Takuji Yamagami

Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study)

BACKGROUNDnAnticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events.nnnMETHODS AND RESULTSnJapan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.4%). [corrected]. Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups.nnnCONCLUSIONSnApixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

PURPOSEnTo present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer.nnnMETHODS AND MATERIALSnFrom 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27xa0Gy/2 fractions for 69 patients (13%), 45.5xa0Gy/7 fractions for 168 (32%), 49xa0Gy/7 fractions for 149 (28%), 54xa0Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1xa0year, 112 (21%) for 1-3xa0years, and 54 (10%) for >3xa0years. Median follow-up time was 5.9xa0years (range, 0.4-18.1xa0years), with a minimum of 2xa0years for surviving patients.nnnRESULTSnAfter 5xa0years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5xa0years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected.nnnCONCLUSIONSnThe findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

CT findings after lipiodol marking performed before video-assisted thoracoscopic surgery for small pulmonary nodules

Background In preoperative lipiodol marking for small pulmonary nodules, lipiodol has a potential risk of distribution in the surrounding lung structure. There are no reports about the detailed accumulation and distribution of lipiodol. Purpose To evaluate computed tomography (CT) findings after lipiodol marking before thoracoscopic surgery for pulmonary nodules. Material and Methods Sixty-four consecutive CT-guided lipiodol markings for 103 nodules were performed in 55 patients. Lipiodol (0.2–0.4u2009mL) was injected using a 21-gauge needle near the nodule. The appearance of lipiodol spots was classified into the following three types on CT: type 1, dense; type 2, punctate; and type 3, unclear. The distribution of lipiodol was also investigated. Statistical analyses were performed on the accumulation and distribution related to nodule factors. Incidences of complications were also investigated. Results A total of 110 markings were performed because of seven additional procedures due to insufficient marking. All nodules were successfully resected on the same day. The appearances of the lipiodol spots were type 1 (82%), type 2 (11%), and type 3 (7.3%). The areas of distribution were lung parenchyma (54%), central bronchus (39%), peripheral bronchovascular bundle (24%), needle tract (20%), pleural space (19%), another segment of ipsilateral lung (5.5%), and contralateral lung (0.9%). Distribution into pleural space and central bronchus was frequently seen in the shallow nodules (Pu2009<u20090.05). Complications were pneumothorax (61%) and pulmonary hemorrhage (35%). There were no serious symptoms. Conclusion The appearance of the lipiodol spot was dense in most cases, despite frequent distribution in the surrounding lung structures without serious complications.

Balloon-occluded arterial stump pressure before balloon-occluded transarterial chemoembolization

Abstract Objective To evaluate balloon-occluded arterial stump pressure (BOASP), which is responsible for effective balloon-occluded transarterial chemoembolization (B-TACE), at each hepatic arterial level before B-TACE using a 1.8-French tip microballoon catheter for unresectable hepatocellular carcinoma (HCC). Material and methods The BOASP at various embolization portions was retrospectively investigated. “Selective” and “non-targeted” BOASP was defined as the BOASP at the subsegmental or segmental artery and the lobar artery, respectively. Results The measurement of the BOASP was carried out in 87 arteries in 47 patients. BOASPu2009>u200964u2009mmHg was revealed in the caudate lobe artery (A1) and the left medial segmental (A4), right anterior superior segmental (A8), anterior segmental, right and left hepatic arteries. Significant difference was noted in the incidence of BOASP above 64u2009mmHg between “non-targeted” and “selective” BOASP (pu2009=u20090.01). “Non-targeted” BOASP was significantly greater than “selective” BOASP (pu2009=u20090.0147). In addition, the BOASP in A1, 4, 8 and the anterior segmental arteries were significantly greater than in the other subsegmental and segmental arteries (pu2009=u20090.0007). Conclusion “Non-targeted” B-TACE should be avoided to perform effective B-TACE and “selective” B-TACE at A1, 4, 8 and the anterior segmental arteries may become less effective than at the other segmental or subsegmental arteries.

