Management of adrenal metastasis of hepatocellular carcinoma by asynchronous resection of bilateral adrenal glands

We report on a 65-year-old man who received asynchronous bilateral adrenalectomy for adrenal metastasis of hepatocellular carcinoma. Fifteen months after curative resection of right hepatic lobe for hepatocellular carcinoma, a metastatic lesion of the left adrenal gland was detected and left adrenalectomy was performed. Ten months after the second operation, a metastatic lesion in the right adrenal gland, associated with tumor thrombus in the inferior vena cava, was revealed. Transcatheter arterial embolization of the arteries feeding the metastatic tumor was performed, but its effects were incomplete. As there was the tumor thrombus in the inferior vena cava and no other intrahepatic recurrence or extrahepatic metastasis was found, resection of the right adrenal gland with tumor thrombus, without the employment of veno-venous bypass, was performed, followed by postoperative hormonal supplementation. Changes in the patient's alpha-fetoprotein level were clinically useful for the detection of the metastatic lesions and the evaluation of therapeutic effects. Metastasis to adrenal gland from hepatocellular carcinoma should be actively managed, and the appropriate surgical treatment selected, if intrahepatic recurrence and/or other extrahepatic metastasis are controlled. To achieve higher curability and better outcome in patients with bilateral adrenal metastasis of hepatocellular carcinoma, bilateral total adrenalectomy is indicated, accompanied by effective postoperative hormonal supplementation. (Received Apr. 15, 1998; accepted July 24, 1998)     

Combination therapy of percutaneous mitoxantrone injection, percutaneous ethanol injection, and transcatheter arterial embolization for intrahepatic hepatocellular carcinoma and adrenal metastasis

We treated a 63-year-old man who had recurrent large hepatocellular carcinomas (> 5 cm in diameter) and left adrenal metastasis with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization. He received repeated transcatheter arterial embolization and percutaneous ethanol injection combination therapy for intrahepatic hepatocellular carcinomas, which controlled his disease for 6 months from the first treatment. After that, left adrenal metastasis was detected by biopsy specimen. Therefore, we repeated more transcatheter arterial embolization and percutaneous ethanol injection to the liver and left adrenal gland, but this combination therapy could not control the hepatocellular carcinomas in these organs. With the patient's consent, he was treated with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization for hepatocellular carcinomas of the liver and left adrenal gland. After this combination therapy, we followed-up the viable lesions by color Doppler ultrasonography and computed tomography examination. However, we could not detect these viable lesions of hepatocellular carcinomas in his body until one month before he died. When the degree of hepatic failure worsened due to the natural course of cirrhosis, this combination therapy was stopped 7 months before he died. He died of pulmonary tumor emboli from metastasis of inferior vena cava 24 months after the combination therapy started. However, on autopsy there was almost no remaining hepatocellular carcinoma found in the main lesions of liver and left adrenal gland. We suggest that a combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization may be indicated in elderly cases of intrahepatic large hepatocellular carcinoma and adrenal metastasis, which are not under control only by transcatheter arterial embolization and percutaneous ethanol injection.     

Aggressive surgical resection for hepatocellular carcinoma with tumor thrombus extending to inferior vena cava and synchronous pulmonary metastasis

We describe a 66-year-old man having hepatocellular carcinoma with tumor thrombus extending into the inferior vena cava and synchronous pulmonary metastasis. He was referred to Chiba University Hospital on May, 2000, complaining of emaciation. Radiological findings showed a huge hepatocellular carcinoma in the entire right lobe and tumor thrombus extended into the intrapericardial inferior vena cava. He also had a solitary pulmonary metastasis in the left pulmonary lobe (stage IVB). Right hemihepatomy was performed under total hepatic vascular exclusion without cardiopulmonary bypass, and tumor thrombus was completely removed. Thoracoscopic wedge resection of pulmonary metastasis was also performed. The patient had an uneventful postoperative course. Histopathological examination revealed that the tumor was moderately differentiated hepatocellular carcinoma The patient is still alive after 26 months with pulmonary recurrence, but without hepatic recurrence. To our knowledge, there has been no reported case of resection for both hepatocellular carcinoma invading the inferior vena cava and synchronous pulmonary metastasis. In conclusion, aggressive surgical resection for advanced hepatocellular carcinoma concomitant with pulmonary resection may bring about better prognosis in highly selected patients.     

