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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 50  |  Issue : 1  |  Page : 10-15

Clinical experience of double primary gastric cancer and hepatocellular carcinoma


Department of Surgery, National University Hospital, Taipei, Taiwan

Date of Web Publication28-Feb-2017

Correspondence Address:
Chiung-Nien Chen
Department of Surgery, National Taiwan University Hospital, No. 7, Chan-Shan South Road, Taipei
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_9_17

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  Abstract 

Background: With improvements in the prognosis of gastric cancer, the clinical importance of treating patients with both gastric cancer and hepatocellular carcinoma (HCC) is increasing because of the high prevalence of HCC in Taiwan.
Patients and Methods: We reviewed the medical records of 5468 patients who received a diagnosis of primary gastric cancer at National Taiwan University Hospital between 1980 and 2010. Of these, we identified 18 patients with HCC.
Results: Regarding the double cancer cases, six patients received a diagnosis of synchronous cancers, six patients received a diagnosis of HCC during follow-up for gastric cancer, and six patients had undergone HCC treatment before receiving a gastric cancer diagnosis. All the patients who received an HCC diagnosis after gastric cancer underwent curative therapy, except for one patient who had a large hepatic tumor. By contrast, of the patients who received an HCC diagnosis first, only one received an early gastric cancer diagnosis, and the remaining patients received an advanced gastric cancer diagnosis. Despite the presence of double cancers, surgical mortality did not occur in the patients who underwent curative-intended treatment.
Conclusion: The study results suggest the necessity of closely following up patients with gastric cancer or HCC for the early diagnosis and treatment of the other malignancy. Aggressive treatments including surgery and radiofrequency ablation are safe and can prolong survival in some patients.

Keywords: Double primary cancer, gastric cancer, hepatocellular carcinoma, surgery


How to cite this article:
Chen PD, Chen CN, Hu RH, Lai HS. Clinical experience of double primary gastric cancer and hepatocellular carcinoma. Formos J Surg 2017;50:10-5

How to cite this URL:
Chen PD, Chen CN, Hu RH, Lai HS. Clinical experience of double primary gastric cancer and hepatocellular carcinoma. Formos J Surg [serial online] 2017 [cited 2019 Aug 23];50:10-5. Available from: http://www.e-fjs.org/text.asp?2017/50/1/10/201188


  Introduction Top


With improvements in cancer diagnosis and prognosis, the premortal diagnosis of multiple primary cancers in the same patient is not a rare phenomenon. Despite the decreasing incidence of gastric cancer, it remains a common neoplasm among males in Taiwan.[1] Moreover, with the high prevalence of chronic hepatitis, hepatocellular carcinoma (HCC) is the most common malignancy in Southeast Asia, including Taiwan.[2] The significantly more favorable prognosis of asymptomatic HCC patients with small tumors indicates the necessity of receiving an early HCC diagnosis.[3] In addition, the high incidence of HCC in patients with gastric cancer indicates that these two cancers may have common environmental or genetic factors.[4],[5],[6] In this study, we addressed the clinical problem of double primary cancers of the stomach and liver and provide clinicopathological clues to improve the clinical practice for these two cancers. In addition, we assessed the preliminary results of different treatment modalities for synchronous and metachronous HCC and gastric cancer.


  Patients And Methods Top


We analyzed the medical records of 5468 patients who received a gastric cancer diagnosis at National Taiwan University Hospital between 1980 and 2010 and identified 18 patients with HCC. We reviewed their medical charts and collected information on their demographic characteristics, histological grading, invasion depth, lymphatic and venous invasion, lymph node involvement, gastric cancer and hepatic tumor locations, treatment modalities, and survival intervals. However, because of the limited data, we did not identify “alpha-fetoprotein (AFP)-producing gastric cancer.”

According to the timing of disease diagnosis, the patients with both gastric cancer and HCC were classified into synchronous and metachronous groups. The patients who received a diagnosis of HCC during cancer staging for gastric cancer or during exploratory laparotomy for gastric cancer surgery were included in the synchronous group. Those who received a diagnosis of gastric cancer and HCC during the posttreatment follow-up for gastric cancer or HCC were included in the metachronous group and further subdivided according to which malignancy was diagnosed first.

