Sorafenib prevents escape from host immunity in liver cirrhosis patients with advanced hepatocellular carcinoma.

PURPOSE: It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. METHODS: Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment. RESULTS: Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. CONCLUSIONS: These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC.

Diagnosis of hepatic hemangioma by parametric imaging using sonazoid-enhanced US.

BACKGROUND/AIMS: Comparison of Parametric Imaging (PI) using Sonazoid-enhanced ultrasonography (US) and microflow imaging (MFI) to determine the possibility of hepatic hemangioma diagnosis using PI. METHODOLOGY: Twenty-two hepatic hemangioma nodules (mean±SD diameter: 31.6±19.1mm) undergoing Sonazoid-enhanced US between February 2008 and March 2009. After Sonazoid-enhanced US, COMMUNE ultrasonographic image analysis software was used for analysis of tumor imaging dynamics in the vascular phase using PI and MFI. In PI, 0s was set as the time contrast agent reached the tumor. Imaging within the tumor after 0s was color-coded according to time, and the images were displayed in color. In MFI, 0s was set as the time contrast agent reached the tumor. The path of microbubbles as it flowed through blood vessels was superimposed on the original B-mode images. Three trained physicians used these methods to analyze tumor imaging dynamics. RESULTS: All physicians concluded all cases were hepatic hemangioma regardless of method used. However, compared to MFI, PI allowed determination of more detailed blood flow dynamics in high-flow hepatic hemangioma, where blood flow speed was faster than in normal hepatic hemangioma. CONCLUSIONS: It is possible to diagnose hepatic hemangioma using PI using sonazoid-enhanced US.

[Gastrointestinal hemorrhage associated with concurrent use of sorafenib and warfarin for hepatocellular carcinoma].

A 60-year-old man with liver cirrhosis caused by hepatitis C, who was receiving warfarin anticoagulation following acute myocardial infarction, was diagnosed with advanced hepatocellular carcinoma and multiple lung metastases, and began treatment with sorafenib 200 mg daily. From the treatment's start to 14 and 63 days later, sorafenib was increased to 400 mg and 600 mg, respectively. After increasing the quantity to 600 mg, he had an increase in PT-INR values and experienced a lower-extremity hemorrhage. For the patient with liver cirrhosis, who is receiving warfarin, PT-INR values might be elevated during the early period of sorafenib treatment dosage as for the increase in quantity. Therefore, when increasing dosage, a frequent measurement of PT-INR and a careful follow-up for PT-INR is necessary.

Splenic artery aneurysm that gradually increased in size over 4 years until threatening rupture.

A 47-year-old man was referred to our hospital due to a splenic artery aneurysm. The course of the disease was monitored by ultrasound every 6 months. At each examination, the tumor was found to have increased in size by several millimeters, but the sonographer decided that the increase was within the range of error. After 4 years, the tumor showed a rapid increase in size. With a diagnosis of threatened rupture, the patient's life was saved by surgical intervention. In this case, the observations were only compared to the findings from the previous examination, and the slight increase in tumor size was considered within the range of error. It is important to compare the findings not only with those from the previous examination but also with earlier results.

Recurrence incidence of small HCC in cirrhosis patients by ablation versus injection.

BACKGROUND/AIMS: The incidence of local recurrence of hypervascular hepatocellular carcinoma (HCC) (15 mm or less) was compared retrospectively between a group treated with radiofrequency ablation (RFA) using cool-tip (Radionics, USA) 10-mm electrodes and a group treated with percutaneous ethanol injection (PEI). METHODOLOGY: There were 23 patients who were treated for a total of 25 tumors during a 3-year period at our hospital. Ten of the tumors (11.1 +/- 2.7mm) were treated with RFA using cool-tip 10-mm electrodes and 15 tumors (10.6 +/- 2.7 mm) were treated with PEI. After treatment, progression was evaluated in enhanced CT scans every 3-6 months to confirm presence or absence of local recurrence. RESULTS: The number of recurrences, mean observation period, and mean recurrence period in the RFA group were 2 (20%), 6.6 months, and 6 months. The number of recurrences, mean observation period, and mean recurrence period in the PEI group were 2 (13.3%), 19.1 months, and 18 months. The period between treatment and recurrence tended to be longer in the PEI group than in the RFA group to be significant p < 0.05. CONCLUSIONS: The results suggest that PEI treatment is more effective in local treatment of hypervascular HCC with tumor diameters of 15 mm or less.

Evaluation of local recurrence after treatment for hepatocellular carcinoma by contrast-enhanced ultrasonography using Sonazoid: comparison with dynamic computed tomography.

