Takanori Oyama

Activated T cells and soluble molecules in the portal venous blood of patients with cholestatic and hepatitis C virus-positive liver cirrhosis. Possible promotion of Fas/FasL-mediated apoptosis in the bile-duct cells and hepatocyte injury.

We investigated the immune responses of patients with cholestatic and hepatitis C virus-positive (HCV-positive) liver cirrhosis by analysing T-cell subsets and cytokine levels in the portal and peripheral veins, using flow cytometry and enzyme-linked immunosorbent assay. In cholestatic liver cirrhosis, the proportion of natural-killer (NK) T cells and interleukin (IL) 6 and IL-18 levels in the portal venous blood were significantly higher than those in the peripheral venous blood. In HCV-positive liver cirrhosis, the proportions of NK T cells and Fas+ T cells and IL-6 and soluble Fas levels in the portal venous blood were significantly higher than those in the peripheral venous blood. These results suggest that in these diseases, activated T cells and soluble molecules in portal venous blood may promote Fas/FasL-mediated apoptosis of the bile-duct cells and hepatocytes, and contribute to the deterioration in liver function as an inevitable result of positive feedback.

Intraportal Donor Bone Marrow Transplantation Improves Intestinal Allograft Survival in Rats under FK506-Based Immunosuppression

Donor-specific immunosuppression is important in transplant surgery. We examined the effect of intraportal donor-specific bone marrow transplantation on heterotopic small bowel transplantation in the high responder rat combination, ACI to Lewis. The study comprised five treatment groups: untreated controls (group 1); FK506 alone (group 2); low-dose predonine + FK506 (group 3); high-dose predonine + FK506 (group 4); and intraportal donor-specific bone marrow transplantation + FK506 (group 5). Intraportal transplantation was performed pre-operatively and FK506 and predonine given post-operatively. Intestinal allograft survival and changes of intragraft cytokine expression were analysed using the reverse transcription polymerase chain reaction. Allograft survival (mean ± SD) was lowest in group 1 and greatest in group 5. The group 5 treatment regimen also down-regulated interferon-γ and interleukin-2 transcription in the transplanted intestine. Intraportal donor bone marrow transplant combined with FK506 immunosuppression was found therefore to be the most beneficial treatment regimen

Ultrasound-guided block of selective branches of the brachial plexus for vascular access surgery in the forearm: a preliminary report

Purpose The operative field for vascular access (VA) surgery in the forearm is on the volar surface, and motor nerve block is not necessary for regional anesthesia. Therefore, selective block of branches of the brachial plexus may be a more efficient anesthesia technique. Methods Individual nerve blocks in the axillary brachial plexus and selective blocks of the musculocutaneous and medial antebrachial cutaneous nerves in the upper arm were performed using low doses and concentrations of a local anesthetic mixture of lidocaine and ropivacaine under ultrasound (US) guidance in patients undergoing VA surgery in the forearm. The targeted nerves were identified by continuous US tracing along the upper arm to the axilla in a short-axis view. We performed three VA surgeries in the forearm using an axillary brachial plexus block and four using a selective two-nerve bock in the upper arm. We recorded any additional anesthetic requirement and evaluated intraoperative pain using the Wong-Baker Faces Pain Rating Scale (WBFRS; 0 = no pain; 10 = worst pain). Results All of the target nerve branches were clearly identified by US tracing. All patients had satisfactory intraoperative pain control (0 or 2 score on WBFRS). Four patients required small additional doses of local anesthetic. Conclusions US-guided block of individual branches of the brachial plexus at the axilla achieved effective anesthesia using small amounts of local anesthetic. An advanced selective nerve block in the upper arm allows minimum necessary anesthesia and provides safe and efficient analgesia for VA surgery in the forearm.