Cancer staging for gastric cancer was performed through esophagogastroduodenal (EGD) endoscopy, chest and abdominal imaging, and serum tumor marker analysis. Radical gastrectomy including standard D2 lymph node dissection was performed for the patients who underwent curative-intended surgery, and the disease was staged according to the American Joint Committee on Cancer tumor–node–metastasis staging system, 7th edition.[7] Follow-up examinations were arranged every 3 months in the 1st year after surgery and then every 6 months for the subsequent 5 years. For the patients with HCC, surgical intervention or curative local treatment was suggested with a complete survey of the hepatic profile, liver function testing, and indocyanine green liver reserve function testing after image diagnosis. A 1-cm gross margin was targeted during the liver resection, and a complete ablation zone was monitored in real time for patients who chose percutaneous local treatment. The follow-up studies of patients with double cancers included a conventional hemogram, liver function testing, serum AFP and carcinoembryonic antigen (CEA) level analysis, EGD endoscopy, abdominal sonography, and/or abdominal computed tomography.


  Results Top


During the study period, we analyzed the medical records of 5468 patients who received a diagnosis of gastric cancer. Of these, we identified 18 patients (0.3%) with HCC. All 18 patients were men who were aged 40–86 years (mean, 65.7 years). Six of them received a diagnosis of synchronous HCC at the time of gastric cancer diagnosis, 6 received a diagnosis of HCC during follow-up, and six had already undergone HCC treatment before receiving a gastric cancer diagnosis [Figure 1]. The gastric cancers in all these patients were located in the lower third of the stomach (89%), except for one, which was in the proximal third. Eleven of them (61%) had liver cirrhosis when they received the HCC diagnosis. Early gastric cancer was observed in 7 (38%) patients. By contrast, nine patients had advanced gastric cancer with serosal invasion and two patients had advanced gastric cancer with muscular layer invasion. HCC was located in the right lobe in 12 (67%) patients, and the tumor size varied from 1 to 14 cm in diameter.
Figure 1: Relationship of the interval of double cancer and overall survival. HCC: Hepatocellular carcinoma

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Surgical mortality did not occur in these 18 patients; however, postoperative subphrenic abscess and wound infection developed in those who underwent synchronous gastric and hepatic resection. Surgical procedures, survival time, and recurrence status are summarized in Tables relative to the timing of double cancer diagnosis [Table 1]: synchronous group; [Table 2] and [Table 3]: metachronous group). Long-term survival beyond 4 years was achieved in two patients. Of the nine patients who died, four died of gastric cancer dissemination and five died of HCC recurrence. Of the remaining seven patients who were alive, four had recurrent HCC.
Table 1: Clinicopathological findings, surgical procedures, and survival in patients with double primary cancers of the stomach and liver (synchronous group)

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Table 2: Clinicopathological findings, surgical procedures, and survival in patients with double primary cancers of the stomach and liver (metachronous group, gastric cancer first)

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Table 3: Clinicopathologic findings, surgical procedures, and survival in patients with double primary cancers of the stomach and liver (metachronous group, hepatocellular carcinoma first)

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Synchronous group

The patients with synchronous gastric cancer and HCC underwent simultaneous curative resection of both cancers in a single operation. This group of patients had a low CEA level (<3 IU/L), and only two patients had a high AFP level during cancer staging. Only two of them were suspected of having HCC before gastric cancer surgery during image staging, three of them were initially assumed to have liver metastasis before pathological confirmation, and one received an incidental diagnosis of HCC in the left lateral segment during gastric cancer surgery.

Metachronous group (gastric cancer first)

During the period after gastric cancer surgery, six patients received a diagnosis of HCC at intervals of 9, 13, 11, 15 (two patients), and 20 months. HCC treatment was performed according to the guidelines of Barcelona-Clinic Liver Cancer staging system.[8] Of the patients without liver cirrhosis (2/6, 33%), one underwent a hepatic lobectomy and the other received transarterial embolization (TAE) because of disseminated hepatic tumors. By contrast, of the patients with cirrhosis, 2 underwent radiofrequency ablation (RFA) and one underwent TAE for a large liver tumor (5 cm). One patient with cirrhosis (case 11) underwent wedge hepatic resection for a presumed metastatic hepatic cancer and repeated hepatic resection for HCC recurrence 1 year later. However, HCC recurred again 18 months after the last hepatic resection, and the patient opted for TAE rather than another hepatic resection.

Metachronous group (hepatocellular carcinoma first)

In total, six patients initially received a diagnosis of HCC. During the follow-up, their gastric cancers were detected through endoscopy at intervals of 6, 13, 14, 18, 30, and 50 months after undergoing a hepatectomy as they developed new gastrointestinal symptoms (three patients for epigastralgia, two for upper gastrointestinal bleeding, and one for gastric outlet obstruction). Although only one patient (17%) had a high CEA level at the time of diagnosis, five patients (83%) had advanced gastric cancer and four (67%) had serosal invasion. In this group, liver cirrhosis was not considered as the exclusion criterion for gastric cancer surgery. Four of these patients underwent a gastrectomy with curative intent, and two patients elected to receive palliative treatment because of the high surgical risk and disseminated gastric disease.


