Thermosensitive liposomal doxorubicin plus radiofrequency ablation increased tumor destruction and improved survival in patients with medium and large hepatocellular carcinoma: A randomized, double-blinded, dummy-controlled clinical trial in a single center

Background: Lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox) consists of doxorubicin encapsulated contained within a heat-sensitive liposome. Aims and Objectives: We sought to evaluate whether the use of combined radiofrequency ablation (RFA) and LTLD would result in larger coagulation volume and longer overall survival (OS) compared with the use of RFA alone in patients with 3–7 cm unresectable hepatocellular carcinoma (HCC). Materials and Methods: Between 2010 and 2012, 22 HCC patients were randomly assigned to one of two treatments in our center: (1) ultrasound-guided percutaneous RFA plus intravenous (IV) infusion of LTLD (combination, n = 11) or (2) RFA plus IV dummy (RFA, n = 11). Four patients withdrew from the study, and the remaining 18 patients entered the final analysis. There were 14 male and 4 female patients with an average age of 61.1 ± 9.3 years (range: 40–73 years). The average tumor size was 4.2 ± 1.0 cm (range: 3.1–6.1 cm). One-month enhanced computed tomography was used to evaluate the ablation efficacy and coagulation volume after RFA. Regular follow-up after RFA was performed to assess toxicity, local response rates, and OS rates. Results: A major complication (empyema) occurred in one case in the combination group. Combination treatment region did not induce any additional toxicity beyond doxorubicin. The primary ablation success rate was 93.3% (14/15 tumors) in the combination group and 77.8% (7/9 tumors) in the RFA group (P = 0.308). The difference in coagulation volume between pre- and post-RFA in the combination group was significantly larger than that of the RFA group (105.7 ± 73.8 cm 3 vs. 37.3 ± 8.5 cm 3, P = 0.013). The follow-up period ranged from 11 to 80 months (average: 49.1 ± 24.8 months). The local progression rate was 6.7% (1/15 tumors) in the combination group and 22.2% (2/9 tumors) in the RFA group. The mean OS for the combination group was 68.5 ± 7.2 months, which was significantly greater compared with the RFA group (46.0 ± 10.6 months, P = 0.045). Conclusions: RFA with heat target delivery chemotherapy facilitated better tumor coagulation necrosis without additional toxicity. This combined treatment may improve the clinical efficacy of RFA or free doxorubicin and prolong survival in patients with medium to large HCC

The role of contrast enhanced ultrasound in evaluating and guiding radiofrequency ablation of hepatocellular carcinoma and feeding vessels / 中华医学超声杂志（电子版）

Objective To investigate the role of contrast enhanced ultrasound (CEUS) in evaluating and guiding radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) and its feeding vessels. Methods From January 2006 to June 2007, 71 patients with 75 hypervascular HCC in Peking University Cancer Hospital who underwent RFA were included in the study. The diagnosis was conifrmed by ultrasound guided biopsy for all patients. These patients were not suitable for transcatheter arterial chemoembolization (TACE) or had poor responds to TACE. They were divided into two groups, which included group percutaneous artery ablation (PAA) combining RFA and group RFA. There were 38 patients with 39 HCC in group PAA combining RFA and CEUS were used to identify the range of HCC inifltration. Firstly, PAA of the feeding vessels was conducted under the guidance of color doplor lfow imaging (CDFI). Then CEUS was performed to evaluate HCC perfusion after blocking the feeding vessels. Finally, the rest of the tumor was ablated by RFA. In group RFA, there were 33 patients with 36 HCC, who did not undertake PAA before RFA. Generally, the RFA was planned based on tumor size and location, and the ablation started with deep part of HCC or portion close to nearby organs. Contrast CT was used as a post-RFA imaging for follow-up at 1, 3 and 6 months post-RFA. T test was used to compare the difference in focal lesions number between two groups, andχ2 tests were used to compare the difference in necrosis rate between two groups after treatment. Results In group PAA combining RFA, post-PAA CEUS showed intratumor perfusion decreased more than 70%in 31 HCC (79.5%, 31/39). Of them, 13 HCC (33.3%, 13/39) showed complete perfusion defect with clear margin, called“solar eclipse sign”. The rest 8 HCC (20.5%, 8/39) showed 40%-70%of perfusion defect. In group PAA combining RFA, CDFI showed 35 (83.3%, 35/42) feeding vessels were blocked, and 3 vessels (7.1%, 3/42) showed signiifcant decreased lfow signal after PAA. There were average 3.18±1.42 ablations per HCC in group PAA combining RFA, and 4.32±1.56 in group RFA. The number of ablations per HCC in group PAA combining RFA was signiifcantly less than group RFA (t=2.524, P=0.015). The tumor necrosis rate at 1 month post-RFA in group PAA (92.3%, 36/39) combining RFA was signiifcantly higher than that of group RFA (66.7%, 24/35) (χ2=8.264, P=0.001). Conclusions With CEUS, PAA can effectively block the feeding vessels of HCC, enhance ablated necrosis in the tumor and signiifcantly increase necrosis rate post-RFA for large hypervascular HCC. CEUS-assisted PAA can improve efifciency of RFA with less ablation number and better result.

