Thermal ablation and immunomodulation: From preclinical experiments to clinical trials.

Accumulating evidence has shown that thermal ablation can induce spontaneous distant tumor regression, which is also known as abscopal effect. Abscopal effect might depend upon the activation of antitumor immune response. However, such responses induced by thermal ablation had been thought to be usually weak and that they rarely induce distant tumor regression. Recently, results of several preclinical and clinical studies have suggested that thermal ablation can induce therapeutically effective systemic antitumor immune response if appropriate immunomodulators are combined. To elucidate the mechanisms of these promising strategies, effects of thermal ablation on the immune system are overviewed. Furthermore, recent promising preclinical and clinical studies examining enhancement of systemic antitumor immune response by combining thermal ablation and immunomodulation are summarized.

Percutaneous drainage of pancreatic fistula following pancreatectomy with CT-fluoroscopic guidance.

PURPOSE: To evaluate the clinical utility of percutaneous drainage of pancreatic fistula following pancreatectomy with real-time CT-fluoroscopic guidance. MATERIAL AND METHODS: During January 2007 through March 2013, of 295 patients who underwent pancreatectomy, 20 patients received percutaneous drainage of pancreatic fistula with real-time CT-fluoroscopic guidance. The mean diameter of pancreatic fluid collections was 8.1±2.7 (SD)cm (range: 3.5-15.0cm). Feasibility, safety, and clinical success were evaluated. Primary and secondary clinical successes were defined respectively as the resolution of pancreatic fistula by initial drainage alone, and after additional intervention. Factors affecting primary clinical success and the drainage period were also evaluated. RESULTS: Drainage catheters were placed in planned sites in all patients. No major complication occurred except in 1/20 patient (5%) who experienced endotoxin shock. Primary and secondary clinical success rates were, respectively, 50% (10/20) and 90% (18/20). An amylase level greater than 30,000IU/L in the fluid collection was a significant factor lowering the primary clinical success rate (P<0.02) and prolonging the drainage period (>30 days) (P<0.02). CONCLUSION: Real-time CT-fluoroscopic guided drainage is a feasible, safe, and useful therapeutic option for the management of pancreatic fistula after pancreatectomy. The fluid amylase level is a useful indicator to predict refractory pancreatic fistula.

Changes in liver stiffness on real-time tissue elastography before and after occlusion of spontaneous portosystemic shunts.

PURPOSE: This study was conducted to evaluate changes in liver stiffness, volume, and function before and after occlusion of spontaneous portosystemic shunt. MATERIALS & METHODS: Twenty-four patients (13 men and 11 women) with a mean age of 68.2 years±10.1 (SD) (age range, 49-82 years) underwent percutaneous occlusion of spontaneous portosystemic shunt because of gastric varices (n=17) or hepatic encephalopathy (n=7) from March 2011 to June 2013. The liver fibrosis index indicating liver stiffness was calculated by using ultrasound elastography before and after shunt occlusion. Liver volume and liver profile were also evaluated. RESULTS: Spontaneous portosystemic shunt occlusion was uneventfully performed in all patients. The mean liver fibrosis index was significantly decreased from 2.7±1.0 before shunt occlusion to 2.0±0.9 (P<0.001) at 1 month, 2.2±1.0 at 3 months (P=0.004), and 1.6±0.7 at 6 months (P=0.001) afterwards. A significant increase in the liver volume was observed from 1035.3±340.1mL before shunt occlusion to 1116.8±298.4mL (P=0.006) at 1 month and 1174.2±354.1mL (P<0.001) at 3 months afterwards. Significant improvement in the Child-Pugh score was also found at 1 month (6.2±1.4, P<0.001), 3 months (6.5±1.1, P=0.022), and 6 months (6.0±0.9, P=0.004) after shunt occlusion as compared with that (7.2±1.9) before. CONCLUSION: The liver stiffness decreases along with an increase in liver volume and improvement in liver function after spontaneous portosystemic shunt occlusion.