Application of ultrasound-guided selective sensory nerve block for the endovascular treatment of hemodialysis fistula in the forearm

scanned along the upper limb by using a continuous US tracing method (1-3). Thus, selective blockades of the nerves – which enabled anesthesia of the area of vascular sheath insertion and balloon dilation for the vessel strictures of the AVFs – were performed. Short-acting lidocaine (LA; 1%, 2.5 mL) was administered around each nerve via the in-plane method (1). The SBRN was blocked at the mid-third of the forearm, as it is relatively separate from the radial artery and cephalic veins (2). The mean duration required for 1 nerve block was 80.0 ± 5.6 seconds (Tab. I). Additional 1% LA was used only during 1 EVT session (EVT No. 1), wherein the sheath insertion site could not be located in the innervated area of the blocked MCN. The Wong-Baker Faces® Pain Rating Scale scores (0: no DOI: 10.5301/jva.5000578

Arterial Access Port: A Shunt‐Less Vascular Access Using a Blind‐Ending Artificial Graft Anastomosed to the Brachial Artery

We retrospectively investigated the usability of arterial access ports (AAPs), which are blind‐ending short prosthetic grafts anastomosed to the brachial artery (BA) and implanted subcutaneously, via which cannulation and blood‐drawing from the BA was performed. Nineteen AAPs in 16 patients were evaluated. The AAP cumulative functional usage rate tended to drop within a year after its implantation because of infection and inappropriate positioning; however, its usability was extended for a maximum of 97 months after re‐implantation. The operative modification of minimal superficial repositioning of the BA anastomosed with the graft significantly improved its usage rate by easing the cannulation via the graft and eliminated usage withdrawal caused by infection and dislocation. Occlusion, thrombus, and ligation of the BA never occurred even after surgical repairs for infectious AAP. The use of an AAP as a shunt‐less vascular access could be an alternative to BA superficialization with avoidance of direct BA puncture.

Sorafenib treatment for papillary thyroid carcinoma with diffuse lung metastases in a child with autism spectrum disorder: a case report

BackgroundPediatric papillary thyroid carcinoma frequently presents with lymph node involvement and distant metastases. Sorafenib, an oral multikinase inhibitor, has been used to treat radioactive iodine (RAI) therapy-refractory thyroid carcinoma in adults; however, pediatric experience is limited. Medical procedures and hospitalization for children with autism spectrum disorder may be challenging.Case presentationAn 11-year-old boy with autism spectrum disorder and moderate intellectual impairment presented with dyspnea on exertion with thyroid carcinoma and diffuses lung metastases. Total thyroidectomy and adjuvant RAI therapy is the standard treatment; however, the latter therapy was impractical because of his respiratory status and challenging behaviors. He was therefore started on sorafenib 200xa0mg/day (150xa0mg/m2/day) and this dosage was increased to 400xa0mg/day (300xa0mg/m2/day). The adverse effects were mild and tolerable. After administration of medication, his dyspnea improved and surgery was performed. We attempted to administer RAI therapy after surgery; however, we abandoned it because he had difficulty taking care of himself according to isolation room rules. Thyrotropin suppression therapy was therefore started and sorafenib treatment (400xa0mg/day) resumed. Follow-up imaging showed regression of pulmonary metastases. The metastases have remained stable for over 24xa0months on continuous sorafenib treatment without serious adverse events.ConclusionWe inevitably used sorafenib as an alternative to standard therapy because of the patient’s specific circumstances. Individualized strategies for pediatric cancer patients with autism spectrum disorder are needed.

