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This study investigated the usefulness of postvascular images of contrast-enhanced ultrasonography (CE-US) in the gross classification of hepatocellular carcinoma (HCC) in comparison with contrast-enhanced CT (CE-CT) findings.This is a prospective study with consecutive HCC patients who had both CE-US and CE-CT prior to surgical resection. Fifty-one patients (32 men, 19 women; mean age, 68.9 years) with 61 HCCs were enrolled. The maximal diameters of all tumors ranged from 1.0 to 5.0 cm (mean ± SD, 2.5 cm ± 1.1). Weighted kappa statistics were used to assess the agreement of the sonographic or CT findings versus the results of macroscopic configurations.Thirty-nine tumors were macroscopically diagnosed as simple nodule type; 19 tumors were macroscopically diagnosed as simple nodular type with extranodular growth, and 3 were macroscopically diagnosed as confluent multinodular type from the resected specimen. The diagnostic accuracy was 86.9% (53/61) for CE-US and 65.6% (40/61) for CE-CT. The differences in accuracy between CE-US and CE-CT were statistically significant (McNemar; p = 0.007). Agreement analysis between gross classification using CE-US and final macroscopic results gave a kappa value of 0.74 (95% CI: 0.65–0.82), which was considered a good agreement. On the other hand, kappa coefficient value was 0.38 (95% CI: 0.28–0.48) between gross classification using CE-CT and final macroscopic results.CE-US is a more reliable tool than CE-CT to evaluate the gross type of HCC than CE-CT. Accurate gross classification using imaging is considered to be essential for the determination of the correct treatment strategy and the estimates of the patients' prognosis.

Purpose: New tracking navigation imaging software was used to evaluate the usefulness of three dimensional (3D) CT angiography for transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Materials and Methods: Fifty-two patients with 73 HCCs were enrolled in this study retrospectively. Rotational angiography was performed from the hepatic artery for evaluation of the tumor feeding vessels. Arteries feeding the tumor were traced automatically by adjusting the region of interest around the targeted tumor on axial and coronal images using tracking navigation imaging with 3D cone-beam CT angiography. Results: Using final selective angiographic findings as the gold standard, the detection of feeding vessels was 90.4% (66/73) for tracking navigation imaging and 50.7% (37/73) for celiac trunk angiography. This difference was statistically significant (Wilcoxon rank sum test, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value for the detection of feeding arteries were 97.1% (66/68), 80.0% (4/5), 98.5% (66/67), and 66.7% (4/6), respectively. The kappa coefficient had a value of 0.638 (95% CI: 0.471-0.805), which is considered to indicate a good degree of agreement. With the assistance of tracking navigation imaging, the disease control rate of TACE for HCC was 67.3% (35/52) according to the modified Response Evaluation Criteria in Solid Tumors. During follow-up periods of 1-11 months, 10 patients (19.2%) remained cancer-free after TACE. Conclusion: Tracking navigation imaging with 3D cone-beam CT angiography should be useful for TACE in HCC patients with complicated feeding arteries.

The present reaction proceeds not only for silylated alkynes but also for substrates bearing a carbonaceous substituent.

Purpose. To evaluate the detectability of tumor vascularity in hepatic tumors by second harmonic imaging with the administration of a microbubble contrast agent, Levovist. Materials and methods: Twenty-four patients with hepatic tumors (21 hepatocellular carcinoma, one focal nodular hyperplasia and two liver metastasis) were studied using Aloka SSD 5500 with the administration of Levovist. Intermittent harmonic gray-scale imaging (HGSI) and intermittent harmonic power Doppler imaging (HPDI) were performed on every tumor and the detectability of the two harmonic imaging modes were compared with that of dynamic CT. Results: Tumor vessels and tumor parenchymal blood flow were obtained in hypervascular tumors in the early arterial phase, and metastasis presented peripheral enhancement. When dynamic CT was taken as a gold standard, the sensitivity, specificity and accuracy of detecting tumor vascularity for intermittent HGSI were 55.6, 100 and 66.7%, and for intermittent HPDI were 83.3, 100 and 87.5%, respectively. The difference of detectability between the two modes was statistically significant (P

The patient was a 21-year-old man. He crashed head-on with a truck while driving a car. He was admitted by ambulance. He vomitted blood a little and his abdomen showed muscular defence. Abdominal computed tomography showed free air and food remnant in the abdominal cavity. We diagnosed gastric rupture. At laparotomy, the stomach was observed to have been lacerated at the anterior wall of the angle. The laceration was sharp and was 5cm in length, so we closed it without debridement. Astriction to the subcapsular injury of the liver and spleen was carried out. The patient had also sustained pulmonary injury, hemothorax, and fractures of the left ribs and right femur, which required blood transfusion of large quantities. At laparotomy, a large amount of food remnant both inside and outside of the stomach was present, so we surmised that the cause of the gastric rupture was increased intraluminal pressure in the stomach. Besides this case, there have been only 12 case reports of adult gastric rupture from abdominal blunt trauma in the Japanease literature.

