Effect of Subcutaneous Adrenaline/Saline/Lidocaine Injection on Split-Thickness Skin Graft Donor Site Wound Healing

[Background] Subcutaneous injection of tumescent solution, which contains local anesthetic, adrenaline, and saline, before split-thickness skin graft harvesting, shows a significant hemostatic effect. This method can reduce the initial bleeding from the donor site. The aim of this study is to assess the benefits of controlling the bleeding from donor sites by tumescent injection. A randomized, controlled trial was performed to compare the wound healing of split-thickness skin graft donor sites treated with or without tumescent injection. [Methods] This randomized, controlled trial examined donor site healing days as the main measure of outcome. postoperative pain, donor site ulceration, and scar quality were evaluated as secondary outcome measures. Patients planned for split-thickness skin graft harvest were randomly assigned to receive either pre-harvest subcutaneous injection of local anesthetic, adrenaline, and saline solution (tumescent solution) (Group 1) or post-harvest application of adrenaline solution-soaked gauze to the skin graft donor sites (Group 2). Donor sites were treated with calcium alginate dressings after graft harvesting. On the 10th postoperative day, the dressings were removed and donor site healing were measured. Follow-up evaluation of scar quality was performed 6 months after surgery. Postoperative pain was evaluated on the 1st day after operating. [Results] Forty-five patients (26 males; average age 61.8 years) completed the late follow-up evaluation (6 months postoperatively), with 26 patients in group 1 and 19 in group 2. There were no significant differences between the two groups in any of the outcome measures. [Conclusion] Tumescent technique provides sufficient hemostasis in split skin graft donor sites, especially the initial bleeding just after graft harvesting, without any negative effects. Larger series should be studied to evaluate the effect in donor site wound healing

Hemodynamic Analysis of a Microanastomosis Using Computational Fluid Dynamics

[Background] Technical issues in free flap transfer, such as the selection of recipient vessels and the positioning and method of anastomosis of the vascular pedicle, have been the subject of vigorous debate. Recent developments in computational fluid dynamics (CFD) have enabled the analysis of blood flow within microvessels. In this study, CFD was used to analyze hemodynamics in a microanastomosis. [Methods] In the fluid calculation process, the fluid domain modelizes microvessels with anastomosis. The inlet flow conditions were measured as venous waveform, and the fluid is simulated as blood. Streamlines (SL), wall shear stress (WSS), and oscillatory shear index (OSI) at the anastomosis were visualized and analyzed for observing effects from the flow field. [Results] Some flow disruption was evident as the SL passed over the sutures. The maximum recorded WSS was 13.37 Pa where the peak of a suture was exposed in the lumen. The local maximum value of the OSI was 0.182, recorded at the base of the anastomosis on the outflow side. [Conclusion] In the ideal anastomosis, the SL is disrupted as little as possible by the sutures. The WSS indicated that thrombus formation is unlikely to occur at suture peaks, but more likely to occur at the base of sutures, where the OSI is high. Tight suture knots are important in microanastomosis

Risk Factors of Free Flap Complications in Reconstruction for Head and Neck Cancer

Background: Although head and neck reconstruction using free flaps has become a common procedure, flap complications remain a concern. This study aimed to analyze the risk factors of free flap complications and to identify the causes of these complications. Methods: We studied 97 patients with head and neck cancer with intraoral defects who underwent reconstruction using free flaps at Tottori University Hospital between 2011 and 2020. We used a retrospective cohort study design to investigate whether flap complications, including flap necrosis (total and partial) and flap dehiscence, were related to various factors, including the underlying disease condition, treatment status, and surgical factors. Results: Of the 97 patients analyzed, total flap necrosis was observed in one patient (1.0%). The incidence rate of flap complications, including flap necrosis and flap dehiscence, was 29.9%. When the time taken to perform one vascular anastomosis, including preparation of the recipient vessel and flap vessel, exceeded 30 min, the incidence rates of flap necrosis (total and partial) (odds ratio, 8.30; 95% confidence interval, 1.91-36.00; P = 0.005) and flap dehiscence (odds ratio, 3.46; 95% confidence interval, 1.05-11.36; P = 0.041) increased significantly. Conclusion: The time taken to perform one vessel anastomosis was the factor that contributed the most to the incidence of flap complications. Reconstructive surgeons should reduce the incidence of flap complications by keeping the known risk factors of the surgery in mind and by aiming to complete a vascular anastomosis time, including the time taken for the preparation of vessels, of ≤ 30 min per vessel during surgery

