A precise and sustainable doxycycline-inducible cell line development platform for reliable mammalian cell engineering with gain-of-function mutations.

For mammalian synthetic biology research, multiple orthogonal and tunable gene expression systems have been developed, among which the tetracycline (Tet)-inducible system is a key tool for gain-of-function mutations. Precise and long-lasting regulation of genetic circuits is necessary for the effective use of these systems in genetically engineered stable cell lines. However, current cell line development strategies, which depend on either random or site-specific integration along with antibiotic selection, are unpredictable and unsustainable, limiting their widespread use. To overcome these issues, we aimed to establish a Robust Overexpression via Site-specific integration of Effector (ROSE) system, a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated streamlined Tet-On3G-inducible master cell line (MCL) development platform. ROSE MCLs equipped with a landing pad facilitated the transcriptional regulation of various effector genes via recombinase-mediated cassette exchange. Long-term investigation revealed that the modular design of genetic payloads and integration sites significantly affected the induction capacity and stability, with ROSE MCLs exhibiting exceptional induction performance. To demonstrate the versatility of our platform, we explored its efficiency for the precise regulation of selection stringency, manufacturing of therapeutic antibodies with tunable expression levels and timing, and transcription factor engineering. Overall, this study demonstrated the effectiveness and reliability of the ROSE platform, highlighting its potential for various biological and biotechnological applications.

External validation of subclassification system and progression pattern analysis in hepatocelluar carcinoma with macroscopic vascular invasion.

BACKGROUND AND PURPOSE: The present study aimed to validate the performance of a previously proposed subclassification model to predict prognosis after combined transarterial chemoembolization (TACE) and external beam radiotherapy (RT) for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) in an independent cohort that received the same first-line treatment for the patients with the similar disease extent characteristics, and analyzed the progression patterns as well as progression-free survival (PFS). MATERIALS AND METHODS: This study was conducted using prospectively collected data from the XXXXX HCC registry for newly diagnosed, previously untreated HCC between 2005 and 2018. Finally, 417 patients who satisfied the eligibility criteria were included and analyzed. RESULTS: The median PFS and overall survival (OS) were 5.2 and 13.9 months, respectively. Similar to a previous study, subclassification of patients into very low-, low-, intermediate-, and high-risk groups showed a median OS of 98.4, 18.3, 9.7, and 5.8 months, respectively (P < 0.001). Additionally, subclassification of patients into the very low-, low-, intermediate-, and high-risk groups showed median PFS of 18.7, 6.7, 3.3, and 2.3 months, respectively (p < 0.001). Overall, intrahepatic progression was the most common pattern of progression; however, extrahepatic progression was more common in the intermediate- and high-risk groups. CONCLUSION: The previously proposed subclassification model was successfully validated in an independent cohort. Treatment modification should be considered in the intermediate- and high-risk patient groups because of their frequent extrahepatic as well as intrahepatic progressions after combined TACE and RT.

Factors Contributing to Successful Transvenous Retrograde Thoracic Duct Cannulation.

PURPOSE: To identify key factors for successful transvenous retrograde cannulation (TVRC) of the thoracic duct. MATERIALS AND METHODS: A total of 47 consecutive patients (62.1 ± 13.2 years; 32 men) who underwent attempted TVRC between July 2016 and July 2021 were included. Reasons for interventions were chylous leakage from the chest (n = 36), abdomen (n = 6), and other sites (n = 5). Patient age, sex, access vein (femoral vs brachial), anatomic classification (presence of dominant channel vs plexiform) of the terminal thoracic duct, and engagement of a diagnostic catheter into the jugulovenous junction were included in the analyses. Anatomic details were evaluated according to catheter-based high-pressure lymphangiography and conventional intranodal lymphangiography. The Firth bias-reduced penalized-likelihood logistic regression model was used to analyze prognostic factors. RESULTS: TVRC was successful in 33 of the 47 patients (70%). In univariate analysis, femoral access, diagnostic catheter engagement, and presence of dominant channel were significant positive prognostic factors (P <.05). In multivariate analysis, diagnostic catheter engagement and presence of dominant channel were significant prognostic factors (P <.05). Diagnostic catheter engagement showed the highest prognostic performance (accuracy = 0.872), followed by presence of a dominant channel. High-pressure catheter-based lymphangiographic findings showed better performance (accuracy, 0.844 vs 0.727) than intranodal lymphangiography to delineate the anatomy of the terminal thoracic duct. CONCLUSIONS: A secure selection of the jugulovenous junction and the presence of a dominant channel in the terminal portion of the thoracic duct were significant prognostic factors for successful TVRC.