Budd-Chiari syndrome (BCS) is a rare condition characterized by hepatic venous outflow obstruction. In this report, we present 4 cases of BCS with complete and incomplete obstruction of the inferior vena cava (IVC) and hepatic vein (HV). Each case showed different and unique features of liver damage, which were attributed to the site and degree of obstruction. Interestingly, improved liver functions such as increased serum albumin levels, decreased hyaluronic acid levels and a normal indocyanine green clearance test were evident within 1 month of the balloon angioplasty. Pericellular fibrosis and hypervascular regenerative nodules were also reversible after obstruction removal. Therefore, it is very important to manage this rare disease before it progresses to liver cirrhosis.

Objective: To evaluate whether iatrogenic hemorrhage can be prevented by intrahepatic tract ablation following radiofrequency ablation (RFA) therapy for hepatic malignancies. Methods: A retrospective cohort study analyzing a prospective database in a single institution was conducted. The incidence of postprocedural complications was compared in two groups: one with cauterization of the needle tracts after RFA and the other without. Results: The complication rates of intraperitoneal hemorrhage were 1.05% (4/380) and 0.92% (6/652) in the nonablation group and the ablation group, respectively (p = 0.90). All of these 10 patients with iatrogenic bleeding were classified as Child-Pugh grade A. Among the 15 hemodialysis patients in this study, hemorrhage was seen in 2 (13.3%), compared with 8 (0.79%) of the nonhemodialysis patients (p = 0.0002). There were no statistically significant differences in the incidence of other complications including pleural effusion, serous ascites, pneumothorax, hemothorax, hepatic infarction, bile duct injury and pericardial effusion between the two groups. Gastrointestinal perforation, peritonitis or tumor seeding were not observed. Conclusion: Our study found a high incidence of bleeding after RFA among hemodialysis patients. Irrespective of tract ablation being after RFA, iatrogenic hemorrhage appeared to be equivalent in this population.

Global DNA hypomethylation is a characteristic feature of cancer cells that closely associates with chromosomal instability (CIN). However, the association between these characteristics during hepatocarcinogenesis remains unclear. Herein, we determined the relationship between hypomethylation and CIN in human hepatocellular carcinoma (HCC) by analyzing 179 HCCs, 178 matched non-tumor livers and 23 normal liver tissues. Hypomethylation at three different repetitive DNA (rDNA) sequences and hypermethylation of 12 CpG loci, including 11 tumor suppressor gene (TSG) promoters, were quantified using MethyLight or combined bisulfite restriction analysis. Fractional allelic loss (FAL) was used as a marker for CIN, calculated by analyzing 400 microsatellite markers. Gains and losses at each chromosome were also determined using semi-quantitative microsatellite analysis. The associations between rDNA hypomethylation and FAL, as well as between TSG hypermethylation and FAL were investigated. Significantly more hypomethylation was observed in HCC tissues than in normal liver samples. Progression of hypomethylation during carcinogenesis was more prominent in hepatitis C virus (HCV)-negative cases, which was in contrast to our previous reports of significantly increased TSG methylation levels in HCV-positive tumors. Absence of liver cirrhosis and higher FAL scores were identified as independent contributors to significant hypomethylation of rDNA in HCC. Among the chromosomal alterations frequently observed in HCC, loss of 8p, which was unique in the earliest stages of hepatocarcinogenesis, was significantly associated with hypomethylation of rDNA by multivariable analysis (p = 0.0153). rDNA hypomethylation was also associated with a high FAL score regardless of tumor differentiation (p = 0.0011, well-differentiated; p = 0.0089, moderately/poorly-differentiated HCCs). We conclude that DNA hypomethylation is an important cause of CIN in the earliest step of HCC, especially in a background of non-cirrhotic liver.

Cross-coupling reactions of dibromoarenes (I), (IV), and (VI) with HOMSi reagents (organo[2-hydroxymethylphenyl]dimethylsilanes) (II) or alternatively bromoarenes (IX) and arylene-bisHOMSi reagents, e.g. (VIII), afford ter- or quaterarenes (III), (V), (VII), and (X), resp., in high yields.

Objective: A number of studies have reported reactivation of hepatitis B during intensive immunosuppressive therapy such as cases of hematological malignancy, whereas little has been reported for characteristics of reactivation triggered by chemotherapy for solid cancer. Methods: A total of 130 patients underwent chemotherapy for treatments of common solid cancer between May 2011 and May 2012 at Kinki University Hospital. Among them, 27 patients were suspected for a past infection of hepatitis B virus (HBV), showing positive for hepatitis B core antibody or surface antibody but negative for hepatitis B surface antigen, and were eligible for this study. Results: Hepatitis B reactivation was observed in 2 of 27 cases (7.4%). The duration between the start of chemotherapy and increase of serum HBV load was 30 days in both cases. Conclusions: We reported the 2 cases of hepatitis B reactivation receiving chemotherapy for solid cancer in terms of patterns and characteristics of reactivation. Accumulation of such cases will help in clarifying the clinical importance of hepatitis B reactivation during treatment of solid malignancies.