Adrenal metastasis from hepatocellular carcinoma without intrahepatic recurrence after hepatic resection

Although the adrenal gland is a common site of metastasis from hepatocellular carcinoma (HCC), adrenal metastases are rarely seen in clinical practice because of its lower metastatic potential compared to the other malignancies. Adrenal metastases usually were detected at the time of diagnosis of primary HCC or simultaneously with intrahepatic recurrence after curative management of HCC. It is very rare that only metastatic HCC is detected without evidence of intrahepatic recurrence. Hereby, we report two cases of adrenal metastasis from HCC without intrahepatic recurrence after hepatic resection.     

Recurrent fibrolamellar hepatocellular carcinoma with biliary invasion: Successful resection

A jaundiced 17-year-old man was diagnosed as having a local recurrence of fibrolamellar hepatocellular carcinoma 2 years and 4 months after left hepatic trisegmentectomy with total caudate lobectomy had been performed. The patient had a tumor occupying the upper part of the extrahepatic and intrahepatic bile ducts. Complete resection of the recurrent tumor was carried out. The patient remains well 3 years after the second surgery. Fibrolamellar hepatocellular carcinoma, a rare type of liver cancer, is a well defined disease entity with distinct clinical and histopathological features and a favorable prognosis. The good prognosis seems to warrant aggressive surgical intervention in patients with recurrences. Therefore, additional surgery for tumor recurrence should be considered. To our knowledge, this is the first report of a case in which a recurrent tumor of fibrolamellar hepatocellular carcinoma invaded the entire bile duct wall was successfully resected.     

Bilateral adrenal metastases from hepatocellular carcinoma after liver transplantation

Therapeutic management of hepatocellular carcinoma is a controversial issue. Orthotopic liver transplantation is an alternative for the treatment of hepatocellular carcinoma in a selected group of patients, but recurrence is possible. A 51-year-old patient with liver transplantation due to hepatocellular carcinoma presented bilateral adrenal metastases in a successive manner. A left adrenal gland metastasis was diagnosed five months after liver transplantation, and a left adrenalectomy was carried out. Eight months later, a right adrenal gland metastasis was diagnosed, and a right adrenalectomy was performed. Pathological examination confirmed the diagnosis of a well-differentiated hepatocellular carcinoma. At present, there is no evidence of recurrence 35 months after the second adrenalectomy. Bilateral adrenal gland metastases from hepatocellular carcinoma after liver transplantation have not been previously reported in English literature. Surgical resection of metastases may be indicated in similar patients with successful treatment of the primary tumor, absence of additional metastasic disease, and good performance status.     

Prolonged survival after repeat resection of pulmonary metastasis from hepatocellular carcinoma

We report a patient in whom two pulmonary resections were performed for lung metastasis after hepatic resection of hepatocellular carcinoma (HCC). A 56‐year‐old Japanese man with an 8‐year history of chronic liver disease was admitted with elevated serum alpha‐fetoprotein (AFP) and a liver tumor that had been detected by ultrasonography. Computed tomography showed a 6‐cm tumor in the medial segment of the liver, and partial resection of the medial segment was performed. Thirty‐six months after the first operation, pulmonary resection was performed for a solitary metastasis in the left lung. Fifty‐one months after the second operation, a solitary metastatic tumor was detected in the right lung, without any evidence of recurrence or other metastatic foci, and thoracoscopic partial resection of the right lung was performed as the third operation. The patient is alive 36 months after the second pulmonary resection, has a normal AFP value, and shows no signs of recurrent or metastatic foci. Repeat pulmonary resection for metastasis from HCC resulted in long‐term survival in this patient.     

