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Purpose : To evaluate the histological findings in both tumor and surrounding non-tumoral liver parenchyma after trans-arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) in patients who subsequently underwent hepatectomy. Material and methods : This study included six patients with an HCC (size 15-61 mm). DEB-TACE was performed using polyvinyl alcohol-based hydrogel microspheres loaded with epirubicin. Radiological tumor response was evaluated after DEB-TACE and before hepatectomy, according to the Modified Response Evaluation Criteria in Solid Tumors. Surgical specimens were histologically evaluated with hematoxylin and eosin, and elastic Van Gieson's staining. Results : Segmental, sub-segmental, or partial hepatectomy were performed 14-58 days after DEB-TACE. There was no remarkable destructive change and minimal to absent inflammatory cell infiltration in the surrounding non-tumoral liver parenchyma. There was no evidence of biliary tract or arterial wall impairment. Complete and partial histological tumor necrosis were found in three cases, respectively, in agreement with the complete and partial responses seen during the radiological evaluation. Conclusion : Histological examination of resected liver specimens after DEB-TACE showed substantial tumor necrosis without any severe inflammatory or destructive changes in the non-tumoral liver parenchyma.

A randomized, phase III trial of orantinib in combination with transcatheter arterial chemoembolization (TACE) did not prolong overall survival (OS) over placebo (ORIENTAL study). A subgroup analysis was conducted to evaluate the efficacy and safety of orantinib in Japanese patients enrolled in the ORIENTAL study. The data of Japanese patients from this study were analyzed. The overall survival (OS), time to progression (TTP), and time to TACE failure (TTTF) were compared between orantinib and placebo arms using stratified log-rank test. Since TTTF in patients with Barcelona Clinic Liver Cancer stage B (BCLC-B) showed favor outcome in this study, the OS and TTTF according to BCLC staging system were also analyzed. The subgroup analysis consisted of 219 and 213 patients in the orantinib and placebo arms. Median OS was 32.5 vs 33.0 months (p = 0.906), median TTP was 4.7 vs 3.1 months (p = 0.011), and median TTTF was 25.3 vs 18.2 months (p = 0.160) in the orantinib and placebo groups, respectively. Patients with BCLC-B in the orantinib and placebo groups showed a median OS of 33.7 and 30.1 months, respectively (p = 0.260), while the corresponding median TTTF were 25.3 and 14.0 months (p = 0.125). The Japanese population safety profile was similar to all over population in the ORIENTAL study. No significant differences were observed in the OS and TTTF though the TTP was significantly improved in the orantinib arm. The OS and TTTF showed a tendency to be prolonged following orantinib treatment of Japanese HCC patients with BCLC-B in the ORIENTAL study.

We retrospectively evaluated the safety and efficacy of artificial pneumothorax induction to perform computed tomography (CT)-guided radiofrequency ablation (RFA) for sub-diaphragm hepatocellular carcinomas (HCCs). From June 2008 to October 2010 at our institution, 19 HCCs (16 patients) were treated using CT-guided RFA after artificial pneumothorax induction. A 23-G needle was inserted into the liver surface at a site of 2 connected pleurae without lung tissue. After a small amount of air was injected, the pleural space widened, creating a small pneumothorax. Additional air was insufflated via a newly inserted 18-G cannula to raise the lung away from the planned puncture line for RFA. The electrode was then advanced transthoracically. Ablation was performed using a cool-tip electrode with manual impedance control mode. The injected air was then aspirated as much as possible. Artificial pneumothorax was successfully induced in all cases. The average total volume of injected air in each case was 238ml. No artificial pneumothorax-related complication occurred; lung injury occurred in one case during RF electrode insertion. No local progression occurred during follow-up. Recurring HCCs were observed in eight patients. Artificial pneumothorax induction is safe and effective for CT-guided RFA of sub-diaphragm HCCs, which are difficult to locate on US.

Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death. A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents. We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy. The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years. Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section. Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver. No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified. At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases.This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation.