Objectives: A unique causative aspect of hepatocellular carcinoma (HCC) is a gender difference in its incidence. To determine the specific factors that contribute to a male predominance, we analyzed the clinicopathological factors, and genetic and epigenetic alterations of HCCs in male and female patients. Methods: We retrospectively analyzed three cohorts of patients: the first cohort consisted of 547 patients identified with the first event of HCC, the second cohort included 176 HCC patients, and the third 127 patients with chronic hepatitis C (CHC). Results: Male patients were found to have HCC more frequently than female patients in cases of non-cirrhotic liver (p = 0.0030 by the χ2 test), especially in hepatitis C-positive cases. However, there were no gender-specific differences in the genetic and epigenetic alterations of cancer-related genes. Deposition of iron was more severe in male CHC patients than in female patients. Conclusions: Male patients with CHC develop HCC more frequently when they have a non-cirrhotic liver than do female patients. This gender difference could be, at least partially, attributed to a different degree of iron deposition, which contributes to the development of HCC in the absence of liver cirrhosis in men with CHC.

Objective: Increasing evidence suggests the efficacy of maintenance therapy with interferon (IFN) for chronic hepatitis C (CHC) in reducing the risk of hepatocellular carcinoma (HCC). The aim of this study was to determine clinical characteristics on the risk of occurrence of HCC in CHC patients receiving maintenance IFN therapy. Methods: A total of 55 patients were treated in a single center with PEG-IFNα-2a monotherapy for CHC and evaluated for variables predictive of the occurrence of HCC. Results: The cumulative incidences of HCC were 0.092, 0.117 and 0.161 at 3, 5 and 7 years, respectively. Serum ALT level (>40 IU/l) in the 6th month after commencement of IFN therapy and BMI >25 were associated with shorter time-to-HCC emergence using multivariate analysis (relative risk 16.034, p = 0.01 for ALT >40 IU/l; relative risk 6.020, p = 0.026 for BMI >25, respectively). The IL28B SNP was extracted as a significant factor for the occurrence of HCC. Conclusions: Maintenance therapy with the use of long-term low-dose PEG-IFNα-2a is effective for preventing HCC occurrence irrespective of the IL28B SNP, at least for a subset of CHC patients. The initial response of serum ALT levels and BMI provides a prognostic value for determining the risk of developing HCC later in life.

Among patients with later stage hepatocellular carcinoma (HCC), only 1–12% manifest obstructive jaundice as the initial complaint. Endoscopic retrograde biliary drainage (ERBD) and percutaneous transhepatic biliary drainage (PTBD) are the two main non-surgical treatment options for obstructive jaundice in patients with HCC. ERBD is usually the first-line treatment because of its low hemorrhage risk. Some have reported that the successful drainage rate ranges from 72 to 100%. Mean stent patency time and mean survival range from 1.0 to 15.9 and 2.8 to 12.3 months, respectively. PTBD is often an important second-line treatment when ERBD is impossible. With regard to materials, metallic stents offer the benefit of longer patency than plastic stents. The dominant effect of biliary drainage suggests that successful jaundice therapy could enhance anti-cancer treatment by increasing life expectancy, decreasing mortality, or both. We present an overview of the efficacy of endoscopic and percutaneous drainage for obstructive jaundice in patients with HCC who are not candidates for surgical resection and summarize the current indications and outcomes of reported clinical use.

Silylalkynyl aryl ethers and internal alkynes give under optimized conditions silylmethylidene-substituted chromenes.

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly defined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in difficult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an efficient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer.

Objective: The purpose of this study was to evaluate the role of des-γ-carboxyprothrombin (DCP) as a marker for the efficacy of sorafenib therapy for hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC treated with sorafenib were retrospectively evaluated, focusing on DCP levels and clinical characteristics. Results: 50 patients with advanced HCC were treated with sorafenib alone. In 25 of these patients, the serum levels of DCP were evaluated twice (pretreatment and within 2 weeks after starting therapy). The time to progression was significantly longer in patients in whom the DCP level at 2 weeks after starting sorafenib was ≧2-fold higher than the pretreatment levels, as compared with patients without an increase in DCP (p = 0.0296). Conclusions: The serum level of DCP is a surrogate marker for tissue hypoxia and can be a predictive marker to assess the tumor response to sorafenib therapy.

Radiofrequency ablation (RFA) of liver cancers can be performed safely using percutaneous, laparoscopic, or open surgical techniques, and much of the impetus for the use of RFA has come from cohort series that have provided an evidence base for this technique. Here, we give an overview of the current status of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), including its physical properties, to assess the characteristics that make this technique applicable in clinical practice. We review the technical development of probe design and summarize current indications and outcomes of reported clinical use. An accurate evaluation of treatment response is very important to secure successful RFA therapy since a sufficient safety margin (at least 0.5 cm) can prevent local tumor recurrences. We also provide a profile of side effects and information on the integration of this technique into the general management of patients with HCC. To minimize complications of RFA, physicians should be familiar with each feature of complication. Appropriate management of complications is essential for successful RFA treatment. Moreover, adjuvant therapy, such as molecular targeted therapies following curative therapy, is expected to further improve survival after RFA.

