CT-Guided Femoral Approach for Psoas Muscle Abscess Drainage.

PURPOSE: To evaluate the feasibility and safety of the computed tomography (CT)-guided femoral approach for draining a psoas muscle abscess (PMA). MATERIALS AND METHODS: Between January 2014 and November 2018, the CT-guided femoral approach was employed for 9 abscesses in 8 patients who could not tolerate the prone position because of advanced age or other underlying conditions. A 17-gauge blunt metal needle was used to puncture the iliacus muscle below the groin under CT fluoroscopic guidance. A drainage catheter was then placed within the abscess cavity in the psoas major muscle. Technical success, clinical success, complications, the drainage therapy duration, susceptibility to antibiotics, survival, and recurrence were evaluated. RESULTS: The technical success rate was 100% among all nine lesions. The clinical success rate was 89% among all eight patients. One patient died of concomitant meningitis 15 days after the procedure. No patients developed therapy-related complications. The median duration of the drainage therapy was 15 days (range 6-71 days). Appropriate antibiotics based on the culture susceptibility were achieved in all patients. Four patients survived, and the remaining four died at 15 to 758 days (median, 36 days) after the procedure; no therapy-related deaths occurred. No recurrence was seen. CONCLUSION: The CT-guided femoral approach seems feasible, effective, and safe for draining psoas muscle abscesses in ill patients who cannot tolerate the prone position.

A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors.

Xentuzumab is an insulin-like growth factor (IGF) ligand-neutralizing antibody. This phase 1 trial assessed xentuzumab in Japanese patients with solid tumors. Patients aged ≥20 y old with solid tumors that were refractory or not amenable to standard therapy were enrolled. Patients received xentuzumab intravenously at a starting dose of 750 mg/wk. Dose escalation used a 3 + 3 design with dose de-escalation. The primary endpoint was to determine the maximum tolerated dose (MTD) of xentuzumab. Safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity were also assessed. Fifteen patients received xentuzumab in the dose escalation part (750 mg/wk [n = 6]; 1000 mg/wk [n = 3]; 1400 mg/wk [n = 6]). There were no dose-limiting toxicities at any dose; the MTD of xentuzumab was not reached. Xentuzumab 1000 mg/wk was recommended as the relevant biological dose. Six further patients received xentuzumab 1000 mg/wk in an expansion cohort. Of 21 patients, 13 (61.9%) experienced a drug-related adverse event, most commonly fatigue (23.8%), neutropenia (19.0%), diarrhea, nausea, white blood cell count decrease, and muscle spasms (14.3% each). No relevant deviations from dose linearity of xentuzumab exposure were observed during dose escalation. Total IGF-1 and IGF-2 levels increased and bioactive IGF levels decreased from baseline to 24 h after the first infusion in cycle 1. Partial response was observed in 2 (9.5%) patients with desmoid-type fibromatosis. Disease control was achieved in 6 (28.6%) patients (median duration 42.4 mo). Xentuzumab monotherapy was well tolerated in Japanese patients and showed evidence of anti-tumor activity. This study was registered with www.clinicaltrials.gov (NCT02145741).

Correction to: Reply to the letter: N-Butyl Cyanoacrylate-Lipiodol Mixture for Endovascular Purpose: Polymerization Kinetics Differences Between In Vitro and In Vivo Experiments.

We would like to correct one of the references that was listed incorrectly in our article.

A randomized, controlled trial of the efficacy of percutaneous transesophageal gastro-tubing (PTEG) as palliative care for patients with malignant bowel obstruction: the JIVROSG0805 trial.

