- Email: [email protected]
Gastric Metastasis of Hepatocellular Carcinoma With Gastrointestinal Bleeding After Liver Transplant: A Case Report
Gastric Metastasis of Hepatocellular Carcinoma With Gastrointestinal Bleeding After Liver Transplant: A Case Report L. Lia, W.H. Zhanga, F.P. Menga, X.M. Maa, L.J. Shena, B. Jina, H.W. Lia,*, J. Hana, G.D. Zhoub, and S.H. Liub a Liver Cirrhosis Treatment Center, 302 Military Hospital of China, Beijing, China; and bDepartment of Pathology, 302 Military Hospital of China, Beijing, China
ABSTRACT Gastrointestinal (GI) metastasis of hepatocellular carcinoma is very rare. This is the first report of post-transplantation gastric metastasis. A 43-year-old man with a history of hepatitis Berelated hepatocellular carcinoma (HCC) in the right anterior segment of the liver received an orthotopic liver transplant. Three months after the transplantation, pulmonary metastasis was found by chest computed tomography, and he received 1 course of gamma knife treatment. He complained of melena with anemia 17 months post liver transplantation. Abdominal CT scan showed new occupying lesions in the liver and a mass in the stomach and around the spleen with embolus in the splenic vein. Endoscopy revealed a large irregular cauliflower-like mass in fundus with ulceration and bleeding on the surface. He received symptomatic treatment, but died of cancer-related bleeding 4 months later. GI bleeding may due to gastric metastasis after liver transplantation.
H
EPATOCELLULAR CARCINOMA (HCC) constitutes the sixth most frequent form of cancer worldwide and is the third most common cause of malignancy-related mortality [1]. About 650,000 new HCC patients are diagnosed every year worldwide, half of them in China. Chronic hepatitis B is the major risk factor for developing HCC in China. Eighty percent of liver cancers are found in patients with cirrhosis, which itself carries a high risk for developing HCC. Despite considerable progress concerning the diagnosis and therapy of HCC, its prognosis has not improved very much over time. Here we report a case of post-transplantation gastric metastasis of HCC in an HBsAg-positive patient who had liver cirrhosis.
CASE REPORT A 43-year-old Chinese male was found to be HBsAg positive by chance in 2000 during a routine health examination. In 2008, an abdominal ultrasound showed findings consistent with liver cirrhosis and splenomegaly. At that time, he appeared to have normal liver function. On September 10, 2010, he was referred to our hospital complaining of abdominal distention and diarrhea for longer than 20 days and bloody stools for 1 night. Physical examination was normal except for weak breathing sounds of the lungs and positive shifting dullness. Laboratory examination
revealed white blood cells 19.95 109/L (4e10 109/L), neutrophils 0.838 (0.50e0.70), red blood cells 3.17 1012/L (3.5e5.5 1012/L), hemoglobin 93 g/L (110e160 g/L), platelets 353 109/L (100e300 109/L), liver function markers ALB 37.9 g/L (35e55 g/ L), total bilirubin 31.8 mol/L (2e22 mol/L), direct bilirubin 18.4 mol/L (0e6 mmol/L), ALT 35.5 U/L (0e40 U/L), AST 40.5 U/L (0e40 U/L), ALP 188.2 U/L (40e150 U/L), r- glutamyl transferase 391.8 U/L (0e50 U/L), BUN 10.58 mmol/L (1.7e8.1 mmol/L), creatinine 94.3 mol/L (40e106 mol/L), alpha fetal protein 59.78 ng/ mL (<25 ng/mL). Serology was positive for hepatitis BsAg, and HBV DNA was 2.4 103 IU/mL. Gastroscopy 12 hours after admission showed acute hemorrhagic gastritis without esophageal and gastric varices. Abdominal CT scan disclosed an 8 5 cm lesion in the right anterior segment of the liver, and ascites. Preoperative lung CT showed right hydrothorax. According to Hangzhou Criteria of China [2], he received an orthotopic liver transplantation on September 28, 2010. Postoperative histological examination demonstrated a moderately differentiated (histopathologic grade II) hepatocellular carcinoma (HCC). Immunohistocehmical staining revealed: CK8 (þþ), Hepa (þþþ), CK19 (), CK7 (), CK10 (), CD34 (þ), Ki67 (>30%), HBsAg (þ).