CT fluoroscopy-guided percutaneous drainage: comparison of the one step and the Seldinger techniques

Abstract Objective: To evaluate the one step technique compared with the Seldinger technique in computed tomography (CT) fluoroscopy-guided percutaneous drainage of abdominal and pelvic abscess. Material and methods: Seventy-six consecutive patients (49 men, 27 women; mean age 63.5 years, range 19–87 years) with abdominal and pelvic abscess were included in this study. Drainages were performed with the one step (nu2009=u200946) and with the Seldinger (nu2009=u200948) technique between September 2012 and June 2014. Results: The technical success and clinical success rates were 95.8% and 93.5%, respectively, for the one step group, and 97.8% and 95.7%, respectively, for the Seldinger group. The mean procedure time was significantly shorter with the one step than with the Seldinger method (15.0u2009±u20094.3u2009min, range 10–29u2009min vs. 21.0u2009±u20099.5u2009min, range 13–54u2009min, pu2009<u2009.01). The mean abscess size and depth were 73.4u2009±u200944.0u2009mm and 42.5u2009±u200919.3u2009mm, respectively, in the one step group, and 61.0u2009±u200922.8u2009mm and 35.0u2009±u200920.7u2009mm in the Seldinger group. Conclusion: The one step technique was easier and faster than the Seldinger technique. The effectiveness of both techniques was similar for the CT fluoroscopy-guided percutaneous drainage of abdominal and pelvic abscess.

Therapeutic response to a novel enzyme-targeting radiosensitization treatment (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas) in patients with recurrent breast cancer

Linear accelerator-based radiotherapy has little effect on the majority of locally advanced neoplasms. Thus, the novel radiosensitizer Kochi Oxydol Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate, was developed. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases has been previously demonstrated. The present study evaluated the safety and effectiveness of KORTUC II in patients with recurrent breast cancer. A total of 20 patients (age range, 39–84 years) were enrolled in the study. The majority of patients underwent positron emission tomography (PET)-computed tomography (CT) examinations prior to and 1–7 months following KORTUC II treatment, and every 6 months thereafter when possible. The radiotherapy regimen was 2.75 Gy/fraction, 5 fractions/week, for 16–18 fractions, with a total radiation dose of 44.00–49.50 Gy (X-ray irradiation), or 4.00 Gy/fraction, 3 fractions/week, for 10–12 fractions, with a total radiation dose of 40.00–48.00 Gy (electron beam irradiation). The injection of 3–6 ml of the KORTUC II agent was initiated at the fifth radiotherapy fraction, and was performed twice/week under ultrasonographic guidance. The therapeutic effects were evaluated by PET-CT examinations prior and subsequent to KORTUC II treatment, which was observed to be well tolerated with minimal adverse effects. Of the 24 lesions presented by the 20 patients, 18 exhibited complete response, 5 partial response, 0 stable disease and 1 progressive disease. The overall survival rate was 100% at 1 year and 95% at 2 years. The mean duration of follow-up at the end of June 2014 was 51 months. Based on the results of the PET-CT studies conducted, KORTUC II treatment demonstrated marked therapeutic effects, with satisfactory treatment outcomes and acceptable adverse events.

Therapeutic response to a novel enzyme-targeting radiosensitization treatment (KORTUC II) for residual lesions in patients with stage IV primary breast cancer, following induction chemotherapy with epirubicin and cyclophosphamide or taxane.

Linac-based radiotherapy has a negligible effect on the majority of advanced neoplasms. Therefore, a novel radiosensitization treatment Kochi Oxydol Radiation Therapy for Unresectable Carcinomas II (KORTUC II), which utilizes hydrogen peroxide and sodium hyaluronate was developed. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases and recurrent breast cancers has previously been demonstrated. The present study evaluated the safety and efficacy of KORTUC II in patients with stage IV primary breast cancer. Seven patients (age range, 36–65 years) were enrolled. All patients received induction chemotherapy prior to KORTUC II treatment and underwent positron emission tomography-computed tomography (PET-CT) examinations prior to and 2–7 months following KORTUC II treatment, and every six months thereafter where possible. The radiotherapy regimen (x-ray irradiation) was 2.75 gray (Gy)/fraction, 5 fractions/week for 16–18 fractions with a total radiation dose of 44–49.5 Gy. Administration of the KORTUC II agent (3–6 ml: 3 ml for a lesion <3 cm in diameter and 6 ml for a lesion ≥3 cm) was initiated from the sixth radiotherapy fraction, and was conducted twice a week under ultrasonographic guidance. The therapeutic effects were evaluated by PET-CT examinations prior to and following KORTUC II treatment. Of the seven lesions from the seven patients, five exhibited complete responses, two exhibited partial responses and none exhibited stable disease or progressive disease. The overall survival rate was determined to be 100% at 1 and 86% at 2 years post-treatment. The mean duration of follow-up by December 2014 was 51 months. The results of the PET-CT studies indicated that KORTUC II treatment demonstrated marked therapeutic effects with satisfactory treatment outcomes and acceptable adverse effects.