BACKGROUND: A randomized, controlled trial to evaluate the superiority of percutaneous transesophageal gastro-tubing over nasogastric tubing as palliative care for bowel obstruction in patients with terminal malignancy was conducted. SUBJECTS AND METHODS: The subjects were patients with malignant bowel obstruction with no prospect of improvement, for whom surgery was not indicated and with a Palliative Prognostic Index of < 6. They were randomly allocated in a 1:1 ratio to receive either percutaneous transesophageal gastro-tubing (PTEG group) or nasogastric tubing (NGT group). Their symptom scores (the worst 0 to no symptoms 10) were measured for a 2-week period after enrollment, and the areas under the curves for the two groups were compared. The EQ-5D and SF-8 were also used to assess overall quality of life. RESULTS: Forty patients were enrolled between October 2009 and January 2015, with 21 allocated to the PTEG group and 19 to the NGT group. The mean areas under the curves (95% confidence intervals) for the PTEG group and the NGT groups were 149.6 (120.3-178.8) and 44.9 (16.4-73.5), respectively, significantly higher for the NGT group (p < 0.0001). The secondary endpoints of quality of life as assessed by the EQ-5D and SF-8 scores were also significantly higher for patients in the PTEG group (p = 0.0036, p = 0.0020). There was no difference in survival between the groups. No serious adverse events were observed. CONCLUSIONS: In terms of quality of life, percutaneous transesophageal gastro-tubing was superior to nasogastric tubing as palliative care for patients with bowel obstruction due to terminal malignancy.

Is the Cessation of Blood Flow Faster than the Polymerization of an n-Butyl Cyanoacrylate-Lipiodol Mixture? An In Vitro Phantom Study.

PURPOSE: To compare the polymerization time of n-butyl cyanoacrylate (NBCA) and lipiodol mixture in a static model and a pulsating flow model simulating embolization procedure of small caliber arteries. MATERIALS AND METHODS: The polymerization time of NBCA-lipiodol mixture was measured by the morphological changes of a glue droplet in a petri dish. For the flow model, we used a 2-mm-inner-diameter polyvinyl alcohol tube connected to a pulsation pump. Bovine serum was supplied from the pump and circulated into the system at 30 ml/min and 60 bpm. A 0.64-mm-inner-diameter silicon microcatheter was inserted into this system, and then, 0.5 ml of glue was injected into the tube. The flow cessation time was defined as the time it took to stop the serum draining from the end of the tube. Six samples of 100, 66, 50, 40, 33, and 20 vol% NBCA were assessed. RESULTS: The median polymerization times for each concentration were 0.12, 3.72, 12.30, 27.41, 57.68, and 63.67 s, respectively. The median flow cessation times were 0.28, 0.78, 1.43, 3.75, 4.50, and 9.29 s, respectively. The flow cessation time was significantly shorter than the polymerization time for all samples except for 100 vol% cyanoacrylate (p < 0.05). CONCLUSION: The flow cessation time of cyanoacrylate glue was significantly shorter than the polymerization time in an in vitro experiment. The injected glue possibly stops the blood flow before the completion of polymerization in the vascular system.

Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors.

BACKGROUND: Focal adhesion kinase (FAK) inhibitors have demonstrated anti-tumor activity preclinically and are currently being evaluated in humans. A first-in-human study evaluating the novel FAK inhibitor BI 853520 in a predominantly Caucasian population with advanced or metastatic non-hematologic malignancies demonstrated acceptable tolerability and favorable pharmacokinetics. OBJECTIVE: This study was undertaken to investigate the safety, tolerability, and maximum tolerated dose (MTD) of BI 853520 in Japanese and Taiwanese patients with advanced solid tumors. PATIENTS AND METHODS: In this open-label, phase I, dose-finding study, BI 853520 was administered once daily (QD) in a continuous daily dosing regimen with 28-day cycles and escalating doses to sequential cohorts of patients. Twenty-one patients (62% male; median age 65 years) were treated at two sites in Japan and Taiwan. RESULTS: The median duration of treatment was 1.2 months (range 0.2-7.7). As no dose-limiting toxicities were observed during cycle 1 in the 50, 100, or 200 mg cohorts, the MTD of BI 853520 was determined to be 200 mg QD. Drug-related adverse events were reported in 19 patients (90%), and all except one were of grade 1 or 2. Pharmacokinetic parameters were supportive of a once-daily dosing schedule. A confirmed objective response rate of 5% and disease control rate of 29% were achieved; median duration of disease control was 3.7 months. CONCLUSIONS: This trial demonstrated a manageable and acceptable safety profile, favorable pharmacokinetics, and potential anti-tumor activity of BI 853520 in pretreated Japanese and Taiwanese patients with advanced or metastatic solid tumors. CLINICAL TRIALS REGISTRATION: NCT01905111.

