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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. 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. 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). 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.

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.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.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 duration2 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.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.

Background The rationale behind left renal vein division (LRVD) is the assumption that adequate collateral draining channels will develop. Purpose To describe computed tomography (CT) findings after LRVD during aortic surgery. Material and Methods Among 61 consecutive patients who underwent LRVD during aneurysm repair or revascularization for aortic occlusive disease between January 2003 and December 2017, 51 patients (40 men, mean age 71.4 ± 8.4 years) were enrolled. Contrast-enhanced CT images were analyzed to evaluate collateral drainage, patency, left renal vein diameter, and left renal parenchymal thickness. A total of 115 radiologic reports were reviewed to check whether these findings were accurately mentioned. Results The median time period of the first postoperative follow-up CT was 36 days (range 7–1351 days). The gonadal vein (n = 47) was the most common collateral draining channel, followed by the retroperitoneal veins (n = 42) and adrenal vein (n = 33). Thrombosis occurred in five patients between postoperative days 7 and 17 in the remnant renal vein (n = 3), remnant renal vein plus gonadal and adrenal veins (n = 1), and gonadal vein (n = 1). There was a significant decrease in renal vein diameter (–0.48 ± 2.12 mm, P = 0.006). There was no significant difference in parenchymal thickness (−0.25 ± 1.27 mm, P = 0.193). Neither LRVD nor any associated findings were correctly stated on radiologic reports. Conclusion Postoperative contrast-enhanced CT can delineate collateral draining channels and complications following LRVD. However, these findings tend to be either missed or misinterpreted.

Background Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear. Patients and methods This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) for the BM cohort and overall survival (OS) (H1 = 5 months) for the LM cohort. Results The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0–16.6]; the median OS was 16.9 months [95% CI 7.9–not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1–NR); the median PFS was 8.0 months (95% CI 7.2–NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1–2. Conclusion Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs.

Background Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear. Patients and methods We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy. Detailed clinical characteristics were collected on these patients. We designed a new method to estimate human leukocyte antigen (HLA)-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of HLA from conventional TMB. We carried out external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients. Results Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS; P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR: 20% versus 59%, P = 0.0363; PFS: hazard ratio = 2.91, P = 0.007; OS: hazard ratio = 3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved. Conclusion HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies.

Seven consecutive female patients with pathologically confirmed arteriovenous malformation (AVM) with intravenous leiomyomatosis (IVL) of the uterus (age range, 32-61 years; mean age, 43 years) treated between 2005 and 2021 from a single institution were reviewed. Computed tomography (CT) findings of congenital pelvic AVM of 10 female patients were compared with those of AVM with IVL. Characteristic CT findings of AVM with IVL revealed a focal soft tissue mass inside a dilated venous structure of the AVM. Multiple sessions of transvenous coil embolization of the AVM with or without the injection of ethanol were performed. After complete (6/7, 86%) or partial (1/7, 14%) embolization of the AVM, complete surgical resection of the IVL and embolized AVM mass was performed in 4 patients. Patients with lung metastasis or residual embolized AVM masses are under follow-up with antiestrogen hormonal therapy.

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.

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.