Abstract 2448: Suppression of MYCN-driven neuroblastoma malignant phenotype by telomerase-targeted tumor suppressor p53 transactivation

Background: Neuroblastoma (NB) is a primary malignant tumor in the peripheral sympathetic nervous system. High-risk group of NB has an unfavorable clinical course, even after treatment with current chemotherapy regimens and aggressive surgical resection. Therefore, a novel therapeutic strategy is needed for the treatment of high-risk group of NB. Recent accumulating evidences in whole-genome sequencing analysis have shown that human telomerase reverse transcriptase (hTERT) gene rearrangement and MYCN gene amplification are predictive biomarkers for the high-risk group of NB, in which massive transcriptional activation of hTERT mRNA was frequently observed. We recently developed two types of hTERT-driven oncolytic adenoviruses, OBP-301 and OBP-702, in which the hTERT promoter drives the expression of the viral E1A and E1B genes for tumor-specific virus replication, and OBP-702 further expresses tumor suppressor p53 protein. In this study, we investigated whether OBP-301 and OBP-702 inhibit cell viability and MYCN protein expression in human NB cells with different MYCN status. Methods: We used 3 human NB cell lines with or without MYCN amplification, including IMR-32 (MYCN-amplified), LA-N-5 (MYCN-amplified), SK-N-SH (MYCN-not amplified). The antitumor effects of OBP-301, OBP-702, and Ad-p53, a replication-defective adenovirus expressing p53 gene, were evaluated using XTT assay. Virus-induced apoptosis and MYCN suppression were analyzed by Western blot analysis. Results: OBP-301, OBP-702, and Ad-p53 suppressed the viability of all 3 NB cell lines, whereas OBP-702 showed the most profound anti-tumor effect especially in MYCN-amplified NB cells. OBP-702 induced higher p53 expression than Ad-p53, resulting in the p53-mediated apoptotic cell death. Although MYCN expression in NB cells with MYCN amplification was downregulated after infection with all types of adenoviruses, the inhibitory effect of OBP-702 was the strongest among these adenoviruses. Conclusions: These results suggest that a hTERT-driven oncolytic adenovirus OBP-702 is a promising antitumor agent to induce profound apoptotic cell death through p53 transactivation and MYCN suppression in human NB cells with or without MYCN amplification. In vivo experiments are under way to investigate the antitumor effect of OBP-702 against xenograft NB tumors. Citation Format: Terutaka Tanimoto, Hiroshi Tazawa, Hiroshi Noso, Takanori Oyama, Yasuo Urata, Shunsuke Kagawa, Takuo Noda, Toshiyoshi Fujiwara. Suppression of MYCN-driven neuroblastoma malignant phenotype by telomerase-targeted tumor suppressor p53 transactivation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2448.

Suspected early onset of congenital Langerhans cell histiocytosis involving ectopic cervical thymus and mediastinal thymus, simultaneously

To the Editor: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by accumulation of Langerhans cells [1,2]. Congenital LCH chiefly affects the skin and is selfhealing (Hashimoto–Pritzker disease), but rare involvements of the lung, bone, or liver have been reported [3]. Thymus is one of the uncommon organs involved by LCH [4]. Ectopic thymus is an extremely rare etiology of a neck mass in an infant which results from abnormal embryogenesis of the thymus [5,6]. We present a case of congenital LCH with simultaneous involvement of ectopic cervical thymus and mediastinal thymus. A 2-month-old female without any significant medical history through the prenatal and neonatal period was brought to a physician complaining of left submandibular swelling. On physical examination, there was an elastic, soft, and poorly movable mass in the left submandibular area. The mass was 3 cm in diameter and had a smooth surface. Computed tomography (CT) revealed cystic and solid components in the mass (Fig. 1A). An open biopsy of the mass was performed. The mass was well demarcated from surrounding tissues and was resected without macroscopic leaving residues. The pathological examination showed proliferation of CD1a positive cells with a round nuclear and rich cytoplasm in an eosinophil rich background (Fig. 1B–D). Diagnosis of LCH was made. Moreover, the resected mass contained ectopic thymic tissue whose architecture was partly effaced by infiltration of Langerhans cells (Fig. 1B and E). Reconfirmation of the CT image revealed the enlarged mediastinal thymus with multiple cysts and punctate calcifications which are specific findings of the thymic involvement of LCH (Fig. 1A) [7]. Although biopsy of the mediastinal thymic LCH