  Discussion Top


In Taiwan, HCC is the leading malignancy among men and is closely associated with hepatitis B virus infection.[9],[10] However, of our 18 patients, only 44% were hepatitis B surface antigen (HBsAg)-positive and 38% had a high AFP level; this percentage was different in the patients with HCC only.[11],[12] Regarding genetic factors, several reports have described familial aggregation of HCC irrespective of being HBsAg-positive.[13],[14] However, no family history of HCC was noted in these 18 patients. Moreover, none of our patients had weakened immunocompetence favoring the development of a second malignancy,[15] for they did not receive previous chemotherapy or radiotherapy and none had known congenital or acquired immunodeficiency diseases.

Although the assessment of all potential factors in the pathogenesis of HCC in the patients with double cancers of the stomach and liver was difficult in this small series, common environmental factors may have a more critical role in the pathogenesis of double cancers of the stomach and liver. Some compounds including nitrosamides have been suggested to be secondary to high levels of glutathione in the glandular stomach mucosa and livers of rats.[16],[17] A study reported that a nitroso compound found in pickled food may be the causative factor of both these malignancies in rats.[18] Therefore, a common dietary factor may cause double primary cancers of the stomach and liver. Furthermore, all gastric cancers in patients with double cancers occurred in men and nearly all of them (94%) were located in the lower third of the stomach. Distally located gastric cancers are epidemic in nature and are related to dietary variations, whereas proximally located cancers are endemic in nature, have a diffuse-type histology, and are less related to dietary factors.[19]

Surgical resection is the most effective and potentially curative treatment for both gastric cancer and HCC. Therefore, performing synchronous resection of both cancers is desirable because these two cancers are rapidly progressive, with an average life expectancy of 4–6 months for patients with HCC.[9],[20] However, in metachronous cases, the problem of severe adhesion of the adjacent operative field is typically encountered during second abdominal cancer surgery. Our data revealed a high association of liver cirrhosis with HCC (61%). Furthermore, during the second operation, the fragile liver parenchyma and collateral circulation increase the surgical risk and lead to poor surgical outcomes.[21] RFA is currently considered an effective treatment for primary liver cancer.[22] Two patients in our series underwent RFA for HCC after gastric cancer treatment, and both of them had prolonged survival of 30 and 77 months without recurrence. RFA can be beneficial for patients who have limited residual liver function and are failing candidates for hepatectomy. Furthermore, minimally invasive surgery can be considered a possible modality for recurrence during follow-up.[23]

During cancer staging, the liver metastasis of gastric cancer should be carefully distinguished from the primary liver cancer.[24] Beyond the 0.1% incidence detected through endoscopy in a large series of routine checkups in Taiwan,[19] the incidence of gastric cancer is up to 4.1% in patients who have already received an HCC diagnosis.[5] In fact, compared with the synchronous double cancer patients and those who received an HCC diagnosis after their gastric cancer diagnosis, advanced gastric cancer was observed more frequently in those who received a gastric cancer diagnosis first (50% vs. 50% vs. 83%). Although the low number of patients in this group is insufficient for further statistical evaluation, the tendency of poor survival in those who received a gastric cancer diagnosis after an HCC diagnosis suggests the inadequate follow-up modality after HCC diagnosis. Therefore, surveillance endoscopy is necessary in patients with HCC for the diagnosis of early gastric cancer. However, considering other malignancies that might occur after HCC, whether endoscopy is statistically beneficial should be evaluated in future studies investigating large populations.


  Conclusion Top


The rates and patterns of the occurrence of double primary cancers of the stomach and liver may be rudimentary, and the observed population in this hospital-based study was relatively small. Nevertheless, we can apply these clues to the clinical management of patients who receive an HCC or gastric cancer diagnosis. The results of this study suggest that the occurrence of double cancers of the stomach and liver is not coincidental. Simultaneous or subsequent hepatic tumors detected in patients who have already received a gastric cancer diagnosis are not always of a metastatic nature. Close follow-up in patients with gastric cancer or HCC is necessary for the early detection of the other cancer. A synchronous or metachronous curative treatment of these two cancers is safe and optimal in some patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Dai WC, Fan ST, Cheung TT, Chok KS, Chan AC, Tsang SH, et al. The impact of family history of hepatocellular carcinoma on its patients' survival. Hepatobiliary Pancreat Dis Int 2012;11:160-4.  Back to cited text no. 13
    
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Liu L, Li L, Zhou S, Jiang Q, Chen S, Gao Y, et al. Familial correlations of onset age of hepatocellular carcinoma: A population-based case-control family study. PLoS One 2014;9:e108391.  Back to cited text no. 14
    
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