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We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4 years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12 months, and she was alive 18 months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3 years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17 months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3 years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30 months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence., (© 2023. Japanese Society of Gastroenterology.)

We herein report a case of huge hepatocellular carcinoma (HCC) with adrenal metastasis and vascular invasion successfully treated by conversion hepatectomy after atezolizumab-bevacizumab treatment. A 77-year-old male patient with chest pain was admitted. He had a history of HCC treatment; however, the patient stopped receiving follow-up treatment based on his own decision. This time, he visited the emergency department of our hospital for the first time in 5 years. The tumor at the right lobe had grown into a lump with adrenal metastases and was 15 cm in diameter. It had invaded the inferior vena cava. Atezolizumab-bevacizumab treatment was selected for HCC treatment. Before starting treatment, his liver function was preserved (Child-Pugh A5). His alpha fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels were 759.0 ng/mL and 5,681 mAU/mL, respectively. Atezolizumab-bevacizumab treatment resulted in a marked decrease in tumor marker levels and tumor staining. After nine courses of atezolizumab-bevacizumab treatment, it became difficult to continue the administration of bevacizumab because of proteinuria. Because the tumor had decreased in size and the tumor markers were in the normal range, we decided to perform conversion hepatectomy. The tumor was completely removed by combined resection of the diaphragm, and pathological analyses showed a complete response to atezolizumab-bevacizumab treatment. No viable tumor cells remained on histological analyses. The patient is doing well without any signs of recurrence at 3 months after conversion surgery., (© 2022. Japanese Society of Gastroenterology.)

We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence., (© 2021. Japanese Society of Gastroenterology.)