皮下埋没縫合および皮下閉鎖式陰圧ドレーン挿入による、回腸人工肛門閉鎖術後創部感染の減少効果について

Purpose: The purpose of this study was to evaluate the effectiveness of a wound closure method using a combination of subcuticular sutures and subcutaneous closed-suction drainage (SS closure) for preventing incisional surgical site infection (SSI) in loop ileostomy closure. Methods: A total of 178 consecutive patients who underwent loop ileostomy closure at Nara Medical University Hospital between 2004 and 2018 were retrospectively assessed. The patients were divided into 2 groups: the conventional skin closure (CC) group from 2004 to 2009 (75 patients) and the SS closure (SS) group from 2010 to 2018 (103 patients). The incidence of incisional SSI was compared between the two groups, and the factors associated with incisional SSI were examined by univariate and multivariate analyses. Results: Incisional SSI occurred in 7 cases (9.3%) in the CC group but was significantly reduced to only 1 case (0.9%) in the SS group (p = 0.034). In the univariate analysis, the hemoglobin levels, serum creatinine levels, and SS closure were associated with incisional SSI. SS closure was the only independent preventive factor for incisional SSI according to the multivariate analysis (hazard ratio = 0.24, p = 0.011). Conclusion: The combination of subcuticular sutures and subcutaneous closed-suction drainage may be a promising way of preventing incisional SSI in loop ileostomy closure.博士（医学）・乙第1496号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02128-x

Associations among Preoperative Malnutrition, Muscle Loss, and Postoperative Walking Ability in Intertrochanteric Fractures: A Retrospective Study

Sarcopenia and malnutrition are increasing in older adults and are reported risk factors for functional impairment after hip fracture surgery. This study aimed to investigate the associations between skeletal muscle mass loss, malnutrition, and postoperative walking ability in patients with hip fracture. We retrospectively reviewed patients who underwent intertrochanteric fracture surgery at our institute. The psoas muscle index, controlling nutritional status score, and functional ambulation category (FAC) were used to evaluate skeletal muscle mass, nutritional status, and walking ability, respectively. Six months after surgery, walking ability was assessed as either “gait disturbance” or “independent gait”. Multivariate binomial logistic regression analysis, with skeletal muscle mass, nutritional status, and other factors, was used to predict the risk of being assigned to the gait disturbance group. This study included 95 patients (mean age, 85.2 years; 70 women). Sixty-six patients had low skeletal muscle mass, 35 suffered from malnutrition, and 28 had both. Malnutrition and low skeletal muscle mass were significantly associated with postoperative gait disturbance (FAC < 3). Preoperative low skeletal muscle mass and malnutrition were risk factors for postoperative poor walking ability. Further preventive interventions focusing on skeletal muscle mass and nutritional status are required

Analysis of the Optimum Tapering Angle in Microanastomosis Using Computational Fluid Dynamics

Background: In free flap transfer, size discrepancy between the vascular pedicle and recipient vessel can create a problem for microsurgeons and sometimes induces postoperative thrombus formation. When there is a major difference between the diameters of the vascular pedicle and the recipient vessel, the larger vessel is often tapered to perform the anastomosis properly. However, the decision on the tapering angle used depends mostly on the operator’s experience. In this study, computational fluid dynamics (CFD) was used to investigate the optimum tapering angle. Methods: Using ANSYS ICEM 16.0 (ANSYS Japan, Tokyo, Japan), simulated vessels of diameters 1.5 mm and 3.0 mm were designed and then used to produce four anastomosis models with the 3.0-mm vessel tapered at angles of 15º, 30º, 60º, and 90º (no tapering). Venous perfusion with a mean value of 13.0 mL/min was simulated, and this was passed through the four anastomosis models in both the forward direction (F), from the smaller to the larger vessel, and the retrograde direction (R), from the larger to the smaller vessel. The velocity, wall shear stress (WSS), and oscillatory shear index (OSI) were measured in these eight patterns and then analyzed using OpenFOAM version 5. Results: The decrease in velocity was limiting. The WSS was greater in the R direction than the F direction at every tapering angle. The OSI also tended to be almost the same in the F direction, and lower at smaller tapering angles in the R direction. And, it was greater in the F direction than in the R direction at every tapering angle. The OSI values for 15º and 30º were almost identical in the R direction. Conclusion: The risk of thrombus formation is thought to be lower when tapering is used for anastomosis if the direction of flow is from the larger to the smaller vessel, rather than vice versa. These results also suggest that the optimum tapering angle is approximately 30º in both directions