This study used independent, real-world, patient-level data to examine whether the dosage or frequency of paclitaxel exposure correlated with mortality during follow up. We conducted a retrospective analysis of patients treated with a drug-coated balloon (DCB) for an atherosclerotic femoropopliteal lesion from February 2013 to December 2018, excluding patients with non-atherosclerotic lesions or restenosis after DCB treatment in another hospital. We investigated the causes of death, comorbidities (including cancer status), and the initial and total cumulative dosages and frequency of paclitaxel use. To determine whether the dosage or frequency of paclitaxel exposure affected mortality during follow up, we analyzed the risk factors for all-cause death by conducting a time-dependent Cox regression analysis that considered demographics, comorbidities, lesion and procedural characteristics, and paclitaxel exposure data (dosage and frequency). Our analysis examined 225 patients (mean age 71 ± 9 years, range 38–93 years, male 81%). During a mean follow-up duration of 35 months (range 1–89 months), 56 patients (24.9%) died from cardiac disorders (16%, including acute myocardial infarction, heart failure, or sudden cardiac arrest), malignancy (14.3%), respiratory failure with pneumonia (12.5%), septic shock (12.5%), or another cause. Univariable and multivariable Cox regression analyses identified age (hazard ratio, HR, 1.057, 95% confidence interval, CI, 1019–1096, p = 0.0032), critical limb ischemia (CLI) (HR, 4135, 95% CI, 2171–7876, p &lt, 0.0001), and the total dosage of paclitaxel (mg) (HR, 1.040, 95% CI, 1006–1074, p = 0.0210) as predictors of mortality during follow up. The subgroup analysis found that the total dosage of paclitaxel (mg) was also a predictor of mortality during follow up in the CLI group (HR, 1.046, 95% CI, 1007–1087, p = 0.0198). The estimated cut-off value of total cumulative paclitaxel dosage for predicting mortality was 12 mg as evaluated by minimum p value approach. This patient-level analysis identified the total cumulative dosage of paclitaxel as a predictor of mortality after the use of paclitaxel-coated balloons. Our results provide limited information about the potential dose–response relationship underlying paclitaxel-associated mortality concerns.

Background : Previous randomized controlled trials of revascularization for atherosclerotic renal artery stenosis (ARAS) were not successful. We investigated the effects of percutaneous transluminal angioplasty with stent insertion (PTA/S) on kidney function and blood pressure (BP) control in patients with ARAS. Methods : From 2000 to 2017, 47 subjects who underwent PTA/S for ARAS were identified. A high-risk group was defined, composed of patients having one or more of the following clinical presentations: pulmonary edema, refractory hypertension, and rapid deterioration of kidney function. Subjects who met the criteria of ‘kidney function improvement’ or ‘hypertension improvement’ after PTA/S were classified as responders. Results : Twenty-one (44.7%) subjects were classified into the high-risk group. Two subjects (8.0%) in the low-risk group (n = 25) and 5 subjects (27.8%) in the high-risk group (n = 18) showed improvement in kidney function after PTA/S (P = 0.110). In patients with rapid decline of kidney function, estimated glomerular filtration rate improved from 28 (interquartile range [IQR], 10-45) mL/min/1.73 m2 to 41 (IQR, 16-67) mL/min/1.73 m2 at 4 months after PTA/S, although the difference was not significant (P = 0.084). Regarding BP control, 9 (36.0%) and 14 (77.8%) subjects showed improvement after PTA/S in the low- (n = 25) and high-risk (n = 18) groups, respectively (P = 0.007). In patients with refractory hypertension, the systolic BP dropped from 157 (IQR, 150-164) mmHg to 140 (IQR, 131-148) mmHg at 4 months after PTA/S (P = 0.005). Twenty-five subjects were defined as responders and comprised a significant proportion of the high-risk group (P = 0.004). Conclusion : PTA/S might improve BP control and kidney function in patients with ARAS presenting with high-risk clinical features. The optimal application of PTA/S should be based on individual assessment of the clinical significance of renal artery stenosis.

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.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.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).With an accumulation of AVM treatment experience, the number of treatment sessions and the rate of treatment failures were significantly reduced.

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.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.

Introduction A combination of portal vein embolization (PVE) and preoperative biliary drainage (PBD) in hilar cholangiocarcinoma (CCC) increase the resectability and help to reduce postoperative complications. To date, there is no study on the optimal timing of PVE after PBD in hilar cholangiocarcinoma. The purpose of this study is to identify the optimal timing of PVE after PBD in patients undergoing liver resection for hilar CCC. Methods We retrospectively reviewed 64 patients who underwent combined treatment PBD and PVE followed by liver resection for hilar CCC between January 2005 and December 2018 at Samsung Medical Center. The patients were classified into 3 groups: PBD-PVE interval (≤ 7 days)-Group1, PBD-PVE interval (8-14 days)-Group 2 and PBD-PVE interval (>14 days)-Group 3. The primary end points were 90 days mortality and posthepatectomy liver failure (PHLF). Results There was no significant difference in primary end points between three groups. The PBD-PVE interval showed a marginally significant relationship with Clavien-Dindo grade ≥ 3 complication (p = 0.053) and wound infection (p = 0.099). In univariable analysis, risk factors for PHLF were PTBD (p = 0.050), Bismuth type IIIb or IV (p = 0.023) and ERH or right trisectionectomy (p = 0.045). In multivariable analysis, independent risk factors for PHLF was Bismuth type IIIb or IV (HR 4.782, 95% CI 1.365-16.759; p = 0.014). Conclusions Considering that the PBD-PVE interval did not affect PHLF, and the surgical complication increases as the interval increases, it is more beneficial for the patient to performing PVE as early as possible after PBD. This will help to perform the operation faster.