*Address correspondence to Han Wei Li, Liver Cirrhosis Treatment Center, 302 Military Hospital of China, Beijing 100049, China. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.09.012
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2544
Transplantation Proceedings, 47, 2544e2547 (2015)
GASTRIC METASTASIS OF HCC Three months post-transplantation, pulmonary metastasis was found by chest CT. He received gamma knife for 1 course of treatment (10 times), and the nodules in his lungs decreased after 3 months. In February 2012, he was admitted to our hospital again complaining of melena for half a month. Laboratory examination revealed HGB 22 g/L, AFP 191 ng/mL, HBV DNA 1.9 103 IU/ mL. Abdominal CT scan showed new occupying lesions in the liver, lesions in the stomach and around the spleen with a thrombus in the splenic vein, and peripheral celiac artery lymph node enlargements suggesting metastases (Fig 1). Upper endoscopy showed a large irregular cauliflower-like mass in fundus with ulceration and bleeding of the surface (Fig 2). Pathologic examination of biopsies of the mass revealed gastric metastasis of moderate differentiated HCC (Fig 3). An immunohistochemical staining profile showed that the tumor was CK8 (þþ), Hepa (þþþ), AFP (þ), CK19 (), CK7 (), CK10 (), CD34 (þ), Ki67 (þ<70%), which was identical to the original HCC. He received conservative management including proton pump inhibitors and blood transfusions. He refused further palliative treatment, and was discharged from the hospital when his condition became stable. On June 7, 2012, he died from upper gastrointestinal (GI) hemorrhage at the local hospital.
2545
Fig 2. Upper endoscopy showed an irregular cauliflower-like mass in fundus with ulceration and bleeding in the surface.
Extrahepatic metastasis from HCC has been reported to occur frequently in 30% to 75% of patients [3]. The most common sites of metastasis are the lungs, regional lymph nodes, bones, and adrenal glands. However, gastrointestinal metastasis of HCC is very rare. Shiota et al [4] first reported a patient with an unresectable HCC who survived 44 months without active treatment. However, his condition deteriorated rapidly following GI bleeding due to the direct invasion of the stomach by HCC 2 months before death. Chen et al [5] reported 8 of 396 patients (2%) with HCC were diagnosed with GI tract metastasis, and the sites of involvement were the stomach (3), duodenum (4), and jejunum (1). Lin et al [6] reported that 11 of 2237 hepatoma patients (0.49%) had GI tract
metastasis, including stomach (5), duodenum (2), colon (3), and duodenum and colon (1). Hu et al [7] also reported that 7 of 8267 HCC patients (0.08%) developed gastric metastasis. There have been more than 30 case reports of HCC patients with gastric invasion during the course of the disease, including our report (see Table 1). However, this is the first case study to report gastric involvement with bleeding after orthotopic liver transplantation in a HCC patient. Thirty-two patients with gastric involvement by HCC have been reported in the literature. Ten patients underwent TAE, and 8 received surgical resection. Palliative treatment for control of bleeding was undertaken to improve the condition and prolong life in 11 patients, including the present case. When the GI tract is involved, the prognosis is dismal. In cases of gastric invasion, the prognosis is even worse, with a poor 1-year survival rate [14]. Patients who
Fig 1. CT scan showed new occupying lesions in liver; lesions in stomach and around spleen with a thrombus in splenic vein; and peripheral celiac artery lymph node enlargement.
Fig 3. Microscopic appearance of gastric metastasis of moderate differentiated HCC-10.