Background: The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients., Methods: We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT)., Results: Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18%, p < 0.01) and PVTT (45 vs. 18%, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively)., Conclusions: CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

Objective: We retrospectively evaluated the effect of transpulmonary radiofrequency ablation (RFA) of liver tumours on the lung., Methods: 16 patients (10 males and 6 females; mean age, 65.2 years) with 16 liver tumours (mean diameter 1.5 cm) underwent transpulmonary RFA under CT fluoroscopic guidance. The tumours were either hepatocellular carcinoma (n=14) or liver metastasis (n=12). All 16 liver tumours were undetectable with ultrasonography. The pulmonary function values at 3 months after transpulmonary RFA were compared with baseline (i.e. values before RFA)., Results: In 8 of 16 sessions, minor pulmonary complications occurred, including small pneumothorax (n=8) and small pleural effusion (n=1). In two sessions, major pulmonary complications occurred, including pneumothorax requiring a chest tube (n=2). These chest tubes were removed at 4 and 6 days, and these patients were discharged 7 and 10 days after RFA, respectively, without any sequelae. The pulmonary function values we evaluated were forced expiratory volume in 1 s (FEV1.0) and vital capacity (VC). The mean values of FEV1.0 before and 3 months after RFA were 2.55 l and 2.59 l, respectively; the mean values of VC before and 3 months after RFA were 3.20 l and 3.27 l, respectively. These pulmonary values did not show any significant worsening (p=0.393 and 0.255 for FEV1.0 and VC, respectively)., Conclusion: There was no significant lung injury causing a fatal or intractable complication after transpulmonary RFA of liver tumours.

Purpose: To retrospectively evaluate technical success, effectiveness, complications, patient survival, and prognostic factors with percutaneous radiofrequency (RF) ablation for pulmonary metastases resulting from hepatocellular carcinoma (HCC)., Materials and Methods: Thirty-two patients from six institutions were included, with a total of 83 pulmonary metastases treated in 65 sessions. RF ablation was always performed percutaneously with computed tomography (CT) guidance. Primary endpoints were technical success and technique effectiveness. Technique effectiveness was evaluated based on sequential follow-up CT images. Secondary study endpoints were complications, patient survival, and determination of prognostic factors. Complications were classified as major or minor. Prognostic factors were determined by analyzing multiple variables with the log-rank test., Results: Technical success rate was 100%. Primary technique effectiveness rates were 92% each at 1, 2, and 3 years. Major and minor complications occurred after 16 (25%) and 23 (35%) of the 65 sessions, respectively. The median follow-up period was 20.5 months. Overall survival rates were 87% at 1 year and 57% each at 2 and 3 years (median and mean survival times, 37.7 mo and 43.2 mo, respectively). Significantly better survival rates were obtained in cases of (i) no viable intrahepatic recurrence (P < .001), (ii) Child-Pugh class A disease (P < .001), (iii) absence of liver cirrhosis (P < .001), (iv) absence of hepatitis C virus infection (P = .006), and (v) α-fetoprotein level of 10 ng/mL or lower (P = .007) at the time of RF ablation., Conclusions: RF ablation appears effective, with an acceptable safety profile, in selected patients with pulmonary metastases resulting from HCC., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

We administered hepatic arterial infusion chemotherapy (HAIC) prior to FOLFOX to three patients with unresectable liver metastases from colorectal cancer. The patients' disease state was found to be highly advanced based on both computed tomography findings and liver function tests. The treatment strategy included an initial administration of HAIC to control liver metastases and improve liver function in order to facilitate the subsequent safe administration of FOLFOX without drug loss. As the HAIC regimen, 1,000 mg/m2 of 5-FU was administered weekly by continuous 5-h infusion after performing laboratory investigations through an implanted port-catheter system. After 3 HAIC cycles administered over 3 consecutive weeks, the mean alkaline phosphatase levels decreased from 969.3IU/l to 422IU/l due to shrinkage of the liver metastases. Thereafter, FOLFOX without drug loss could be safely initiated for all patients. Two patients succumbed 488 and 333 days after HAIC was initiated;the third patient is still alive and has been followed-up for 1215 days. The combined use of HAIC and standard systemic chemotherapy could be a feasible and efficacious treatment in highly advanced cases of liver dysfunction.

Objective: : To retrospectively evaluate the effect of tumor type on local control by radiofrequency ablation in the lungs., Materials and Methods: : This study included 252 lung tumors (mean size, 13.5mm) in 105 patients (73 men and 32 women; mean age, 66.6 years) who underwent radiofrequency ablation with a multitined expandable electrode. Those tumors comprised five tumor types: primary lung cancer (n=35) and pulmonary metastases from colorectal cancer (n=117), lung cancer (n=23), renal cell carcinoma (n=49), and hepatocellular carcinoma (n=28). Local control was evaluated with contrast-enhanced computed tomography. The overall local control rates were estimated as well as those for each tumor type using the Kaplan-Meier analysis. Local control rates for a given tumor type were compared with those for the four other types. Then, multivariate multilevel analysis was performed using the variables of tumor type, tumor size, contact with a vessel or bronchus, and procedure period., Results: : The overall local control rates were 97%, 86%, 81%, and 76% at 6, 12, 18, and 24 months, respectively. Local control rates varied among the tumor types, and metastatic colorectal cancer showed significantly (P=.023) higher local control rates than those of the four other types. However, multivariate analysis indicated that the relative risk of local progression for a given tumor type was comparable to the risks for the four other types., Conclusion: : Tumor type per se did not significantly influence local control., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