Cholangiocellular carcinoma in a patient who has survived for 6 years after extended left hepatic lobectomy and caudate lobe resection with pancreatoduodenectomy

We describe a case of cholangiocellular carcinoma in a 66-year-old woman. A well-defined, hypoechoic tumor, 9 cm in greatest diameter, was detected in the left lobe of the liver by ultrasonography in December 1988. Celiac angiography showed a faintly stained tumor at the same location, with interruption of the left portal vein. Computed tomography revealed invasion of the inferior vena cava and lymph node enlargement around the head of the pancreas. In January 1989, the patient underwent extended left hepatic lobectomy with caudate lobe resection, pancreatoduodenectomy, partial resection of the inferior vena cava, and lymph node dissection around the hepatoduodenal ligament and the common hepatic artery. Postoperative histopathological examination revealed a moderately differentiated tubular adenocarcinoma. Cancer cells had invaded only the portal region, unlike the features of most cholangiocellular carcinomas. There was no evidence of lymph node metastasis in the dissected specimens. Six years after operation, there have been no signs of recurrence, and the patient is still alive and well.     

A case of cholangiolocellular carcinoma asynchronously developing 3 years after the resection of hepatocellular carcinoma

Cholangiolocellular carcinoma (CLC) is a rare malignant primary liver tumor, categorized as a subtype of cholangiocellular carcinoma. CLC is considered to originate from hepatic progenitor cells, and sometimes accompanies a component of cholangiocellular carcinoma and/or hepatocellular carcinoma (HCC). We report herein a case of a 53-year-old Japanese male with CLC occurring asynchronously after a resection of HCC. At the age of 50, the patient underwent a first hepatectomy due to HCC, followed by intrahepatic recurrence. At 53, a new type of hepatic tumor was detected. Dynamic computed tomography revealed a multinodular enhanced tumor in the hepatic arterial phase, and an iso-density tumor in the portal venous and delayed phases. Living donor liver transplantation was performed for the treatment of this liver tumor because of his poor liver function. Histological findings confirmed the diagnosis of CLC. Nineteen months after the liver transplantation, bone metastasis of CLC was detected. Although the preoperative diagnosis of CLC is difficult in general, CLC should be considered as a differential diagnosis when a tumor with atypical image findings for HCC is observed after the resection of HCC. Once the diagnosis of CLC is made, postoperative surveillance of the patient must be performed, including the bone.     

Long-term survival following resection of peritoneal implantation from hepatocellular carcinoma: a case report

This study presents a rare case of long-term survival following the resection of peritoneal implantation from hepatocellular carcinoma (HCC). A 33-year-old female patient with hepatitis B infection presented with a huge pedunculated HCC and underwent left lateral segmentectomy in 1995. She received regular follow-up and peritoneal implantation was diagnosed 30 months after hepatic resection using abdominal computed tomography due to elevated alpha-fetoprotein (AFP). Subsequently, the patient received segmental resection of jejunum and a solitary peritoneal implantation from HCC in the mesentery of the jejunum. No peritoneal carcinomatosis, direct invasion of the surrounding tissue, or lymph node involvement existed and the postoperative course was uneventful. Meanwhile, histopathological examination of the resected nodule revealed metastatic hepatocellular carcinoma. With regular follow-up with AFP, abdominal ultrasonography, and or computed tomography, no intrahepatic tumor recurrence or extrahepatic metastasis was observed. The patient survived for 90 months following hepatic resection, and survived disease free for 60 months after resection of peritoneal implantation from HCC.     