Risk factors for stent occlusion after catheter-directed thrombolysis and iliac vein stenting in the treatment of May-Thurner syndrome with iliofemoral deep vein thrombosis: a retrospective cohort study.

Background: This study aimed to identify the risk factors for stent occlusion in patients with iliofemoral deep vein thrombosis (DVT) secondary to May-Thurner syndrome (MTS) who underwent catheter-directed thrombolysis (CDT) and iliac vein stenting. Methods: A retrospective analysis was performed on 44 patients who underwent CDT and iliac vein stenting for MTS with iliofemoral DVT between October 2001 and March 2018. MTS was diagnosed based on extrinsic compression of the left common iliac vein (CIV) by the overlying right common iliac artery (CIA) on computed tomography (CT). Clinical records of the study population were reviewed to collect baseline data, procedural characteristics, and outcomes. Final venograms showing diffuse and irregular wall thickening in the iliofemoral vein were considered to indicate a chronic post-thrombotic lesion. The stent position was categorized as follows: confluence coverage without touching the contralateral inferior vena cava (IVC) wall, IVC extension contacting the contralateral IVC wall, or distal to the iliocaval junction. Stent patency was assessed using duplex ultrasonography. Risk factors for stent occlusion were assessed using univariate and multivariate Cox proportional hazard models. Results: The median duplex ultrasound follow-up period was 25 months (range, 1-196 months). The overall cumulative patency rate at 12 months was 70.0%. In the univariate Cox regression, factors significantly associated with stent occlusion included symptom duration >2 weeks before CDT, partial thrombolysis (50-99% of thrombus removal), chronic post-thrombotic lesions, and stent position. Multivariate Cox regression showed that chronic post-thrombotic lesions [hazard ratio (HR) =7.15; 95% confidence interval (CI): 1.32-38.81; P=0.023] and a stent distal to the iliocaval junction (HR =5.59; 95% CI: 1.46-21.38; P=0.012) were significantly associated with stent occlusion. Conclusions: Chronic post-thrombotic lesion and a stent distal to the iliocaval junction were important risk factors for stent occlusion in patients who underwent CDT and iliac vein stenting.

Guidewire-catheter induced hydrodissection to assist radiofrequency ablation for subcapsular hepatocellular carcinoma with iodized oil retention in patients with failed artificial ascites due to perihepatic adhesion.

PURPOSE: We aimed to evaluate the usefulness of guidewire-catheter induced hydrodissection (GIH) to assist radiofrequency ablation (RFA) for subcapsular hepatocellular carcinoma (HCC) with iodized oil retention in patients with failed artificial ascites due to perihepatic adhesion. METHODS: This retrospective study included 17 patients with small subcapsular HCC ineligible for ultrasonography-guided RFA who received RFA under guidance of fluoroscopy and cone-beam computed tomography immediately after iodized oil transarterial chemoembolization (TACE) between April 2011 and January 2016. In the study patients, creation of artificial ascites to protect the perihepatic structures failed due to perihepatic adhesion and GIH was attempted to separate the perihepatic structures from the ablation zone. The technical success rate of GIH, technique efficacy of RFA with GIH, local tumor progression (LTP), peritoneal seeding, and complications were evaluated. RESULTS: The technical success rate of GIH was 88.24% (15 of 17 patients). Technique efficacy was achieved in all 15 patients receiving RFA with GIH. During an average follow-up period of 48.1 months, LTP developed in three patients. Cumulative LTP rates at 1, 2, 3, and 5 years were 13.3%, 20.6%, 20.6%, and 20.6%, respectively. No patient had peritoneal seeding. Two of the 15 patients receiving RFA with GIH had a CIRSE grade 3 liver abscess, but none had complications associated with thermal injury to the diaphragm or abdominal wall near the ablation zone. CONCLUSION: GIH can be a useful method to assist RFA for subcapsular HCC with iodized oil retention in patients with failed artificial ascites due to perihepatic adhesion.

Long term clinical outcomes of portal vein stenting for symptomatic portal vein stenosis after pancreaticoduodenectomy.

