no. 10
Nagai Y, Kato T, Harano M, Satoh D, Choda Y, Tokumoto N, et al. A case of AFP-producing esophagogastric junction cancer with liver metastases with a good response to chemotherapy. Gan To Kagaku Ryoho 2014;41:2349-51.  Back to cited text no. 11
Nishiwada S, Watanabe A, Yoshikawa T, Ishioka K, Mukogawa T, Matsusaka M, et al. A case of AFP-producing gastric cancer with peritoneal metastasis treated effectively with chemotherapy, mainly using S-1 and trastuzumab. Gan To Kagaku Ryoho 2013;40:511-4.  Back to cited text no. 12
Liu X, Sheng W, Wang Y. An analysis of clinicopathological features and prognosis by comparing hepatoid adenocarcinoma of the stomach with AFP-producing gastric cancer. J Surg Oncol 2012;106:299-303.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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