A long-term survivor of ruptured hepatocellular carcinoma after hepatic resection

Abstract We treated a patient who had previously undergone a hepatic resection for ruptured hepatocellular carcinoma (HCC) but developed a solitary peritoneal recurrence at the site of the incision 8 years and 9 months later. Since no other recurrence was evident, we resected the tumour. The primary tumour was 2.5 cm in size and histological examination revealed HCC without any histological risk factors for intrahepatic recurrence. The peritoneal tumour consisted of less differentiated cancer cells than those found in the primary tumour. The positive rates of Ki-67 were 10% in the primary tumour and 23.3% in the peritoneal recurrence. The DNA indexes in both tumours were considered to be identical.
The comparison between the primary and peritoneal tumours suggested that the histological differentiation and proliferation activity can change after recurrence, in spite of consistent DNA ploidy contents. Clinically, a patient who undergoes a hepatic resection for ruptured HCC can survive for a long time, such as 10 years, if they have good liver function and small HCC without any histological risk factors for intrahepatic recurrence. However, since late recurrence is possible, a follow up for as long as 10 years is recommended.     

Solitary recurrence of hilar cholangiocarcinoma in a mediastinai lymph node two years after curative resection

We recently encountered an unusual case of hilar cholangiocarcinoma in which a solitary recurrence in a mediastinal lymph node occurred two years after curative resection of the primary tumor. A 64-year old woman was admitted to our hospital with a complaint of right hypochondrial discomfort. After imaging studies demonstrated a hilar cholangiocarcinoma in the left hepatic duct, a curative resection of the tumor was performed, consisting of a left hepatic lobectomy along with caudate lobectomy, regional lymph node dissection, and resection of the extrahepatic bile duct. No nodal metastasis was observed histologically. Two years after surgery, the patient was found to have a nodule in the posterior mediastinum, which was thoracoscopically resected. No other swollen lymph nodes, local recurrence, or distant metastasis were noted. Histologically, the nodule proved to be a metastatic lymph node, and adjuvant chemoradiation therapy was initiated. The patient remained well for the four years following her first operation and had no evidence of disease recurrence 28 mo after her second operation. To our knowledge, this case is the first report of solitary recurrence in a mediastinal lymph node after curative resection of hilar cholangiocarcinoma.     

Solitary recurrence of hilar cholangiocarcinoma in a mediastinal lymph node two years after curative resection

We recently encountered an unusual case of hilar cholangiocarcinoma in which a solitary recurrence in a mediastinal lymph node occurred two years after curative resection of the primary tumor. A 64-year old woman was admitted to our hospital with a complaint of right hypochondrial discomfort. After imaging studies demonstrated a hilar cholangiocarcinoma in the left hepatic duct, a curative resection of the tumor was performed, consisting of a left hepatic lobectomy along with caudate lobectomy, regional lymph node dissection, and resection of the extrahepatic bile duct. No nodal metastasis was observed histologically. Two years after surgery, the patient was found to have a nodule in the posterior mediastinum, which was thoracoscopically resected. No other swollen lymph nodes, local recurrence, or distant metastasis were noted. Histologically, the nodule proved to be a metastatic lymph node, and adjuvant chemoradiation therapy was initiated. The patient remained well for the four years following her first operation and had no evidence of disease recurrence 28 mo after her second operation. To our knowledge, this case is the first report of solitary recurrence in a mediastinal lymph node after curative resection of hilar cholangiocarcinoma.     

The value of ultrasonography for hepatic surgery.

Ultrasonography plays an important role in the early detection of hepatocellular carcinoma. Ultrasonography detected 53% of 287 patients with small (less than or equal to 5 cm) hepatocellular carcinomas. Among 486 patients with hepatocellular carcinomas, sensitivities of intra-operative ultrasonography in detecting 451 small primary hepatocellular carcinoma nodules, intrahepatic metastasis in 330 patients with small hepatocellular carcinoma and 63 tumor thrombi were 98, 48 and 67%, respectively. The sensitivity of intra-operative ultrasonography in detecting small primary tumors was 10% better than ultrasonography, computed tomography, and angiography. The sensitivity of intra-operative ultrasonography in intrahepatic metastasis and tumor thrombus was two to three times better than pre-operative examination. Intra-operative ultrasonography was useful in detecting nonpalpable tumors and in guiding the transection of the liver, biopsy, and cryosurgery. Moreover, intra-operative ultrasonography made possible new hepatectomy procedures: systematic subsegmentectomy and hepatectomies which preserve the inferior right hepatic vein. Systematic subsegmentectomy guided by intra-operative ultrasonography resulted in better survival rates than the limited resection in patients with small hepatocellular carcinoma two years after hepatectomy; by the sixth year, this difference was significant (p less than 0.05). Ultrasonography and intra-operative ultrasonography are indispensable in the early detection, accurate diagnosis, operative guidance and postoperative care of hepatocellular carcinoma.     