Rubinstein–Taybi syndrome (RSTS) is a human genetic disorder characterized by distinctive craniofacial features, broad thumbs and halluces, and intellectual disability. Mutations in the CREB binding protein (CREBBP) and E1A binding protein p300 (EP300) are the known causes of RSTS disease. EP300 regulates transcription via chromatin remodeling and plays an important role in cell proliferation and differentiation. Plasminogen activator, urokinase (PLAU) encodes a serine protease that converts plasminogen to plasmin and is involved in several biological processes such as the proteolysis of extracellular matrix-remodeling proteins and the promotion of vascular permeability and angiogenesis. Recently, we discovered a patient who presented with RSTS-related skeletal anomaly and peripheral arterial vasculopathy. To investigate the genetic cause of the disease, we performed trio whole genome sequencing of the genomic DNA from the proband and the proband’s parents. We identified two de novo variants coined c.1760T>G (p.Leu587Arg) and c.664G>A (p.Ala222Thr) in EP300 and PLAU, respectively. Furthermore, functional loss of EP300a and PLAUb in zebrafish synergistically affected the intersegmental vessel formation and resulted in the vascular occlusion phenotype. Therefore, we hypothesize that the de novo EP300 variant may have caused RSTS, while both the identified EP300 and PLAU variants may have contributed to the patient’s vascular phenotype.

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. 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. 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. 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. • Percutaneous transarterial ethanol embolization reduces AML size and alleviates symptoms. • Embolization can be performed safely without permanent impairment of renal function.

Arteriovenous malformations (AVMs) are direct communications between primitive reticular networks of dysplastic vessels that have failed to mature into capillary vessels. Based on angiographic findings, peripheral AVMs can be classified into six types: type I, type IIa, type IIb, type IIc, type IIIa, and type IIIb. Treatment strategies vary with the types. Type I is treated by embolizing the fistula between the artery and the vein with coils. Type II (IIa, IIb, and IIc) AVM is treated as follows: first, reduce the blood flow velocity in the venous segment of the AVM with coils; second, perform ethanol embolotherapy of the residual shunts. Type IIIa is treated by transarterial catheterization of the feeding arteries and injection of diluted ethanol. Type IIIb is treated by transarterial or direct puncture approaches. A high concentration of ethanol is injected through the transarterial catheter or direct puncture needle. When the fistula is large, coil insertion is required to reduce the amount of ethanol. Type I and type II AVMs showed the best clinical results; type IIIb showed a satisfactory response rate. However, type IIIa showed the poorest response rate, either alone or in combination with other types. Clinical success can be achieved by using different treatment strategies for different angiographic AVM types.

BackgroundWhile 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.PurposeTo 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 MethodsBetween 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).ResultsEmbolotherapy 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.ConclusionCombined 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.