PURPOSE: To evaluate the effectiveness of contrast-enhanced ultrasonography (CEUS) using Sonazoid for the diagnosis of the local recurrence after treatment for hepatocellular carcinoma (HCC) by comparing it with dynamic CT. METHODS: Seventy-one patients with 87 HCC lesions (mean +/- SD; 19.5 +/- 9.6 mm) underwent CEUS using Sonazoid and dynamic CT after radiofrequency ablation (n = 55), transcatheter arterial chemoembolization (n = 22), or radiofrequency ablation combined with transcatheter arterial chemoembolization (n = 10). Two hepatologists (observer 1; 10 years of experience, and 2; 20 years of experience) reviewed the CEUS and dynamic CT images independently and evaluated presence or absence of the local recurrence. Diagnostic performance for the local recurrence was assessed using receiver operating characteristic curve analysis. RESULTS: The Az value for dynamic CT was significantly lower in observer 1 than 2 (p < 0.05). The sensitivity of CEUS was 79% in observer 1 and 83.9% in observer 2, and that of dynamic CT was 83.9% and 90.3%, respectively. The specificity of CEUS was 96%, and that of dynamic CT was 92%, in both observers. CONCLUSION: This study suggests that CEUS using Sonazoid is less affected by the observer's experience and is more accurate in the diagnosis of local recurrence after treatment for HCC than dynamic CT.

Analysis of patients with rapid aggressive tumor progression of hepatocellular carcinoma after percutaneous radiofrequency ablation.

BACKGROUND/AIMS: Rapid aggressive tumor progression of hepatocellular carcinoma is one of the major complications after radiofrequency ablation. We statistically analyzed hepatocellular carcinoma patients with rapid aggressive tumor progression after radiofrequency ablation regarding patient characteristics, computed tomography findings, radiofrequency ablation methods, and the course of clinical and imaging changes and outcomes. METHODOLOGY: We defined the tumor not detected by previous CT and US rapidly increased more than double in compared with the ablated area as rapid aggressive tumor progression. Ten hundred seventy three lesions of 538 patients underwent ultrasound-guided radiofrequency ablation in our hospital between April 1999 and March 2008. Of these patients, the risk factors for rapid aggressive tumor progression of 7 with 7 lesions were analyzed. RESULTS: The rate of rapid aggressive tumor progression was 0.65%. Subcapsular lesions, a pretreatment Protein Induced by Vitamin K Absence-II level > or = 40mAU/ml, and initial treatment for hepatocellular carcinoma were significantly identified as risk factors. CONCLUSIONS: There is possibility that portal vein invasion by hepatocellular carcinoma is an important factor involved in rapid aggressive tumor progression after radiofrequency ablation from the results of this study. In our opinion, these hepatocellular carcinomas need to be sufficiently ablated.

Cool-tip 10-mm electrode useful for radiofrequency ablation of hepatocellular carcinoma.

BACKGROUND/AIMS: Whether a cool-tip 10mm electrode is useful for radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) has not been established. Accordingly, the present study goal was to determine this electrode is indicated for RFA of HCC. METHODOLOGY: This study was conducted with 30 HCC patients who were treated with a cool-tip 10-mm electrode over a period of about 3 years. Ten had hypervascular HCC nodules and 20 had hypovascular HCC nodules; mean tumor diameter was 10.5 +/- 1.8mm. Patients underwent follow-up CT scans every 3 to 6 months to detect local progression. RESULTS: Of the 30 lesions, 4 (13.3%) showed local progression. Enhanced CT imaging of the four cases with local progression revealed that two had hypervascular HCC. The remaining two cases had hypovascular HCC. CONCLUSIONS: The present study results suggest that, RFA with a cool-tip 10-mm electrode is indicated in cases of hypovascular HCC nodules if the lesion diameter is no more than 10mm. In addition, in order to avoid skin burns, only lesions at a depth of at least 16mm below the liver surface are suitable for this treatment. Because of its lesser invasiveness, the cool-tip 10-mm electrode appears to be more useful than other, more powerful, devices in patients with hepatic carcinoma.

[Case of phlegmonous esophagogastritis associated with hypopharyngeal abscess].

A 62-year-old man was admitted to our hospital complaining of sore throat and epigastralgia. Laboratory tests revealed leukocytosis and an elevated CRP level. CT showed a low density area in the right hypopharynx, wall thickening of the esophageal and gastric wall with an intramural low density area. Phlegmonous esophagogastritis associated with hypopharyngeal abscess was diagnosed. The infection was extension and his condition was serious because of his accompanying poorly controlled diabetes. He was successfully treated by antibiotics and drainage of the hypopharyngeal abscess. CT was useful for early diagnosis, confirmation of the extent of inflammation and follow-up.

Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma.

PURPOSE: We have previously reported that 24-h intra-arterial combination chemotherapy (IACC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, it has also been reported that 5-fluorouracil (5-FU) exacerbates liver damage in patients with liver cirrhosis (LC). The aim of this study was to clarify the hepatotoxicity of IACC in LC patients with aHCC. METHODS: Twenty-one adult Japanese patients (20 men and 1 woman) with aHCC and LC underwent IACC between 2004 and 2007 at our hospital. These patients showed multiple partial responses or stable disease, except for five patients who showed no response and three patients with tumors more than 30 mm in diameter. All patients had inoperable disease on the basis of computed tomography (CT) findings. IACC (leucovorin at 12 mg/h, cisplatin at 10 mg/h, and 5-FU at 250 mg/22 h) was delivered via the proper hepatic artery every 5 days for 4 weeks. RESULTS: Twelve patients were in Child-Pugh class A (group A), and nine were in class B (group B). The Child-Pugh score was significantly increased after chemotherapy compared with before chemotherapy in both groups. Serum albumin was significantly decreased after chemotherapy, and the number of patients with ascites also increased after chemotherapy. Serum type IV collagen and N-terminal propeptide of type III procollagen were significantly increased after chemotherapy, although there was no significant change in serum aminotransferases. CONCLUSIONS: IACC might cause hepatotoxicity that induces fibrosis without releasing aminotransferases.

Risk factors for the local recurrence of hepatocellular carcinoma after single-session percutaneous radiofrequency ablation with a single electrode insertion.

Radiofrequency ablation (RFA) is a new local therapy for hepatocellular carcinoma (HCC). In this study, we investigated the risk factors associated with local recurrence of HCC after single-session RFA with a single electrode insertion. From April 2003 to December 2007, we treated 138 HCC lesions by single-session RFA with a single electrode insertion using the Cool-tip RFA, RTC 2000 and RTC 3000 Systems. Risk factors for the local recurrence of these lesions and complications after RFA were analyzed. The mean size of the 138 lesions was 16.9±5.4 mm in diameter (range 7-33 mm). Local recurrence rates were 6.6 and 22.0% at 1 and 2 years, respectively, during the mean follow-up period of 16.4 months. Univariate analysis showed that tumor diameter (≥20 mm), tumor location, pre-treatment AFP-L3 fraction level and ablation pattern were significant variables. Multivariate analysis of these four variables identified only the tumor diameter as an independent risk factor for local recurrence. Complications occurred in 2.2% of the lesions (3/138). Single-session RFA is an effective treatment for HCC in that it reduces serious complications. This study demonstrated that a tumor size ≥20 mm influenced the local recurrence of single-session RFA with a single electrode insertion.

Analysis of patients with tumor seeding after percutaneous radiofrequency ablation of hepatocellular carcinoma.

To determine the incidence and risk factors associated with tumor seeding after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), 781 lesions from 352 patients who had undergone ultrasound (US)-guided RFA at our hospital between April 1999 and December 2005 were examined. Of these patients, 6 presented HCC lesions (6 lesions in total) and tumor seeding (7 seedings in total), which were analyzed. RFA using RITA 500 PA, the Cool-tip RFA System or the RTC 2000 System was performed. RFA sessions were repeated until complete necrosis was confirmed by imaging. Subsequently, follow-up was performed every 3-4 months by means of computed tomography (CT) and US scans. The 6 patients were retrospectively analyzed for patient characteristics, CT and histopathological findings, RFA method and complications, and clinical and imaging progress and outcome. Of the 6 lesions, 2 were in a subcapsular location at S7. Mean tumor diameter was 23.3±9 mm. Tumor biopsies indicated that 1 of the 6 lesions was well-differentiated, 4 were moderately-differentiated, and 1 was undifferentiated. The RITA 500 PA was used in 2 cases, and the Cool-tip RFA System in 4. Seeding was identified 14.6±13 months after RFA. Four of the cases with seeding were located on the abdominal wall, 2 on the thoracic wall and 1 in the Douglas pouch. Four of the patients underwent surgical resection, 1 radiation, and 1 conservative treatment for seeding. Five of the 6 patients died 12.6±9 months after seeding was detected, with the exception having undergone surgical treatment. The seeding risks identified in this study include treatment of subcapsular lesions and patient treatment over multiple sessions. The selection of the proper RFA system to avoid multiple sessions and the use of ablation technique are important for the prevention of seeding. Additionally, long-term follow-up after RFA by extensive imaging of the pelvic cavity and the thoracoabdominal wall is needed.