Occurrence of hepatocellular carcinoma after hepatoblastoma resection in an adult with hepatitis C virus

Hepatoblastoma is a rare malignancy in adults. It is often diagnosed after the appearance of symptoms, therefore, the tumor size tends to be larger. In patients with no indication for a hepatic resection, the prognosis of adult hepatoblastoma is quite poor. A 54-year-old man with hepatitis C virus-associated liver cirrhosis was initially treated with a hepatic resection for a hepatic tumor, 3 cm in diameter. The tumor consisted of osteoid-like and cartilaginous foci, myxomatous stroma, and poorly differentiated hepatocellular carcinomatous cells and was diagnosed as a mixed epithelial and mesenchymal hepatoblastoma. Two years after the first operation, multicentric hepatocellular carcinomas developed in the remnant liver and were successfully treated with a secondary hepatic resection combined with radio-frequency ablation. The patient is now alive with no recurrence at 5 years after the initial hepatectomy. To the best of our knowledge, the primary hepatoblastoma was the smallest such tumor reported and this is the first report of a metachronous hepatoblastoma and hepatocellular carcinoma in an adult hepatitis patient.     

Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma

BACKGROUND/AIMS: None of the previous studies have compared the prognosis or clinicopathological factors between the patients with extrahepatic recurrence and those with intrahepatic recurrence of hepatocellular carcinoma after a hepatic resection. METHODOLOGY: The clinicopathological features and prognoses of patients with extrahepatic recurrence after a curative hepatectomy for hepatocellular carcinoma were investigated. RESULTS: Twenty-three patients with extrahepatic recurrence had more advanced-stage hepatocellular carcinoma at the primary operation compared to 186 patients with intrahepatic recurrence. After adjusting for tumor size, the prognosis of the 2 groups were comparable. However, among the patients with hepatocellular carcinoma exceeding 5 cm in diameter, the number of patients whose plasma levels of des-gamma-carboxy prothrombin was higher than 2.0 AU/mL in the patients with extrahepatic recurrence (62.5%) was significantly more (P < 0.05) than that in the patients with intrahepatic recurrence (20.0%). On the other hand, the prognosis of the 13 patients with extrahepatic recurrence alone was significantly better than in the 10 patients with both intrahepatic and extrahepatic recurrences. The prognoses of the 3 patients who underwent a surgical resection for isolated extrahepatic recurrence were markedly better than that of the remaining 10 patients only treated palliatively. CONCLUSIONS: If patients have tumors exceeding 5 cm in diameter and their plasma levels of des-gamma-carboxy prothrombin are higher than 2.0 AU/mL, more careful follow-up examinations than usual may thus be necessary in order to detect extrahepatic recurrence as early as possible. Furthermore, a surgical resection for the isolated extrahepatic recurrence of hepatocellular carcinoma is also recommended to produce long-term survivors.     

