Yukimasa Sakai

Radiofrequency Ablation and Immunostimulant OK-432: Combination Therapy Enhances Systemic Antitumor Immunity for Treatment of VX2 Lung Tumors in Rabbits

PURPOSE To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. MATERIALS AND METHODS Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. RESULTS The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. CONCLUSION Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.

Dual Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varix Draining into the Left Adrenal Vein and Left Inferior Phrenic Vein

A 66-year-old woman with a gastric varix, draining into a dilated left adrenal vein and a left inferior phrenic vein, was treated with dual balloon-occluded retrograde transvenous obliteration (B-RTO). Under balloon occlusion of the left adrenal vein and the left inferior phrenic vein, retrograde injection of a sclerosant (5% ethanolamine oleate) into the gastric varix was performed. Two weeks later, disappearance of flow in the gastric varix was confirmed on endoscopic ultrasound examination.

New oily agents for targeting chemoembolization for hepatocellular carcinoma.

AbstractPurpose: The evaluation of new oily agents for targeting chemoembolization for hepatocellular carcinoma. Methods: Five types of oily preparation were injected into the hepatic artery of 54 rabbits inoculated with VX2 carcinoma cells in order to evaluate (1) the safety of these preparations, (2) their histologic distribution and the amount of agents remaining at tumor sites, and (3) computed tomographic (CT) images obtained. Of these preparations, three were made by mixing non-iodinated poppy seed oil and a thickener and then adjusted to have a viscosity lower than, equal to, or higher than that of lipiodol. A fourth preparation was a mixture of lipiodol and a thickener with a higher viscosity than lipiodol alone, and the fifth preparation are lipiodol alone. Results: (1) No injury to the hepatic parenchyma was observed hematologically or histologically. (2) With increase in the viscosity, a significantly larger amount of agent remained at the tumor site. No agent was present at normal sites 14 days after intraarterial injection, regardless of which preparation was given. (3) On CT scans following intraarterial injection, tumor cells were visibly deeply stained in the non-iodinated preparation groups, while the lipiodol groups were not evaluable because of excessively high attenuation. Conclusion: The non-iodinated oily preparations and highly viscous oily preparations developed in the present study were more useful than lipiodol for treatment of hepatic tumors.

Homemade endovascular treatment of postoperative aortobronchial fistulas.

Successful treatments of aortobronchial fistulas were achieved in two cases using a homemade endovascular stent graft. In one, a 75-year-old man was operated on for a distal arch aneurysm 11 years previously. In the other, a 73-year-old woman was operated on for a ruptured type B aortic dissection 2 months previously. In both cases, the chief complaint was repeated hemoptysis, and the communication between the aorta and the airway tract was at the distal anastomotic site in the descending aorta. To minimize risks associated with reoperation, endovascular stent grafting was selected electively. Postoperative courses were uneventful and there were no recurrences of hemoptysis.

Selective balloon-occluded retrograde transvenous obliteration of gastric varix with preservation of major portacaval shunt.

1All authors: Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-bu, Osaka, Japan 545-8585. Address correspondence to N. Nishida (norifumin@med.osakacu.ac.jp). alloon-occluded retrograde transvenous obliteration (B-RTO) has been performed instead of endoscopic and surgical treatment in the management of gastric varix. The procedure is indicated for gastric varix with a major portacaval shunt, such as a gastrorenal shunt or a shunt involving the left inferior phrenic vein, and usually obliterates the gastric varix and the connecting major portacaval shunt. BRTO is safe, feasible, and effective in the treatment of patients with gastric varix; however, aggravation of esophageal varix is an important complication caused by increasing portal pressure [1–3]. We report the first case, to our knowledge, of selective B-RTO with preservation of the major portacaval shunt. MDCT during splenic and superior mesenteric arterial portography was useful for confirming the morphologic features and developing a precise therapeutic plan.

Efficacy and safety of intra-arterial steroid infusions in patients with steroid-resistant gastrointestinal acute graft-versus-host disease

There is no established second-line treatment for steroid-resistant acute graft-versus-host disease (GVHD). We prospectively assessed the safety and efficacy of intra-arterial steroid infusions (IASIs) for steroid-resistant acute gastrointestinal (GI) GVHD and compared the outcomes with those of historical controls at our institution. Nineteen consecutive, allogeneic hematopoietic stem cell transplantation subjects aged 31-67 years (median 52) were enrolled between October, 2008, and November, 2012. Acute GVHD was confirmed by biopsy in all cases. The enrolled patients were treated with infusions of methylprednisolone into the mesenteric arteries and/or gastroduodenal and left gastric arteries. Fourteen consecutive patients who developed steroid-resistant acute GI GVHD between 2001 and 2008 were used as controls. For the primary endpoint at day 28, the overall and complete responses in the IASI group trended higher (79% vs. 42%, p = 0.066) and were significantly higher (63% vs. 21%, p = 0.033) than those in the control group. Although not statistically significant, owing to the small population, the crude day-180-nonrelapse mortality rate was about 20% lower and the day-180-overall-survival rate tended to be higher than the control (11% vs. 29%, p = 0.222; 79% vs. 50%, p = 0.109, respectively). There were no serious IASI-related complications. Our results suggest that IASI can safely provide excellent efficacy for refractory acute GI GVHD without increasing infection-related complications and may improve prognosis.