Evaluation of stent placement for vena cava syndrome: phase II trial and phase III randomized controlled trial.

PURPOSE: Vena cava syndrome (VCS) from stenosis of the superior vena cava or inferior vena cava caused by compression from a malignant tumor is one of the typical clinical conditions in patients with advanced stage malignant disease. VCS is difficult to manage and painful, reducing patients' quality of life. Although several reports have investigated stent placement for VCS, this treatment has never been established as the standard because of the lack of evidence of the safety and efficacy. We conducted a phase II trial and a phase III randomized controlled trial to clarify the role of stent placement in managing patients with VCS. METHODS: In the phase II trial, 28 eligible patients were treated with stent placement. The efficacy of stent placement for VCS was evaluated based on the reduction of patients' symptom scores during 14 days following treatment. Technical success, technical feasibility, overall survival, recurrence of symptoms, and adverse events were evaluated. In the phase III trial, 32 patients were enrolled and randomly assigned to the test (n = 16) and control groups (n = 16). The area under the symptom score curve was compared between the groups. The EQ-5D, SF-8, and adverse events were evaluated until discontinuation of the protocol treatment or 28 days after enrollment. RESULTS: In the phase II trial, the median patients' symptom scores significantly decreased from 10.50 before the procedure to 3.00 after the procedure. Technical success and technical feasibility rates were 96.4% and 100%, respectively. The incidence of treatment-related grade 3 or higher adverse events was 14.3%. In the phase III trial, significant superiority of stent placement was observed in the test, compared to that in the control, group. There was no significant difference in most other evaluations between the groups. CONCLUSIONS: Stent placement significantly improved the symptoms of VCS; thus, it might be accepted as the standard treatment to manage the symptoms of VCS. TRIAL REGISTRATION: JIVROSG-0402, JIVROSG-0807.

Phase II Trial of Transarterial Embolization Using an n-Butyl-2-Cyanoacrylate/Lipiodol Mixture (JIVROSG-0802).

PURPOSE: To evaluate the embolic effect and the safety of transarterial embolization (TAE) using n-butyl-2-cyanoacrylate (NBCA) in a prospective multicenter trial. MATERIALS AND METHODS: This study was an open-label, multicenter, phase II trial. The inclusion criteria were (1) active bleeding or pseudoaneurysm, (2) true aneurysm, (3) arteriovenous malformation (except cerebral lesion), (4) arteriovenous fistula, or (5) need for arterial distribution before transarterial treatment. Selective TAE with NBCA diluted 2-10 times was performed. The primary endpoint was the success rate of embolization with a per-patient analysis based on the angiographic findings. Secondary endpoints were safety, evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) version 4, and the success rate of embolization with a per-vessel calculation. RESULTS: Sixty-five patients were initially enrolled, but due to protocol violation in two patients, efficacy was ultimately analyzed in 63 patients (103 vessels) and safety was analyzed in 64 patients. The success rate per patient was 98.4% (62/63; 95% confidence interval (CI), 91.5-100.00), and the success rate per vessel was 99.0% (102/103; 95% CI, 94.7-100.0). Adverse events of grade 3 or above based on CTCAE version 4 occurred in 22/64 patients (34.4%). Twelve intraoperative or postoperative adverse events grade 3 or above, which may have been related to embolization using NBCA, occurred in 11/64 patients (17.2%). Three patients died after embolization using NBCA, but their deaths were unrelated to TAE. CONCLUSION: In this prospective multicenter clinical trial, the efficacy of TAE using NBCA was 98.4% and adverse events were clinically acceptable. LEVEL OF EVIDENCE: Level 3b.