Technical Feasibility and Clinical Outcomes of Interventional Endovascular Treatment for Hepatic Artery Thrombosis After Living-donor Liver Transplantation.

OBJECTIVES: Hepatic artery thrombosis (HAT) is a serious complication after living-donor liver transplantation (LDLT) leading to patient death in the absence of revascularization. With the recent advances in interventional radiology, interventional endovascular techniques have been used as alternative therapeutic options for HAT. This study evaluates the feasibility and clinical outcomes of endovascular treatment for HAT after LDLT. METHODS: The medical records of 120 patients who underwent adult-to-adult LDLT between February 2002 and February 2015 in our hospital were retrospectively reviewed to evaluate the frequency of HAT and outcomes of endovascular treatment. RESULTS: A total of nine patients (7.5%) developed HAT after LDLT, and the all patients underwent endovascular treatment. Overall technical success with endovascular treatment was achieved in 77.8% (7 of 9) of the patients. Intra-arterial thrombolysis was successful in one patient. Further intervention after intra-arterial thrombolysis was performed in the form of percutaneous transluminal angioplasty in six patients, and percutaneous transluminal angioplasty with stenting in two patients. Two patients with failure of revascularization by endovascular treatment were treated conservatively and developed hepatic arterial collaterals, and the both patients could avoid the graft failure. The overall survival rates did not differ significantly between the patients without HAT (n = 111) and those with HAT (n = 9) (1-, 3-, and 5-year overall survival rates of the patients without HAT vs. with HAT: 78.1%, 67.8%, and 65.3% vs. 66.7%, 66.7%, and 66.7%, respectively; P = .77). CONCLUSION: Interventional endovascular treatment of HAT in LDLT is a feasible and reliable procedure in avoiding early graft failure with acceptable long-term patient outcome.

CT-fluoroscopy in chest interventional radiology: sliding scale of imaging parameters based on radiation exposure dose and factors increasing radiation exposure dose.

AIM: To verify the usefulness of a sliding scale of imaging parameters to reduce radiation exposure during chest interventional radiology (IR), and to identify factors that increase radiation exposure in order to obtain acceptable computed tomography (CT)-fluoroscopy image quality. MATERIALS AND METHODS: The institutional review board approved this retrospective study, for which the need for informed consent was waived. Interventional radiologists determined the optimal CT-fluoroscopy imaging parameters using the sliding scale based on the radiation exposure dose. The imaging parameters were changed from those generating low radiation (120 kV/10 mA, 1.2 mGy/s) to others generating higher radiation exposure until acceptable image quality was obtained for each procedure. Validation of the imaging parameter sliding scale was done using regression analysis. Factors that increase radiation exposure were identified using multiple regression analysis. RESULTS: In 125 patients, 217 procedures were performed, of which 72 procedures (33.2%, 72/217) were performed with imaging parameters of minimum radiation exposure, but increased radiation exposure was necessary in 145 (66.8%, 145/217). Significant correlation was found between the radiation exposure dose and the percentage achievement of acceptable image quality (R(2) = 0.98). Multivariate regression analysis showed that high body weight (p < 0.0001), long device passage (p < 0.0001), and lesions above the aortic arch (p = 0.04) were significant independent factors increasing radiation exposure. CONCLUSION: Although increased radiation exposure dose might be necessary to obtain acceptable chest CT-fluoroscopy images depending on the patient, lesion, and procedure characteristics, a sliding scale of imaging parameters helps to reduce radiation exposure.

Intractable bronchopleural fistula caused by radiofrequency ablation: endoscopic bronchial occlusion with silicone embolic material.

A 58-year-old man with primary lung cancer underwent lung radiofrequency (RF) ablation. Pneumothorax developed 12 days after lung RF ablation. Despite chest drainage for 1 month, air leakage continued through a bronchopleural fistula. Bronchial occlusion was performed with a silicone embolus, causing cessation of the air leakage.