We encountered a case of systemic air embolism during preoperative pulmonary marking with a short hook wire and suture system under CT fluoroscopy guidance. The pulmonary tumor was present in the right S3, and the procedural position was supine. The patient experienced cardiac symptoms, and systemic air embolism was confirmed on CT images. With the patient in the Trendelenburg position, 100% oxygen was immediately administered as therapy for the embolism. Subsequently, the symptoms and systemic air embolism were resolved. The patient underwent video-assisted thoracoscopic wedge resection after 5 days and was then discharged without any sequelae.

A 56-year-old man had a lung metastasis from hepatocellular carcinoma 4.7 cm x 3.4 cm in size located directly adjacent to the pulmonary hilar vessels. The tumor was treated with radiofrequency ablation combined with earlier bronchial arterial chemoembolization and subsequent radiation therapy. A complete remission of the tumor has been observed for 6 months since completion of therapy. Considering that complete treatment of such an intermediate-sized tumor adjacent to the large vessels is usually difficult with radiofrequency ablation alone, this result suggests a possible role for combined therapy for pulmonary neoplasms.

A 64-year-old man with unresectable sigmoid adenocarcinoma due to peritoneal dissemination (P3) and liver metastasis (H2) treated with TS-1, showed a complete response. TS-1 is an oral anticancer drug that produces biochemical modulation. It is composed of tegafur, gimestat and ostat potassium in a molar ratio of 1:0.4:1 to increase the effect of 5-FU and to decrease toxicity in the digestive canal. Treatment with TS-1 requires no hospitalization and can enhance the quality of life of the patient. TS-1 is expected to be an effective agent for the treatment of colon cancer with liver metastasis and peritoneal dissemination.

Objective: Liver regeneration after hepatectomy is correlated with liver fibrosis. Retrospectively, we compared three quantitative indices (HH15, LHL15 and LU15) of Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m-GSA) liver scintigraphy with liver fibrosis; in particular, we compared the HH15 index and the rate of remnant liver regeneration., Methods: Fifty-three patients who had undergone hepatectomy were enrolled in this study. The non-neoplastic parts of their resected specimens were divided into 5 groups (F0-F4) according to the degree of liver fibrosis, as determined using the New Inuyama classification system: F0, no fibrosis (n = 12); F1, portal fibrosis widening (n = 12); F2, portal fibrosis widening with bridging fibrosis (n = 14); F3, bridging fibrosis plus lobular distortion (n = 7); F4, liver cirrhosis (n = 8)., Results: When the cases were divided into a no or mild fibrosis group (F0 and F1) and a moderate or severe fibrosis or cirrhosis group (F2, F3 and F4), all of the indices were significantly different between the two groups. In this analysis, the areas (Az) under the receiver operating characteristic (ROC) curves for the HH15 and LHL15 indices were very similar, while the Az for the LU15 index was smaller. An HH15 index equal to 0.52 was the most accurate, producing a 79.3% sensitivity and a 75.0% specificity rating. When 18 patients that had received a CT scan one month after hepatectomy were divided into 2 groups according to their HH15 value (group A, HH15 < or = 0.52; group B, HH15 > 0.52), group A exhibited a better regeneration rate., Conclusion: Tc-99m-GSA scintigraphy is well correlated with liver fibrosis and may be useful for non-invasive, preoperative evaluations of liver fibrosis. The HH15 index, in particular, may be useful for predicting the rate of liver regeneration after hepatectomy.