Value of Percutaneous Radiologic Gastrostomy for Patients with Advanced Esophageal Cancer.

BACKGROUND: Nutritional management is important throughout the treatment period for esophageal cancer patients. This study aimed to evaluate the feasibility of percutaneous radiologic gastrostomy (PRG) and to investigate whether PRG can be applied for patients with advanced esophageal cancer. METHODS: In this study, 89 patients (74 men and 15 women) with advanced esophageal cancer underwent PRG using computed tomography and fluoroscopic guidance. These patients were unsuitable candidates for endoscopic intervention because of esophageal stricture. Primary placement of a mushroom-retained gastrostomy catheter was intended. The end points were technical success and complications after PRG as well as clinical outcomes and survival of the patients. These end points also were compared between the pre-chemoradiotherapy (pre-CRT) and post-CRT groups using the Chi square test, Fisher's exact test, and the Wilcoxon rank sum test. The survival rate was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: All the patients had a successful PRG. The mushroom-tip gastrostomy catheter was primarily inserted in 77 patients (86.5 %) and finally achieved for all the patients. Complications occurred for 14 patients (15.7 %) including Dindo-Clavien classification grade 3 (1 catheter dislodgement), grade 2 (2 gastric hemorrhages), and grade 1 (7 skin infections and 4 oozing hemorrhages) complications. During the follow-up period (median, 6 months), 60 patients (67.4 %) died, giving a 12-month survival rate of 37.7 %. Gastrostomy removal was more common in the pre-CRT group (P = 0.011). The pre-CRT group had higher survival rates than the post-CRT group (P = 0.021). CONCLUSIONS: Because PRG provided high technical success with limited complications, it can be used for patients with advanced esophageal cancer whose treatment plan involves multimodal therapy.

Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with advanced solid tumors.

PURPOSE: This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical effects of volasertib, a selective Polo-like kinase inhibitor that induces mitotic arrest and apoptosis, in Japanese patients with advanced solid tumors (NCT01348347; 1230.15). METHODS: In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) received volasertib (200-350 mg) as a single dose by intravenous infusion over 2 h on day 1 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the MTD of volasertib in Japanese patients with an advanced solid tumor; secondary endpoints included safety, pharmacokinetics, and clinical benefit. RESULTS: Fifteen patients with an advanced solid tumor were treated. Dose-limiting toxicities of grade 4 neutropenia for ≥7 days and grade 4 thrombocytopenia were both experienced by 2/6 patients in the 350 mg cohort. The MTD of volasertib in Japanese patients was 300 mg. The most common (≥3 patients) drug-related non-hematologic adverse events included fatigue, decreased appetite, and nausea. Exposure to volasertib and its metabolite increased with increasing doses. A partial response in a patient with gastric cancer and stable disease in eleven patients were observed. CONCLUSIONS: Volasertib had a manageable safety profile up to the MTD determined as 300 mg. Exposure to volasertib and its metabolite increased with increasing doses. The safety profile of volasertib in Japanese patients is comparable with those previously obtained in Caucasian patients. These data support enrollment of Japanese patients in global clinical trials without dose modification.

Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701.

PURPOSE: This multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors. METHODS: Thirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1-3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors. RESULTS: The RFA procedure was completed in 100% (95% confidence interval [CI] 89-100%) of all 33 patients. There were no severe adverse events (0% [95% CI 0-11%]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85%), 0 (0%), one (3%), and one (3%) patient(s), respectively, with a tumor response rate of 85% [95% CI 68-95%]). Three patients (9%), including one ineligible patient (3%), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93%). CONCLUSION: The current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

Balloon Blocking Technique (BBT) for Superselective Catheterization of Inaccessible Arteries with Conventional and Modified Techniques.