We describe a case of agenesis of the left lobe of the liver. The patient was a 61-year-old man with a chief complaint of a continuous, blunt pain in the left side of the back. Examinations were conducted using ultrasonography (US), enhanced computed tomography (CT), and magnetic resonance angiography (MRA). No liver tissue or falciform ligament were visualized at the left portion of the gallbladder fossa. The portal and hepatic veins lacked left branches, and the right branches of the hepatic vein were dilated. Here we discuss the differential diagnosis of agenesis of the left lobe of the liver.

The process affords functionalized 1-azadienes, generally with excellent (E) or (Z) selectivity.

Ablation therapy is one of the best curative treatment options for malignant liver tumors, and can be an alternative to resection. Radiofrequency ablation (RFA) of primary and secondary liver cancers can be performed safely using percutaneous, laparoscopic, or open surgical techniques, and RFA has markedly changed the treatment strategy for small hepatocellular carcinoma (HCC). Percutaneous RFA can achieve the same overall and disease-free survival as surgical resection for patients with small HCC. The use of a laparoscopic or open approach allows repeated placements of RFA electrodes at multiple sites to ablate larger tumors. RFA combined with transcatheter arterial chemoembolization will make the treatment of larger tumors a clinically viable treatment alternative. However, an accurate evaluation of treatment response is very important to secure successful RFA therapy. Since a sufficient safety margin (at least 0.5 cm) can prevent local tumor recurrences, an accurate evaluation of treatment response is very important to secure successful RFA therapy. To minimize complications of RFA, clinicians should be familiar with the imaging features of each type of complication. Appropriate management of complications is essential for successful RFA treatment.

Pd-catalyzed iminothiolation of alkynes took place to afford 4-SR substituted 1-azadienes regioselectively.

Most hepatocellular carcinomas (HCC) are diagnosed in patients with cirrhosis and/or when tumor burden is too advanced for surgical treatment. In many of these cases the only suitable therapy is locoregional, percutaneous and/or intraarterial treatment. Moreover, the best way to guide and assess response to locoregional HCC treatment are two issues under discussion today. First-generation and subsequent second-generation microbubble contrast agents, together with contrast-enhanced ultrasound (US) imaging, have expanded the role of US techniques in HCC treatments. In this review our purpose is to illustrate the advantages, limits and potential of contrast-enhanced US application for locoregional HCC treatment.

Purpose: To confirm the safety and effectiveness of techniques to assist radiofrequency ablation (RFA) for difficult cases, we retrospectively evaluated successful treatment rates, early complications and local tumor progressions. Patients and Methods: Between June 1999 and April 2009, a total of 341 patients with 535 nodules were treated as difficult cases. Artificial pleural effusion assisted ablation was performed on 64 patients with 82 nodules. Artificial ascites-assisted ablation was performed on 11 patients with 13 nodules. Cooling by endoscopic nasobiliary drainage (ENBD) tube-assisted ablation was performed on 6 patients with 8 nodules. When the tumors were not well visualized with conventional B-mode ultrasonography (US), contrast-enhanced US-assisted ablation with Levovist® or Sonazoid® or virtual CT sonography-assisted ablation was performed. Contrast-enhanced US-assisted ablation was performed on 139 patients with 224 nodules and virtual CT sonography-assisted ablation was performed on 121 patients with 209 nodules. Results: In total, complete ablation was achieved in 514 of 535 (96%) nodules in difficult cases. For RFA with artificial pleural effusion, artificial ascites and ENBD, complete response was confirmed in all cases. For contrast-enhanced US- and CT sonography-assisted ablation, complete response was 95%. Early complications were recognized in 24 cases (4.5%). All cases recovered with no invasive treatment. Local tumor recurrence was investigated in 377 nodules of 245 patients, and 69 (18%) nodules were positive. Tumor recurrences in each assisted technique were 14.7% in artificial pleural effusion cases, 7% in artificial ascites, 12.5% in ENBD tube cases, 31% in virtual CT sonography, and 8.5% in contrast-enhanced US. Conclusion: Although local tumor progression needs to be carefully monitored, assisted techniques of RFA for difficult cases are well tolerated and expand the indications of RFA.