Prediction of the ablated area prior to radiofrequency ablation for liver tumor under CT guidance

Abstract Purpose: To evaluate the usefulness of a method we developed to predict the ablation area at the time of CT guided radiofrequency (RF) ablation for liver tumors on a CT workstation. Material and methods: Ten tumors (mean diameter 15.5u2009mm, range, 9.0–21.5u2009mm) in seven patients with hepatocellular carcinoma for which CT guided RF ablation was performed were subjects of this study. After advancing the electrode, plain CT was obtained. Then a simulated ball to predict the ablated area was created on the workstation. After confirming that the tumor was sufficiently within the ball, ablation was performed. The distance of the edge of the actual ablated area from that of the predicted ablated area was measured at six points in three cross-sectional directions on CT images after ablation. Results: The procedures were successfully performed without complications. No local recurrence occurred. Mean absolute value of the distance of the gap between the actual and predicted ablated areas was 3.06u2009±u20092.18u2009mm (range: 0 to 9u2009mm). At 29 (55.8%) points, the actual ablated area was smaller than the predicted ablated area; it was larger in 17 (32.7%), and was the same in 6 (11.5%) points. Conclusion: Our method produces an acceptable simulation during RF ablation under CT guidance.

Microballoon-related interventions in various endovascular treatments of body trunk lesions

Abstract Occlusion balloon catheters of 5.2- or 6-French have been used for a few decades in various endovascular treatments of body trunk vascular lesions. However, these catheters may be difficult to place in cases of excessive vessel tortuosity, small vessels, and anatomic complexity. Recently, the introduction of the double lumen microballoon catheters for body trunk vascular lesions has allowed operators to advance them into more distal, smaller, and more tortuous vessels. Since the launch of the first generation microballoon catheters onto the market in Japan in 2011, the microballoon catheters have evolved and are now generally available for clinical use. The purpose of this article is to review the evolution and current clinical applications of the microballoon catheters in the field of interventional radiology.

New Diagnostic Criteria for the Localization of Insulinomas with the Selective Arterial Calcium Injection Test: Decision Tree Analysis

PURPOSEnTo explore optimal diagnostic criteria for localizing insulinomas with the selective arterial calcium injection (SACI) test using decision tree analysis.nnnMATERIALS AND METHODSnA retrospective study included 86 vessels of 18 patients (5 men, 13 women; mean age 67 y; range, 49-73xa0y) with insulinomas who underwent SACI test between June 2007 and May 2016. Of 27 insulinomas, 7 were found in the head, 13 in the body, and 7 in the tail of the pancreas. Two patients had multiple tumors. To identify optimal diagnostic criteria, decision tree analysis was performed, and sensitivity, specificity, and accuracy of the conventional and the proposed new diagnostic criteria (plasma insulin concentration after calcium injection [ICpost] > 2.0xa0× plasma insulin concentration before calcium injection [ICpre]) were compared.nnnRESULTSnThe proposed new diagnostic criteria for insulinoma obtained by decision tree analysis were (i) ICpost > 2.7xa0× ICpre and maximum insulin concentration > 60.3 μIU/mL or (ii) ICpost > 2.7xa0× ICpre and maximum insulin concentration < 60.3 μIU/mL with ICpre being ≥ 7.5 μIU/mL. Sensitivity, specificity, and accuracy of the new criteria for the SACI test were 100%, 91.4%, and 94.2; sensitivity, specificity, and accuracy of conventional criteria were 100%, 69.0%, and 79.1%.nnnCONCLUSIONSnNew diagnostic criteria for localization of insulinomas with the SACI test yielded higher diagnostic performance than conventional criteria.