Percutaneous radiofrequency ablation with artificial hydrothorax for liver cancer in the hepatic dome / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the value of application of percutaneous radiofrequency ablation (RFA) with artificial hydrothorax for liver cancer in the hepatic dome.</p><p><b>METHODS</b>Thirty-two patients with 43 lesions of hepatic malignant tumors in the hepatic dome underwent ultrasound-guided percutaneous radiofrequency ablation (RFA) with artificial hydrothorax. Artificial hydrothorax was created by infusion of saline via an intrathoracically placed 14-G central venous catheter, which was ultrasound-guided percutaneously inserted before RFA, separating the right lung from the hepatic dome. The adverse reaction and therapeutic efficacy were also analyzed.</p><p><b>RESULTS</b>In the 32 patients with 43 lesions in the hepatic dome (4 tumors in segment IV 21 tumors in segment VII and 18 tumors in segment VIII), 18 lesions of 14 patients were not observed by ultrasound before the operation. Thirty-two patients received the ultrasound-guided placement of intrathoracical catheter, and (1606.3 ± 485.9) ml (1000 - 2500 ml) saline solution was infused successfully. After obtaining an image of the whole tumor, 31 patients received percutaneous RFA therapy on schedule, and 22 patients received percutaneous transdiaphragmatic RFA therapy. One patient with 2 lesions gave up the treatment, because one of his tumors was not detectable by ultrasound. Diaphragmatic muscle hemorrhage was seen in two patients, subcutaneous edema in two patients, and pneumothorax in one patient. All the complications were cured, and no serious complications or related death occurred. 1-month follow-up with contrast-enhanced CT/MRI images showed that 29 patients had complete ablation, and the effective rate of this technique was 93.5% (29/31).</p><p><b>CONCLUSIONS</b>Artificial hydrothorax helps us not only to visualize the whole tumor in the hepatic dome, but also offers a transdiaphragmatic route for therapy. Ultrasound-guided percutaneous RFA with artificial hydrothorax is a feasible, safe, and effective technique for treating liver cancer in the hepatic dome and worthy of being promoted.</p>

Contrast-enhanced ultrasound of hepatocarcinogenesis in liver cirrhosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatocellular carcinoma (HCC) often occurs in association with liver cirrhosis. A stepwise carcinogenesis for HCC has been proposed. The purpose of this study was to observe the enhancement pattern of hepatocellular nodules in cirrhotic patients using contrast-enhanced ultrasound (CEUS) and to correlate patterns of enhancement at CEUS with the diagnosis of hepatocellular nodules using pathologic correlation as the gold standard.</p><p><b>METHODS</b>Ninety-three cirrhotic patients with indeterminate hepatocellular nodules at ultrasound, underwent biopsy of each indeterminate nodule. Patients with nodules found to have pathologic diagnoses of regenerative nodules (RNs), dysplastic nodules (DNs), or DNs with focus of HCC (DN-HCC), were enrolled in this study. Enhancement patterns of all nodules were examined throughout the various vascular phases of CEUS and classified into five enhancement patterns: type I, isoenhancement to hepatic parenchyma at all phases; type II, hypoenhancement in the arterial phase, and isoenhancement in the portal venous phase and late phase; type III, iso-to-hypoenhancement in arterial and portal venous phase, and hypoenhancement in the late phase (washout); type IV, slight hyperenhancement in the arterial and portal venous phase and hypoenhancement in the late phase (washout); and type V, partial hyperenhancement in the arterial phase and hypoenhancement in the late phase; and another partial iso-to-hypoenhancement in the arterial and portal venous phase and hypoenhancement in the late phase (washout). The correlation between the contrast enhancement patterns and the pathological diagnoses was analyzed by the chi-squared test.</p><p><b>RESULTS</b>Totally 132 lesions were examined with CEUS in 93 patients. Pathologic diagnoses included 45 DN, 68 RN, and 19 DN-HCC. The enhancement patterns observed were as follows: type I, 49 (37.1%); type II, 27 (20.5%); type III, 28 (21.2%); type IV, 9 (6.8%); type V, 19 (14.4%). Nodules with type I enhancement showed dysplasia in 5 (10.2%) cases; nodules with type II were dysplastic in 11 (40.7%) of cases; nodules with type III enhancement pattern were dysplastic in 22 (78.6%), and those with type IV enhancement contained dysplasia in 7 (77.8%) of cases. Type V enhancement corresponded to DN-HCC in 19 (100%) of cases. CEUS enhancement pattern was correlated with likelihood of dysplasia at pathologic analysis (Trend chi-square test, P < 0.001). Pathological diagnosis was HCC in the enhanced area and hepatocyte dysplasia in the un-enhanced area in the 19 DN-HCC.</p><p><b>CONCLUSION</b>Pattern of enhancement at CEUS correlates with the pathologic diagnosis of hepatocellular nodules in liver cirrhosis, and may be helpful in predicting the progress from RN to HCC nodules.</p>