Case report: Radiofrequency ablation for the treatment of painful isolated wound recurrence after resection of gastric cancer.

A 75-year-old woman underwent radiofrequency (RF) ablation for the treatment of two painful disseminated tumours that appeared and rapidly became larger at the anterior abdominal wound 16 months after she had undergone surgery for gastric cancer. RF ablation was performed under CT-fluoroscopic guidance for both tumours, which measured 5 cm and 3 cm in maximum diameter. Pain was relieved immediately after RF ablation, and both tumours showed significant involution upon physical examination and CT studies. The patient is still alive 15 months after RF ablation, with no evidence of tumour recurrence.

Complications after lung radiofrequency ablation: risk factors for lung inflammation.

This retrospective study was conducted to review the complications of lung radiofrequency (RF) ablation and to clarify the effects of inflammation after lung RF ablation on mortality and morbidity. Complications were evaluated by reviewing medical records on an RF session basis. The C-reactive protein (CRP) value was used as an indicator of inflammation and was measured before and every 1-2 days during the hospital stay after RF ablation. The relationships between CRP values and patient baselines were evaluated to identify factors affecting lung inflammation. 130 patients who underwent 327 lung RF ablation sessions were enrolled in this study. The major complication rate was 18.3% (60/327). Inflammation-related complications such as interstitial pneumonia (n = 2) and aseptic pleuritis (n = 2) developed in four sessions (1.2%). Death occurred in two patients with interstitial pneumonia (0.6%). The mean CRP value increased significantly from 1.3+/-2.6 mg dl(-1) to 3.4+/-5.6 mg dl(-1) (p<0.01) after RF ablation. Large tumour size (>or=2 cm) and previous external-beam radiotherapy were significant factors associated with an increased CRP value in both univariate and multivariate analyses. In conclusion, although the incidence rate is low, fatal lung inflammation may develop after lung RF ablation. Large tumour size and previous external-beam radiotherapy are risk factors for severe lung inflammation.

Predictive factors for distant recurrence of HCV-related hepatocellular carcinoma after radiofrequency ablation combined with chemoembolization.

BACKGROUND: Radiofrequency ablation (RFA) therapy for hepatocellular carcinoma has enabled good local control to be possible. However, after successful local control, distant recurrences frequently occur in the remnant liver. AIM: To identify the predictive factors for distant recurrence after RFA. METHODS: A total of 117 patients with initial non-advanced hepatocellular carcinoma with HCV who underwent RFA in our hospital were selected for this study. After transcatheter chemoembolization, RFA was performed under real-time computed tomography-fluoroscopic guidance. We studied survival rates, local (adjacent to treated tumour) and distant (intrahepatic site distant from the treated tumours) recurrence rates, as well as predictive factors for distant recurrence. RESULTS: After RFA, survival rates were 98.2% and 64.7% at 1 and 5 years, respectively. Child B patients had a significantly worse survival than Child A. Recurrence rates were 2.4% at 5 years for local, and 17.1% and 76.9% at 1 and 5 years, respectively, for distant. The Kaplan-Meier method revealed significantly high recurrence rates in cases with low albumin levels (Alb < 3.5 g/dL), high aspartate aminotransferase levels (AST > 60 IU/L), high alanine aminotransferase levels (ALT > 60 IU/L), low platelet counts (Plt < 10 x 10(4)/microL), and high alpha-fetoprotein levels (AFP > 50 ng/mL). On multivariate analysis, low Alb levels and high AST levels were independent predictive factors for distant recurrence. CONCLUSIONS: Although RFA enables good local control for initial hepatocellular carcinoma, distant recurrence is observed at high rates in HCV patients. Low albumin and high AST levels are predictive factors for distant recurrence.

[Recurrent lung cancer with interstitial pneumonia treated with percutaneous radiofrequency ablation].