Treatment for extrahepatic metastasis of hepatocellular carcinoma following successful hepatic resection

BACKGROUND/AIMS: Recent advances in both the diagnosis and treatment of hepatocellular carcinoma (HCC) have improved its prognosis. Intrahepatic recurrence after hepatectomy can be treated with repeated hepatectomy, transhepatic arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), or microwave coagulo-necrotic therapy. However, treatment for extrahepatic recurrence is also important in prolonging survival in some patients. METHODOLOGY: After radical hepatectomy in 155 patients, extrahepatic recurrences were found in 15 patients that underwent subsequent treatment. The interval between completing treatment for the primary tumor and the discovery of metastasis, the location and mode of treatment of the metastasis, and the outcomes were analyzed. RESULTS: Distant metastasis was detected at a mean of 7 months after radical resection of the primary tumor. Location of the metastasis included lung, bone, and adrenal gland. Four patients had no intrahepatic recurrence and 11 patients had simultaneous intrahepatic recurrence. Six patients with intrahepatic and extrahepatic recurrence that underwent systemic chemotherapy had poor prognoses, and all died within 12 months as a result of progression of the intrahepatic tumor. Five patients with intra- and extrahepatic recurrence that underwent systemic chemotherapy combined with hepatic arterial infusion chemotherapy had relatively good outcomes; all survived for more than 12 months. CONCLUSIONS: These results suggest that to obtain a good prognosis for extrahepatic metastasis coexisting with intrahepatic recurrence, intrahepatic recurrence should be controlled by locoregional therapy, and extrahepatic metastasis should be controlled by systemic chemotherapy and/or irradiation therapy.     

Histopathologically-diagnosed splenic metastasis in a hepatocellular carcinoma case with adrenal metastasis

We encountered a patient with hepatocellular carcinoma (HCC), with adrenal gland metastasis, in whom splenic metastasis was diagnosed histopathologically. A 59-year-old man visited our hospital in May 2001 with chief complaints of abdominal distension and pretibial pitting edema. Multiple HCCs associated with HCV-positive liver cirrhosis were detected. Transarterial embolization (TAE) was performed a total of 4 times for HCCs. A left adrenal gland metastatic lesion was detected and it was found to increase in diameter from 3 cm to 6 cm over a four-month period; left adrenalectomy was performed in June 2002. Because of marked splenomegaly and findings of hypersplenism, the spleen was also resected. Although no metastatic lesions were evident on macroscopic examination of the spleen, a small metastatic lesion from moderately differentiated HCC, approximately 0.5 mm in diameter, was detected histopathologically. Splenic metastasis from HCC is rare, usually occurring with metastases involving other organs. Our patient also had adrenal gland metastasis. Therefore, hematogenous metastasis to the congested spleen via the systemic circulation was suspected.     

Resected case of a double cancer,a hepatocellular carcinoma and a cholangiocellular carcinoma,and their spread to the skin

Combined hepatocellular and cholangiocellular carcinomas are rare. Moreover, double cancer cases of hepatocellular carcinoma and cholangiocellular carcinoma are very rare. This report describes a patient with double cancer. A correct clinical diagnosis was made with successful resection, and cutaneous metastases occurred near the exit site of an abdominal drain after the resection of the tumor. The patient, a 66-year-old man with chronic hepatitis C, was admitted to our hospital because he was suspected of having primary liver cancer. Two liver masses in the anteroinferior segment were detected by using angiography, computed tomography during angiography, and computed tomography during arterioportography. These clinical findings indicated that the tumor in the right lobe was hepatocellular carcinoma. A resection of the S5 subsegmentectomy was performed. One mass was diagnosed histologically as hepatocellular carcinoma, and the other mass was diagnosed as cholangiocellular carcinoma. One year after the operation, the patient palpated a hard subcutaneous nodule 4.0 cm in diameter in the right lower abdominal wall. A subcutaneous tumor was excised, and a histological examination revealed moderately differentiated hepatocellular carcinoma. The patient is currently doing well without further recurrence of hepatocellular carcinoma or cholangiocellular carcinoma, 18 months after subsegmentectomy and six months after excision of the subcutaneous tumor.     

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma (HCC) complicating hepatitis B virus (HBV) cirrhosis. In 2001 (12 years after liver transplantation), he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCCmetastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater thanthat of those who do not receive immunosuppressive therapy.