Efficacy of radiofrequency ablation to treat advanced hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To retrospectively investigate the feasibility of radiofrequency ablation (RFA) in treating advanced hepatocellular carcinoma (HCC) using standard ultrasound-guided percutaneous RFA.</p><p><b>METHODS</b>A total of 655 patients with unresectable advanced HCC underwent ultrasound-guided percutaneous RFA therapy at our institution between July 2000 to September 2001. Ninety-two of those patients, representing 136 tumors, were selected for analysis based on the following criteria: presence of UICC/AJCC-TNM (6th edition) stage III and IV advanced HCC, (III: n=82 patients, with 126 tumors; IV: n=10 patients, with 10 tumors); extensive portal vein or inferior vena cava tumor thrombus; extrahepatic metastasis after surgical resection; and complete follow-up data. Follow-up consisted of enhanced computed tomography (CT) performed at one month post-RFA treatment, then every three months. Contrast-enhanced ultrasound (CEUS) was performed in 51 (55.4%) patients before RFA. The standard treatment using optimal strategies were applied in (72.8%) 67 patients. The established strategies included: (1) select RFA indications based on CEUS results; (2) design radical protocols based on invasive range showed by CEUS; (3) multiple overlapping ablations based on mathematical protocols; (4) two or three bipolar RFA electrodes with three-dimensional localization; (5) color ultrasound-guided percutaneous ablation of tumor feeding artery (PAA)/transcatheter arterial chemoembolization (TACE) + RFA for HCC with rich supply. The other 25 patients (27.2 %) were treated with conventional RFA protocols. The ablation procedure was considered a success if no abnormal enhancement or wash-out was detected in the treated area on the CT scan at one month. All patients had received liver protection treatments following RFA. Chi-squared test or Fisher's exact test were used to compare the early complete tumor necrosis rates and the local recurrence rates. Survival was estimated by Kaplan-Meier analysis and log-rank test. P less than 0.05 was considered statistically significant.</p><p><b>RESULTS</b>The RFA-treated tumors ranged in size from 1.5 to 7.0 cm (average: 4.5 cm). Fifty-nine patients had solitary tumor, and the remaining 33 had multiple tumors (2 to 4 tumors). Patients were classified by Child-Pugh score as A (n=58), B (n=32) and C (n=2). Early complete tumor necrosis rate after initial RFA was 90.4% (123/136 tumors). Serious complications developed in two patients (2.2%). No treatment-related death occurred. Follow-up ranged from 3-134 months. Local recurrence rate was 16.9% (23/136 tumors). The 1-, 3- and 5-year overall survival rates were 83.3%, 48.3% and 21.9%, respectively, and the median survival time was 35 months. Stratification analysis indicated the early complete tumor necrosis rate was higher in groups of patients with Child-Pugh A score (98.3%) , CEUS administration (98.0%), and standard treatment (97.0%). The local recurrence rate was lower in groups of patients with tumors less than or equal to 3.0 cm (5.9%), CEUS administration (11.8%), and standard treatment (16.4%). The 5-year survival was significantly higher in patients with Child-Pugh A, tumors less than or equal to 3.0 cm, CEUS administration, and standard treatment (all, P less than 0.05).</p><p><b>CONCLUSION</b>RFA treatment of patients with advanced HCC, tumors less than 7.0 cm, and without thrombosis in the main vessels was efficacious. The RFA treatment strategy and subsequent liver protection therapy in RFA may improve survival.</p>

Ultrasound-guided assistant infusion technique for percutaneous radiofrequency ablation of liver cancer / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the value of an infusion-based separation technique to assist in ultrasound (US)-guided percutaneous radiofrequency ablation (RFA) of liver cancers abutting the liver edge.</p><p><b>METHODS</b>Twenty-four cases of malignant liver tumors abutting the hepatic edge were treated with US-guided puncture accompanied by the assistant infusion technique. The US-guided puncture was made with a 22-G needle through the hepatic tissue and into the abdominal cavity near the target tumor. Infusion of a saline solution was used to separate the liver from any surrounding structures so that percutaneous RFA could be safely performed. Complications, including gastrointestinal injury, hemorrhage and death, were recorded. Technical efficacy and safety were evaluated.</p><p><b>RESULTS</b>Among the 24 patients, the target tumors were adjacent to the right kidney (n=6), colon (n=6), stomach (n=5), pericardium (n=4), and gall bladder (n=3). Twenty-three patients received a successful radical percutaneous RFA with assistant infusion. The assistant infusion volumes ranged from 80-390 ml and created spaces ranging from 0.8-2.5 cm between the liver and surrounding structures. Five of the cases with tumors adjacent to the stomach or colon received the largest volume infusions. The infusion failed to create a separation space in only one case, due to the presence of an adhesion; as a result, this patient was treated with palliative RFA. The mean hospital stay for all 24 patients was four days after surgery. No severe complications or deaths occurred. At 1-month follow-up, computed tomography images showed that 22 cases had complete ablation, yielding a technical success rate of 95.7% (22/23). No needle track implantation was observed.</p><p><b>CONCLUSION</b>Assistant infusion for percutaneous radiofrequency ablation creates a protective space between the liver and surrounding structures in patients with liver tumors abutting the liver edge. This safe and effective assistant technique broadens the range of patients available for percutaneous RFA treatment.</p>