Objective To identify predictors of post-thrombotic syndrome in patients with iliofemoral deep venous thrombosis who underwent catheter-directed thrombolysis. Methods Fifty-two consecutive patients who underwent catheter-directed thrombolysis were included in this retrospective study. In addition to catheter-directed thrombolysis, aspiration thrombectomy or stent placement was performed if needed. At six months, duplex ultrasound was performed to assess iliofemoral patency and deep venous reflux. Post-thrombotic syndrome was assessed using the clinical, etiologic, anatomic, and pathophysiologic classification (post-thrombotic syndrome present ≥3 on a scale from 0 to 6). Univariate analysis and multivariate logistic regression were used to identify predictors of post-thrombotic syndrome. Results Median follow-up was 52 months and post-thrombotic syndrome developed in nine patients (17.3%). In univariate analysis, stent placement (odds ratio 0.16, p = 0.022) was negatively associated with post-thrombotic syndrome, whereas iliofemoral venous obstruction with reflux at six months (OR 6.08, p = 0.037) was positively associated with post-thrombotic syndrome. Multivariate analysis indicated that stent placement was associated with reduced risk of post-thrombotic syndrome (OR 0.17, p = 0.043), and iliofemoral obstruction with reflux was associated with increased risk (OR 6.67, p = 0.046). Conclusion Stent placement and iliofemoral venous obstruction with reflux, respectively, were important protective and risk factors for post-thrombotic syndrome in patients who underwent catheter-directed thrombolysis.

We evaluated the therapeutic outcomes of embolotherapy for bone arteriovenous malformations (AVMs) affecting the extremities using ethanol, coils, and n-butyl cyanoacrylate (NBCA).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.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).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.

The purpose of the study is to report the efficacy and safety of combined transarterial chemoembolization (TACE) of the right inferior phrenic artery (IPA) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) near the diaphragm supplied by the right IPA.From July 2009 through April 2015, 11 patients with small (≤ 3 cm) HCC near the diaphragm, which was infeasible for ultrasound-guided RFA and supplied by the right IPA, received TACE of the right IPA and subsequent RFA in one session. The safety and therapeutic efficacy, including technique effectiveness and local tumor progression (LTP), were evaluated.Technique effectiveness was achieved in all the 11 patients (100%). During average follow-up period of 39.2 months (range 13-89 months), LTP occurred in none of the 11 patients. There were twelve minor complications in eight patients, including right shoulder pain (n = 4), right pleural effusion (n = 2), diaphragmatic thickening (n = 2), transient lung change (n = 2), subsegmental intrahepatic bile duct stricture (n = 1), and subsegmental hepatic infarction (n = 1). No major complications were encountered CONCLUSION: Combined TACE of the right IPA and RFA can be a safe and effective treatment for small HCC near the diaphragm that is supplied by the right IPA.

Intraosseous arteriovenous malformations (AVMs) have been associated with distortion, hypertrophy, osteolytic skeletal changes, bleeding, leg length discrepancy, and pathologic fracture. Computed tomography or magnetic resonance imaging is helpful in the evaluation of the extent and depth of intraosseous AVMs and associated soft-tissue AVMs. Treatment approaches can differ, depending on the angiographic classification. Embolotherapy with ethanol, coils, or n-butyl cyanoacrylate is the primary treatment for symptomatic intraosseous AVMs, and the goal of treatment is symptom improvement with few complications.

Purpose: Femorofemoral crossover bypass (FCB) is a good procedure for patients with unilateral iliac artery disease. There are many articles about the results of FCB, but most of them were limited to 5 years follow-up. The purpose of our study was to analysis the results of FCB with a 10-year follow-up period. Materials and Methods: Between January 1995 and December 2010, 133 patients were operated in Samsung Medical Center (median follow-up: 58.8 months). We retrospectively analysed patient characteristics, the preoperative treatment, the operative procedure, and material used. Results: The indications for FCB were claudication in 110 and critical limb ischemia in 23 patients. Three patients were died due to myocardiac infarction, intracranial hemorrhage, and acute respiratory failure within 30 days after surgery. The one-year primary and secondary patency rates were 89% and 97%, the 5-year primary and secondary patency rates were 70% and 85%, and the 10-year primary and secondary patency rates were 31% and 67%. The 5-year and 10-year limb salvage rates were 97% and 95%, respectively. Conclusion: Our long term analysis suggests that FCB might be a valuable alternative treatment modality in patients with unilateral iliac artery disease.