Transapical Endovascular Repair of Thoracic Aortic Pathology

BACKGROUND Alternative access for thoracic endovascular aortic repair (TEVAR) has been explored for patients with unsuitable femoral and iliac access, but few cases of transapical access have been described. We report our experience with transapical access for various aortic pathologies. METHODS We reviewed 6 cases undergoing transapical access for endovascular repair of thoracic aortic pathology between December 2013 and August 2015. Five patients had an aortic arch aneurysm and 1 patient presented with Stanford type A subacute aortic dissection. Transapical access was indicated to avoid approach through the severely atherosclerotic thoracic descending aorta in 4 patients and severely kinked aorta in 1 patient and to treat an ascending aortic dissection lesion in 1 patient. RESULTS Transapical endografting was completed in all patients. Significant aortic valve regurgitation occurred in 3 patients when a large bore sheath was placed across the aortic valve. There was 1 death attributed to global cerebral ischemia due to carotid dissection after carotid bypass and chimney stent-graft insertion. There were no access-related complications. Computed tomography revealed complete exclusion of the aortic aneurysm in 4 patients, and shrinkage of the false lumen in 1 patient with aortic dissection. CONCLUSIONS Transapical access for TEVAR would be a potential alternative when the anatomy is unfit for routine retrograde approach. This method might have potential benefit of reducing the risk of embolism in patients with severe atherosclerotic thoracic descending aorta. However, certain safety concerns must be addressed, including maintenance of hemodynamics, wire exteriorization for navigation of the device tip, and rapid pacing during deployment.

Injectable cell scaffold restores impaired cell-based therapeutic angiogenesis in diabetic mice with hindlimb ischemia

The clinical success of cell-based therapeutic angiogenesis has been limited in diabetic patients with critical limb ischemia. We previously reported that an injectable cell scaffold (ICS), which is a nano-scaled hydroxyapatite (HAp)-coated polymer microsphere, enhances therapeutic angiogenesis. Subsequently, we developed a modified ICS for clinical use, measuring 50 μm in diameter using poly(l-lactide-co-ε-caprolactone) as a biodegradable polymer, which achieved appropriately accelerated absorption in vivo. The aim of the present study was to evaluate the effectiveness of this practical ICS in diabetic hindlimb ischemia. Bone-marrow mononuclear cells (BMNCs) were intramuscularly injected, without or with a practical ICS, into the ischemic hindlimbs of mice (BMNCs or ICS+BMNCs group, respectively). Kaplan-Meier analysis demonstrated that the beneficial effects of BMNC transplantation for limb salvage after ischemic surgery were almost entirely abrogated in streptozotocin-induced diabetic mice. In contrast, injection of ICS+BMNCs revealed significant limb salvage in diabetic mice to a similar extent as in non-diabetic mice. The number of apoptotic transplanted BMNCs was 1.8-fold higher in diabetic mice 10 days after transplantation compared to non-diabetic mice, while that in the ICS+BMNCs group was markedly lower (8.3% of that in the BMNCs group) even in diabetic mice. The proangiogenic factors VEGF and FGF2, also known as antiapoptotic factors, mostly co-localized with transplanted GFP-positive BMNCs that were closely aggregated around the ICS in ischemic tissue. In conclusion, the practical ICS significantly augmented cell-based therapeutic angiogenesis even in diabetic animals, through local accumulation of proangiogenic factors and antiapoptotic effects in transplanted cells.

Successful embolization of a ruptured pancreaticoduodenal artery aneurysm associated with the median arcuate ligament syndrome

Celiac axis compression caused by the median arcuate ligament (MAL) syndrome is a rare entity. Occasionally, the resultant celiac axis stenosis increases blood flow in the pancreaticoduodenal arcade, and the consequent volume overload can lead to arterial dilatation and aneurysm formation.[1] Recently, transcatheter embolization has become an alternative initial treatment for ruptured aneurysms.[2] Previously reported cases have indicated that ruptured aneurysms should be isolated by coils or other embolic agents.[3] However, efforts at such isolation carry the potential risk of re-bleeding if the ruptured aneurysm has other arterial communications.

Prediction for Improvement of Liver Function after Balloon-Occluded Retrograde Transvenous Obliteration for Gastric Varices to Manage Portosystemic Shunt Syndrome.

PURPOSE To investigate predictive factors and cutoff value of transient elastography (TE) measurements for assessing improvement in liver function after balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GV). MATERIALS AND METHODS Retrospective analysis was performed of 50 consecutive patients followed for > 3 months after BRTO, who had undergone TE before BRTO between January 2011 and February 2015. The correlation between change in liver function (total bilirubin, albumin, and prothrombin time) and baseline liver function values and liver stiffness measurement (LSM) by TE was evaluated by Pearson correlation test. Receiver operating characteristic curves were used to determine cutoff values for discriminating between patients who had improved liver function and patients who did not. The time interval from BRTO to aggravation of esophageal varices (EV) (worsening morphology, development of new varices, or variceal rupture) grouped by cutoff values was also analyzed. RESULTS Serum albumin was significantly improved at 3 months after BRTO (3.57 g/dL vs 3.74 g/dL, P < .001). There was a significant negative correlation between change in albumin and baseline LSM (r = -0.50, P < .001). The best cutoff point for LSM was ≤ 22.9 kPa, with sensitivity and specificity of 78.4% and 69.2%, respectively, for predicting which patients would have improved albumin after BRTO. Among 33 patients, 29 (88%) patients had improved albumin. The 1-year progression rate of EV after BRTO was 13.6% in patients with LSM ≤ 22.9 kPa. CONCLUSIONS The predictive factor for improvement in albumin after BRTO was lower LSM (≤ 22.9 kPa) using TE.