Intrahepatic biliary injuries associated with radiofrequency ablation of hepatic malignancies / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Biliary injury after radiofrequency ablation can cause serious consequences including death. However, there are limited data regarding bile duct changes with or without complications associated with radiofrequency ablation of hepatic malignancies. This study aimed to assess the incidence, prognosis and risk factors of intrahepatic biliary injury associated with radiofrequency ablation.</p><p><b>METHODS</b>Between June 2001 and January 2009, 638 patients with hepatic malignancies (405 with hepatocellular carcinoma, and 233 with liver metastasis) who had 955 treatment sessions were enrolled in this study. Imaging and laboratory data, the course of treatment, and patient outcomes were reviewed retrospectively. The risk factors of biliary injury and the impact on overall survival of patients were analyzed. The chi-square test, Fisher's exact test, Kaplan-Meier curves and stepwise Logistic regression model were used for statistical analysis where appropriate.</p><p><b>RESULTS</b>Biliary injury was observed in 17 patients after 17 ablation sessions based on imaging findings. The overall incidence of biliary injury was 1.8% (17/955) with an average onset time of 12 weeks (2-36 weeks). Mild, moderate and severe complications of biliary injury were identified in 9, 6 and 2 cases, respectively. The median survival time after detection of biliary injury was 40 months. There seemed no notable difference in overall survival between patients with and those without biliary injuries. By multivariate analysis, vessel infiltration (P = 0.034) and treatment session ≥ 4 times (P = 0.025) were independent risk factors for biliary injury of hepatocellular carcinoma; while tumor located centrally was the only independent risk factor in the metastasis group (P = 0.043).</p><p><b>CONCLUSIONS</b>The incidence of biliary injury was not frequent (1.8%). Through appropriate treatment, intrahepatic bile duct injuries seemed not affect the patients' long-term survival. Additionally, risk factors may be helpful for selecting radiofrequency ablation candidates and predicting biliary complications.</p>

Efficacy and feasibility of radiofrequency ablation for decompensated cirrhotic patients with hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Most HCC patients with decompensation of liver function lost the chance of surgical and/or interventional treatment. The aim of this study was to evaluate feasibility and outcome of radiofrequency ablation (RFA) in treating hepatocellular carcinoma (HCC) patients with poor liver function (Child-Pugh class C), who are not suitable for surgery or hepatic artery chemo-embolization.</p><p><b>METHODS</b>Thirteen HCC patients (the number of tumors was 17) with liver function of Child-Pugh C (scores: 10.2 +/- 0.4) were included in the study. Among the patients, 8 were male and 5 were female with the average age of (61.6 +/- 10.9) years old. The average size of HCC was (3.8 +/- 1.0) cm. Two patients were recurrent HCC and 30.8% of the patients had multiple tumors (2 - 3 tumors). All the patients were treated with RFA.</p><p><b>RESULTS</b>There were 22 RFA sessions (1 - 4 sessions per patient) in all, average ablations per tumor at first session was 3.1. One week after RFA, the liver enzymes elevated in 9 patients (69.2%), in 7 of them, the liver enzyme returned to pre-RFA level in 1 - 3 months. One month after RFA, the Child-Pugh grading was 10.3 +/- 0.8 (Child-Pugh C), while that of pre-RFA was 10.2 +/- 0.4 (Child-Pugh C), with no significant difference. Computer tomography (CT) one month after RFA showed that the tumor necrosis rate was 88.2% (15/17). Five patients had 2 - 4 repeated RFA due to HCC recurrence. During the follow-up of 2- 69 months in this group, survival rate of one year was 53.8%, two years was 30.8%, and three year was 15.4%. The incidence of RFA-related complications was 13.6% (3/22 sessions), including 1 case of GI hemorrhage and 1 sub-capsular hemorrhage of the liver. One patient with HCC over 5 cm who had fever and liver abscess after RFA, and was dead 2 months later due to liver function failure.</p><p><b>CONCLUSIONS</b>Minimal invasive RFA provides possible treatment modality for HCC patients with poor liver function, who are not candidates for surgical and/or interventional therapy. For large HCC, due to the required extended treatment region, special attention should be paid to the possibility of acute liver failure.</p>

A tailored approach to radiofrequency ablation of hepatocellular carcinoma and its outcome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effectiveness of a tailored approach to radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Ultrasound-guided percutaneous RFA was performed in 274 tumors of 228 patients located at liver periphery, including 59 near the bowel, 115 near the diaphragm, 54 near the gallbladder, and 46 near the liver surface. The tumor sizes ranged 1.2-7.0 cm [mean (3.7 +/- 1.2) cm]. A tailored treatment strategy was established for tumors in different locations. Contrast-enhanced CT was performed one month later to evaluate the early necrosis rate of the treated tumors.</p><p><b>RESULTS</b>Early tumor necrosis rate was 91.6% of the peripherally located HCC, including 91.5% of the tumors near the bowel, 90.4% near the diaphragm, 92.6% near the gallbladder, and 93.5% near the liver surface. Local tumor recurrence rates were 8.5%, 9.6%, 7.4%, and 6.5% for tumors near the bowel, diaphragm, gallbladder, and liver surface, respectively. The 1-, 2-, and 3-year survival rate of this group were 82.3%, 62.9%, and 53.7%, respectively. Major complications occurred in 3.3% of the treatment sessions, including haemorrhage (n = 2), nearby structure injury (n = 6), and needle tract seeding (n = 4).</p><p><b>CONCLUSION</b>The tailored approach to RFA provides a promising treatment option for refractory peripherally located HCC with satisfactory tumor necrosis rate and low complication rate.</p>

Preliminary clinical experience of transrectal ultrasonography in early rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the accuracy of transrectal ultrasonography (TRUS) in the assessment of the invasion depth of rectal cancer, and analyze the value of TRUS in diagnosis of early rectal cancer.</p><p><b>METHODS</b>TRUS was performed preoperatively in 163 patients with rectal cancer, and the results was compared with the postoperative pathological findings according to TNM staging. The early rectal cancer was diagnosed if the lesion was limited to mucosa and submucosa. The tumor located in mucosa was defined as mucosal cancer, while as submucosal cancer when the tumor invading into submucosa. Sixteen cases were confirmed as early cancer by pathology after the operation. No patients received chemotherapy and radiotherapy before operation.</p><p><b>RESULTS</b>The sensitivity of TRUS in the staging of the early rectal cancer was 87.5% (14/16), specificity was 98.6% (145/147), and the positive predictive value was 87.5% (14/16). The sensitivity of TRUS in predicting mucosal and submucosal cancer was 85.7% (6/7) and 66.7% (6/9), respectively. Sixteen patients with early rectal cancer were examined before and after filling rectum with water. After filling rectum, all tumors were visualized clearly, while 14 tumors were correctly diagnosed as early rectal cancer. Before filling rectum, only 6 tumors were visualized clearly, and 3 tumors were staged correctly. The ultrasonographic appearance of early rectal cancer manifested in two kinds: protruded and ulcerative, and most were protruded (81.6%).</p><p><b>CONCLUSIONS</b>TRUS is a valuable imaging examination for diagnosis of early rectal cancer preoperatively. Visualization rate and diagnostic accuracy of early rectal cancer are improved dramatically after filling rectum with water.</p>

Feasibility of improving radiofrequency ablation of hepatocellular carcinoma by percutaneously blocking tumor-feeding vessels / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasibility and outcome of radiofrequency ablation (RFA) in blocking feeding vessels of hypervascular hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Totally 101 patients pathologically confirmed hypervascular HCC were included in the study. In percutaneous arterial ablation (PAA) + RFA group, 71 patients with 74 HCC underwent PAA before classical RFA of the other regions of the tumors, while in the RFA group, another 83 patients with 102 HCC were treated with RFA directly. For another 30 patients who responded poorly to transcatheter arterial chemoembolization were treated with percutaneous arterial embolization (PAE), followed by RFA; another 23 patients were treated with RFA alone were regarded as the control group. Contrast-enhanced CT and magnetic resonance imaging were used as post-RFA imaging follow-up at 1, 3, and 6 month.</p><p><b>RESULTS</b>In PAA + RFA group, post-PAA imaging showed blocked blood flow in 65 (87.8%) HCC. There were average 2.76 +/- 1.12 ablated foci per HCC in PAA + RFA group and 3.36 +/- 1.60 ablated foci per HCC in control group (P = 0.01). The tumor necrosis rate at 1 month after RFA was 90. 5% (67/74) in PAA + RFA group and 90.2% (92/102) in control group. HCC recurrence rate at 6 month after RFA was 17.6% (13/74) in PAA + RFA group and 31.4% (32/102) in control group (P = 0.038). In PAE + RFA group, 88.6% of the main feeding vessels were blocked. The tumor necrosis rate at 1 and 6 month after FRA was 92.6% (25/27) and 85.2% (23/27) in PAA + RFA group and 65.2% (15/ 23) (P = 0.030) and 56.5% (13/23) (P = 0.024) in control group.</p><p><b>CONCLUSION</b>PAA and PAE can block the feeding vessels of HCC, enhance the ablated necrosis in the tumor, decrease post-RFA recurrence, and therefore provides a safe and feasible method for treating hypervascular HCC.</p>

Evaluation of the ultrasonographic features of axillary lymph node metastasis in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the ultrasonographic features of axillary lymph node metastasis in breast cancer patients, and to evaluate the accuracy of these features by Receiver Operating Characteristic (ROC) curve.</p><p><b>METHODS</b>Ultrasonography was carried out in 113 patients (mean age 56.5 yr, range 29 - 77 yr). The ultrasonographic features of the primary tumor and the axillary lymph node were observed. Univariate analysis was performed by Chi-squared test and Fisher exact test, and multivariate analysis to determine independent significant individual variables by multiple logistic regression analysis. ROC curve analysis was done to determine the sensitivity and specificity of individual and combined ultrasonographic features in distinguishing metastatic lymph node from the normal one.</p><p><b>RESULTS</b>The primary tumor size, abundance of blood supply in the primary tumor, longitudinal-transverse diameter ratio, cortex-hilum thickness ratio (on the longitudinal section), abnormal cortex thickness, distribution of intra-nodal vascularity of axillary lymph nodes were found to be statistically significant factors by univariate analysis. The primary tumor size, longitudinal-transverse ratio and cortex-hilum thickness ratio of lymph node were proved to be significant independent predictors of axillary lymph node metastasis by logistic regression analysis. Through ROC analysis, the combination of these independent ultrasonographic feature predictors was found to contribute significantly in differentiating metastatic lymph node from the normal with a sensitivity of 88.6% and specificity of 84.5%.</p><p><b>CONCLUSION</b>Axillary ultrasonography is helpful in staging the axillary lymph node in breast cancer patient. The primary tumor size, longitudinal-transverse diameter ratio and cortex-hilum thickness ratio of lymph node are the main features to determine whether metastatic involvement is present or not.</p>

Survival and prognostic analysis of radiofrequency ablation of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the survival of radiofrequency ablation (RFA) and investigate the prognostic factors affecting overall survival, local recurrence-free survival and disease-free survival in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A total of 192 HCC patients underwent RFA treatment in our department and were enrolled into this study. Among them, 151 patients were males and 41 were females (mean age, 59.2 years, range, 24 - 87 years old). The average tumor size was (3.9 +/- 1.3) cm (range, 1.2 - 8.0 cm). Of these 192 HCC patients, their Child-Pugh grade of A, B and C were 106, 77 and 9, respectively. According to UICC-TNM system, 57, 85, 44 and 6 patients were in stage I, II, III and IV respectively. Kaplan-Meier model and log-rank test were used in univariate analysis and COX regression model was used in multivariate analysis to identify prognostic factors for survival.</p><p><b>RESULTS</b>The 1-, 2-, 3- and 4-year overall survival were 84.9%, 69.1%, 60.4% and 52.8%, respectively. Local recurrence-free survival were 75.1%, 53.8%, 43.9% and 40.8%, respectively. Disease-free survival were 64.3%, 43.2%, 37.1% and 25.0%, respectively. The following factors were identified as independent prognostic factors for survival by multivariate model: (1) Overall survival: Child-Pugh classification, standard treatment protocol and UICC-TNM staging. (2) Local recurrence-free survival: Child-Pugh classification and UICC-TNM staging. (3) Disease-free survival: UICC-TNM staging, Child-Pugh classification and daughter lesion. Among these, both Child-Pugh classification and UICC-TNM staging were independent prognostic factors for three kinds of survivals.</p><p><b>CONCLUSIONS</b>Degree of tumor progress (UICC-TNM stage, daughter lesion), treatment method (applying of standard treatment protocol) and patients' liver function are the most important factors for survival after RFA. So application of proper treatment strategy before, during and after RFA should be required to improve survival.</p>

Intraperitoneal hemorrhage during and after percutaneous radiofrequency ablation of hepatic tumors: reasons and management / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intraperitoneal hemorrhage is one of the most common complications of radiofrequency (RF) ablation of hepatic tumors. This study was designed to investigate the reason and management of intraperitoneal hemorrhage occurred during or after percutaneous RF ablation of hepatic tumors.</p><p><b>METHODS</b>Three hundred and fifty-six patients with hepatic tumors have been treated at 592 procedures of ultrasound guided RF ablation. Intraperitoneal hemorrhage occurred in 5 patients (0.8%). The reasons and management of intraperitoneal hemorrhage in these 5 cases were retrospectively analyzed.</p><p><b>RESULTS</b>Two patients with liver metastasis and one hepatocellular carcinoma (HCC) patient suffered from hemorrhage during the RF treatment. Two patients with recurrent HCC after surgery developed hemorrhage 20 minutes or 4 hours after RF treatment. One case of hemorrhage was due to the inappropriate electrode positioning induced liver laceration while treating a 1 cm liver metastasis near the liver capsule. One was due to the injury of a small vessel by the RF needle in another liver metastasis patient. Three cases were due to tumor rupture with two cases induced by cough or position change after treating large protruding HCC lesions. Four (80%) of the 5 cases of hemorrhage were rapidly identified by ultrasound. The causes and sites of bleeding during the RF treatment in three cases were confirmed through ultrasound, which were successfully treated using RF coagulation to achieve hemostasis of the bleeding site. Two patients with post-ablation hemorrhage recovered in one hour and 24 hours, respectively after given blood transfusion and other conservative measures. No surgical intervention was required. Two patients died of wide spread metastasis 23 - 36 months afterwards and the other three patients have lived for 18 - 25 months to date.</p><p><b>CONCLUSIONS</b>It is important to perform close monitoring during and after RF ablation in order to identify intraperitoneal hemorrhage in time. RF ablation of the bleeding sites was a simple and effective management when the bleeding site could be confirmed by ultrasound. The hemorrhage due to the rupture of large and protruding liver tumors could be serious and should be considered as contraindication for RF treatment.</p>

Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the efficiency and safety of radiofrequency ablation (RFA) of recurrent hepatocellular carcinoma (RHCC) after hepatectomy and to investigate efficacy of RFA for patients with early and late phase recurrence, separately, setting 1 year as the cut-off between the early and late phases.</p><p><b>METHODS</b>A total of 42 patients with 77 RHCC and a history of hepatic resection for hepatocellular carcinoma (HCC) underwent ultrasound-guided percutaneous radiofrequency ablation in our department and entered this study (RHCC group). The average diameter of RHCC was (3.8 +/- 1.4) cm (range, 1.5-6.6 cm). 21 of the 42 RHCC patients had Child-Pugh class A cirrhosis 19, class B and two, class C cirrhosis. The average interval between initial surgery and the diagnosis of recurrence was 22.8 months (range, 1-96 month). 42 RHCC patients were divided into two groups as early recurrence group including 20 patients with 40 RHCC, and late recurrence group including the other 22 patients with 37 RHCC according to the recurrence interval. During the same period 148 patients with 217 primary HCC were also treated by RF ablation and regarded as primary HCC group. The average diameter of primary HCC was (4.0 +/- 1.4) cm (range, 1.2-7.0 cm). Regular follow-up with enhanced CT was performed to evaluate the treatment results. Ablation was considered a success if no contrast enhancement was detected in the treated area on 1 month CT scans.</p><p><b>RESULTS</b>The ablation success rate, local recurrence rate, new tumor incidence and mean survival in RHCC group were 90.5%, 14.3%, 38.1% and (28.0 +/- 3.5) months, respectively, which were similar to the corresponding results of 87.2%, 16.2%, 37.8% and (39.0 +/- 2.1) month in primary HCC group. However, when further comparison was performed between early recurrence group, late recurrence group and primary HCC group, there were some significant differences. The incidence of new tumors in early recurrence group was significantly higher than that in late recurrent group (60.0% vs. 18.2%, P = 0.005); early recurrence group survived shorter than primary HCC group [(15.4 +/- 2.3) vs. (39.0 +/- 2.1) months, P < 0.005]. The survival time was similar between late recurrence group and primary HCC group. One case was found haemorrhage after RFA and recovered with conservative treatment. No major complications occurred in the remaining 41 patients.</p><p><b>CONCLUSIONS</b>RF ablation is generally effective and safe in treating RHCC. And it's more effective in late recurrence than in early recurrence.</p>

Results of enhanced ultrasonography in assessing hepatoma treated with radiofrequency ablation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical value of enhanced ultrasonography before and after ultrasound guided radiofrequency ablation (RFA) of hepatomas.</p><p><b>METHODS</b>Eighteen patients with 17 primary hepatocellular carcinoma and 1 hepatic metastasis were studied. Sixteen were confirmed by operation or needle puncture biopsy, 2 by clinical examinations including CT scanning, MRI etc. New contrast agent, SonoVue, Technos DU6 and Contrast Tuned Imaging (CnTI) technique were adopted. Enhanced ultrasonography was performed before or after the RFA procedure.</p><p><b>RESULTS</b>Twenty-six lesions were observed with enhanced ultrasonography before RFA, 24 of which showed ball-carrying sign or diffuse enhancement at the early artery phase favoring the fast diagnosis; 9 lesions showed feeding vessels; twelve of the 26 lesions (46.2%) tended to be larger, especially those with unclear margins (78.6%, 11/14) and those without halo sign (68.8%, 11/16). Enhanced ultrasonography revealed 13 satellite foci in four cases which had been undetectable with routine ultrasound, CT scanning or MRI. The final diagnosis of either inactivation or residual disease would rely upon more than two kinds of images, levels of tumor marks, biopsy pathology and more than 7 months of follow-up. Twenty-two lesions were observed with enhanced ultrasonography after RFA, with an accuracy of 95.5% (21/22), being similar to the enhanced CT and was significantly superior to the routine color ultrasonography whose accuracy was only 63.6% (14/22).</p><p><b>CONCLUSION</b>Enhanced ultrasonography may provide more information on the characters, size, number and feeding vessels of the tumor before radiofrequency ablation, thus helping choose the indicator, establish and carry out the treatment protocol. This technique may also help to assess the therapeutic response to RFA.</p>