Management of arteriovenous malformations (AVMs) remains challenging because of their unpredictable course and high morbidity rate. In this case report, we present a patient with a huge AVM on the right calf who suffered complications of compartment syndrome, rhabdomyolysis, skin necrosis, and nerve damage after sclerotherapy. Limb salvage was achieved in spite of these devastating complications. A multidisciplinary team approach is important especially when making decisions for the management of a complicated AVM.

Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC.ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B).Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B).In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC25%). Safety profiles were consistent with previous studies.Clinicaltrials.gov identifier: NCT02352948.

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.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.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).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.

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.

Background Atezolizumab (anti–programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non–small-cell lung cancer based on OAK—a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). Methods In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported. Results Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated. Conclusions After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1–negative patients. Long-term survival was not limited to responders.

Purpose To evaluate the efficacy and safety of transvenous coil embolization of the venous sac for type II renal arteriovenous malformation (AVM). Materials and Methods A retrospective review was conducted of 8 patients (5 women and 3 men; mean age, 57 years; age range, 41–69 years) who underwent transvenous coil embolization for type II congenital renal AVM at 5 different hospitals between 2012 and 2018. Additional intra-arterial ethanol injection was performed if shunt flow persisted after venous sac coiling. Technical success was defined as complete occlusion of shunt flow with coil embolization. Clinical success was defined as no symptom recurrence during the follow-up period. The renal parenchymal infarction rate was measured on computed tomography (CT), and procedure-related complications were reviewed. Results Nine sessions of embolization were performed for 8 patients. The mean venous sac size was 24 mm (range, 10–39 mm), and a mean of 14 micro and/or micro-detachable coils (range, 3–50) were used. The technical success rate was 88% (7 of 8) using coil embolization. One patient (12%) required additional ethanol injection to complete occlusion of the shunt flow and had a less than 10% parenchymal infarction on follow-up CT. No procedure-related complications or recurrences occurred during a mean clinical follow-up period of 20.8 months (range, 4.7–76.6 months). Conclusions Transvenous coil embolization of type II renal AVM showed an 88% technical success rate. One patient (12%) showed less than 10% renal parenchymal infarction after additional ethanol injection. No additional complications or recurrences occurred during the follow-up period.

Purpose To retrospectively investigate the impact of hyperbilirubinemia on future liver remnant (FLR) volume after percutaneous transhepatic portal vein embolization (PVE) and incidence of post-hepatectomy liver failure in primary biliary malignancy. Materials and methods Eighty-seven patients (62 men, overall mean age 66.9 y) who underwent PVE, using Gelfoam and coils before major hepatectomy between January 2004 and June 2016, were included in this study and divided into a hyperbilirubinemia (serum total bilirubin level at PVE 5.80 ± 2.44 mg/dL; n = 41) group and a control group (1.09 ± 0.73 mg/dL; n = 46). Liver volume was measured from computerized tomographic data before and 18.5 days, on average, after PVE. Correlation between FLR hypertrophy (degree of hypertrophy and percentage increase in future liver remnant [%FLR]) and total bilirubin were analyzed. FLR hypertrophy and incidence of post-hepatectomy liver failure were compared. Simple and multiple regressions were used for univariable and multivariable analyses, respectively. Results Mean FLR volumes before and after PVE were 529.1 cm3 and 640.5 cm3, respectively. Degree of hypertrophy and %FLR were 7.64 ± 4.22 and 21.77 ± 13.34, respectively. There was no significant correlation between FLR hypertrophy and total bilirubin (P > .5). FLR hypertrophy was not significantly different between the 2 groups. Planned major hepatectomy was performed in 73 patients (83.9%). Grade 3 post-hepatectomy liver failure occurred in 6 patients (8.2%; 2 in the hyperbilirubinemia group and 4 in the control group), and its incidence was not significantly different between the groups (P = .354). Conclusions Hyperbilirubinemia at the time of PVE seems to have no effect on FLR hypertrophy. The incidence of grade 3 post-hepatectomy liver failure is not likely to be influenced, either.

Background MET exon 14 skipping (METex14), reported in 3–4% of NSCLC patients (pts), is sensitive to MET inhibition. We report interim data from Cohort A of the phase II VISION study (NCT02864992) of tepotinib, an oral potent highly selective MET inhibitor in NSCLC pts with METex14 skipping. Methods Pts with advanced wt EGFR/ALK NSCLC and METex14 skipping identified by liquid (L+) or tumor (T+) biopsy enrolled at 124 sites in 11 countries (35 in Asia: Japan [from Dec 2016], Republic of Korea, Taiwan [from Oct 2018]) received tepotinib 500 mg once daily until progression, intolerable toxicity or withdrawal. Primary endpoint is objective response rate (ORR) by independent review (IRC). Secondary endpoints include investigator-assessed ORR (INV), duration of response (DOR), PFS and safety (CTCAE 4.0). Pts evaluable for ORR have ≥2 post-baseline assessments or have discontinued for any reason. Predefined analysis sets include pts who are L+ or T+. Results As of 14 June 2019, 1071 of 5102 prescreened pts were from Asia, 28 had been enrolled (17 Japan, 8 Korea, 3 Taiwan). At data cutoff (18 Feb 19) for efficacy and safety analyses, 87 pts had received tepotinib, treatment was ongoing in 47. In evaluable pts, ORR was 45–55% (Table). mDOR was >1 year in all groups (12.4–17.1 months) and >50% of pts were event free at 12 months (55–70%). mPFS was 9.5–12.2 months. 14 pts were from Asia (all from Japan), treatment was ongoing in 8. Of 11 evaluable pts from Japan, 6 were L+, 9 were T + (with overlap). In L+ pts, confirmed ORR (95% CI) was 66.7% (22.3, 95.7) by IRC and 83.3% (35.9, 99.6) by INV. In T+ pts, it was 33.3% (7.5, 70.1) by IRC, 55.6% (21.2, 86.3) by INV. Any/grade 3 treatment-related adverse events (TRAEs) reported by ≥ 15% of 87 treated pts were peripheral edema (48.3/8.0%), nausea (23.0/0%), diarrhea (20.7/1.1%). No TRAEs were grade 4/5. The safety profile was similar in pts from Japan.Table62OTableL +T +IRCInv n = 47IRC n = 51Inv n = 51n = 48ORR,* n (%)24 (50.0)26 (55.3)23 (45.1)28 (54.9)95% CI35.2, 64.840.1, 69.831.1, 59.740.3, 68.9mDOR, months 95% CI12.417.115.714.35.8, ne7.1, ne9.0, ne5.7, ne12-month event-free rate 95% CI58%55%70%59%30, 7828, 7640, 8732, 79n = 57n = 58PFS events22242322mPFS, months 95% CI9.59.510.812.26.7, ne5.3, 21.16.9, ne6.3, ne12-month event-free rate39%42%49%55%95% CI21, 5625, 5831, 6439, 69CI, confidence interval; ne, not estimable.*ORR: confirmed complete response/partial response. Patients evaluable for ORR have ≥2 post-baseline assessments or have discontinued for any reason. Conclusions Tepotinib has durable clinical activity and an acceptable safety profile in NSCLC pts with METex14 skipping detected by liquid or tissue biopsy. Clinical trial identification NCT02864992. Editorial acknowledgement Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Matthew deSchoolmeester, PhD of Bioscript Science (Macclesfield, UK). Legal entity responsible for the study Merck KGaA. Funding Merck KGaA. Disclosure K. Park: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Clovis; Elli Lilly; Hanmi; ONO; Roche; Novartis. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blueprint Medicines; Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Celgene, Guardant Health; Speaker Bureau / Expert testimony: MSD, Novartis, Pfizer, Roche, Takeda. R. Veillon: Research grant / Funding (institution): Takeda, AbbVie, Merck KGaA, BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: DMS; Advisory / Consultancy: Pfizer, Novartis. A. Cortot: Research grant / Funding (institution): Merck KGaA; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda. J. Mazieres: Advisory / Consultancy: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis. H. Sakai: Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS, Ono, Chugai, MSD, Lilly, AstraZeneca; Research grant / Funding (institution): Merck KGaA, Regeneron, Taiho. N. Reinmuth: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer. J-Y. Han: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Research grant / Funding (institution): ONO. M. Morise: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Chugai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Taiho, Boehringer Ingelheim, Novartis, EMD, Kissei. T. Tokito: Honoraria (self): MSD, Chu-gai, Ono, Boehringer Ingelheim, Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca. R. Bruns: Full / Part-time employment: Merck KGaA. J. Scheele: Full / Part-time employment: Merck KGaA. J. Straub: Full / Part-time employment: Merck KGaA. X. Le: Advisory / Consultancy: AstraZeneca, Lilly. P.K. Paik: Research grant / Funding (self), Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: AbbVie, BMS, Lilly, Takeda. All other authors have declared no conflicts of interest.