ABSTRACT: Gastrointestinal bleeding caused by portal vein (PV) stenosis is serious complication after pancreaticoduodenectomy (PD) The purpose of this study is to reveal the long-term clinical outcomes of PV stenting for symptomatic PV stenosis and risk factors of stent related complication.Fifteen patients who underwent portal vein stenting for symptomatic PV stenosis after PD between 2000 and 2018 were retrospectively reviewed. The whole cohort was divided into 9 patients with benign stenosis group (Group-B) and 6 patients with recurrence group (Group-R).The median follow up period was 17.0 (interquartile range 12.0-38.0) months. The technical success rate and clinical success rate was revealed at 93.3% and 86.7%. The primary patency rate of stents was 79.4% and mean patency period was 14.0 (4.0-28.0) months. There was significant difference in time to stenosis and proportion of anticoagulation treatment between 2 groups [2.0 (1.0-4.0) months vs 18.5 (2.5-50.3) months, P  = .035 and 100% vs 50%, P  = .044. In univariable analysis, stent diameter was found to have a significant correlation with stent occlusion (P  = .036).PV stenting was found to be feasible and safe in the treatment of symptomatic PV stenosis from a long term point of view.

Combined transarterial chemoembolization and radiofrequency ablation for subphrenic versus nonsubphrenic hepatocellular carcinoma: a propensity score matched study.

PURPOSE: To compare therapeutic outcomes of combined transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) treatment for small hepatocellular carcinoma (HCC) in subphrenic versus nonsubphrenic locations by propensity score matching. METHODS: This retrospective study included 293 patients with single HCC (≤ 3 cm) ineligible for ultrasound-guided RFA who received iodized oil TACE and subsequent RFA between June 2010 and January 2017. The patients were divided into two groups according to the tumor location: subphrenic (n = 99) and nonsubphrenic (n = 194). Subphrenic HCC was defined as a tumor abutting the diaphragm. Local tumor progression (LTP) and overall survival (OS) rates were compared by propensity score matching. Procedure-related complications were also assessed. RESULTS: Matching yielded 93 matched pairs of patients. In the matched cohorts, cumulative 1-, 3-, and 5-year LTP rates were 5.4%, 12.1%, and 12.1% in the subphrenic group and 1.1%, 7.5%, and 8.6% in the nonsubphrenic group, respectively, with no significant differences (p = 0.278). Corresponding OS rates were 100%, 80.2%, and 71.3% in the subphrenic group and 97.9%, 88.1%, and 75.6% in the nonsubphrenic group, respectively, with no significant differences (p = 0.308). The subphrenic location was not a significant risk factor for LTP and OS in multivariate analysis. There were no significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The therapeutic outcomes of combined TACE and RFA for small subphrenic HCC were similar to those for nonsubphrenic HCC. The combination therapy seems to be an effective and safe method in treating small subphrenic HCC.

Controlling Ratios of Plasmid-Based Double Cut Donor and CRISPR/Cas9 Components to Enhance Targeted Integration of Transgenes in Chinese Hamster Ovary Cells.

Chinese hamster ovary (CHO) cells are the most valuable expression host for the commercial production of biotherapeutics. Recent trends in recombinant CHO cell-line development have focused on the site-specific integration of transgenes encoding recombinant proteins over random integration. However, the low efficiency of homology-directed repair upon transfection of Cas9, single-guide RNA (sgRNA), and the donor template has limited its feasibility. Previously, we demonstrated that a double-cut donor (DCD) system enables highly efficient CRISPR/Cas9-mediated targeted integration (TI) in CHO cells. Here, we describe several CRISPR/Cas9 vector systems based on DCD templates using a promoter trap-based TI monitoring cell line. Among them, a multi-component (MC) system consisting of an sgRNA/DCD vector and Cas9 expression vector showed an approximate 1.5-fold increase in knock-in (KI) efficiency compared to the previous DCD system, when a systematically optimized relative ratio of sgRNA/DCD and Cas9 vector was applied. Our optimization efforts revealed that concurrently increasing sgRNA and DCD components relative to Cas9 correlated positively with KI efficiency at a single KI site. Furthermore, we explored component bottlenecks, such as effects of sgRNA components and applicability of the MC system on simultaneous double KI. Taken together, we improved the DCD vector design by tailoring plasmid constructs and relative component ratios, and this system can be widely used in the TI strategy of transgenes, particularly in CHO cell line development and engineering.

Radiologic and clinical results of transarterial ethanol embolization for renal angiomyolipoma.

OBJECTIVE: We sought to determine the efficacy and safety of selective arterial embolization for renal angiomyolipoma (AML) using ethanol alone or ethanol with additional embolic materials and to analyze the factors influencing safety and efficacy. METHODS: One hundred nineteen AMLs treated with embolization were included retrospectively during a 15-year period. Technical, radiologic, and clinical success were recorded and risk factor analysis was performed. Complications on follow-up images, post-embolization syndrome (PES), major complications, and changes in renal function were also evaluated. RESULTS: Technical success was achieved in 106 of 119 tumors. Tumor size significantly decreased after treatment (reduction rate: 55%). Significant risk factors for tumor reduction included tumor enhancement on preprocedural CT and residual tumor staining. Radiologic success was achieved in 114 of 119 tumors (risk factor: residual tumor staining), and clinical success was achieved in 22 of 23 patients. Complications on follow-up images occurred in 40 of 119 tumors, and PES occurred in 53 of 104 patients. No major complications occurred. There were no cases of renal function impairment. CONCLUSION: Selective transarterial embolization using ethanol alone or ethanol with additional embolic materials reduced AML size, alleviated symptoms, and can be performed safely without permanent impairment. KEY POINTS: • Percutaneous transarterial ethanol embolization reduces AML size and alleviates symptoms. • Embolization can be performed safely without permanent impairment of renal function.

Percutaneous radiologic gastrostomy with single gastropexy: outcomes in 636 patients.

OBJECTIVES: This study aimed to assess the technical success and overall complication rate of percutaneous radiologic gastrostomy (PRG) with single gastropexy using a separate tract from that used for tube placement. METHODS: From January 2014 to December 2018, 636 patients (469 men, 167 women; mean age 66.8 years; age range, 22-98 years) underwent PRG using single gastropexy at a tertiary center. Preprocedural computed tomography (CT) was recommended if there were no data on the location of the stomach on previous CT. After a single anchor was applied, the PRG tube was inserted through a separate tract from that used for tube placement. The technical success rate and major and minor complications were retrospectively reviewed. The number of patients and percentages were used as descriptive statistics for evaluating the complication rate. RESULTS: The technical success rate of PRG with single gastropexy was 99.2% (631/636). There were 32 complications among the 631 procedures. There were 19 (3.0%) major complications, including peritonitis (n = 7), migration (n = 5), infection (n=4), malposition (n = 2), and bleeding (n = 1). There were 13 (2.1%) minor complications, including local infection (n = 11), malfunction (n = 1), and pneumoperitoneum (n = 1). The overall complication rate within 30 days of PRG placement was 4.1% (26/631). CONCLUSIONS: PRG with single gastropexy using a separate tract from that used for tube placement is technically feasible with a low complication rate. KEY POINTS: • Percutaneous radiologic gastrostomy with single gastropexy using a separate tract from that used for tube placement is technically feasible. • Complications including peritonitis and bleeding were comparatively low with the conventional technique.

Hydroxyurea selection for enhancement of homology-directed targeted integration of transgenes in CHO cells.

Site-specific integration via genome editing technologies has been implemented in Chinese hamster ovary (CHO) cells for predictable and efficient cell line development and engineering. Various strategies have been employed to enhance knock-in (KI) efficiency for precise homology-directed repair (HDR)-mediated targeted integration of transgenes in CHO cells. Given the cell cycle-dependent regulation of the DNA damage repair pathway, cell cycle synchronization to the HDR-favored S/G2 phase has been successfully utilized in mammalian cells, but the effect is limited in CHO cells. Here, we describe a cell cycle enrichment method to increase HDR-mediated KI efficiency in CHO cells. Existing G1 cell cycle synchronization methods showed transient cell cycle arrest and did not improve KI efficiency. Rather than cell cycle arrest with a high concentration of chemicals followed by a release step, cells were incubated in the presence of a lower concentration of hydroxyurea (HU) to enrich cells in the S phase. HU selection allowed for robust S phase enrichment of CHO cells by up to 70 % and maintained cell viability. This short-term selection resulted in improved KI efficiency by 1.2-1.5 fold compared with cells in the control condition. Overall, this approach serves as a simple and effective strategy for enhancement of site-specific genome engineering in CHO cells.

Combined therapy with bronchial artery embolization and tranexamic acid for hemoptysis.

