Macrophage-secreted TGF-ß1 contributes to fibroblast activation and ureteral stricture after ablation injury.

Iatrogenic injury to the healthy ureter during ureteroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-ß1-mediated scar formation is considered to underlie ureteral stricture, but the cellular sources of this cytokine and the sequelae preceding iatrogenic stricture formation are unknown. Using a swine model of ureteral injury with irreversible electroporation (IRE), we evaluated the cellular sources of TGF-ß1 and scar formation at the site of injury and examined in vitro whether the effects of TGF-ß1 could be attenuated by pirfenidone. We observed that proliferation and α-smooth muscle actin expression by fibroblasts were restricted to injured tissue and coincided with proliferation of macrophages. Collagen deposition and scarring of the ureter were associated with increased TGF-ß1 expression in both fibroblasts and macrophages. Using in vitro experiments, we demonstrated that macrophages stimulated by cells that were killed with IRE, but not LPS, secreted TGF-ß1, consistent with a wound healing phenotype. Furthermore, using 3T3 fibroblasts, we demonstrated that stimulation with paracrine TGF-ß1 is necessary and sufficient to promote differentiation of fibroblasts and increase collagen secretion. In vitro, we also showed that treatment with pirfenidone, which modulates TGF-ß1 activity, limits proliferation and TGF-ß1 secretion in macrophages and scar formation-related activity by fibroblasts. In conclusion, we identified wound healing-related macrophages to be an important source of TGF-ß1 in the injured ureter, which may be a paracrine source of TGF-ß1 driving scar formation by fibroblasts, resulting in stricture formation.

Safety and Clinical Outcomes of Percutaneous Radiofrequency Ablation for Intermediate and Large Bone Tumors Using a Multiple-Electrode Switching System: A Phase II Clinical Study.

PURPOSE: To evaluate the safety and clinical outcomes of radiofrequency (RF) ablation using a multiple-electrode switching system in patients with bone tumors > 3 cm. MATERIALS AND METHODS: This prospective study enrolled 20 subjects (15 men, 5 women; mean age 70.0 y ± 7.4 [SD]; range, 60-80 y) with malignant unresectable bone tumors. The maximum mean tumor diameter was 5.5 cm ± 2.0 (range, 3.1-10.0 cm). Two to three RF electrodes were placed into each bone tumor. Real-time CT fluoroscopic guidance was used with a multiple-electrode switching system. The primary endpoint was safety, as evaluated by Common Terminology Criteria for Adverse Events, until 12 months after bone RF ablation. As secondary endpoints, pain relief was evaluated by visual analog scale (VAS) scores before and 1 week after RF ablation; tumor response, by contrast-enhanced magnetic resonance imaging studies until 4 weeks after bone RF ablation; and survival, by Kaplan-Meier method. RESULTS: No adverse event was found in 19 of 20 patients (95%). Grade 2 fever occurred in 1 patient (5%; 1/20). VAS scores decreased by ≥ 2 in 11 of 13 patients (84.6%) who had painful bone tumors. Tumor response (complete or partial response) was achieved in 16 of 18 patients (88.9%) who underwent follow-up imaging studies. The 1-year overall survival rate was 60.9%, and the median survival time was 14.1 months. CONCLUSIONS: Bone RF ablation using this system is safe and achieves local tumor control and pain relief in patients with large bone tumors.

Radiofrequency Ablation Using a Multiple-Electrode Switching System for Lung Tumors with 2.0-5.0-cm Maximum Diameter: Phase II Clinical Study.