犬モデルにおける ex vivo および in vivo 遺伝子治療のための代替遺伝子導入技術の開発

Introduction: Gene therapy have recently attracted much attention as a curative therapeutic option for inherited single gene disorders such as hemophilia. Hemophilia is a hereditary bleeding disorder caused by the deficiency of clotting activity of factor VIII (FVIII) or factor IX (FIX), and gene therapy for hemophilia using viral vector have been vigorously investigated worldwide. Toward further advancement of gene therapy for hemophilia, we have previously developed and validated the efficacy of novel two types of gene transfer technologies using a mouse model of hemophilia A. Here we investigated the efficacy and safety of the technologies in canine model. Especially, validations of technical procedures of the gene transfers for dogs were focused. Methods: Green fluorescence protein (GFP) gene were transduced into normal beagle dogs by ex vivo and in vivo gene transfer techniques. For ex vivo gene transfer, blood outgrowth endothelial cells (BOECs) derived from peripheral blood of normal dogs were transduced with GFP gene using lentivirus vector, propagated, fabricated as cell sheets, then implanted onto the omentum of the same dogs. For in vivo gene transfer, normal dogs were subjected to GFP gene transduction with non-viral piggyBac vector by liver-targeted hydrodynamic injections. Results: No major adverse events were observed during the gene transfers in both gene transfer systems. As for ex vivo gene transfer, histological findings from the omental biopsy performed 4 weeks after implantation revealed the tube formation by implanted GFP-positive BOECs in the sub-adipose tissue layer without any inflammatory findings, and the detected GFP signals were maintained over 6 months. Regarding in vivo gene transfer, analyses of liver biopsy samples revealed more than 90% of liver cells were positive for GFP signals in the injected liver lobes 1 week after gene transfers, then the signals gradually declined overtime. Conclusions: Two types of gene transfer techniques were successfully applied to a canine model, and the transduced gene expressions persisted for a long term. Toward clinical application for hemophilia patients, practical assessments of therapeutic efficacy of these techniques will need to be performed using a dog model of hemophilia and FVIII (or FIX) gene.博士（医学）・乙第1517号・令和3年12月21日© 2021, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

超吸水性ポリマー球状塞栓物質の高張食塩水を用いた膨潤抑制法の開発

PURPOSE: To analyze size changes of superabsorbent polymer (SAP) microspheres with the reduced expansion technique, and to evaluate pharmacological advantages of transarterial chemoembolization using cisplatin-loaded SAP microspheres with the reduced expansion technique. MATERIALS AND METHODS: In an in vitro study, diluted contrast materials containing different concentrations of sodium ions were examined to expand SAP microspheres and determined the reduced expansion technique. Size distributions of cisplatin-loaded SAP microspheres were analyzed. In an in vivo study, TACE was performed using cisplatin-loaded SAP microspheres with the reduced expansion and control techniques in 18 VX2 rabbits. RESULTS: The degree of expansion was reduced to the greatest extent by using a mixture of non-ionic contrast material and 10% NaCl at a 4:1 ratio. The mean diameter of the reduced expansion of cisplatin-loaded SAP microspheres was 188.4 μm, while that of the control expansion was 404.9 μm. The plasma platinum concentrations of the reduced expansion group at 5 min after TACE were significantly higher than those of the control expansion group (2.19 ± 0.77 vs. 0.75 ± 0.08 μg/mL, P = .01). The tumor platinum concentrations of the reduced expansion group at 1 h were significantly higher than those of the control expansion group (10.76 ± 2.57 vs. 1.57 ± 0.14 μg/g, P = .044). CONCLUSION: The expanding level of SAP microspheres can be reduced by using hypertonic saline. Cisplatin-loaded SAP microspheres with the reduced expansion technique have the advantages of achieving higher cisplatin tissue concentration in TACE for liver tumors.博士（医学）・甲第709号・令和元年6月26日© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular and interventional radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00270-018-1990-4

Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin