Annals of Surgical Oncology 9:863-868 (2002)
© 2002 Society of Surgical Oncology
Resection of Peritoneal Implantation From Hepatocellular Carcinoma
Chun-Nan Yeh, MD,
Miin-Fu Chen, MD, FACS and
Long-Bin Jeng, MD
From the Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Correspondence: Address correspondence and reprint requests to: Miin-Fu Chen, MD, FACS, Department of Surgery, Chang Gung Memorial Hospital, 5 Fu-Hsing St., Kwei-Shan, Taoyuan, Taiwan; Fax: 886-3-3285818; E-mail: chenmf{at}adm.cgmh.org.tw
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ABSTRACT
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Background: Peritoneal implantation is a rare presentation of hepatocellular carcinoma (HCC). This article presents the clinical features and surgical outcomes of 16 patients with HCC in whom isolated peritoneal implantation from HCC was found and who underwent surgical resection.
Methods: From 1988 to 2000, 16 patients with HCC after hepatic resection who underwent resection of peritoneal implantation of HCC were retrospectively reviewed.
Results: Four hundred sixty-five of 749 patients (62.1%) had recurrence of HCC after hepatic resection. Sixteen (3.4%) developed isolated peritoneal implantation and underwent resection. During the detection of the peritoneal implantation, the alfa fetoprotein level was increased in 13 of these 16 patients. Five of 15 patients had a peritoneal mass discovered by ultrasonography, and 14 of 15 patients had a mass discovered by computed tomography. The follow-up period ranged from 2.1 to 81.6 months (median, 16 months). The median disease-free and overall survivals of the 16 patients were 7.89 and 15.98 months, respectively.
Conclusions: Peritoneal implantation occurs infrequently in posthepatectomy patients. Increased alfa fetoprotein values after hepatic resection should suggest recurrence of HCC. Computed tomography is superior to ultrasonography in detection of peritoneal implantation from HCC. Surgical resection of peritoneal implantation from HCC might prolong survival in selected patients.
Key Words: Carcinoma • Hepatocellular • Peritoneal • Implantation
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INTRODUCTION
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Hepatocellular carcinoma (HCC), a common disease in Taiwan, with an age-adjusted incidence of 27.7 per 100,000 population per year, continues to be the leading cause of cancer-related death among men and the second among women.1 Although recent advances in both diagnosing and treating HCC have improved patients’ prognoses, the incidence of intrahepatic recurrence of HCC remains high. Peritoneal implantation from HCC is a rare clinical presentation of HCC, with the reported incidence ranging from 2% to 16% in autopsy or laparoscopy cases.2 It is widely recognized that patients with HCC who develop peritoneal implantation are in the terminal stages of the disease. Therefore, surgical treatment is considered of little value in improving patient survival. Case reports have shown that patients can survive for several months after the detection of peritoneal metastasis.3 However, the optimal treatment of patients with this unusual spread of HCC remains unclear, and reports on surgical management of peritoneal implantation from HCC are limited. This investigation reports surgical outcome on 16 HCC patients after hepatic resection with isolated peritoneal implantation from HCC who underwent surgical resection.
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MATERIALS AND METHODS
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From 1988 to 2000, 749 consecutive patients with HCC underwent hepatic resection at the Department of Surgery, Chang-Gung Memorial Hospital, Taipei, Taiwan. Preoperative evaluation of HCC included routine laboratory examination, ultrasonography (US), abdominal computed tomography (CT), selective angiography, and magnetic resonance imaging (MRI). Of the 749 patients discharged from the hospital after hepatic resection, all of the patients were closely followed up at regular intervals until death or until we wrote this article. The duration of follow-up ranged from 1.2 to 180.3 months (median, 26.0 months). During the follow-up period, 465 patients (62.1%) had a recurrence of HCC after hepatic resection. Of these, 382 patients (82.2%) developed intrahepatic recurrence, 57 (12.2%) developed distant metastasis, and 26 (5.6%) developed peritoneal implantation. Sixteen of the 26 patients with isolated peritoneal implantation underwent resection. The isolated peritoneal implantation was defined as solitary and metachronous occurrence of HCC in the peritoneum after hepatic resection for primary HCC. Those with concomitant peritoneal involvement or distant metastasis of HCC were excluded from this study.
Follow-Up Study
Follow-up evaluation involved clinical physical examinations and blood chemistry tests at each visit. Serum alfa fetoprotein (AFP) was measured by radioimmunoassay at least every 3 months. The remnant liver was examined with US every 3 months. When a new lesion was detected with US or when increased AFP was noted, abdominal CT, MRI, or liver scan was performed for confirmation. Chest x-ray examination was performed every 6 months to evaluate pulmonary metastasis. When a patient complained of bone pain, a bone scan was performed for the detection of metastasis. If any of these procedures indicated recurrence, the patient was readmitted for further investigation, including angiographic evaluation or MRI.
Treatment
The principle of selection for treatment was that resection of the peritoneal implantation was the first choice whenever the tumor was considered resectable. Sixteen patients with isolated peritoneal implantation were considered eligible for resection because they met the criteria of fewer than four recurrent foci and no distant metastasis. Medical records of these 16 patients were retrospectively reviewed. All 16 patients were discharged with an uneventful postoperative course and were regularly followed up at outpatient clinics with a follow-up period ranging from 2.1 to 81.6 months (median, 16 months). Disease-free survival was defined as the interval between surgery for primary HCC and the appearance of metastatic lesions. Survival was calculated and plotted by using the Kaplan-Meier method from the time of liver resection. All statistical analyses were performed with SPSSTM computer software (SPSS Inc., Chicago, IL).
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RESULTS
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Age and Sex
There were 13 male patients and 3 female patients with ages ranging from 8 to 87 years (median, 45.5 years).
Associated Cirrhosis and Hepatitis Viral Status
Radioimmunoassay was used to assess hepatitis B surface antigen, and this was positive in 11 of the 15 patients. Fourteen patients were studied for the presence of hepatitis C virus antibody, and three were positive for anti-hepatitis C virus antibody. Only six patients developed liver cirrhosis. According to the Child-Pugh classification, four patients were classified as Child’s A (score 5; patients 8, 10, 14, and 15) and two as Child’s B (score 7; patients 2 and 6).
Laboratory Data
Table 1 lists the laboratory data collected 1 day before surgery. Serum AFP and serum carcinoembryonic antigen were measured by radioimmunoassay. Increased AFP was defined as a value >20 ng/mL in our institute. Twelve of 15 patients tested for serum AFP had increased levels.
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TABLE 1. Laboratory data of the 16 patients with hepatocellular carcinoma who underwent hepatic resection with peritoneal implantation
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Clinicopathologic Features of the Primary Lesions
Table 2 lists the clinicopathologic features of HCC of these 16 patients. The size of the primary HCC ranged from 3.0 to 21 cm (median, 6.0 cm). The locations of the tumors are also listed in Table 2. Six of the 16 patients had satellite lesions, and the other 10 patients had a single tumor. Eleven of the 16 patients had tumors with capsule formation, and 9 of these 11 patients had capsule invasion. Only 4 of the 16 patients had rupture of the HCC. Histopathologic study of these 16 patients showed typical pictures of HCC; 9 had grade II HCC, 3 had grade III, and 1 had grade IV. The types of hepatic resection of HCC in these 16 patients are listed in Table 2. No operative mortality occurred in this investigation.
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TABLE 2. Operative findings and pathologic features of the 16 patients with hepatocellular carcinoma who underwent hepatic resection with peritoneal implantation
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Clinicopathologic Features of Peritoneal Implantation From HCC
During the detection of the peritoneal implantation, the AFP value increased in 13 of these 16 patients. Three patients had normal AFP values, and two of these three patients (patients 1 and 12) had a normal AFP value with the primary HCC. Five of 15 patients revealed peritoneal masses with US, with 33.3% sensitivity (Fig. 1). Fourteen of 15 patients tested had intra-abdominal masses discovered with CT, with 93.3% sensitivity (Fig. 2). The peritoneal implantation was discovered in patient 2 by liver scan and in patient 16 by MRI. Table 3 lists the site of peritoneal implantation from HCC. Eight patients developed implantation in the omentum, three on the abdominal wall, one at the duodenum, one in the mesentery of the jejunum, one in the mesentery of the ileum, and two at the colon.
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FIG. 1. Abdominal ultrasound demonstrated a mass with heterogenous echogenicity, measuring 7.6 x 4.2 cm.
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FIG. 2. Abdominal computed tomography demonstrated a lobulated mass with heterogenous density, measuring 4 cm, located in the middle abdomen.
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TABLE 3. Clinical features of the 16 patients with hepatocellular carcinoma who underwent hepatic resection with peritoneal implantation
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Follow-Up
The follow-up period ranged from 2.1 to 81.6 months (median, 16.0 months). The median disease-free and overall survivals were 7.89 and 15.98 months, respectively (Fig. 3). Neither intrahepatic recurrence/peritoneal implantation nor distant metastasis occurred in five patients.
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FIG. 3. Overall survival (OS) and disease-free survival (DFS) of 16 patients with peritoneal implantation from hepatocellular carcinoma who underwent resection.
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DISCUSSION
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HCC is a highly malignant cancer that frequently metastasizes to other organs. The most common sites of HCC metastasis are lungs, bones, brain, and skin. Other sites of metastasis, including portal lymph nodes, spleen, pancreas, bowel, kidney, adrenal glands, and ovaries, are not usually detected until autopsy.4–6 The mode of extrahepatic spread from HCC is usually hematogenous metastasis, most frequently to the lung. Lymphogenous and infiltrating metastases are relatively infrequent. Peritoneal implantation is a rare presentation of HCC, with a reported incidence of 2% to 16% in autopsy or laparoscopy cases. Nakashima et al.5 reported an incidence of 6.2% of HCC metastasis to the Douglas pouch in an autopsy study. In our investigation, the incidence of peritoneal implantation from HCC after hepatectomy was 3.4%, and the omentum was the most common site of peritoneal implantation from HCC.
The mechanism of peritoneal implantation from HCC is thought to be a rupture of exophytic HCC into the peritoneal cavity and subsequent seeding of metastatic deposits. Ong et al.7 and Dixon et al.8 reported similar observations. Sonoda et al.9 reported that ruptured HCC evokes the risk of implanted metastasis. However, in our investigation, only 4 (25%) of 16 patients had peritoneal implantation from preexisting ruptured HCC. Peritoneal seeding may be the mechanism of peritoneal implantation; however, the real mechanism still needs to be investigated. As seen in our investigation, implantation is usually manifested by tumor nodules on the serosal surfaces of the bowel, including the duodenum, jejunum, ileum, and colon.10
Diagnosis of peritoneal implantation from HCC after hepatic resection starts with clinical suspicion of recurrence. Our investigation revealed that the AFP value of patients developing peritoneal implantation from HCC after hepatectomy was high (mean, 3311.3 ng/mL). Consequently, tumor markers played an important role in indicating the presence of peritoneal implantation from HCC. Regular checks of the tumor marker AFP values should be used for early detection of recurrence. In our series, increasing levels of tumor markers suggested that recurrent lesions might be present. Subsequent surveillance of the abdominal cavity with US, CT, or both should be performed to reveal the peritoneal implantation.
Yunoki et al.11 reported that US is useful in establishing the presence of this peritoneal tumor with a mosaic pattern. In our investigation, the echogenicity of the peritoneal implantation was heterogenous. The sensitivity of US to diagnose peritoneal tumors was only 33% in our investigation. Use of US to detect the peritoneal implantation was operator and reader dependent. The location of the peritoneal implantation might explain the low sensitivity in this investigation. We observed that implantation near the previous operative field was diagnosed more easily with US.
In our investigation, CT was more useful for detecting peritoneal implantation from HCC. CT manifestations of the usual carcinomatosis peritonei, which occur frequently in gastric and pancreatic carcinoma cases, are ascites, peritoneal thickening with enhancement, and omentum changes, such as enhancing nodules and omental cakes.12 In contrast, the usual radiological finding of the peritoneal spread of HCC in our investigation was a discrete mass located in the peritoneal cavity. The internal heterogeneity and necrosis frequently seen in the peritoneal masses reflect the characteristics of hepatic HCC (Fig. 2). The occasional finding of engorgement of the omental vessels adjacent to the peritoneal masses corresponded to the prominent draining veins seen on angiography.13 We also observed that peritoneal implantation from HCC was hypervascular, like primary hepatic masses, and was most often supplied by the omental branches and even spontaneous rupture with bleeding. Regarding the use of fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect HCC recurrence after hepatectomy, the role is still unclear. Generally, the sensitivity of fluorine-18 fluorodeoxyglucose PET for the imaging of HCC is low when compared with US and CT. However, PET may have its role in assessing tumor differentiation and staging of HCC, because PET could detect distant metastasis of HCC.14,15
The prognoses of patients who have advanced gastrointestinal cancer with peritoneal metastasis are very poor, with most patients dying within 6 months. Usually, peritoneal metastases arising from gastrointestinal cancer are widespread, affect the whole abdominal cavity, and lead to the development of ascites. Nakayama et al.3 reported that resection of peritoneal metastases arising from HCC may be of value in improving patient survival. In this study, the long survival time of selected patients with resectable lesions justifies an aggressive therapeutic approach for recurrence caused by peritoneal implantation from HCC. It is extremely encouraging that five patients have disease-free and overall survivals ranging from 11.8 to 81.6 months after salvage therapy.
In conclusion, peritoneal implantation occurs infrequently in posthepatectomy patients with HCC. Increased AFP values after hepatic resection should suggest the recurrence of HCC. CT is superior to US in the detection of peritoneal implantation from HCC in patients with increased AFP after hepatectomy. Surgical resection of peritoneal implantation from HCC might prolong survival in selected patients.
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Footnotes
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Peritoneal implantation occurs infrequently in posthepatectomy patients with hepatocellular carcinoma (HCC). Computed tomography is superior to ultrasonography in the detection of peritoneal implantation from HCC in patients with increased alfa fetoprotein after hepatectomy. Surgical resection of peritoneal implantation from HCC might prolong survival in selected patients.
Received for publication April 12, 2002.
Accepted for publication July 1, 2002.
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- Kasai Y, Tamaki A, Kakita, et al. Surgical treatment of primary hepatocellular carcinoma. Geka Shinryo 1977; 19: 46–54.
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- Khan MA, Combs CS, Brunt EM, et al. Positron emission tomography scanning in the evaluation of hepatocellular carcinoma. J Hepatol 2000; 32: 792–7.[CrossRef][Medline]
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INTRODUCTION