Background: Liver fibrosis and cancer are serious hepatic complications for patients with congenital heart diseases. We present a rare case of combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA) after the repair of tetralogy of Fallot (TOF)., Case Presentation: A 54-year-old Japanese woman had undergone biventricular repair for TOF at 7 years old. She presented with abdominal distension. Abdominal CT revealed ascites and a 90-mm tumor involving the liver's left lobe. Tumor marker values were: alpha-fetoprotein, 16,208 ng/mL and des-gamma-carboxy prothrombin, 33,920 mAU/mL. The preoperative diagnosis was malignant tumor of the liver (e.g., HCC or intrahepatic CCA). We performed a left lobectomy of the liver. Histopathologically, the tumor was composed of two components growing in trabecular and irregular tubular patterns accompanied by a transitional area; the tumor was diagnosed as cHCC-CCA. The non-cancerous area showed fibrous change mainly surrounding a central vein and sinusoid, expanding toward the portal area without inflammation., Conclusions: We provide the details of our patient's cHCC-CCA that developed from fibrous congestive liver associated with right-sided heart failure after TOF repair, diagnosed based on histopathological features. We discuss liver fibrosis as a hepatic complication and a careful follow-up maneuver for improving the outcomes of patients with chronic hepatic congestion., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Congestive hepatopathy and hepatocellular carcinoma is a serious complication after Fontan procedure. Liver fibrosis due to hepatic congestion could occur also in adult patients after repair of tetralogy of Fallot (rTOF). However, the incidence and severity remain unclear., Methods: A total of 111 patients with adult congenital heart disease between 2009 and 2016 were enrolled. Liver fibrosis markers and hemodynamic parameters assessed by cardiac magnetic resonance imaging and catheterization were analyzed in 50 rTOF patients having significant pulmonary regurgitation and/or stenosis, 50 Fontan patients and 11 controls., Results: Liver fibrosis markers in patients with rTOF were significantly higher than controls, and tended to be lower than Fontan patients (median, hyaluronic acid: 25.8 vs. 15.9 vs. 40.8, type IV collagen: 129 vs. 113 vs. 166, ng/mL, p < 0.05, respectively). Patients with rTOF showed abnormal hyaluronic acid levels more frequently than controls, and less frequently than Fontan patients (22% vs. 0% vs. 38%, respectively, p < 0.05). Multivariate analyses indicated a positive association of right atrial pressure with type IV-collagen or hyaluronic acid levels (each, p < 0.001, p = 0.003). Abdominal ultrasonography revealed hepatic congestion in 50% of rTOF patients tested. Liver biopsy of the two rTOF patients with highest hyaluronic acid levels showed pathological evidence of moderate and severe (F2 and F3) liver fibrosis and one had combined hepatocellular and cholangiocarcinoma., Conclusions: We first demonstrated elevated liver fibrosis markers in adult patients with rTOF. These levels may help to predict the progressive liver disease as well as consider the timing of pulmonary valve replacement., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A male patient underwent conventional transcatheter chemoembolization for advanced recurrent hepatocellular carcinoma (HCC). Even after the injection of 7 mL of lipiodol followed by gelatin sponge particles, the flow of feeding arteries did not slow down. A repeat angiography revealed a newly developed vascular lake draining into systemic veins; however, embolization was continued without taking noticing of the vascular lake. The patient's level of consciousness deteriorated immediately after the procedure, and non-contrast computed tomography revealed pulmonary and cerebral lipiodol embolisms. The patient's level of consciousness gradually improved after 8 wk in intensive care. In this case, a vascular lake emerged during chemoembolization and drained into systemic veins, offering a pathway carrying lipiodol to pulmonary vessels, the most likely cause of this serious complication. We should be aware that vascular lakes in HCC may drain into systemic veins and can cause intratumoral arteriovenous shunts., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Purpose: To investigate clinical features and results of follow-up in patients with arterial injury during transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma., Methods: From 2005 to 2015, 2219 TACE procedures were performed in 906 patients in our hospital. Iatrogenic arterial injury occurred during 38 TACE procedures (sessions) in 35 patients (24 men, 11 women; mean age 71.8 years). The incidence of arterial injury was 1.7%. We evaluated the characteristics of arterial injury, and evaluated the risk factors for incomplete recanalization of the injured artery at follow-up angiography conducted after 1-11 months (mean 102.5 days)., Results: Iatrogenic arterial injury was caused by the microcatheter in 34 of 38 cases (86.8%). There were 15 cases (39.5%) in which the replaced hepatic artery or the extrahepatic artery was the parasitic supply. Extravasation occurred in five cases. In 36 of 38 cases, follow-up angiography was performed. We divided 36 cases into two groups: complete reopening (n = 24) and non-complete reopening (n = 12). The two groups were compared regarding the factors associated with incomplete recanalization of the injured artery at follow-up. Injury length >3 cm (p = 0.0002) and proximal arterial injury (proximal to the segmental artery; p = 0.03) were significant risk factors for non-complete reopening of the injured artery., Conclusion: Iatrogenic arterial injury frequently occurred in the extrahepatic artery or replaced hepatic artery. Recanalization rate of arterial injury was high; however, injury length >3 cm and proximal arterial injury were risk factors for non-complete reopening of the injured artery.

Objectives: The aim of the study was to clarify the clinical significance of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in terms of technetium-99m galactosyl human serum albumin (99mTc-GSA) scintigraphy. To this end, we examined the relationship using data from surgical records of 67 patients with hepatocellular carcinoma who underwent hepatectomy., Materials and Methods: Liver functional parameters or functional volume was estimated by 99mTc-GSA scintigraphy and computed tomography volumetry was used to estimate morphological volume., Results: Liver uptake ratio at 15 min (LHL15) was correlated with the indocyanine green retention rate at 15 min (ICGR15; R=-0.608, P<0.01); however, five patients (7.5%) had values outside this correlation. In these patients, LHL15 reflected clinical status and patient outcomes more. Although morphological and functional volumes were well correlated (P<0.01), functional volume was decreased in the diseased liver with portal vein tumor thrombus or portal vein embolization. By applying 99mTc-GSA volumetry, portal pressure and alkaline phosphatase level were correlated with decreased volume of the embolized liver, and platelet count and cholesterol level were correlated with increased volume of the nonembolized liver (P<0.05). By measuring functional volume, four patients who were functionally borderline on the basis of the ICGR15 test safely underwent scheduled major hepatectomy., Conclusion: Under the ICGR15 test as the standard for preoperative hepatic function, auxiliary application of LHL15 and functional volumetry provides useful information on hepatocellular carcinoma patients undergoing hepatectomy.