We performed radiofrequency ablation (RFA) for 14 patients with hepatocellular carcinoma (HCC) between May 2001 and March 2002. The underlying hepatic disease was type C liver cirrhosis in all patients. Seven patients had a solitary lesion, and 7 patients had multiple lesions. RFA was chosen for the primary tumor in 5 cases and for a recurrent tumor in 9 cases. Three cases of well differentiated HCC were included. Transcatheter arterial embolization (TAE) was performed in 10 cases simultaneously. Nine patients received RFA under general anesthesia (open laparotomy: 5 cases, transthoracic: 1 case, CT guided: 2 cases, US guided: 1 case) and 5 patients under local anesthesia (CT guided: 2 cases, US guided: 3 cases). RFA was performed for 12 minutes in each session and the mean number of sessions per patient was 3.2. Excellent ablation was achieved in all cases according CT evaluation, and no additional therapy was needed. No recurrences have been found in any cases so far. RFA for HCC achieved excellent therapeutic effect in combination with other therapies as multimodal therapy.

We report a case of Sipple's syndrome with a hepatic tumor. A 28-year-old male with medullary thyroid cancer and bilateral pheochromocytomas was diagnosed as having Sipple's syndrome. The hepatic tumor was found to be hypervascular by means of a dynamic abdominal CT scan. An I-131-MIBG scan showed no increased accumulation in the tumor. A whole body Tc-99m-MIBI scan had shown, however, increased accumulation in the tumor by 10 minutes after i.v. Tc-99m-MIBI. The hepatic tumor was diagnosed histologically as a metastasis from the medullary thyroid cancer. To our knowledge, there have been no previous reports of increased Tc-99m-MIBI accumulation in hepatic metastases from medullary thyroid cancer.

Nontutimorous decrease in 99mTc-GSA accumulation has not been well covered in the literature. Understanding of this phenomenon is, however, essential for accurate evaluation of regional hepatic function. Scintigrams (transaxial SPECT) of 269 patients who underwent 99mTc-GSA liver scintigraphy were reviewed for the presence of nontumorous decreases in 99mTc-GSA accumulation. Nontumorous decreases in 99mTc-GSA accumulation were seen in 32 of 269 patients (12%). In 16 of the 32 patients (6%), nontumorous decreases in 99mTc-GSA accumulation corresponded to regional decrease in portal venous flow. The causes of such decrease in portal venous flow were portal thrombus of hepatocellular carcinomas in eight patients, portal venous stenosis or occlusion by hilar cholangiocarcinomas in five patients, inter alia. In eight patients (3%), the regions with decreased 99mTc-GSA accumulation correlated with massive hepatic necrosis in fulminant hepatitis, scar in hepatitis, or confleuent in portal venous flow, lobar biliary stasis, or both. In four patients (1.5%), the exact causes of nontumorous decrease in 99mTc-GSA accumulation could not be determined.

Unlabelled: Regional attenuation/signal intensity differences seen on CT/magnetic resonance imaging can be a clue in detecting regional hepatic blood flow abnormality. Sometimes, however, they can be misinterpreted as a hepatic neoplasm or, in the case of a true neoplasm, they can lead to an overestimation of its size because these regions often have similar attenuation or signal intensity to hepatic neoplasms. We evaluated 99mTc-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-DTPA-GSA) liver scintigrams in patients manifesting regional attenuation/signal intensity differences to further analyze the findings., Methods: Technetium-99m-DTPA-GSA scintigrams of 23 patients with regional attenuation/signal intensity differences in the liver at dynamic contrast-enhanced CT/magnetic resonance imaging were evaluated. The causes of the differences were arterioportal (AP) shunts in seven patients, decreases in the portal venous flow in seven patients, occlusion of right hepatic vein in one patient, confluent hepatic fibrosis in one patient and unknown in seven patients. The accumulation of 99mTc-DTPA-GSA was compared with each known cause of attenuation/signal intensity difference. Count ratios of the regions to normal hepatic parenchyma also were calculated in all cases., Results: In AP shunts, none of seven patients showed any decreased accumulation in the region. Accumulation of 99mTc-DTPA-GSA decreased in six of seven patients who had decreases in portal venous flow; this incidence was significantly higher than that in patients who had AP shunts (p < 0.005). In cases of unknown cause, two of seven patients showed a decrease in accumulation, but the other five showed no such decrease. The one patient with occlusion of the right hepatic vein showed no decrease, but the confluent hepatic fibrosis showed a significant decrease. The count ratio in AP shunts was significantly larger than that of the decrease in the portal venous flow (p < 0.005)., Conclusion: Technetium-99m-DTPA-GSA accumulation in AP shunts has a different pattern from that found in patients with a decrease in portal venous flow. Therefore, differentiation between AP shunts, which showed no decrease in 99mTc-DTPA-GSA accumulation, and hepatic neoplasms can be made more easily.