PURPOSE: To prospectively evaluate the safety and effectiveness of radiofrequency ablation (RFA) by using a multiple-electrode switching system to treat 2.0-5.0-cm lung tumors. MATERIALS AND METHODS: The institutional review board approved this prospective phase II study. Written informed consent was obtained from all patients. Between September 2009 and July 2011, RFA using two or three radiofrequency (RF) electrodes and a multiple-electrode switching system was performed for malignant lung tumors with a maximum tumor diameter of 2.0-5.0 cm in nonsurgical candidates. The primary endpoint was safety, as evaluated using the Common Terminology Criteria for Adverse Events. Patients were observed for at least 1 year. Local tumor progression and overall survival were analyzed with the Kaplan-Meier method. RESULTS: Thirty-three patients (26 men, seven women; mean age, 70.5 years ± 10.0; age range, 46-87 years) with 35 lung tumors with a mean maximum diameter of 3.0 cm ± 0.7 (standard deviation; range, 2.0-4.4 cm) underwent treatment in 35 sessions. No procedure-related death or grade 4 adverse events (AEs) occurred. Grade 3 AEs occurred in four patients (12%), with pleural effusion requiring chest tube placement in two patients, pneumothorax requiring pleural adhesion in one patient, and pulmonary hemorrhage requiring pulmonary artery coil embolization in one patient. Grade 2 AEs were detected in 13 patients (39%). The 1-year local tumor progression and overall survival rates were 12.7% (95% confidence interval [CI]: 1.0, 25.5) and 81.2% (95% CI: 67.6, 94.8). CONCLUSION: RFA with a multiple-electrode switching system may be a safe therapeutic option with which to treat 2.0-5.0-cm lung cancer tumors.

Unresectable Adrenal Metastases: Clinical Outcomes of Radiofrequency Ablation.

PURPOSE: To retrospectively evaluate the clinical outcomes of radiofrequency (RF) ablation for the treatment of unresectable adrenal metastasis. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and informed consent to perform adrenal RF ablation was obtained from all patients. From February 2005 through May 2014, 35 patients (25 men and 10 women; mean age, 64.7 years ± 9.6; age range, 39-82 years) underwent RF ablation to treat 41 metastatic adrenal tumors from lung cancer (n = 15), renal cell carcinoma (n = 9), colorectal cancer (n = 5), hepatocellular carcinoma (n = 4), and other tumors (n = 2). Tumors ranged in size from 1.2 to 8.2 cm (mean, 3.3 cm ± 1.6). The diagnosis was established mainly on the basis of radiologic findings. Adrenal arterial embolization was combined with RF ablation in 12 of the 35 patients (34%). Technical success, safety, local tumor progression, and survival were evaluated. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate prognostic factors. RESULTS: There were 48 completed sessions with planned procedures and treatment protocols with no mortality and a major complication rate of 8.3% (four of 48 sessions). Tumor enhancement disappeared after initial adrenal RF ablation in 33 of the 35 patients (94%). Local tumor progression developed in eight of the 35 patients (23%); two patients received repeated RF ablation, resulting in adrenal tumor control in 27 of the 35 patients (77%) at the last follow-up (mean, 30.1 months ± 27.5; range 1.2-96.8 months). The 1-, 3-, and 5-year overall survival rates were 75% (95% confidence interval [CI], 61%, 90%), 34% (95% CI: 17%, 52%), and 30% (95% CI: 13%, 48%), respectively, with a median survival time of 26.0 months. Existence of extra-adrenal tumors (P = .005) and age of 65 years or older (P = .04) were significant indicators of a poor prognosis. CONCLUSION: Adrenal RF ablation is a feasible and useful method for controlling adrenal metastases and offers patients opportunities for improved survival.

CT-Guided Percutaneous Cryoablation in Renal Cell Carcinoma: Factors Affecting Local Tumor Control.