BACKGROUND: While most previous studies have viewed tranexamic acid as a bridging or temporary therapy, our preliminary study offers insights into the combined therapy of antifibrinolytic agent with endovascular treatment for hemoptysis. PURPOSE: To investigate the feasibility and safety of combined therapy, to analyze factors affecting the outcomes of combined therapy, and to compare the effectiveness of combined therapy between groups with different etiologies. MATERIAL AND METHODS: Between January 2011 and December 2014, 64 patients (33 men, mean age 64.6 years) underwent combined therapy for hemoptysis. The median follow-up time was 14.7 months (range 174-2435 days). Patients were divided into a tuberculosis group (GroupTB, n=37) and a non-tuberculosis group (Groupnon-TB, n=27). RESULTS: Embolotherapy was technically successful in 62/64 (96.9%) cases. The immediate clinical success rate was 96.8% (60/62). The short-term and long-term recurrence rates were 12.9% (n=8) and 19.4% (n=12), respectively. The one-, two-, and four-year recurrence-free survival rates were 61%, 49%, and 32%, respectively. There was no significant survival difference between the two groups. Suboptimal embolization was a significant risk factor for immediate clinical failure (odds ratio 29.624, P = 0.023). Optimal embolization (hazard ratio [HR] 0.199, P = 0.023) and older age (HR 0.956, P = 0.013) were significantly associated with lower recurrence risk. CONCLUSION: Combined therapy is an effective and safe treatment modality for hemoptysis of various etiologies, with potential benefits for short-term recurrence vis-a-vis current literature evidence. Suboptimal embolization was the most important modifiable risk factor for treatment failure and recurrence after combined therapy.

Therapeutic outcomes of embolotherapy of extremity bone intraosseous arteriovenous malformation with ethanol, coils, and n-butyl cyanoacrylate.

OBJECTIVE: We evaluated the therapeutic outcomes of embolotherapy for bone arteriovenous malformations (AVMs) affecting the extremities using ethanol, coils, and n-butyl cyanoacrylate (NBCA). METHODS: We reviewed the data from 36 patients (18 males, 18 females; mean age 25 years; age range, 1-64 years) with bone AVMs affecting their extremities who had undergone embolotherapy using ethanol, coils, and NBCA from December 1996 to July 2019. Of the 36 patients, 19 had had pure bone AVMs and 17 mixed bone and soft tissue (MBS) AVMs. Embolotherapy was performed using direct puncture or a transvenous or an intra-arterial approach (range, 1-18 procedures; mean, 5 procedures). During the 178 embolotherapy procedures, ethanol was used in all 36 patients, except for 1. Coils were used in 14 patients, and NBCA and a lipiodol mixture in 9 patients. The therapeutic outcomes were evaluated by the clinical symptom response and the degree of devascularization on follow-up angiography or computed tomography. The major and minor complications were also evaluated. RESULTS: The clinical success (cure or markedly improvement) rate of embolotherapy for pure bone AVMs was significantly better than that for the MBS AVMs (88% vs 18%; P < .001). The complete devascularization rate of the bone AVM component of the MBS AVMs was 71%; however, the cure rate of the MBS AVMs was 0% owing to the remaining soft tissue AVMs. Of the 36 patients, 12 experienced complications, including 11 minor (2 skin bullae formation and 10 transient peripheral nerve injury) and 1 major (longstanding nerve palsy). CONCLUSIONS: Embolotherapy for bone AVMs affecting the extremities using ethanol, coils, and an NBCA mixture is effective and safe for the resolution or improvement of symptoms, especially in those with pure bone AVMs.

Comprehensive Analysis of Genomic Safe Harbors as Target Sites for Stable Expression of the Heterologous Gene in HEK293 Cells.

Human cell lines are being increasingly used as host cells to produce therapeutic glycoproteins, due to their human glycosylation machinery. In an attempt to develop a platform for generating isogenic human cell lines producing therapeutic proteins based on targeted integration, three well-known human genomic safe harbors (GSHs)-AAVS1, CCR5, and human ROSA26 loci-were evaluated with respect to the transgene expression level and stability in human embryonic kidney (HEK293) cells. Among the three GSHs, the AAVS1 locus showed the highest eGFP expression with the highest homogeneity. Transgene expression at the AAVS1 locus was sustained without selection for approximately 3 months. Furthermore, the CMV promoter showed the highest expression, followed by the EF1α, SV40, and TK promoters at the AAVS1 locus. Master cell lines were created using CRISPR/Cas9-mediated integration of the landing pad into the AAVS1 locus and were used for faster generation of recombinant cell lines that produce therapeutic proteins with recombinase-mediated cassette exchange.

Optimized CRISPR/Cas9 strategy for homology-directed multiple targeted integration of transgenes in CHO cells.

Site-specific integration has emerged as a promising strategy for precise Chinese hamster ovary (CHO) cell line engineering and predictable cell line development (CLD). CRISPR/Cas9 with the homology-directed repair (HDR) pathway enables precise integration of transgenes into target genomic sites. However, inherent recalcitrance to HDR-mediated targeted integration (TI) of transgenes results in low targeting efficiency, thus requiring a selection process to find a targeted integrant in CHO cells. Here, we explored several parameters that influence the targeting efficiency using a promoter-trap-based single- or double-knock-in (KI) monitoring system. A simple change in the donor template design by the addition of single-guide RNA recognition sequences strongly increased KI efficiency (2.9-36.0 fold), depending on integration sites and cell culture mode, compared to conventional circular donor plasmids. Furthermore, sequential and simultaneous KI strategies enabled us to obtain populations with ~1-4% of double-KI cells without additional enrichment procedures. Thus, this simple optimized strategy not only allows efficient CRISPR/Cas9-mediated TI in CHO cells but also paves the way for the applicability of multiplexed KIs in one experimental step without the need for sequential and independent CHO-CLD procedures.

Selective Versus Non-selective Transarterial Chemoembolization via the Intercostal Artery for the Treatment of Hepatocellular Carcinoma.

PURPOSE: To report the 1-month tumor response and safety of selective transarterial chemoembolization (TACE) via the intercostal artery (ICA) for the treatment of hepatocellular carcinoma (HCC) in comparison with those of non-selective TACE. METHODS: This retrospective study included 79 HCC patients who underwent TACE via the ICA selectively (selective TACE group; n = 26) or non-selectively (non-selective TACE group; n = 53) between January 2001 and December 2016. Selective TACE was defined when TACE was performed with selective catheterization of the tumor feeding branch of the ICA. TACE performed without selective catheterization of the tumor feeding branch was defined as non-selective TACE. One-month target and overall tumor responses and complications of the two groups were compared. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Selective TACE group showed better 1-month target and overall tumor responses and lower frequency of complications than non-selective TACE group (P = .007, P = .018, and P < .001, respectively). Performing selective TACE was the only significant favorable factor for better target and overall tumor responses (P = .001 and P = .028, respectively). In univariate analysis for complications, serum α-fetoprotein > 200 ng/mL and non-selective TACE were statistically significant. However, multivariate analysis showed that performing non-selective TACE was the only significant risk factor (odds ratio 13.56; 95% confidence interval 3.51-52.5; P < .001). CONCLUSION: Compared to non-selective TACE via the ICA, selective TACE via the ICA for the treatment of HCC can achieve better tumor response and safety.

Subclassification and Treatment Results of Ethanol Embolotherapy of Type II Arteriovenous Malformations of the Extremity and Body.

PURPOSE: To evaluate the safety and efficacy of ethanol and coil embolization of type II arteriovenous malformation (AVM) according to a new subtype classification. MATERIALS AND METHODS: Eighty-four type II AVMs in the body or extremity of 79 patients who underwent AVM treatment from 1996 to 2017 were retrospectively subclassified according to the angiographic morphology of the draining vein as type IIa (arterioles shunt to focal segment of single draining vein), type IIb (arterioles shunt to venous sac with multiple draining veins), and type IIc (arterioles shunt along long segment of draining vein). Coil and ethanol embolization of the focal or long segment of the draining vein or the venous sac was performed with direct puncture or transvenous approach according to subtype. Treatment outcomes, number of treatment sessions, and complications were analyzed. RESULTS: AVM cure (ie, complete embolization) rates were 95%, 76%, and 65% in types IIa, IIb, and IIc AVMs, respectively. The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs (P = .015). Median numbers of treatment sessions were 1 in types IIa and IIb AVMs and 2.5 in type IIc AVMs, with a significant difference between type IIc and the other 2 types (P < .05). Minor complications occurred in 20% of patents and major complications occurred in 7%. CONCLUSIONS: The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs, which also required significantly more treatment sessions than the other 2 types.

Long-term clinical outcomes after endovascular management of ruptured pseudoaneurysm in patients undergoing pancreaticoduodenectomy.