Background JAVELIN Lung 200, a randomized, open-label, phase III study, did not meet its primary endpoint of significantly improving overall survival (OS) with avelumab vs docetaxel in patients with PD-L1+ NSCLC. However, OS may have been affected by the larger proportion of patients in the docetaxel arm who received a subsequent CPI. We present post hoc analyses assessing the effect of subsequent CPIs on OS in the JAVELIN Lung 200 study. Methods Patients with stage IIIB/IV NSCLC and disease progression after platinum doublet treatment were randomized 1:1 to receive avelumab 10mg/kg every 2 weeks or docetaxel 75mg/m2 every 3 weeks. The primary analysis population for OS was patients with PD-L1+ tumors (≥1% PD-L1 expression in tumor cells using the IHC 73-10 assay); OS was also analyzed in the full analysis set (FAS). To assess the impact of subsequent CPI treatment (after discontinuation of randomly assigned study treatment) on OS, a preplanned naive sensitivity analysis and a post hoc inverse probability of censoring weighted (IPCW) analysis were performed. Results A subsequent CPI (anti–PD-1, anti–PD-L1, or anti–CTLA-4) was received by 16/396 (4.0%) in the avelumab arm and 104/396 (26.3%) in the docetaxel arm in the FAS, including 15/264 (5.7%) and 70/265 (26.4%) in the PD-L1+ population, respectively. Median time to subsequent CPI was shorter in the docetaxel arm than the avelumab arm (5.68 vs 10.53 months; FAS). Hazard ratios for OS with avelumab vs docetaxel were lower in the IPCW model than in the primary analysis and naive sensitivity analysis, both in the FAS and in the PD-L1+ population (Table).Table1492PTableFull Analysis SetPD-L1+ PopulationAvelumab (n=396)Docetaxel (n=396)Avelumab (n=264)Docetaxel (n=265)OS events248207161137Subsequent CPI events161041570Primary analysis (intent to treat)mOS (95% CI)10.5 (9.2-12.9)9.9 (8.1- 11.8)11.4 (9.4-13.9)10.3 (8.5- 13.0)HR (95% CI)0.90 (0.76-1.07)0.90 (0.73-1.11)Naive sensitivity analysis (patients censored at subsequent CPI)mOS (95% CI)10.5 (9.1-12.8)9.5 (8.4- 11.3)10.8 (9.4-13.8)10.3 (8.5- 13.0)HR (95% CI)0.89 (0.74-1.07)0.86 (0.68-1.09)IPCW adjusted modelHR (95% CI)0.85 (0.70-1.05)0.80 (0.62-1.04) Conclusions IPCW analyses suggest that the primary OS analysis in this study was impacted by the relatively high proportion of patients in the docetaxel arm who received a subsequent CPI. Clinical trial identification NCT02395172. Editorial acknowledgement ClinicalThinking; funded by Merck Healthcare KGaA and Pfizer Inc. Legal entity responsible for the study Merck Healthcare KGaA. Funding Merck Healthcare KGaA and Pfizer Inc. Disclosure F. Barlesi: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Boehringer–Ingelheim; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): F. Hoffmann–La Roche Ltd; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Takeda; Honoraria (institution): AbbVie; Honoraria (institution): ACEA; Honoraria (institution): Amgen; Honoraria (institution): Bayer; Honoraria (institution): Eisai; Honoraria (institution): Genentech; Honoraria (institution): Ipsen; Honoraria (institution): Ignyta; Honoraria (institution): Innate Pharma; Honoraria (institution): Loxo; Honoraria (institution): Sanofi-Aventis. M. Ozguroglu: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Astellas; Travel / Accommodation / Expenses: Bristol-Myers Squibb. J.F. Vansteenkiste: Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Apotex. D. Spigel: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck KGaA; Advisory / Consultancy: Moderna Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Nektar; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: TRM Oncology; Advisory / Consultancy: Precision Oncology; Advisory / Consultancy: Evelo Therapuetics; Advisory / Consultancy: Illumina; Advisory / Consultancy: PharmaMar; Research grant / Funding (institution): University of Texas Southwestern Medical Center - Simmons Cancer Center; Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): Neon Therapeutics; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono, Inc; Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): GRAIL; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Aeglea Biotherapeutics; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): ARMO Biosciences; Research grant / Funding (institution): Millenium; Travel / Accommodation / Expenses: Genzyme; Travel / Accommodation / Expenses: Intuitive Surgical; Travel / Accommodation / Expenses: Purdue Pharma; Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Travel / Accommodation / Expenses: Sysmex. J.C. Yang: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Chugai Pharmaceutical; Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Yuhan Pharmaceuticals; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ono Pharmaceuticals; Advisory / Consultancy: Daiichi-Sankyo; Advisory / Consultancy: Hansoh Pharmaceuticals; Advisory / Consultancy: Takeda Pharmaceuticals; Advisory / Consultancy: Blueprint Medicines; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: G1 Therapeutics. M. Bajars: Full / Part-time employment: EMD Serono, Inc. M. Ruisi: Full / Part-time employment: EMD Serono, Inc. J. Manitz: Full / Part-time employment: EMD Serono, Inc. K. Park: Advisory / Consultancy: AMGEN; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: BluePrint; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: GSK; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Kyowa Hakko Kirin; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ono Pharmaceuticals; Advisory / Consultancy: Roche.