PURPOSE: To retrospectively evaluate factors affecting local tumor control in cryoablation of renal cell carcinomas (RCCs). MATERIALS AND METHODS: This study examined 61 patients (43 men, 18 women) with a mean age of 69.1 years ± 10.8 (range 38-87 y) who underwent computed tomography (CT)-guided percutaneous cryoablation for a single RCC and were followed for 6 months or longer. Maximum tumor diameter was 0.8-4.8 cm (mean ± standard deviation, 2.4 ± 0.9 cm). Factors affecting local tumor control were evaluated. Deep tumor location was defined as the center side of the body perpendicular to the kidney midline. RESULTS: Median follow-up was 12.7 months. Residual unablated tumors and local tumor progression were observed after initial cryoablation in 4 patients each (13%, 8 of 61). All uncontrolled tumors were located in the deep side of the kidney (100%, 8 of 8), and were covered by an ice-ball margin of 5 mm or less. Deep tumor location (P = .005) and ice-ball margin (P = .002) were detected as significant factors affecting local tumor control on univariate analysis, and ice-ball margin remained significant in a stepwise logistic regression model (P = .006; odds ratio, 0.57; 95% confidence interval, 0.38-0.83). Complete tumor control rates were 42.9% (3 of 7), 92.6% (50 of 54), and 100% (20 of 20) with ice-ball margins of less than 3 mm, 3 mm or larger, and 6 mm or larger, respectively. CONCLUSIONS: Deep tumor location and ice-ball margins less than 6 mm were associated with incomplete local control following CT-guided percutaneous cryoablation for RCC.

Radiofrequency ablation versus radical nephrectomy: clinical outcomes for stage T1b renal cell carcinoma.

PURPOSE: To compare clinical outcomes of radiofrequency (RF) ablation retrospectively with those after radical nephrectomy in patients with stage T1b renal cell carcinoma (RCC). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. From June 2002 to March 2012, 60 patients (mean age, 65.2 years; age range, 39-86 years) with a single RCC measuring 4.1-7.0 cm (stage T1b) underwent RF ablation (n = 21) or radical nephrectomy (n = 39). Selective renal artery embolization was performed before RF ablation in eight patients. The overall, RCC-related, and disease-free survival rates, the percentage decrease in the glomerular filtration rate (GFR), and safety were compared by using the log-rank (survival), paired and Student t (GFR), and Fisher exact (safety) tests. RESULTS: The overall survival rate was significantly lower in the RF ablation group than in the radical nephrectomy group (48% vs 97% at 10 years, respectively; 95% confidence interval [CI]: 12.4%, 76.7% vs 78.2%, 99.5%; P < .009). The RCC-related survival rate (94% [95% CI: 62.6%, 99.1%] with RF ablation vs 100% with radical nephrectomy at 10 years) and the disease-free survival rate (88% [95% CI: 59.2%, 96.9%] with RF ablation vs 84% [95% CI: 60.6%, 94.3%] with radical nephrectomy at 10 years, P = .99) were comparable between the two groups. No treatment-related deaths occurred. Although major complication rates were similar between the two patient groups (8.0% [two of 25 patients] vs 5.1% [two of 39 patients], P = .61), the percentage decrease in the GFR was significantly lower in the RF ablation group than in the radical nephrectomy group at the last follow-up (12.5% ± 23.4 vs 32.3% ± 20.8, respectively; P < .003). CONCLUSION: RF ablation is a safe procedure for patients at substantial surgical risk for radical nephrectomy, providing comparable RCC-related and disease-free survival and preserving renal function.

Cytoskeletal Remodeling and Gap Junction Translocation Mediates Blood-Brain Barrier Disruption by Non-invasive Low-Voltage Pulsed Electric Fields.

High-voltage pulsed electric fields (HV-PEF) delivered with invasive needle electrodes for electroporation applications is known to induce off-target blood-brain barrier (BBB) disruption. In this study, we sought to determine the feasibility of minimally invasive PEF application to produce BBB disruption in rat brain and identify the putative mechanisms mediating the effect. We observed dose-dependent presence of Evans Blue (EB) dye in rat brain when PEF were delivered with a skull mounted electrode used for neurostimulation application. Maximum region of dye uptake was observed while using 1500 V, 100 pulses, 100 µs and 10 Hz. Results of computational models suggested that the region of BBB disruption was occurring at thresholds of 63 V/cm or higher; well below intensity levels for electroporation. In vitro experiments recapitulating this effect with human umbilical vein endothelial cells (HUVEC) demonstrated cellular alterations that underlie BBB manifests at low-voltage high-pulse conditions without affecting cell viability or proliferation. Morphological changes in HUVECs due to PEF were accompanied by disruption of actin cytoskeleton, loss of tight junction protein-ZO-1 and VE-Cadherin at cell junctions and partial translocation into the cytoplasm. Uptake of propidium iodide (PI) in PEF treated conditions is less than 1% and 2.5% of total number of cells in high voltage (HV) and low-voltage (LV) groups, respectively, implying that BBB disruption to be independent of electroporation under these conditions. 3-D microfabricated blood vessel permeability was found to increase significantly following PEF treatment and confirmed with correlative cytoskeletal changes and loss of tight junction proteins. Finally, we show that the rat brain model can be scaled to human brains with a similar effect on BBB disruption characterized by electric field strength (EFS) threshold and using a combination of two bilateral HD electrode configurations.