PURPOSE: Recent studies have analyzed the short-term clinical outcomes of ndovascular management. However, the long-term outcomes are unknown. This study aimed to investigate clinical outcomes after endovascular management for ruptured pseudoaneurysm in patients after pancreaticoduodenectomy (PD). METHODS: The medical records of 2,783 patients who underwent PD were retrospectively reviewed at a single center. Of 62 patients who received intervention after pseudonaeurysm rupture, 57 patients (91.9%) experienced eventual success of hemostasis. The patients were composed as follows: (embolization only [EMB], n = 30), (stent-graft placement only [STENT], n = 19) and (both embolization and stent-graft placement simultaneously or different times [EMB + STENT], n = 8). Long-term complications were defined as events that occur more than 30 days after the last successful endovascular treatment. RESULTS: Among 57 patients, short-term stent-graft related complications developed in 3 patients (5.3%) and clinical complication developed in 18 patients (31.5%). Nine (15.8%) had long-term stent-graft related complications, which involved partial thrombosis in 5 cases, occlusion in 3 cases and migration in 1 case. Except for 1 death, the remaining 8 cases did not experience clinical complications. The stent graft primary patency rate was 88.9% after 1 month, 84.2% after 1 year, and 63.2% after 2 years. Of 57 patients, 30 days mortality occurred in 8 patients (14.0%). CONCLUSION: After recovery from initial complication, most of patients did not experience fatal clinical complication during long-term follow-up. Endovascular management is an effective and safe management of pseudoaneurysm rupture after PD in terms of long-term safety.

Endovascular treatment results and risk factors for complications of body and extremity arteriovenous malformations.

OBJECTIVE: The objective of this study was to investigate the factors associated with the complication rate and treatment outcomes of arteriovenous malformations (AVMs) during a 20-year period. METHODS: This was a retrospective study of 306 patients (135 men, 171 women; mean age, 30.8 years) with body and extremity AVMs who were treated between 1996 and 2017. A total of 913 sessions of endovascular treatment were performed. Patients were divided into two decades of the study period to compare complications and clinical results. Group 1 comprised 107 patients treated in the first decade of the study period, and group 2 comprised 199 patients treated in the last decade. AVMs were classified according to the angiographic findings. Complication rates, number of treatment sessions, and treatment results were compared between the two groups. RESULTS: Minor complication (group 1, 20.1%; group 2, 18.5%) and major complication (group 1, 3.1%; group 2, 4.1%) rates were similar between groups (P = .79). The mean number of treatment sessions in group 1 and group 2 was 4.2 and 2.3, respectively, indicating a 45% reduction in treatment sessions (P < .0001). The treatment failure rate decreased from 9.3% in group 1 to 1.5% in group 2 (P = .04). The clinical success rate was 54.2% in group 1 and 64.3% in group 2 (P = .10). CONCLUSIONS: With an accumulation of AVM treatment experience, the number of treatment sessions and the rate of treatment failures were significantly reduced.

Combination therapy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma: comparison with TACE or RFA monotherapy.

PURPOSE: To compare the safety and efficacy of combined transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) with those of TACE or RFA monotherapy. METHODS: This study included 34 combined TACE and RFA (TACE-RFA), 87 TACE, and 136 ultrasound-guided RFA, which were performed to treat HCC (≤ 3 cm, 3 or fewer) between March and August 2009. The safety (Child-Pugh score indicating hepatic functional reserve, patient discomfort requiring medication, duration of hospitalization, and complications) and efficacy (1-month, 6-month, and 1-year tumor responses) profiles of each treatment were evaluated and compared. RESULTS: TACE-RFA group showed longer hospital stay and more frequent patient discomfort requiring medication than TACE or RFA group (P < 0.001). The frequency of overall complications after TACE-RFA was higher than TACE (P = 0.006) or RFA (P = 0.009). There were no statistical differences in major complication rates between the three groups (P = 0.094). Child-Pugh score at 1-month follow-up showed no significant difference between the three groups (P = 0.162). 1-month, 6-month, and 1-year tumor responses of TACE-RFA were similar to those of RFA and better than those of TACE. CONCLUSIONS: TACE-RFA appears to result in more frequent patient discomfort requiring medication, longer hospital stay, and more frequent complications than TACE or RFA monotherapy. Tumor response of TACE-RFA seems to be similar to that of RFA and better than TACE monotherapy. Thus, TACE-RFA for treating small HCC may be required for the selected patients, especially patients with small HCC ineligible for RFA monotherapy.