We performed computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) for postoperative recurrent pulmonary metastases developed in a 77-year-old man with interstitial pneumonia. He had received left upper segmentectomy with ND 2a nodal dissection. RFA was safely performed for pulmonary metastases in right S6 and left S6. There was no evidence to suggest any deterioration on interstitial pneumonia, including KL 6 and CT findings. Autopsy revealed residual cancer cells in peripheral lesion in 1 of 2 tumors treated by RFA. Although RFA is palliative, it is a promising treatment for local control of pulmonary malignancy in high-risk patients.

Clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in patients with unresectable extrahepatic bile duct cancer.

The objective of this study was to evaluate the clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in improving stent patency and prognosis in patients with unresectable bile duct cancer as compared with brachytherapy alone. Seventeen patients were treated. Five patients received brachytherapy alone before stent placement. Twelve patients received brachytherapy combined with external-beam radiotherapy (n=5), repeated hepatic arterial infusion chemotherapy using an implanted catheter and port (n=1), or both (n=6). Mean survival was significantly improved in the group that received combined therapy as compared with the group that received brachytherapy alone (16.2 months vs. 4.6 months, p<0.01). Although stent occlusion rates were similar in the two groups (42% vs. 40%), there was a trend towards longer stent patency in the combined therapy group than in the brachytherapy group (22 months vs. 3.6 months, p<0.2). Radiation gastritis necessitating gastrectomy developed in 1 patient who received external-beam radiotherapy at more than 50 Gy. Brachytherapy combined with external-beam radiotherapy and repeated hepatic arterial infusion chemotherapy increases survival compared with brachytherapy alone in patients with unresectable bile duct cancer.

Malignant portal venous obstructions treated by stent placement: significant factors affecting patency.

PURPOSE: To identify factors affecting stent occlusion after stent placement in the portal vein in patients with malignant portal vein invasion. MATERIALS AND METHODS: Forty patients were studied. Twenty-three patients had hepatocellular carcinoma, nine patients had pancreatic cancer, and eight patients had bile duct cancer. Stents were placed in the portal venous system across stenotic (n = 28) or obstructive (n = 12) lesions after percutaneous transhepatic portography. Bare stents were used in 33 patients and covered stents were used in seven patients. Twenty-two variables were analyzed with use of univariate and multivariate analyses to identify significant factors affecting stent occlusion. RESULTS: Stents remained patent during a mean follow-up period of 11.9 months (range, 2-61 mo) in 60% of the patients. Stent occlusion was found in 40% of the patients, with a mean period until occlusion of 3.7 months (range, 0.2-16 mo). In the univariate analysis, the following five factors were significantly associated with a higher probability of stent occlusion: (i) splanchnic vein involvement, (ii) Child-Pugh class C, (iii) obstruction of the portal venous system, (iv) pancreatic cancer, and (v) lack of anticancer treatment after stent placement. In the multivariate analysis, the first three factors were found to have independent value for stent occlusion. CONCLUSIONS: Splanchnic vein involvement, severe hepatic dysfunction, and obstruction of the portal venous system are the most important factors affecting stent occlusion in patients with malignant portal vein invasion.

Treatment of hepatocellular carcinoma and the exacerbation of liver function.

We performed interventional treatments on 50 patients with hepatocellular carcinoma (HCC) and analyzed the relationship between these treatments and the exacerbation of liver function after treatment. The different treatments included transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), selective segmental sclerotherapy (SSS), combined TAE and PEIT, or transcatheter arterial chemo-injection (TAI). Thirteen patients showed an exacerbation of liver function after treatment. The laboratory data on admission, showed the lower levels of serum albumin and cholinesterase in this group. In comparison to patients who did not show any exacerbation of liver function, these 13 patients had undergone combined TAE and PEIT. An analysis of cases after TAE and PEIT treatment revealed that the time from TAE to PEIT was shorter in the exacerbation group than in the non-exacerbation group, however, there was no significant difference in the amount of injected ethanol between the two groups. It is assumed that the values of albumin and cholinesterase before treatment, or the period from TAE to PEIT are related to liver failure after treatment. Combining TAE and PEIT treatment may be effective for HCC, however, we should pay special attention to liver failure after treatment.