DISCUSSION
2546
LI, ZHANG, MENG ET AL
Table 1. Data From Previously Reported Cases of Gastric Invasion With HCC Author, year
Number
Age/gender
Follow up (mo)
Shiota et al, 1983 [4] Chen et al, 1990 [5] Nicoll et al, 1994 [8] Yeo et al, 1995 [9] Maruyama et al, 1999 [10] Srivastava et al, 2000 [11] Lin et al, 2000 [6] Fujii et al, 2004 [12] Inoue et al, 2004 [13] Ong et al, 2007 [14] Kim et al, 2007 [15] Kimura et al, 2008 [16] Hatano et al, 2008 [17] Perini et al, 2009 [18] Kim et al, 2009 [19] Korkolis et al, 2009 [20] Hu et al, 2010 [7] Park et al, 2010 [21] Present case
1 3 1 3 1 1 5 1 1 1 1 1 1 1 1 1 7 1 1
56/m 48,59,86/m 61/m na 65/m 58/m 53e63/na 61/m 71/m 67/m 69/m 54/m 68/m 41/m 67/w 70/m na/m 63/m 43/m
44 1,2,1 7 na 5 0 0.7e9.7 32 na 33 na 3 na 41 3 >16 1.8e4.2 3.5 4
Abbreviations: m, male; na, not available; mo, months.
had undergone oncologic surgery for cure survived for significantly longer times compared to those receiving nonsurgical or supportive treatment [12]. Complete surgical resection should be considered in selected patients with an appropriate hepatic functional reserve [20]. However, most patients were in poor condition when HCC was found to be metastatic to the stomach or other organ involvement. Transplantation has been established as a viable treatment for HCC measuring less than 5 cm. Due to the scarcity of donors and the fact that size is the main prognostic factor, Milan criteria have been used since 1996 to select HCC patients for liver transplantation. In 2001, UCSF criteria showed that inclusion of layer tumors did not reduce survival results. Fernandez [26] concluded that increasing the HCC size among LT according to the UCSF criteria did not reduce survival rates compared with the Milan criteria. The UCSF criteria include a single tumor less than 6.5 cm or multiple tumors with a total size <8 cm, no single one of which is greater than 4.5 cm. The patient in the present case underwent liver transplantation according to the Hangzhou criteria [2], which was suggested by Zheng et al in 2006. Based on the prognostic stratification of different risk groups of patients without macrovascular invasion, Hangzhou criteria were established, containing 1 of the 2 following items: (a) total tumor diameter less than or equal to 8 cm; (b) total tumor diameter more than 8 cm, with both histopathologic grade I or II and preoperative AFP level less than or equal to 400 ng/mL. Upper endoscopy and biopsy constitute the main method to diagnose gastric metastasis in HCC patients. Almost all the reported cases were at an advanced stage of HCC at the time of diagnosis. Moreover, it is sometimes difficult to differentiate gastric metastasis of HCC from gastric hepatocellular adenocarcinoma (HAC) with liver metastasis.