Cronkhite-Canada syndrome (CCS) is a rare, noninherited gastrointestinal polyposis syndrome associated with characteristic ectodermal abnormalities. Here, we report a case of Cronkhite-Canada syndrome with cecal intussusception relieved by colonoscopy. A 52-year-old man who was diagnosed as CCS pathologically two years previously presented abdominal pain and sub fever-up. Physical examination revealed the palpable mass sized approximate 10 cm in diameter in the upper abdominal site, in addition to the symptoms of alopecia, absent fingernails and toenails. However, abdominal wall rigidity and rebound tenderness were never expressed. Abdominal plain CT showed concentric circles from the ascending to the middle of the transverse colon, and a tumor in the lumen at the middle of the transverse colon. Colonoscopic reduction was performed first because we diagnosed it as intussusception due to CCS polyps without peritoneal irritation, and his symptoms were improved dramatically after careful reduction. Therefore, he was able to undergo the laparoscopic ascending colectomy as scheduled.

Aim: Conventional contrast harmonic sonography has the technical problem of a short enhancement time during targeting of hepatic malignancies for radiofrequency (RF) ablation. This study investigated the effectiveness of contrast harmonic sonographic guidance using perfluorocarbon microbubbles (Sonazoid) during RF ablation of hepatic malignancies. Materials and Methods: Nodules were detected on contrast-enhanced computed tomography, but could not be resolved clearly by B-mode sonography. Sixty-six patients (51 men, 15 women; mean age, 65.8 years) with 108 hepatic malignancies were enrolled. Fifty-one patients with hepatocellular carcinoma and 15 patients with liver metastases were treated by RF ablation guided by contrast harmonic sonography using perfluorocarbon microbubbles for a target lesion identified as a defect image after the administration of contrast medium. Results: The maximal diameters of all tumours ranged from 0.7 to 3.5 cm (mean ± SD, 1.7 cm ± 0.9) on sonography. Complete tumour necrosis was achieved by a single session of RF ablation in 62 (94%) of the 66 patients, while two sessions were required for the remaining four (6%) patients. The average number of treatment sessions was 1.1 ± 0.3. In the post-vascular phase, 105 (97%) of a total of 108 malignant hepatic tumours were depicted as a defect with a margin. Clinical courses have been satisfactory without any signs of local tumour progression during 1–12 months of follow-up (mean, 4.3 months). Conclusion: Using perfluorocarbon microbubbles, contrast harmonic sonographic-guided RF ablation is an efficient approach for guiding further ablation of hepatic malignancies that are not clearly demarcated by B-mode sonography.

Intermolecular CO-retained carbothiolation of alkynes using thioesters took place to afford β-SR substituted enone derivatives; the choice of catalyst (Pd(dba)2–dppe) and the introduction of a CF3 group into the thioesters are the key to achieving the transformation.

Intermolecular CO-retained carbothiolation of alkynes using thioesters took place to afford beta-SR substituted enone derivatives; the choice of catalyst (Pd(dba)(2)-dppe) and the introduction of a CF(3) group into the thioesters are the key to achieving the transformation.

Purpose: There are currently no effective treatments for patients with advanced hepatocellular carcinoma (HCC) with vascular invasion or extrahepatic metastases. We evaluated the efficacy and safety of combination therapy with S-1 and pegylated interferon (PEG-IFN)-α for advanced HCC. Methods: A total of 22 patients received combination therapy with S-1 and PEG-IFN. One cycle of the combination therapy consists of oral S-1 (80 mg/m2) administration and subcutaneous PEG-IFN injection (PEG-IFN-α-2a 90 μg weekly or PEG-IFN-α-2b 50 μg weekly) for 4 weeks with 1- to 2-week intervals. Results: One patient was evaluated as complete response, 6 as partial response, 8 as stable disease, and 6 as progressive disease. One patient was not evaluable because therapy had to be discontinued as a result of jaundice. The median survival time was 15.3 months (95% CI: 4.4–26.2 months). The 1- and 2-year survival rates were 54.9 and 36.6%, respectively. The overall response rate was 31.8% and the disease control rate was 68.2%. Grade 3 neutropenia (18.2%), leukopenia (9.1%), anemia (9.1%), and thrombocytopenia (18.2%) were observed. Grade 4 toxicities were not observed. Conclusion: Combination therapy with S-1 and PEG-IFN is effective and feasible, and is therefore a promising regimen for advanced HCC.

Background: The purpose of this study was to investigate if Sonazoid-enhanced harmonic ultrasonography (US) could be used to evaluate the responses of hepatocellular carcinomas (HCCs) to treatment with transcatheter arterial chemoembolization (TACE). Patients and Methods: Forty-three HCCs that had been treated by TACE were evaluated by Sonazoid-enhanced harmonic US and dynamic computed tomography (CT) approximately 1 week after their treatment. The detection rates of residual tumor blood supply using the two modalities were compared. Two months after chemoembolization, 16 of the 43 HCCs, which had no additional local treatment, were followed up with dynamic CT. The results of contrast-enhanced harmonic US and dynamic CT 1 week after chemoembolization were analyzed and compared with follow-up dynamic CT results. Results: The detection rates of positive enhancement with Sonazoid-enhanced harmonic US and dynamic CT 1 week after TACE were 25 (58.1%) of 43 lesions and 17 (39.5%) of 43 lesions, respectively. Sonazoid-enhanced harmonic US was significantly more sensitive than dynamic CT in depicting the residual tumor blood supply to HCCs 1 week after TACE (p < 0.01; χ2 test). The Sonazoid-enhanced harmonic US results of the 16 lesions 1 week after chemoembolization were consistent with the follow-up results of dynamic CT 2 months after chemoembolization. Conclusions: Sonazoid-enhanced harmonic US appears to be a highly sensitive and accurate modality for evaluating responses of HCCs shortly after TACE.