The patient is a 20-year-old man with glycogen storage disease type I (GSD-type I). In his teens, multiple focal hepatic masses were detected on abdominal ultrasonography (US), which were diagnosed as multiple hepatocellular adenomas from the imaging. During follow-up, these masses had shown intermittent growth in size. In the evaluation of Gd-EOB-DTPA (gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid) MR imaging, these masses showed various signal intensities from hypo- to hyperintense during the hepatocyte-specific phase. Intermittent growth and elevation of serum PIVKA-II levels indicate the potential for malignant transformation, so the patient underwent partial hepatectomy. The resected masses were all consistent with benign hepatocellular adenomas histopathologically.

Background: α-fetoprotein (AFP) is used as a marker for hepatocellular carcinoma (HCC), which is influenced by hepatitis. Protein-induced vitamin K absence or antagonist II (PIVKA-II) is a sensitive diagnostic marker. Changes in these markers after treatment may reflect curability and predict outcome., Methods: We conducted an analysis of prognosis in 470 HCC patients who received curative treatments, and examined the relationship between changes in AFP and PIVKA-II levels after 1 month of treatment in 156 patients. Subjects were divided into three groups according to changes in both levels: (1) normal (L) group before treatment, (2) normalization (N) or (3) decreased but still above normal level or unchanged (ANU) group after treatment., Results: High AFP and PIVKA-II levels were significantly associated with poor tumor-free and overall survival. The presence of large size and advanced stage were significantly associated with prevalence of DU group. Overall survival in the AFP-L group was significantly better than that of other groups and overall survival in PIVKA-II-L and N groups were significantly better than that of the PIVKA-II-ANU groups. The combination of changes in the AFP- ANU and PIVKA-II- ANU groups showed the worst tumor-free and overall survivals. Multivariate analysis identified high pre-treatment levels of AFP and PIVKA-II and combination of AFP- ANU and PIVKA-II- ANU as significant determinants of poor tumor-free and overall survival, particularly in patients who underwent hepatectomy., Conclusion: We conclude that high levels of AFP or PIVKA-II after treatment for HCC did not sufficiently reflect curative efficacy of treatment and reflected a poor predictor of prognosis in HCC patients.

Objective: The purpose of this article is to review the angiographic changes, development of collaterals, and possible complications after transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC)., Conclusion: Extrahepatic collateral arteries can supply the tumor after repeated TACE. Knowledge of hepatic artery changes can help in repeated TACE procedures and reduce TACE time. Appreciation of the complications and collaterals may improve the outcome of patients with HCC.

Background/purpose: While lipiodolized transarterial chemoembolization (lip-TACE) is effective for treating unresectable hepatocellular carcinoma (HCC), its effect for treating recurrent HCC after curative liver resection needs to be clarified., Methods: Of 163 patients who had undergone curative liver resection between 1992 and December 2003, 65 patients (39.8%) had recurrent HCC in the liver without extrahepatic recurrence and were indicated for lip-TACE. The overall survival rate after lip-TACE was calculated, and its correlation with factors such as the histology of the primary HCC and background noncancerous tissue were analyzed., Results: The overall survival rates after lip-TACE after the detection of the first recurrent HCC were 82.6%, 44.5%, and 24.8% at 1, 3, and 5 years, respectively. The factors affecting patient survival after lip-TACE were microscopic portal venous involvement of HCC at liver resection, grade of inflammation in the noncancerous liver parenchyma, and recurrence within 1 year after the initial liver resection. Multivariate analysis showed that the period between the resection and first recurrence had the highest hazard ratio., Conclusions: Lip-TACE is a reasonable procedure for treating recurrent HCC in selected patients who are not eligible for hepatic re-resection. When HCC recurred within 1 year from the primary liver resection, the effect of lip-TACE on patient survival was limited.