Gastric HAC is a very rare type of stomach cancer. Nagai et al [22] suggested that a diagnosis of HAC of the stomach should be based on recognition of characteristic histologic features. The evidence for the diagnosis of gastric HAC included (1) the gastric cancer was the primary lesion, with characteristics of both hepatocellular and poorly differentiated adenocarcinoma histologically; (2) AFP, a-AAT, aACT were positive by immunohistological staining; and (3) HCC is excluded when HAC develops liver metastasis [27]. When primary HCC invades the stomach, the serosa is involved first. This is in contrast to the route of progression in primary HAC arising from the gastric mucosa. Both HAC and HCC can secrete AFP. However, HAC is usually HepPae1 negative, and MOC-31 positive. In HCC, the opposite is usually the case [28]. Direct invasion by adherent tumor is presumed to be the major mode of GI tract involvement [16]. Several reports have suggested that transarterial chemoembolization (TACE) or intra-arterial chemotherapy in HCC patients may induce tumor necrosis and subcapsular tumor adhesion to the GI serosa [5,7]. Inoue et al [13] noted swelling of an extrahepatic lymph node rather than hepatoma invasion directly to the stomach, suggesting the metastasis to the GI tract via lymph nodes. Park et al [23] reported that the main factors for the direct invasion were growth pattern, tumor size, and location as determined by radiologic findings of GI involvement. Some authors [24,25] have suggested that metastasis of HCC may due to portal vein thrombosis, and hepatofugal blood flow to the GI tract. It is unclear why the present patient had lung metastases 3 months post liver transplantation and gastric involvement 17 months after the operation. It is possible that hepatofugal blood flow was responsible for the route of the metastasis. However, the abdominal CT scan showed many small lesions in the liver and enlarged peripheral celiac artery lymph nodes, suggesting that the metastasis in the current case had occurred via a translymphatic route. REFERENCES [1] Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet 2013;381:1987e2015. [2] Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation 2008;85:1726e32. [3] El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557e76. [4] Shiota T, Watanabe A, Mitani K, Ito T, Tobe K, Nagashima H. Long-term survival in a case of hepatocellular carcinoma. Acta Med Okayama 1983;37:73e8. [5] Chen LT, Chen CY, Jan CM, et al. Gastrointestinal tract involvement in hepatocellular carcinoma: clinical, radiological and endoscopic studies. Endoscopy 1990;22:118e23. [6] Lin CP, Cheng JS, Lai KH, et al. Gastrointestinal metastasis in hepatocellular carcinoma: radiological and endoscopic studies of 11 cases. J Gastroenterol Hepatol 2000;15:536e41. [7] Hu ML, Tai WC, Chuah SK, et al. Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway. J Gastroenterol Hepatol 2010;25:408e12.
GASTRIC METASTASIS OF HCC [8] Nicoll AJ, Ireton HJ, Crotty B. Gastrointestinal bleeding from hepatocellular carcinoma invading the stomach. J Gastroenterol Hepatol 1994;9:533e5. [9] Yeo W, Sung JY, Ward SC, et al. A prospective study of upper gastrointestinal hemorrhage in patients with hepatocellular carcinoma. Dig Dis Sci 1995;40:2516e21. [10] Maruyama A, Murabayashi K, Hayashi M, et al. Hepatocellular carcinoma complicated by gastrointestinal hemorrhage caused by direct tumor invasion of stomach. J Hepatobiliary Pancreat Surg 1999;6:90e3. [11] Srivastava DN, Gandhi D, Julka PK, Tandon RK. Gastrointestinal hemorrhage in hepatocellular carcinoma: management with transhepatic arterioembolization. Abdom Imaging 2000;25:380e4. [12] Fujii K, Nagino M, Kamiya J, et al. Complete resection of hepatocellular carcinoma with direct invasion to the stomach remnant. J Hepatobiliary Pancreat Surg 2004;11:441e4. [13] Inoue H, Sawada Y, Ochiai K, et al. Hepatocellular carcinoma with direct invasion to the stomach. Intern Med 2007;46:845e8. [14] Ong JC, Chow PK, Chan WH, Chung AY, Thng CH, Wong WK. Hepatocellular carcinoma masquerading as a bleeding gastric ulcer: a case report and a review of the surgical management. World J Gastroenterol 2007;13:4523e5. [15] Kim JH, Park JW, Choi JI, et al. Gastric metastasis of hepatocellular carcinoma treated by transarterial chemoembolization: a case report. Korean J Hepatol 2007;13:91e5. [16] Kimura K, Miura H, Saito S, et al. Hepatocellular carcinoma with direct invasion to the stomach causing gastrointestinal hemorrhage. Intern Med 2008;47:671e4. [17] Hatano K, Kita R, Sakamoto Y, et al. Case of moderately differentiated hepatocellular carcinoma with gastric metastasis. Nihon Shokakibyo Gakkai Zasshi 2008;105:404e11. [18] Perini MV, Herman P, Pessoa R, Saad WA, D’Albuquerque LA. Unusual cause of gastrointestinal bleeding in a cirrhotic patient: hepatocellular carcinoma with gastric invasion. Hepatobiliary Pancreat Dis Int 2009;8:431e3.