PURPOSE: The purpose of the study was to retrospectively evaluate the efficacy and safety of the balloon blocking technique (BBT). MATERIALS AND METHODS: The BBT was performed in six patients (all males, mean 73.5 years) in whom superselective catheterization for transcatheter arterial embolization by the conventional microcatheter techniques had failed due to anatomical difficulty, including targeted arteries originating steeply or hooked from parent arteries. All BBT procedures were performed using Seldinger's transfemoral method. Occlusive balloons were deployed and inflated at the distal side of the target artery branching site in the parent artery via transfemoral access. A microcatheter was delivered from a 5-F catheter via another femoral access and was advanced over the microguidewire into the target artery, under balloon blockage of advancement of the microguidewire into non-target branches. After the balloon catheter was deflated and withdrawn, optimal interventions were performed through the microcatheter. RESULTS: After success of accessing the targeted artery by BBT, optimal interventions were accomplished in all patients with no complications other than vasovagal hypotension, which responded to nominal therapy. CONCLUSION: The BBT may be useful in superselective catheterization of inaccessible arteries due to anatomical difficulties.

Ultrasonography-guided central venous port placement with subclavian vein access in pediatric oncology patients.

BACKGROUND/PURPOSE: To evaluate the technical success and complications of image-guided central venous port (CVP) placement with subclavian vein (SCV) access in pediatric oncology population. MATERIALS AND METHODS: Ninety-two children (52 boys, 40 girls; mean age, 8.5 years) underwent CVP implantation under local anesthesia with conscious sedation. SCV access was firstly attempted under ultrasonographic guidance and CVP implantation was performed under fluoroscopic guidance. Technical success, peri-procedural (<24h) complication, and post-procedural (>24h) complication were assessed. RESULTS: In total, 102 CVPs were implanted in 92 children with a mean catheter time of 364 days (total, 38,224 days; range, 14-1911 days). In three small children, conversion of SCV access to internal jugular vein access yielded a primary technical success rate of 97.1% and overall technical success rate of 100%. Three minor peri-procedural complications were observed (2.9%) and seven post-procedural infectious complications occurred (infection rate, 6.7%; 0.18/1000 catheter days). No pneumothorax, catheter malposition, venous thrombosis, or mortality occurred. CONCLUSION: Image-guided CVP placement with SCV access in a pediatric population was performed with high technical success and low complication rate without general anesthesia. This procedure can be taken into account as a choice of procedure when internal jugular venous access is not possible.

Guidelines for the use of NBCA in vascular embolization devised by the Committee of Practice Guidelines of the Japanese Society of Interventional Radiology (CGJSIR), 2012 edition.

Cyanoacrylates are a group of fast-acting adhesives. They form low viscosity liquids in the monomer state and instantly polymerize to become adhesive upon contact with ionic substances. Since the 1950s, they have been used around the world for industrial and household purposes. N-butyl cyanoacrylate (NBCA) is a cyanoacrylate that is commonly used for medical care, and the closure of skin wounds with NBCA has been found to promote hemostasis. However, in Japan, the intravascular injection of NBCA is considered to be off-label use, except during the treatment of gastric varices under endoscopy. The use of NBCA in embolotherapy is considered when the target vessels cannot be cannulated superselectively, for vascular diseases that require long segments of the target vessel to be embolized, or for patients in a hypocoagulable state. NBCA-based embolotherapy can be used to treat vascular malformations, acute hemorrhaging, tumors, and venous disease. The complications associated with NBCA-based embolotherapy include tissue ischemia, hemorrhaging, systemic or local reactions, and catheter adhesion to blood vessels. NBCA is mixed with Lipiodol to make it radiopaque and to adjust its polymerization time. Since there are various technical aspects to performing NBCA-based embolotherapy safely, it should be carried out by, or with the assistance of, proficient interventional radiologists.