[Advanced hepatocellular carcinoma--feasibility and clinical impact of high-dose-rate brachytherapy on the treatment of lesions growing into biliary trees, portal veins and the vena cava].

This study was performed to evaluate the feasibility and clinical impact of intraluminal and endovascular high-dose-rate iridium-192 brachytherapy on the treatment of HCC lesions growing into biliary trees, portal veins and the inferior vena cava. HCCs involving biliary trees in 2 patients, the main and/or first-order portal veins in 3 patients, and the inferior vena cava in 2 patients. Brachytherapy was percutaneously performed with a 5F applicator, which was placed adjacent to the lesions. A mean total dose of 23 Gy (range, 5-7 Gy/fr) was irradiated (at a 5 mm radius) to the biliary or the portal venous tumors. A total dose of 10 Gy (5 Gy/fr) was given to the caval tumors. External-beam radiotherapy was combined in 2 patients with caval lesions, stent placement in 2 patients with biliary lesions and hepatic arterial infusion chemotherapy in 5 patients. There was no major complication except hemobilia, which ceased after placing a PTCD tube in the bile duct in one patient. All tumors were significantly reduced in size and remained controlled during the period of patients' survival. Complete tumor necrosis was histologically proved in 2 autopsy cases having biliary lesions. The median survival was 13 months. Intraluminal and endovascular high-dose-rate brachytherapy appears to be a feasible, and effective procedure to treat advanced HCCs invading biliary trees, portal veins and the vena cava.

[Transarterial chemoembolization (TAE) with degradable starch microspheres (DSM) in advanced hepatocellular carcinoma].

This study was undertaken to evaluate the clinical utility of chemoembolization using degradable starch microspheres (DSM), which resolve in a short period in patients with advanced hepatocellular carcinoma (HCC). Twenty-one patients underwent DSM chemoembolization 24 times. After a mixture of iodized oil and epirubicin was injected into the hepatic arteries, the patients were embolized with DSM alone 16 times. In the other 8 times, embolization was done in one hepatic lobe with DSM and in the other hepatic lobe with gelatin sponge (GS). There was no major complication related to chemoembolization. Tumor response (complete, partial, and minor responses) was found in 46% of patients after TAE. Tumor recurrence was found in 64% of responders after a mean period of 2.0 months. The response rate was significantly higher when chemoembolization was performed using both DSM and GS than when it was done with DSM alone (63% vs 37%, p < 0.04). Although the response rate after DSM-TAE is low, its anticancer effect is reinforced when used as an adjuvant therapy of GS-TAE.

[Hepatic intra-arterial infusion chemotherapy using polymer-coated 2.9 Fr implantable catheter-port system--initial experience].

We developed a new 2.9 Fr implantable catheter-port system (reservoir) to perform arterial infusion chemotherapy in patients with unresectable liver tumors. This study was undertaken to evaluate the feasibility of placing this new reservoir system in patients in whom placement of a 5 Fr-reservoir system would seem to be difficult because of severe stricture, tortuosity or angulation of the hepatic artery. A new reservoir system was successfully implanted in 25 patients during 27 sessions. After a side hole was opened, a 2.9 Fr catheter was inserted in the distal hepatic artery or in the gastroduodenal artery in 24 sessions. The catheter tip was then fixed with coils to prevent catheter dislocation. In the other 3 sessions, a 2.9 Fr catheter was inserted without catheter fixation in the replaced right hepatic artery and a small sized collateral artery towards the liver. Arterial infusion chemotherapy was done without any trouble after 20 sessions. Catheter dislocation was found after 2 sessions in which the catheter tip was not fixed or inadequately fixed. Early arterial occlusion was found after placing a 2.9 Fr catheter in the replaced hepatic artery and the small sized-collateral artery after 4 sessions. In conclusion, although sequellae should be evaluated over a long-term period, implantation of a new 2.9 Fr reservoir system is technically feasible and useful in performing arterial infusion chemotherapy.