2547 [19] Kim DH, Eun JR, Moon HJ, et al. A case of peritoneal seeding from a ruptured hepatocellular carcinoma with direct invasion into the stomach causing gastrointestinal hemorrhage. Korean J Gastroenterol 2009;53:194e7. [20] Korkolis DP, Aggeli C, Plataniotis GD, et al. Successful en bloc resection of primary hepatocellular carcinoma directly invading the stomach and pancreas. World J Gastroenterol 2009;15: 1134e7. [21] Park H, Kim SU, Choi J, et al. Hepatogastric fistula caused by direct invasion of hepatocellular carcinoma after transarterial chemoembolization and radiotherapy. Korean J Hepatol 2010;16: 401. [22] Nagai E, Ueyama T, Yao T, Tsuneyoshi M. Hepatoid adenocarcinoma of the stomach. A clinicopathologic and immunohistochemical analysis. Cancer 1993;72:1827. [23] Park MS, Kim KW, Yu JS, et al. Radiologic findings of gastrointestinal tract involvement in hepatocellular carcinoma. J Comput Assist Tomogr 2002;26:95. [24] Hashimoto M, Watanabe G, Matsuda M, Yamamoto T, Tsutsumi K, Tsurumaru M. Case report: Gastrointestinal bleeding from a hepatocellular carcinoma invading the transverse colon. J Gastroenterol Hepatol 1996;11:765. [25] Chen CY, Lu CL, Pan CC, Chiang JH, Chang FY, Lee SD. Lower gastrointestinal bleeding from a hepatocellular carcinoma invading colon. J Clin Gastroenterol 1997;25:373. [26] Fernández JA, Robles R, Marin C, et al. Can we expand the indications for liver transplantation among hepatocellular carcinoma patients with increased tumor size? Transplant Proc 2003;35: 1818. [27] Lu CC, De-Chuan C, Lee HS, et al. Pure hepatoid adenocarcinoma of the stomach with spleen and lymph-node metastases. Am J Surg 2010;199:42. [28] Liu CW, Hsu CC, Chang HC, et al. Hepatoid adenocarcinoma of the stomach with liver metastasis mimicking hepatocellular carcinoma: a case report. Cases J 2009;2:6317.
ABSTRACT Gastrointestinal (GI) metastasis of hepatocellular carcinoma is very rare. This is the first report of post-transplantation gastric metastasis. A 43-year-old man with a history of hepatitis Berelated hepatocellular carcinoma (HCC) in the right anterior segment of the liver received an orthotopic liver transplant. Three months after the transplantation, pulmonary metastasis was found by chest computed tomography, and he received 1 course of gamma knife treatment. He complained of melena with anemia 17 months post liver transplantation. Abdominal CT scan showed new occupying lesions in the liver and a mass in the stomach and around the spleen with embolus in the splenic vein. Endoscopy revealed a large irregular cauliflower-like mass in fundus with ulceration and bleeding on the surface. He received symptomatic treatment, but died of cancer-related bleeding 4 months later. GI bleeding may due to gastric metastasis after liver transplantation.
H
EPATOCELLULAR CARCINOMA (HCC) constitutes the sixth most frequent form of cancer worldwide and is the third most common cause of malignancy-related mortality [1]. About 650,000 new HCC patients are diagnosed every year worldwide, half of them in China. Chronic hepatitis B is the major risk factor for developing HCC in China. Eighty percent of liver cancers are found in patients with cirrhosis, which itself carries a high risk for developing HCC. Despite considerable progress concerning the diagnosis and therapy of HCC, its prognosis has not improved very much over time. Here we report a case of post-transplantation gastric metastasis of HCC in an HBsAg-positive patient who had liver cirrhosis.