Purpose: To analyze local recurrence-free rates and risk factors for recurrence following percutaneous radiofrequency ablation (RFA) or transcatheter arterial chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC)., Methods: One hundred and nine nodules treated by RFA and 173 nodules treated by TACE were included. Hypovascular nodules were excluded from this study. Overall local recurrence-free rates of each treatment group were calculated using the Kaplan-Meier method. The independent risk factors of local recurrence and the hazard ratios were analyzed using Cox's proportional-hazards regression model. Based on the results of multivariate analyses, we classified HCC nodules into four subgroups: central nodules < or =2 cm or >2 cm and peripheral nodules < or =2 cm or >2 cm. The local recurrence-free rates of these subgroups for each treatment were also calculated., Results: The overall local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p = 0.013). The 24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and 48.9%, respectively. In the RFA group, the only significant risk factor for recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a central location was the only significant risk factor for recurrence. In central nodules that were < or =2 cm, the local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p < 0.001). In the remaining three groups, there was no significant difference in local recurrence-free rate between the two treatment methods., Conclusion: A tumor diameter of >2 cm was the only independent risk factor for local recurrence in RFA treatment, and a central location was the only independent risk factor in TACE treatment. Central lesions measuring < or =2 cm should be treated by RFA.

Objective: The purpose of our study was to discuss the incidence, predisposing factors, and clinical course of intrahepatic biloma after transcatheter arterial chemoembolization for hepatic tumors including hepatocellular carcinoma and metastatic liver tumor., Materials and Methods: Nine hundred seventy-two patients with hepatocellular carcinoma (n = 920) or metastatic liver tumor (n = 52) underwent chemoembolization during a 12-year period beginning in January 1989. We retrospectively reviewed the medical records and follow-up radiographs of chemoembolization and analyzed the risk factors associated with the development of intrahepatic biloma., Results: Intrahepatic biloma developed after chemoembolization in 35 patients (3.6%, 35/972) in our series. The incidence of intrahepatic biloma formation in patients with metastatic liver tumor (9.6%, 5/52) was higher than that in patients with hepatocellular carcinoma (3.3%, 30/920) (p < 0.05, Fisher's exact test). The incidence of intrahepatic biloma formation in patients with hepatocellular carcinoma was statistically higher in patients with main tumor size of less than 5 cm and in those with the presence of intrahepatic bile duct dilatation. Technique-related risk factors such as injection site of drugs, repeated chemoembolization with frequency of less than 3 months, and regimen of chemoembolization significantly influenced the incidence of biloma formation in patients with hepatocellular carcinoma. No patient died of infected biloma or septicemia, but one patient died of hepatic failure 2 months after chemoembolization., Conclusion: Biloma formation was significantly more prevalent in the metastatic lesion group than in the hepatocellular carcinoma group. Significant prognostic factors for biloma formation in patients with hepatocellular carcinoma were tumor size of less than 5 cm, bile duct dilatation, proximal injection site, repeated injection with frequency of less than 3 months, and injection of a suspension of anticancer drugs.

Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which indicates the existence of broad-range tumour-suppressor gene(s) at this locus. Truncating mutations in the ST7 gene at this locus are seen frequently in primary colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a novel candidate gene for the tumour suppressor at this locus. However, more recent studies have reported that ST7 mutations are infrequent or absent in primary cancer and cell lines. To ascertain the frequency of mutations of the ST7 gene in cancer cells, we examined mutations in the ST7 coding sequence in 48 colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain reaction-single-strand conformational polymorphism and direct sequencing. We detected somatic mutations, which were located near the exon-intron junction in intron 8, in only three out of 144 cases. We conclude that mutations in the ST7 gene are rare in primary colorectal, gastric, and hepatocellular carcinomas.

Background: We recently reported that the pathologic mode of infiltrative growth (infiltrative [INF]-alpha, INF-beta, and INF-gamma) of colorectal liver metastases had characteristic morphologic findings, and furthermore showed that the INF type was a prognostic factor for disease-free survival after hepatic resection., Hypothesis: Preoperative computed tomographic (CT) findings of the liver nodules may be predictive for pathologic tumor growth pattern., Design: Retrospective study., Setting: Departments of Surgery and Radiology at a university hospital in Japan., Patients: A total of 25 CT examinations (1985-1998) were reviewed, and a comparison was conducted on CT findings of 2 groups with INF-alpha or INF-beta (hereafter noted as INF-alpha-beta) (n = 9 [ie, a patient with INF-alpha plus 8 with INF-beta]) and INF-gamma (n = 16) type liver metastases., Main Outcome Measures: chi(2) Analysis of CT morphologic features was performed between the study groups. The result of multivariate analysis was obtained using the Cox proportional hazards model., Results: The morphologic features observed by CT showed a significant difference between the 2 groups (INF-alpha-beta, and INF-gamma types) in the ratio of length to breadth of nodules (<1.5 vs > or =1.5, P =.008) and in the outline of nodules (regular vs irregular, P =.01). Of these CT imaging features, the outline of the nodule was an independent prognostic factor (P =.02)., Conclusion: Computed tomographic findings of colorectal liver lesions correlated with the pathologic tumor growth pattern and a prognosis.