High mechanical index post-contrast ultrasonography improves tissue structural display of hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The advent of second generation agent-SonoVue and low mechanical index real-time contrast enhanced ultrasonography (CEUS) imaging have been shown to improve the diagnostic performance of ultrasonography in hepatocellular carcinoma (HCC). But no report has described the effect of high mechanical index (MI) post-CEUS. This study aimed to investigate the value of post-CEUS in displaying tissue structures of HCC.</p><p><b>METHODS</b>Seventy-six HCCs in 65 patients were included in the study. Each patient underwent three scans, high-MI (MI: 0.15-1.6) pre-contrast ultrasound, low-MI (MI: 0.04-0.08) CEUS with contrast agent SonoVue, and high-MI post-contrast ultrasound, which was performed within 3 minutes after CEUS. The size, boundary, echogenicity, internal echotexture and posterior acoustic enhancement of the HCCs in the conventional scans before and after CEUS were evaluated. According to pathological evidence, diagnosis rates of pre-contrast, CEUS and post-contrast scans were determined and compared. The potential mechanism of post-contrast ultrasound imaging was also discussed.</p><p><b>RESULTS</b>Compared with pre-contrast, post-contrast ultrasound showed improvement in image quality in most HCCs: twenty-six (34.2%) more lesions showed well defined margins and fourteen (18.4%) more nodules showed halo sign; twenty-three (30.3%) lesions demonstrated enlarged in sizes; changes in echogenicity were seen in 30 lesions (39.5%); eighteen (23.7%) more lesions showed heterogenecity and 20 (26.3%) more lesions showed "mosaic" or "nodule-in-nodule" sign; twelve (15.8%) more lesions showed posterior acoustic enhancement. Post-contrast ultrasound showed increased diagnostic accuracy of 93.4% (71/76), compare with 88.2% (67/76) of CEUS alone.</p><p><b>CONCLUSIONS</b>High-MI post-contrast ultrasound utilizes harmonic signals during the rupture of microbubbles, and significantly improves the display of echo-characteristics of HCCs in ultrasound images, which adds diagnostic values for CEUS. Post-contrast ultrasound could play an important role in tissue characterization, and may be included in CEUS protocols.</p>

Noninvasive evaluation of liver fibrosis in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical usefulness of noninvasive diagnostic methods in evaluating liver fibrosis in hepatitis B virus (HBV) patients.</p><p><b>METHODS</b>102 patients with chronic hepatitis B (CHB) were enrolled from Beijing Friendship Hospital Affiliated to Capital University of Medical Sciences. Noninvasive diagnostic methods including ultrasonography, CT, serum markers of liver function and fibrosis, and HBV DNA were performed and compared with histological fibrotic changes in order to establish a noninvasive method for detecting the degree of liver fibrosis.</p><p><b>RESULTS</b>The total score of liver surface, edge, parenchyma echogenicity, intrahepatic vessels, and the size of spleen had a coefficient of 0.822 with fibrotic stage. By receiver operating curve (ROC) analysis, the sensitivity to distinguish cirrhosis from CHB was 86.1% and the specificity was 95.5% if the total ultrasonic score was more than 10. The CT imaging diagnosed liver cirrhosis with a specificity of 100% and a sensitivity of 48.5%. The change of CT values in cirrhotic patients was lower than that in controls and no cirrhotic patients (F=5.805, P<0.01), when the voltage was increased from 100 KV to 140 KV. Except normal controls and S1 group, S2 and S3 group, the level of HA and collagen IV between the other groups were statistically different. The cut-off value of HA to diagnose cirrhosis was 108 (microg/L) with a sensitivity of 72.2% and a specificity of 80.3%. The cut-off value of collagen IV to diagnose cirrhosis was 188 (microg/L) with a sensitivity of 72.2% and a specificity of 78.8%. When ultrasonography was combined with serum markers, the sensitivity was 72.2% and the specificity was 80.3%.</p><p><b>CONCLUSION</b>Both ultrasonography and serum markers are useful to diagnose cirrhosis. The combination of the two examinations is more valuable than any one alone. The characteristic CT imaging has high specificity but low sensitivity in diagnosing early cirrhosis. HA and collagen IV are correlated more closely with the stage of fibrosis, and can reflect the severity of fibrosis.</p>