Objective: A previous study suggested that temporary occlusion of a segment of the hepatic vein causes an increase in arterial flow and retrograde portal flow in the occluded segment. Such occlusions might improve the efficacy of arterial infusion therapy. Accordingly, we studied the change in blood flow visible on hepatic arteriograms when a segment of the hepatic vein is temporarily occluded in patients with hepatocellular carcinoma., Materials and Methods: The study group consisted of 24 patients with nodular-type hepatocellular carcinoma. Conventional hepatic arteriography was followed by hepatic arteriography performed using a balloon catheter to occlude the hepatic vein that was most closely associated with the tumor. Visualization of the tumor-draining veins, portal vein branches, the degree of tumor vascularity, and the density of the hepatogram on the hepatic arteriogram were retrospectively compared before and during venous occlusion. The veins were evaluated visually; an increase of tumor vascularity was defined as an increase in the number of countable tumor vessels during occlusion, and a dense hepatogram was considered to be a definite sinusoidgram induced by venous occlusion., Results: Conventional hepatic arteriography showed the tumor-draining veins to be branches of the portal vein in only two of the 24 patients (8%). Hepatic arteriography during venous occlusion, however, showed the tumor-draining veins to be branches of the portal vein in four of the patients (17%). An increase in the degree of tumor vascularity with venous occlusion was observed only in a patient with an initial arteriohepatic vein shunt. Dense hepatogram and hepatofugal opacification of the portal vein branches in the occluded, tumor-bearing segment were obtained in 10 patients (42%). Eight of these did not have liver cirrhosis, whereas all of the remaining 14 patients did (p < .001)., Conclusion: Our results suggest that occlusion of a segment of the hepatic vein may be useful during arterial infusion of hepatocellular carcinoma.

A patient with hepatocellular carcinoma (HCC) and coexisting hepatic cavernous hemangiomas with arterioportal and arterio-hepatic vein shunts is reported. Antegrade and retrograde opacifications of portal vein radicles and filling of a branch of the right hepatic vein verging on cavernous hemangiomas were observed in the late arterial phase of hepatic arteriography in addition to HCC. Unenhanced CT scans performed eight days after the arterial infusion of Lipiodol showed clearly the location of the tumors and the shunting vessels. To the authors' knowledge, this is the first reported case of cavernous hemangioma with arterioportal and arterio-hepatic vein shunts accompanied by hepatocellular carcinoma.

We compared the computed tomographic (CT) and angiographic presentations of hepatocellular carcinoma (HCC) with or without cirrhosis in the United States and Japan. Tumors in the United States were advanced and less frequently associated with liver cirrhosis (association of cirrhosis: United States 56.2%, Japan 91.0%. In patients with cirrhosis, the size of the tumor tended to be smaller, and nodular tumors (single or multiple) were frequent. In early stage of HCCs with cirrhosis, tumors were hypovascular without a capsule. In advanced stage, tumors were hypervascular and a capsule was frequently observed around the tumor both with CT and angiography. HCCs without cirrhosis were seen in younger patients. These tumors were large at the time of diagnosis. A massive or diffuse mass without a capsule was frequently seen. Most tumors were hypodense on precontrast CT and hypervascular on angiography. Lymph node enlargement was significantly frequent. The radiological characteristics of HCC in both countries were significantly different depending upon associated cirrhosis, as well as the time of the diagnosis.

Hepatic arteriography with and without temporary segmental hepatic vein occlusion was performed in 10 patients, five of whom had chronic liver injury. Hepatic arteriograms obtained during hepatic venous obstruction demonstrated significantly more peripheral and definite arterial branches in the occluded area and fewer peripheral branches in the non-occluded segment. A prolonged, dense hepatogram (sinusoidogram) showing hepatofugal opacification of the portal vein was obtained in the occluded area. Only one case with a large veno-venous anastomosis did not show these findings. Hepatic arteriograms in two cases with hepatocellular carcinoma provided clear visualization of peripheral portal branches that could act as efferent tumor vessels during regional temporary hepatic vein occlusion. Temporary hepatic venous occlusion may cause a sudden increase of hepatic arterial flow in the occluded area and transsinusoidal arterioportal communication there. This method can be useful for the diagnosis and arterial infusion or embolization therapy of hepatic diseases.

A 55-year-old woman with a giant cavernous hemangioma in the liver with hemoperitoneum due to blunt abdominal trauma was reported. CT findings of the liver at first thought to be hepatic injuries. But serial studies revealed that the CT findings were dependent on giant cavernous hemangioma and apart from hepatic injury.