A 62-year-old Japanese male developed multiple hepatic metastases two years after resection of pheochromocytoma of the right adrenal gland. Transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastases resistant to 27 cycles of combined chemotherapy consisting of cyclophosphamide, vincristine, and dacarbazine. After TAE, the hepatic metastatic lesions decreased in size and hypertension passed its crisis. The present case suggests the utility of TAE for multiple hepatic metastases under careful blood pressure monitoring.

Spontaneous regression of hepatocellular carcinoma is a rare phenomenon. Abscopal regression of tumours resulting from the effect of irradiation of a tissue on a remote non-irradiated tissue is also rare. The case of a 76 year old Japanese man with hepatocellular carcinoma that regressed after radiotherapy for thoracic vertebral bone metastasis is described. Serum levels of tumour necrosis factor-alpha increased after radiotherapy. The findings suggests that such abscopal related regression may be associated with host immune response, involving cytokines such as tumour necrosis factor-alpha.

Transcatheter arterial embolization (TAE) is widely used in the treatment of hepatic tumors. A total of 2,300 TAE procedures were performed with a 2-15-mL injection of a mixture or suspension of anticancer drugs and iodized oil, followed by administration of gelatin sponge particles. One or two chemotherapeutic drugs, including doxorubicin hydrochloride (10-30 mg), epirubicin hydrochloride (10-30 mg), mitomycin C (10-20 mg), and cisplatin (25-100 mg), were used for each procedure. Complications were encountered in 4.4% of cases (n = 102) and were related to the use of chemoembolic agents or the manipulation of a catheter or guide wire. These complications included acute hepatic failure (n = 6), liver infarction (n = 4) or abscess (n = 5), intrahepatic biloma (n = 20), multiple intrahepatic aneurysms (n = 6), cholecystitis (n = 7), splenic infarction (n = 2), gastrointestinal mucosal lesions (n = 5), pulmonary embolism or infarction (n = 4), tumor rupture (n = 1), variceal bleeding (n = 3), and iatrogenic dissection (n = 35) or perforation (n = 4) of the celiac artery and its branches. Knowledge of these complications is important for correct diagnosis and appropriate management.

Purpose: To discuss the mechanism of multiple intrahepatic aneurysm formation after transcatheter arterial embolization (TAE) performed in five patients with hepatocellular carcinoma., Materials and Methods: TAE was performed with gelatin sponge particles and iodized oil as embolic materials. Mitomycin C was also used in four cases., Results: Three to 14 aneurysms 1-6 mm in diameter were found in third-to sixth-order branches of the hepatic arteries at repeat angiography performed 25-45 days after TAE. Follow-up angiograms in three cases revealed that most aneurysms were no longer apparent except in one patient in whom two aneurysms remained and were larger than before. In none of the five cases were any signs of aneurysm rupture noted., Conclusion: Radiologists should be aware of this complication of TAE. It is speculated that the main cause of aneurysm formation in these patients was the embolic agents used.

Seven smaller than 2 cm in diameter hepatocellular carcinomas (HCC) undetectable by hepatic arteriography and computed tomography (CT) after intraarterial injection of iodized oil (Lipiodol CT) were diagnosed by ultrasonography-guided fine-needle biopsy in 6 patients. All lesions were treated by percutaneous ethanol injection (PEI) in 1-3 weekly intervals. No recurrences have been demonstrated after 7-15 months. The treatment of HCCs undetectable by angiography and Lipiodol CT presents a problem as transcatheter arterial embolization is considered ineffective due to poor vascularity. PEI appears to be an excellent treatment for these small HCCs.