Fast 3D dynamic MR imaging of the liver with MR SmartPrep: comparison with helical CT in detecting hypervascular hepatocellular carcinoma.

Dynamic magnetic resonance (MR) imaging with SmartPrep was compared with dynamic enhanced helical computed tomography (CT) for the detection of hepatocellular carcinoma (HCC). Thirty patients with 49 HCCs were studied. Arterial-phase MR images using with SmartPrep were significantly superior to arterial-phase CT in detecting small lesions (< or = 2 cm) (85.3% vs. 67.6%, P < .05). In addition, in six recurrent tumors after arterial chemoembolization, dynamic MR imaging with MR SmartPrep technique was superior to helical CT in detecting of recurrent tumors.

Histologic analysis of the tibial bone tunnel after anterior cruciate ligament reconstruction using solvent-dried and gamma-irradiated fascia lata allograft.

Anterior cruciate ligament (ACL) reconstruction using free tendon graft requires biologic fixation in the bone tunnel. This report describes the intratunnel histology retrieved from a 47-year-old woman who underwent high tibial osteotomy 17 months after ACL reconstruction using a hybrid graft (a solvent-dried and gamma-irradiated fascia lata allograft as a core wrapped with iliotibial autograft). The patient underwent revision because of pain resulting from osteoarthrotic change, and the graft appeared to be taut and healthy on second-look arthroscopy. The sample was taken from the site of the metaphyseal osteotomy site. Histologic examination of the samples was performed with a light microscope (H&E and Masson trichrome stain). Biologic fixation of the graft to the bone was evident from observation of collagen fiber continuities, resembling Sharpey fibers. Integration of the autograft and allograft seemed to have occurred; the junction between the allograft and the autograft could not be determined. However, there was a difference in ligamentization depending on location. In the peripheral region of the graft (the autograft region), the collagen fibers showed a distinct crimped pattern; the fibroblasts were arranged regularly along the major axis of the collagen fiber bundle. In the central part of the graft (the allograft region), remodeling seemed to be delayed. There were acellular, bubbly or myxoid degeneration areas in which the fiber bundles were less oriented and there was increased vascularity.

Binding rate constant of Tc-99m DTPA galactosyl human serum albumin measured by quantitative dynamic SPECT--clinical evaluation as a total and regional liver function test.

To evaluate the clinical utility of a new method with dynamic single photon emission computed tomography (SPECT) and scatter and attenuation compensation to estimate both total and regional liver function quantitatively. Five controls, 20 patients with chronic liver disease, and 2 patients with Budd-Chiari syndrome were studied. Dynamic liver SPECT data were acquired during 20 minutes after injection of Technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) with scatter and attenuation compensation. The binding rate constant of Tc-99m GSA (Ku) was derived quantitatively from the Patlak plot based on kinetic models for GSA receptor binding. The mean Ku was obtained by dividing the Ku value (total Ku) by the liver volume. Both total and mean Ku were significantly lower in patients with chronic liver disease than in controls (302 +/- 112 vs. 523 +/- 78 ml/min; p < 0.001, 0.26 +/- 0.11 vs. 0.43 +/- 0.03 ml/min/cm3; p < 0.001). In the patient group, both total and mean Ku were significantly correlated with the results of conventional liver function tests and the histological severity of chronic liver disease. In 2 patients with Budd-Chiari syndrome, the mean Ku was lower in the right lobe, where the hepatic veins were occluded, than in the left lobe, where draining veins were patent. In conclusion, this method is a reliable diagnostic technique for estimating total and regional liver function.