To evaluate the usefulness of vascular phase images of contrast-enhanced ultrasonography (CE-US) with Sonazoid for hepatocellular carcinomas (HCCs), a retrospective, comparative study was conducted of images of HCCs obtained by CE-US and superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) and evaluated qualitatively and quantitatively.Seventy-seven patients with 88 HCCs who received CE-US and SPIO-MRI were reviewed. The ratio of the echogenicity of the tumor and nontumor areas was calculated with postvascular phase CE-US (postvascular phase ratio). The ratio of the intensity of the nontumor to tumor areas on SPIO-enhanced MRI (SPIO intensity index) was also calculated. The Pearson correlations were calculated for all values between the postvascular phase ratio and SPIO intensity index for quantitative comparison. These images were also compared qualitatively for the detection rate of the tumors.The sensitivities of CE-US and SPIO-MRI in detecting tumors were 98 and 95%, respectively (nonsignificant, chi(2) test). The postvascular phase ratio correlated with the SPIO intensity index for HCCs (Pearson r = 0.803, p0.05). The image conformity of the result from the liver parenchymal phase CE-US and SPIO-MRI was 92%. Dedifferentiation spots of nodule-in-nodule HCCs were detected in 4 (80%) of 5 on postvascular phase images of CE-US, and in 2 (40%) of 5 on SPIO-MRI (nonsignificant, chi(2) test).Postvascular phase images of CE-US with Sonazoid appear promising as an alternative to SPIO-enhanced MRI. Further study cases are needed to confirm the usefulness of postvascular phase images of CE-US compared to SPIO-MRI for the detection of dedifferentiation foci in hepatic tumors.

A 60-year-old woman with polycystic kidney presented with intracystic hemorrhage; renocolic fistula was diagnosed by contrast-enhanced. The patient was admitted due to hematuria, pyuria and pneumaturia. Abdominal B-mode ultrasonography showed that this renal cyst had thickened walls and debris-like internal echo. Truagent Detection, a power Doppler imaging mode, could depict intracystic color signals after Levovist injection by real-time scan. Enhanced spots had increased in the cyst, and were shown as minimal intracystic hemorrhage in real-time. The case of polycystic kidney with renocolic fistula is rare, however contrast-enhanced ultrasonography could successfully identify the site of minute bleeding.

The aim of this study was to evaluate the clinical value of measurement of the AFP-L3 fraction before and after radiofrequency ablation (RFA) therapy for HCC, compared with the measurement of total AFP and des-gamma-carboxy prothrombin (DCP).One hundred and twenty-four patients with HCCs were evaluated for their complete response with a 5-mm-thick safety margin around the tumor. Three tumor markers (AFP, DCP, AFP-L3) were measured after RFA therapy, and their clinical significance was studied.Multivariate analysis revealed that of the three tumor makers only AFP-L3 showed significant differences in the survival and disease-free rates.AFP-L3 is the most reliable tumor marker for estimating overall survival and disease-free survival in patients with HCC effectively treated by RFA in contrast to AFP and DCP.

Objectives: The Japan Integrated Staging (JIS) score has been reported to have good stratification ability in patients with hepatocellular carcinoma (HCC). However, the JIS score could not estimate malignant grade of HCC. The aim of this study was to evaluate the performance of a new staging system: the biomarker combined JIS (bm-JIS) which includes three tumor markers: α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP and des-γ-carboxy prothrombin with the conventional JIS score. Methods: A total of 1,924 HCC patients were included in this study. We compared their overall survival, the stratification ability and suitability as a prognostic model according to the bm-JIS score and the conventional JIS score. Results: There were significant differences between the survival curves for all bm-JIS scores. For the conventional JIS scores of 0, 1, 2 and 3, the survival curves differed greatly according to the bm-JIS score (p < 0.0001). The independent homogenizing ability and the stratification value of the JIS score and the bm-JIS score determined by the likelihood ratio test using the Cox proportional hazard regression model showed the bm-JIS score to have a higher value(χ2 = 717.348) than the JIS score (χ2 = 668.91). Conclusions: The bm-JIS score showed superior stratification ability and thus was found to be a better predictor of the prognosis than the conventional JIS score, especially for the patients with good prognosis.