Superior mesenteric artery (SMA) injuries remain a challenge to most trauma surgeons and continue to result in significant mortality despite aggressive management. We report successful management of a proximal SMA injury through endovascular treatment in a 56-year-old man. The patient presented with hypotension due to a stab wound after the epigastrium. He underwent emergency laparotomy and repair of the penetrated wall of the stomach. Right retroperitoneal hematoma at the initial laparotomy expanded and ruptured, requiring a massive transfusion. At the second laparotomy, we performed lateral arteriorrhaphy of the proximal SMA. Follow-up abdominal computed tomography angiography on post-injury day 7 showed a pseudoaneurysm on the left side of the SMA trunk. The patient was treated successfully with an endovascular stent graft.

To evaluate clinical outcomes and their predictors in patients with venous malformation (VM) treated with foam sodium tetradecyl sulfate (STS) sclerotherapy. We retrospectively evaluated clinical outcomes of foam STS sclerotherapy in 86 patients with 91 VMs to assess reduction in pain and mass after treatment. Univariate and multivariate analysis was performed to determine possible predictors of clinical outcome with foam STS sclerotherapy. A positive response of 49.5 % in pain reduction and 52.7 % in mass reduction was observed. The numerical rating scale (NRS) score improved from 4.36 ± 2.64 to 1.74 ± 1.57, and VM mass volume decreased to 41.7 ± 35.52 % of the initial size. On multivariate analysis, a high baseline NRS score (odds ratio: 1.12, 95 % confidence interval: 1.09–1.15) and VM location in the trunk versus the head and neck (odds ratio: 1.30, 95 % confidence interval: 1.00–1.69) were positive predictors of pain improvement. Minor complications occurred in 11 (12.1 %) patients and recurrence in 12 (13.2 %) patients. Foam STS sclerotherapy is an effective treatment in venous malformation, with low complication risk. A high baseline NRS score and location in the trunk versus the head and neck were positive predictors in improvement of pain. • Foam STS sclerotherapy is effective in VM, with low risk of complications. • Relief of pain tends to be dramatic in patients with severe pain. • Location of VM is a predictor of pain improvement. • The presence of a draining vein does not affect foam sclerotherapy.