CASE REPORT A 43-year-old Chinese male was found to be HBsAg positive by chance in 2000 during a routine health examination. In 2008, an abdominal ultrasound showed findings consistent with liver cirrhosis and splenomegaly. At that time, he appeared to have normal liver function. On September 10, 2010, he was referred to our hospital complaining of abdominal distention and diarrhea for longer than 20 days and bloody stools for 1 night. Physical examination was normal except for weak breathing sounds of the lungs and positive shifting dullness. Laboratory examination
revealed white blood cells 19.95 109/L (4e10 109/L), neutrophils 0.838 (0.50e0.70), red blood cells 3.17 1012/L (3.5e5.5 1012/L), hemoglobin 93 g/L (110e160 g/L), platelets 353 109/L (100e300 109/L), liver function markers ALB 37.9 g/L (35e55 g/ L), total bilirubin 31.8 mol/L (2e22 mol/L), direct bilirubin 18.4 mol/L (0e6 mmol/L), ALT 35.5 U/L (0e40 U/L), AST 40.5 U/L (0e40 U/L), ALP 188.2 U/L (40e150 U/L), r- glutamyl transferase 391.8 U/L (0e50 U/L), BUN 10.58 mmol/L (1.7e8.1 mmol/L), creatinine 94.3 mol/L (40e106 mol/L), alpha fetal protein 59.78 ng/ mL (<25 ng/mL). Serology was positive for hepatitis BsAg, and HBV DNA was 2.4 103 IU/mL. Gastroscopy 12 hours after admission showed acute hemorrhagic gastritis without esophageal and gastric varices. Abdominal CT scan disclosed an 8 5 cm lesion in the right anterior segment of the liver, and ascites. Preoperative lung CT showed right hydrothorax. According to Hangzhou Criteria of China [2], he received an orthotopic liver transplantation on September 28, 2010. Postoperative histological examination demonstrated a moderately differentiated (histopathologic grade II) hepatocellular carcinoma (HCC). Immunohistocehmical staining revealed: CK8 (þþ), Hepa (þþþ), CK19 (), CK7 (), CK10 (), CD34 (þ), Ki67 (>30%), HBsAg (þ).
*Address correspondence to Han Wei Li, Liver Cirrhosis Treatment Center, 302 Military Hospital of China, Beijing 100049, China. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.09.012
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2544
Transplantation Proceedings, 47, 2544e2547 (2015)
GASTRIC METASTASIS OF HCC Three months post-transplantation, pulmonary metastasis was found by chest CT. He received gamma knife for 1 course of treatment (10 times), and the nodules in his lungs decreased after 3 months. In February 2012, he was admitted to our hospital again complaining of melena for half a month. Laboratory examination revealed HGB 22 g/L, AFP 191 ng/mL, HBV DNA 1.9 103 IU/ mL. Abdominal CT scan showed new occupying lesions in the liver, lesions in the stomach and around the spleen with a thrombus in the splenic vein, and peripheral celiac artery lymph node enlargements suggesting metastases (Fig 1). Upper endoscopy showed a large irregular cauliflower-like mass in fundus with ulceration and bleeding of the surface (Fig 2). Pathologic examination of biopsies of the mass revealed gastric metastasis of moderate differentiated HCC (Fig 3). An immunohistochemical staining profile showed that the tumor was CK8 (þþ), Hepa (þþþ), AFP (þ), CK19 (), CK7 (), CK10 (), CD34 (þ), Ki67 (þ<70%), which was identical to the original HCC. He received conservative management including proton pump inhibitors and blood transfusions. He refused further palliative treatment, and was discharged from the hospital when his condition became stable. On June 7, 2012, he died from upper gastrointestinal (GI) hemorrhage at the local hospital.