Objective: The aim of this study was to investigate the accuracy of noninvasive tests, e.g. serum fibrotic markers, transient elastography and real-time tissue elastography, in the diagnosis of hepatic fibrosis, and to determine whether they can replace liver biopsy. Methods: 119 patients with chronic liver disease were included in this study. Serum fibrotic markers including hyaluronic acid, type IV collagen, type IV collagen 7S domain and type III procollagen-N-peptide were measured. Aspartate aminotransferase (AST) and platelet counts were also measured to calculate the AST to platelet ratio index (APRI). Liver stiffness was measured using FibroScan and real-time tissue elastography. Results: The fibrotic stage, determined by histopathological diagnosis of a liver biopsy sample, did not correlate as well with serum fibrotic markers although it was useful to diagnose liver cirrhosis. However, the stage of hepatic fibrosis correlated well with liver stiffness measured by FibroScan. FibroScan was also a much better predictor of liver cirrhosis than APRI. Furthermore, the levels of liver strain measured by real-time tissue elastography correlated well with liver stiffness (p < 0.05). Conclusion: Serum fibrotic markers and FibroScan are useful for distinguishing liver cirrhosis (F4) from chronic hepatitis (F1–F3). In addition, real-time tissue elastography is a novel and promising method to determine the stage of hepatic fibrosis.

Virtual CT sonography with magnetic navigation yields cross-sectional images of CT volume data that correspond to the angle of the transducer in the magnetic field in real time. The purpose of this study was to evaluate the efficiency and feasibility of virtual CT sonography for radiofrequency ablation of hypervascular hepatocellular carcinoma poorly defined on B-mode sonography.One hundred one patients enrolled in the study were separated into two groups. Fifty-one patients with 65 hepatocellular carcinomas underwent prospective virtual CT sonography as guidance for radiofrequency ablation. Fifty patients with 63 hepatocellular carcinomas managed with B-mode sonographic guidance were retrospectively selected under the same conditions as the virtual CT sonography group to act as a historical control group.In the virtual CT sonography group, technically successful ablation was achieved in a single session in 92% (47/51) of the patients and in two sessions in 8% (4/51). In the B-mode sonography group, technical success was achieved in a single session in 72% (36/50) of the patients, in two sessions in 24% (12/50), and in three sessions in 4% (2/50). Treatment analysis showed that the technical success rate after a single treatment session was significantly (p = 0.017) higher for the virtual CT sonography group. The number of treatment sessions was significantly (p = 0.021) lower for the virtual CT sonography group (mean, 1.1 +/- 0.1 vs 1.3 +/- 0.3 sessions).Virtual CT sonographically assisted radiofrequency ablation is an efficient treatment of patients with hepatocellular carcinoma that is poorly defined on B-mode sonography.

Patients with hepatic malignancies are often poor candidates for resection because of the lack of hepatic reserve as a result of coexisting cirrhosis or the presence of multiple tumors. The purpose of this study was to determine the safety and efficacy of open intraoperative radiofrequency ablation of unresectable hepatic malignancies with size larger than 4 cm in diameter and/or more than three in number.Between May 2000 and September 2003, 30 patients (24 men, 6 women; age range, 59-72 years; mean age, 63 years) with 51 hepatic malignancies. The maximal diameter of all tumors ranged from 1.0 to 10cm (mean +/- SD, 3.2 +/- 1.8).All tumors achieved necrosis completely in a single session. The mean follow-up from the initial ablation in this study was 18.9 +/- 10.1 months (range, 0-41). The 1-, 2 and 3-year overall survival rates were 86.1%, 71.6% and 71.6%, respectively. The 1-, 2 and 3-year disease-free survival rates were 70.9%, 37.6% and 25.1%, respectively.Open radiofrequency ablation is a safety and efficient approach for hepatic malignancies sized more than 4 cm in diameter and/or located more than three in number.

Purpose: To observe the visibility and changes in the echogenicity of ablated tumor and ablated nontumor areas after radiofrequency ablation (RFA) over time using gray-scale sonography, and, consequently, to decide on the best timing for contrast-enhanced sonography to evaluate the response of hepatocellular carcinoma to RFA. Materials and Methods: Thirty-eight patients with 48 hepatocellular carcinoma nodules underwent RFA. Consecutive gray-scale sonographic observations were made 10 min before RFA and at five points within 4 days after RFA. Two hepatologists blindly reviewed the sonographic images to assess the identifiability of the boundary of the ablated nodules and to semiquantitatively score the echogenicity of the ablated tumor and ablated nontumor regions in 15 hypoechoic nodules with detectable boundaries within 4 days after RFA. Results: The detection rates of the boundaries of ablated tumors were 56.5, 65.2, 54.3, 43.5, and 39.1% at 3–6 h and 15–22 h and on the 3rd, 4th, and 5th days after RFA. There was a significant difference between the detection rate for ablated tumors at 15–22 h and that on the 3rd and 4th days. The difference in echogenicity between ablated tumor and ablated nontumor tissue reached a maximum at 15–22 h after RFA. Conclusion: Ablated tumor can be clearly identified within the ablated area in 65.2% of cases using gray-scale sonography at 15–22 h after RFA. The day following RFA is most appropriate and practical for the performance of contrast-enhanced sonography to evaluate the therapeutic response, including a safety margin.