Electrolysis products, reactive oxygen species and ATP loss contribute to cell death following irreversible electroporation with microsecond-long pulsed electric fields.

Membrane permeabilization and thermal injury are the major cause of cell death during irreversible electroporation (IRE) performed using high electric field strength (EFS) and small number of pulses. In this study, we explored cell death under conditions of reduced EFS and prolonged pulse application, identifying the contributions of electrolysis, reactive oxygen species (ROS) and ATP loss. We performed ablations with conventional high-voltage low pulse (HV-LP) and low-voltage high pulse (LV-HP) conditions in a 3D tumor mimic, finding equivalent ablation volumes when using 2000 V/cm 90 pulses or 1000 V/cm 900 pulses respectively. These results were confirmed by performing ablations in swine liver. In LV-HP treatment, ablation volume was found to increase proportionally with pulse numbers, without the substantial temperature increase seen with HV-LP parameters. Peri-electrode pH changes, ATP loss and ROS production were seen in both conditions, but LV-HP treatments were more sensitive to blocking of these forms of cell injury. Increases in current drawn during HV-LP was not observed during LV-HP condition where the total ablation volume correlated to the charge delivered into the tissue which was greater than HV-LP treatment. LV-HP treatment provides a new paradigm in using pulsed electric fields for tissue ablation with clinically relevant volumes.

Renal cell carcinoma: radiofrequency ablation with a multiple-electrode switching system--a phase II clinical study.

PURPOSE: To prospectively evaluate the safety and effectiveness of radiofrequency ablation with a multiple-electrode switching system for the treatment of renal cell carcinoma (RCC). MATERIALS AND METHODS: From November 2009 to December 2010, 33 patients (mean age, 70.7 years; range, 44-86 years) with histologically proved RCCs--including 24 men (mean age, 69.5 years [range, 44-86 years]) and nine women (mean age, 74.1 years [range, 64-83 years])--were enrolled in this phase II study. The institutional review board approved the study after patients provided written informed consent. The mean maximum tumor diameter was 2.9 cm ± 1.0 (standard deviation) (range, 1.5-5.0 cm). Radiofrequency ablation was conducted with a multiple-electrode switching system. The primary endpoint was evaluated with the Common Terminology Criteria for Adverse Events. Secondary endpoints were changes in renal function, technique effectiveness, local tumor progression, and survival. Changes in renal function were evaluated by using the Mann-Whitney U test. RESULTS: No severe adverse events occurred, but three of 33 patients (9%) had grade 2 adverse events. Although the mean glomerular filtration rate at 1 year after radiofrequency ablation was similar to the baseline value in 26 patients with bilateral kidneys (P = .14), it was decreased significantly in six patients with a single kidney (P = .03). Tumor enhancement disappeared after a single radiofrequency session in 31 patients and after two radiofrequency sessions in the other two patients (rates of primary and secondary technique effectiveness, 94% [31 of 33] and 100% [33 of 33], respectively). No local tumor progression was found during the mean follow-up of 20.0 months (range, 11.6-27.6 months). The respective 1-year overall and RCC-related survival rates were 97% (95% confidence interval: 91%, 100%) and 100%. CONCLUSION: Radiofrequency ablation with a multiple-electrode switching system is safe and effective for treatment of RCCs. However, further study is warranted to determine whether this technology is superior to other previously described methods.

Radiofrequency ablation for liver metastasis from gastrointestinal stromal tumor.

PURPOSE: To evaluate the feasibility, safety, and clinical outcomes of radiofrequency (RF) ablation for the treatment of liver metastases from gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: Seven consecutive patients with 21 GIST liver metastases received RF ablation under computed tomographic (CT) fluoroscopic guidance. Liver metastases were solitary in two patients and multiple in five patients, with a mean maximum tumor diameter of 2.2 cm±1.1 (range, 1.2-4.2 cm). In addition to feasibility and safety, local tumor progression and overall and GIST-related survival associated with RF ablation were assessed. RESULTS: All liver metastases were treated in 12 RF sessions, after which contrast-enhanced CT showed disappearance of tumor enhancement. No RF procedure-related complications occurred. Local tumor progression developed in one tumor (4.8%) during the mean follow-up period of 30.6 months±27.5 (range, 5.9-76.4 mo). New liver metastasis in untreated liver and lung metastasis developed in one patient each. One patient died of subarachnoid hemorrhage 5.9 months after RF ablation, but no GIST-related deaths occurred. The respective overall and GIST-related survival rates were 85.7% (95% confidence interval, 33.6%-97.8%) and 100% at 1, 3, and 5 years. CONCLUSIONS: RF ablation is a feasible, safe, and useful therapeutic option for the treatment for GIST liver metastases.

Survival with up to 10-year follow-up after combination therapy of chemoembolization and radiofrequency ablation for the treatment of hepatocellular carcinoma: single-center experience.

PURPOSE: To report 10-year outcomes of treating hepatocellular carcinomas (HCCs) by combination therapy of chemoembolization and radiofrequency (RF) ablation. MATERIALS AND METHODS: Combination therapy was administered in 277 patients with 382 treatment-naïve HCCs. Therapeutic effects, safety, survival rate, and prognostic factors were evaluated. RESULTS: Tumor enhancement disappeared after 466 RF sessions in all tumors, resulting in a complete response rate of 100% (277 of 277) based on modified Response Evaluation Criteria In Solid Tumors. Local tumor progression developed in 15 patients (5.4%; 15 of 277) during the mean follow-up of 44.9 months±29.1 (range, 6.0-134.4 mo). Overall and recurrence-free survival rates were 56.3% (95% confidence interval [CI], 52.5%-60.2%) and 22.5% (95% CI, 19.3%-25.6%) at 5 years and 23.5% (95% CI, 17.7%-29.2%) and 9.3% (95% CI, 6.3%-12.4%) at 10 years. The Child-Pugh class was the only significant prognostic factor detected in both the univariate (P<.001) and the multivariate analyses (hazard ratio, 3.8; 95% CI, 2.5-5.6; P<.001). The 5-year and 10-year overall survival rates were 66.4% (95% CI, 62.0%-70.8%) and 30.6% (95% CI, 23.3%-37.9%) in 210 Child-Pugh class A patients. In addition to the Child-Pugh class, the maximum tumor diameter (≤3 cm vs>3 cm) and the tumor number (single vs multiple) were significant independent factors affecting recurrence-free survival. No death was related to the combination therapy. The major complication rate was 3.2% (15 of 466). CONCLUSIONS: RF ablation combined with chemoembolization is a safe and useful therapeutic option for treating HCCs. Prognostic factors detected in this study help to stratify patients who benefit from this combination therapy.

Macrophage activity at the site of tumor ablation can promote murine urothelial cancer via transforming growth factor-ß1.

Cell death and injury at the site of tumor ablation attracts macrophages. We sought to understand the status and activity of these cells while focusing on transforming growth factor-ß1 (TGF-ß1), a potent immunosuppressive and tumorigenic cytokine. Patients with urothelial cancer who underwent ablation using electrocautery or laser demonstrated increased infiltration and numbers of CD8+ T cells, along with FoxP3+ regulatory T cells, CD68+ macrophages and elevated levels of TGF-ß1 in recurrent tumors. Similar findings were reproduced in a mouse model of urothelial cancer (MB49) by partial tumor ablation with irreversible electroporation (IRE). Stimulation of bone marrow derived macrophages with MB49 cell debris produced using IRE elicited strong M2 polarization, with exuberant secretion of TGF-ß1. The motility, phenotypic markers and cytokine secretion by macrophages could be muted by treatment with Pirfenidone (PFD), a clinically approved drug targeting TGF-ß1 signaling. MB49 cancer cells exposed to TGF-ß1 exhibited increased migration, invasiveness and upregulation of epithelial-mesenchymal transition markers α-Smooth Muscle Actin and Vimentin. Such changes in MB49 cells were reduced by treatment with PFD even during stimulation with TGF-ß1. IRE alone yielded better local tumor control when compared with control or PFD alone, while also reducing the overall number of lung metastases. Adjuvant PFD treatment did not provide additional benefit under in vivo conditions.

Transarterial chemoembolization for hepatitis B virus-associated hepatocellular carcinoma: improved survival after concomitant treatment with nucleoside analogues.

PURPOSE: To determine whether nucleoside analogue therapy is associated with improved survival in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) who are treated solely with transarterial chemoembolization. MATERIALS AND METHODS: A retrospective chart review of patients diagnosed with HBV-associated HCC was performed to identify patients treated solely with chemoembolization. Relevant demographic and clinical data were extracted and recorded. The influence of therapy with nucleoside analogues (lamivudine, adefovir dipivoxil, or entecavir) was determined by estimating the survival function using the Kaplan-Meier product-limit method. RESULTS: The inclusion criteria for chemoembolization were met by 81 patients (67 men and 14 women, mean age 60.6 years ± 9.2); 21 (25.9%) of these patients had been treated with nucleoside analogues. The number of chemoembolization treatments was significantly greater in the patients who were treated with nucleoside analogues (3.43 ± 2.32) than in the patients who did not receive nucleoside analogues (1.82 ± 0.95; P = .0022). The 1-year, 3-year, and 5-year survival rates were 89.5%, 66.8%, and 40.5% in the patients treated with nucleoside analogues and 72.6%, 27.5%, and 14.3% in the patients not treated with nucleoside analogues. The survival rate was significantly higher in the patients who received nucleoside analogues (P = .0051). Nucleoside analogue intake was an independent factor that was associated with increased survival (P = .0063). CONCLUSIONS: Administration of nucleoside analogues was associated with longer survival in patients with HBV-associated HCC who were treated with transarterial chemoembolization.

Combination therapy of chemoembolization and radiofrequency ablation for the treatment of hepatocellular carcinoma in the caudate lobe.

PURPOSE: To evaluate the clinical utility of radiofrequency (RF) ablation combined with chemoembolization in treatment of hepatocellular carcinoma (HCC) located in the caudate lobe. MATERIALS AND METHODS: Between September 2000 and October 2011, 20 consecutive patients with single HCC measuring≤5 cm were treated with combination therapy of chemoembolization and RF ablation. Technical success was defined as completion of a planned electrode placement and ablation protocol. The effectiveness of the technique was defined as disappearance of tumor enhancement with an ablative margin of≥5 mm. Technical success, technique effectiveness, local tumor progression, overall and recurrence-free survival, and complications were evaluated. RESULTS: RF electrodes were placed in planned sites of each tumor, and ablation was complete in all patients (technical success rate 100%). Tumor enhancement disappeared with sufficient ablative margins after 20 RF sessions in all patients (technique effectiveness rate 100%). Major and minor complication rates were 10.0% and 15.0%. Local tumor progression was found in 2 of 20 patients (10.0%) with local tumor progression rates of 6.3% at 1 year and 13.5% at 3 years and 5 years. Six patients died during the follow-up period (mean, 40.0 months; range, 2.0-110.5 months). Overall and recurrence-free survival rates were 94.4% and 70.8% at 1 year, 86.6% and 36.9% at 3 years, and 67.5% and 45.5% at 5 years. CONCLUSIONS: RF ablation combined with chemoembolization is a safe and useful therapeutic option to treat HCCs located in the caudate lobe.

Cryptococcus granuloma mimicking local progressed tumor after cryoablation of renal cell carcinoma: A case report.

Infectious granulomas arising in the kidney are rare. However, there are few reports regarding renal granulomas, such as xanthogranulomatous pyelonephritis, sarcoidosis, malakoplakia, and tuberculosis. Here, we report a case of cryptococcal granuloma resembling a locally progressed tumor after percutaneous cryotherapy for renal cell carcinoma. A male patient in his 80s with rheumatoid arthritis underwent computed tomography (CT)-guided cryoablation for biopsy-proven papillary renal cell carcinoma. Follow-up contrast-enhanced CT imaging obtained 4 months after ablation confirmed an enhanced mass on the edge of the ablation zone. There were no symptoms related to the mass. This mass was radiologically diagnosed as local tumor progression and treated with repeated cryoablation. Percutaneous biopsy of the mass was performed immediately after the second cryoablation, and the mass was pathologically diagnosed as granuloma related to Cryptococcus infection. The patient was administered antifungal fluconazole for 1 year with a good outcome.

Percutaneous Thermal Ablation for Managing Small Renal Metastatic Tumors.

Purpose: To retrospectively evaluate the treatment outcomes of thermal ablation for renal metastatic tumors. Materials and Methods: Thirteen consecutive patients with small renal metastatic tumors (≤3 cm), who underwent thermal ablation between 2009 and 2020, were included in this study. Eight patients had extra-renal tumors during renal ablation. The primary tumors were adenoid cystic carcinoma in four patients, lung cancer in three, hemangiopericytoma in three, leiomyosarcoma in two, and thyroid cancer in one. The therapeutic effects, safety, survival rate, prognostic factor, and renal function were evaluated. Results: We performed 18 ablation sessions (cryoablation, n = 13; radiofrequency ablation, n = 5) on 19 renal metastases with a mean diameter of 1.7 cm, which resulted in a primary technique efficacy rate of 100% without procedure-related deaths or major complications. Renal function significantly declined 6 months after ablation (P = 0.0039). During the mean follow-up period of 31.2 ± 22.4 months (range, 2.7-71.4 months), one patient had local tumor progression at 11.9 months following radiofrequency ablation. The overall survival rates at 1 and 3 years after ablation were 76.9% (95% confidence interval [CI], 54.0%-99.8%) and 59.3% (95% CI, 31.3%-87.3%), respectively. Tumor size ≥ 2 cm (P = 0.02) and metastasis from non-small cell lung cancer (P = 0.001) were significant worse prognostic factors in univariate analysis, and metastasis from non-small cell lung cancer (P = 0.01) was significant in multivariate analysis. Conclusions: Percutaneous thermal ablation for small renal metastases is safe and feasible and can control local tumors.

Outcome in partial early virologic responders to combination therapy with peginterferon and ribavirin in patients infected with hepatitis C virus genotype 1b.

The course and outcome in patients infected with hepatitis C virus (HCV) genotype 1b with partial early virologic response during combination therapy with peginterferon and ribavirin, in whom serum HCV RNA is detectable but has decreased by more than 2 log(10) 12 weeks after the start of the therapy, has not been elucidated sufficiently. The outcome in this group of patients was investigated. Serum HCV RNA levels was measured every 4 weeks in 149 patients with HCV genotype 1b infection who underwent combination therapy for 48 weeks. In patients with partial early virologic response, the time point when serum HCV RNA became undetectable as well as the final virologic response to treatment was determined. Sixty-three patients (42.3%) had partial early virologic response. The time when serum HCV RNA became undetectable ranged from 16 to 48 weeks after the start of therapy. Serum HCV RNA remained detectable in 17 patients. The rates of sustained virologic response decreased with the delay of the time when serum HCV RNA became undetectable; sustained virologic responder was not found in patients in whom HCV RNA was still detectable at 24 weeks after the start of treatment. The degree of decrease in serum HCV RNA levels at 12 weeks corresponded to the rate of sustained virologic response in partial early virologic responders. The outcome of partial early virologic responders varied greatly, and close monitoring of serum HCV RNA is required for predicting the outcome of treatment in these patients.

Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium-enhanced MRI.

OBJECTIVE: We sought to determine whether hypointense hepatocellular nodules observed in the hepatobiliary phase of MRI enhanced with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (gadoxetate disodium) progress to hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: Gadoxetate disodium-enhanced MRI was repeated for 30 patients with 49 nodules determined to be hypointense in the hepatobiliary phase but nonenhancing in the arterial phase of dynamic MRI. The correlation between characteristics of hypointense nodules with slightly or markedly low signal intensity relative to surrounding liver parenchyma and their progression to hypervascular hepatocellular carcinoma was analyzed in cirrhotic livers. All patients underwent angiography-assisted CT before MRI. The rate of progression to classic hepatocellular carcinoma was calculated by the Kaplan-Meier method. RESULTS: The overall 6- and 12-month cumulative incidences of vascularization were 27.6% and 43.5%. The 6- and 12-month cumulative incidences of vascularized nodules with a maximum diameter 15 mm or greater were 43.3% and 77.3% and a maximum diameter less than 15 mm were 16.9% and 16.9%. The difference between these incidences was significant (p = 0.0147). CONCLUSION: Hypointense nodules with a maximum diameter of at least 15 mm often become hypervascular. Therefore, patients with hypointense nodules characterized by a maximum diameter of 15 mm or greater should be observed carefully because of the high incidence of vascularization.

[Ruptured aneurysm of a posterior inferior pancreaticoduodenal artery associated with duodenal stenosis after transcatheter arterial embolization].

We describe a 72-year-old man admitted to hospital as an emergency case of epigastric abdominal pain. CT scan visualized massive hemorrhage around the pancreatic head. Computed tomographic angiography showed stenosis at the origin of the celiac artery and a 10 mm aneurysm of the posterior inferior pancreaticoduodenal artery (PIPDA). An emergency angiogram revealed a long aneurysm in the PIPDA. The aneurysm had irregular width and was 75 mm in length. A gastroduodenal artery and the PIPDA were supplied from the superior mesenteric artery. A transcatheter arterial embolization (TAE) was performed. We reviewed 45 cases of pancreaticoduodenal aneurysms after 2000 and cases of the pancreaticoduodenal false aneurysms after 1972. As a result, we inferred that this case without pancreatitis or pancreas surgery was a true aneurysm made by the bloodstream changes caused by the celiac artery stenosis.

Successful endoscopic cyanoacrylate injection therapy for ruptured duodenal varices immediately after balloon-occluded retrograde transvenous obliteration.

We present a rare case of acute duodenal variceal rupture after B-RTO that was successfully treated with endoscopic CA injection therapy. A 74-year-old Japanese woman was transferred to our hospital due to progressive general malaise and hematemesis. Gastroduodenoscopy (GDS) showed duodenal varices without active bleeding in the second portion of duodenum. Balloon-occluded retrograde transvenous obliteration (B-RTO) was carried out to prevent duodenal variceal rebleeding. Good pooling of ethanolamine oleate with iopamidol (EOI) was observed in duodenal varices using balloon catheters. However, massive melena was observed immediately after B-RTO. Emergent GDS revealed a white plug on the treated varix, thus endoscopic cyanoacrylate (CA) injection therapy was performed. We speculated that the injection of EOI increased the pressure in the duodenal varices which resulted in rupture of duodenal varices. B-RTO was effective therapy to prevent duodenal variceal rebleeding, but postprocedural monitoring is required as illustrated by this case. We suggest that careful monitoring and backup system for endoscopy are required during or after B-RTO.