2545
Fig 2. Upper endoscopy showed an irregular cauliflower-like mass in fundus with ulceration and bleeding in the surface.
Extrahepatic metastasis from HCC has been reported to occur frequently in 30% to 75% of patients [3]. The most common sites of metastasis are the lungs, regional lymph nodes, bones, and adrenal glands. However, gastrointestinal metastasis of HCC is very rare. Shiota et al [4] first reported a patient with an unresectable HCC who survived 44 months without active treatment. However, his condition deteriorated rapidly following GI bleeding due to the direct invasion of the stomach by HCC 2 months before death. Chen et al [5] reported 8 of 396 patients (2%) with HCC were diagnosed with GI tract metastasis, and the sites of involvement were the stomach (3), duodenum (4), and jejunum (1). Lin et al [6] reported that 11 of 2237 hepatoma patients (0.49%) had GI tract
metastasis, including stomach (5), duodenum (2), colon (3), and duodenum and colon (1). Hu et al [7] also reported that 7 of 8267 HCC patients (0.08%) developed gastric metastasis. There have been more than 30 case reports of HCC patients with gastric invasion during the course of the disease, including our report (see Table 1). However, this is the first case study to report gastric involvement with bleeding after orthotopic liver transplantation in a HCC patient. Thirty-two patients with gastric involvement by HCC have been reported in the literature. Ten patients underwent TAE, and 8 received surgical resection. Palliative treatment for control of bleeding was undertaken to improve the condition and prolong life in 11 patients, including the present case. When the GI tract is involved, the prognosis is dismal. In cases of gastric invasion, the prognosis is even worse, with a poor 1-year survival rate [14]. Patients who
Fig 1. CT scan showed new occupying lesions in liver; lesions in stomach and around spleen with a thrombus in splenic vein; and peripheral celiac artery lymph node enlargement.
Fig 3. Microscopic appearance of gastric metastasis of moderate differentiated HCC-10.
DISCUSSION
2546
LI, ZHANG, MENG ET AL
Table 1. Data From Previously Reported Cases of Gastric Invasion With HCC Author, year
Number
Age/gender
Follow up (mo)
Shiota et al, 1983 [4] Chen et al, 1990 [5] Nicoll et al, 1994 [8] Yeo et al, 1995 [9] Maruyama et al, 1999 [10] Srivastava et al, 2000 [11] Lin et al, 2000 [6] Fujii et al, 2004 [12] Inoue et al, 2004 [13] Ong et al, 2007 [14] Kim et al, 2007 [15] Kimura et al, 2008 [16] Hatano et al, 2008 [17] Perini et al, 2009 [18] Kim et al, 2009 [19] Korkolis et al, 2009 [20] Hu et al, 2010 [7] Park et al, 2010 [21] Present case
1 3 1 3 1 1 5 1 1 1 1 1 1 1 1 1 7 1 1
56/m 48,59,86/m 61/m na 65/m 58/m 53e63/na 61/m 71/m 67/m 69/m 54/m 68/m 41/m 67/w 70/m na/m 63/m 43/m
44 1,2,1 7 na 5 0 0.7e9.7 32 na 33 na 3 na 41 3 >16 1.8e4.2 3.5 4
Abbreviations: m, male; na, not available; mo, months.