Objective: This study was undertaken to assess the outcome of potentially curative radiofrequency ablation (RFA) therapy for early-stage hepatocellular carcinoma (HCC) in patients with Child-Pugh stage A cirrhosis. Methods: This study retrospectively evaluated clinical outcomes in a cohort of 171 Child-Pugh stage A cirrhotic patients who received RFA for naïve HCC within the Milan criteria. The median follow-up period was 36.7 months. Results: Cumulative survival rates estimated by the Kaplan-Meier method for all patients were 98.8, 91.1 and 76.8% at 1, 3 and 5 years, respectively. Cumulative probabilities of local tumor recurrence at 1, 2 and 3 years were 9.0, 14.1 and 17.7%, respectively. Cumulative survival rates in patients without local tumor recurrence were 96.6, 94.6 and 84.4% at 1, 3 and 5 years, respectively, compared with patients with local tumor recurrence (96.6, 74.8 and 42.1% at 1, 3 and 5 years, respectively; p = 0.0002). Cox regression analysis showed that low serum albumin (p = 0.009, RR 3.04, CI 1.32–6.98), high range of PIVKA-II (prothrombin induced by vitamin K absence or agonist II) (p = 0.025, RR 2.57, CI 1.13–5.89), with multiple (less than 3) nodules (p = 0.021, RR 2.61, CI 1.15–5.91), and with local tumor recurrence (p = 0.004, RR 3.62, CI 1.51–8.69) were significant risk factors for death. Conclusion: Initial complete response of curative RFA therapy in patients with Child-Pugh stage A cirrhosis and early-stage HCC is associated with improved survival. Therefore, clinicians should aim to achieve complete ablation of all detectable HCC nodules with adequate safety margins.

The purpose of this study was to evaluate the safety and feasibility of a real-time integrated system with computed tomography (CT) and sonographic images for radiofrequency (RF) ablation of hepatic malignancies poorly defined on B-mode sonography, and to clarify the suitable phase of CT images for using this virtual sonography.Between September 2004 and December 2004, 12 patients with 16 hepatocellular carcinomas and two metastatic lesions arising from colorectal adenocarcinoma (n = 1) and rectal carcinoid (n = 1) were treated. The maximum diameter of nodules ranged from 1.0 to 2.5 cm (mean +/- SD; 1.5 +/- 0.6 cm) on CT images.Complete tumor necrosis was achieved in a single session in 19 lesions (90%), while a second session was required for the remaining two lesions (10%). Portal phase multi-planar reconstruction images were displayed under a suitable position corresponding to the ultrasound images in 9 patients (HCC = 7, metastasis = 2), and arterial phase multi-planar reconstruction images were displayed in the 3 remaining patients with hepatocellular carcinoma.Percutaneous RF ablation guidance using virtual sonography is an effective treatment for patients with hepatic malignancies. The portal phase of CT images may be the most suitable to indicate the 3-dimensional relationship between the liver vasculature and tumors on virtual sonography.

To assess whether low-dose, long-term maintenance interferon (IFN) therapy inhibits recurrence after complete ablation of hepatocellular carcinoma (HCC) and improves patient survival.From June 1999 through May 2006, a total of 127 HCC cases that met the requirements of both tumor diameter 3 cm or less, and number of tumors three or fewer, were curatively treated by radiofrequency ablation therapy (RFA). Among them, 43 patients received three million IU of IFN-alpha2b twice per week or pegylated IFN-alpha2a 90 microg once per week or once per 2 weeks without discontinuation (IFN maintenance group). The remaining 84 patients, whose sex, age, and platelet counts were randomly matched to those of the IFN maintenance group, did not receive IFN treatment (control group).Cumulative first, second, and third recurrence rates were significantly reduced in the IFN maintenance group compared with the control group by Kaplan-Meier estimate. The 5-year survival rate was 66% for the control group and 83% for the IFN maintenance group (p = 0.004). Multivariate analysis using the Cox proportional hazards model identified IFN maintenance therapy as an independent risk factor for survival, and the risk ratio was 0.21 (95% CI: 0.05-0.73). In conclusion, low-dose, long-term maintenance IFN therapy after curative RFA therapy of HCC significantly inhibits recurrence, and consequently improves patient survival.

Several staging systems have been developed to classify patients with hepatocellular carcinoma (HCC), however, there is no consensus on which of these is the most useful and reliable. In this review article, currently available integrated staging systems taking into account both liver function and tumor progression are presented, and their characteristics and applicability for current HCC patients, many of whom are diagnosed in the early stage of the disease and treated by curative therapy, are discussed. Based on the original andsubsequent validation studies of these staging systems, we recommend that further validation studies of staging systems for HCC should focus on the revised Barcelona Clinic Liver Cancer (BCLC) staging classification, Japan Integrated Staging (JIS) score and Tokyo score.