had undergone oncologic surgery for cure survived for significantly longer times compared to those receiving nonsurgical or supportive treatment [12]. Complete surgical resection should be considered in selected patients with an appropriate hepatic functional reserve [20]. However, most patients were in poor condition when HCC was found to be metastatic to the stomach or other organ involvement. Transplantation has been established as a viable treatment for HCC measuring less than 5 cm. Due to the scarcity of donors and the fact that size is the main prognostic factor, Milan criteria have been used since 1996 to select HCC patients for liver transplantation. In 2001, UCSF criteria showed that inclusion of layer tumors did not reduce survival results. Fernandez [26] concluded that increasing the HCC size among LT according to the UCSF criteria did not reduce survival rates compared with the Milan criteria. The UCSF criteria include a single tumor less than 6.5 cm or multiple tumors with a total size <8 cm, no single one of which is greater than 4.5 cm. The patient in the present case underwent liver transplantation according to the Hangzhou criteria [2], which was suggested by Zheng et al in 2006. Based on the prognostic stratification of different risk groups of patients without macrovascular invasion, Hangzhou criteria were established, containing 1 of the 2 following items: (a) total tumor diameter less than or equal to 8 cm; (b) total tumor diameter more than 8 cm, with both histopathologic grade I or II and preoperative AFP level less than or equal to 400 ng/mL. Upper endoscopy and biopsy constitute the main method to diagnose gastric metastasis in HCC patients. Almost all the reported cases were at an advanced stage of HCC at the time of diagnosis. Moreover, it is sometimes difficult to differentiate gastric metastasis of HCC from gastric hepatocellular adenocarcinoma (HAC) with liver metastasis.
Gastric HAC is a very rare type of stomach cancer. Nagai et al [22] suggested that a diagnosis of HAC of the stomach should be based on recognition of characteristic histologic features. The evidence for the diagnosis of gastric HAC included (1) the gastric cancer was the primary lesion, with characteristics of both hepatocellular and poorly differentiated adenocarcinoma histologically; (2) AFP, a-AAT, aACT were positive by immunohistological staining; and (3) HCC is excluded when HAC develops liver metastasis [27]. When primary HCC invades the stomach, the serosa is involved first. This is in contrast to the route of progression in primary HAC arising from the gastric mucosa. Both HAC and HCC can secrete AFP. However, HAC is usually HepPae1 negative, and MOC-31 positive. In HCC, the opposite is usually the case [28]. Direct invasion by adherent tumor is presumed to be the major mode of GI tract involvement [16]. Several reports have suggested that transarterial chemoembolization (TACE) or intra-arterial chemotherapy in HCC patients may induce tumor necrosis and subcapsular tumor adhesion to the GI serosa [5,7]. Inoue et al [13] noted swelling of an extrahepatic lymph node rather than hepatoma invasion directly to the stomach, suggesting the metastasis to the GI tract via lymph nodes. Park et al [23] reported that the main factors for the direct invasion were growth pattern, tumor size, and location as determined by radiologic findings of GI involvement. Some authors [24,25] have suggested that metastasis of HCC may due to portal vein thrombosis, and hepatofugal blood flow to the GI tract. It is unclear why the present patient had lung metastases 3 months post liver transplantation and gastric involvement 17 months after the operation. It is possible that hepatofugal blood flow was responsible for the route of the metastasis. However, the abdominal CT scan showed many small lesions in the liver and enlarged peripheral celiac artery lymph nodes, suggesting that the metastasis in the current case had occurred via a translymphatic route. REFERENCES [1] Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet 2013;381:1987e2015. [2] Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation 2008;85:1726e32. [3] El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557e76. [4] Shiota T, Watanabe A, Mitani K, Ito T, Tobe K, Nagashima H. Long-term survival in a case of hepatocellular carcinoma. Acta Med Okayama 1983;37:73e8. [5] Chen LT, Chen CY, Jan CM, et al. Gastrointestinal tract involvement in hepatocellular carcinoma: clinical, radiological and endoscopic studies. Endoscopy 1990;22:118e23. [6] Lin CP, Cheng JS, Lai KH, et al. Gastrointestinal metastasis in hepatocellular carcinoma: radiological and endoscopic studies of 11 cases. J Gastroenterol Hepatol 2000;15:536e41. [7] Hu ML, Tai WC, Chuah SK, et al. Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway. J Gastroenterol Hepatol 2010;25:408e12.
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