Yasuhide Morikawa

Prevention of allogeneic cardiac graft rejection by transfer of ex vivo expanded antigen-specific regulatory T-cells.

The rate of graft survival has dramatically increased using calcineurin inhibitors, however chronic graft rejection and risk of infection are difficult to manage. Induction of allograft-specific regulatory T-cells (Tregs) is considered an ideal way to achieve long-term tolerance for allografts. However, efficient in vitro methods for developing allograft-specific Tregs which is applicable to MHC full-mismatched cardiac transplant models have not been established. We compared antigen-nonspecific polyclonal-induced Tregs (iTregs) as well as antigen-specific iTregs and thymus-derived Tregs (nTregs) that were expanded via direct and indirect pathways. We found that iTregs induced via the indirect pathway had the greatest ability to prolong graft survival and suppress angiitis. Antigen-specific iTregs generated ex vivo via both direct and indirect pathways using dendritic cells from F1 mice also induced long-term engraftment without using MHC peptides. In antigen-specific Treg transferred models, activation of dendritic cells and allograft-specific CTL generation were suppressed. The present study demonstrated the potential of ex vivo antigen-specific Treg expansion for clinical cell-based therapeutic approaches to induce lifelong immunological tolerance for allogeneic cardiac transplants.

The use of an ileostomy connector to diminish the frequency of defecation prior to ileostomy closure in patients with a pelvic pouch

A new method for allowing stool passage into the pelvic pouch before ileostomy closure to verify the defecation state and diminish stool frequency is reported herein. This was accomplished by fitting an ileostomy connector connecting the proximal and distal openings of the diverting loop stoma. The ileostomy connector was initially in place for 6 h a day, the length of time being gradually increased until it was able to be left in for 24 h a day over a 3-month period. The calculated daily frequency of stools decreased from 24 to 6 or 7 times, and the mean daily frequency immediately after ileostomy closure was 6.5 times. Physiological study also showed an improvement, with squeeze pressure increasing from 35 cmH2O to 116 cmH2O and the maximum tolerated volume increasing from 35 ml before, to 90 ml 3 months following the use of an ileostomy connector. Thus, we conclude that an ileostomy connector may be useful to predict postoperative functional outcome and its complications, and to diminish the frequency of defecation before ileostomy closure in patients with a covering loop stoma.

Reappraisal of adhesive strapping as treatment for infantile umbilical hernia

Most umbilical hernias spontaneously close by 3–5 years of age; therefore, surgical repair is considered only in children whose hernias have not closed by this point. At present, adhesive strapping is not the preferred treatment for umbilical hernias because of the lack of supporting evidence regarding its efficacy, and its association with skin complications. This aim of this study was to examine umbilical hernia closure on ultrasonography, and reassess the merits of adhesive strapping.

Endoscopic chemocauterization for pyriform sinus fistula in children

Although complete excision is the standard treatment for pyriform sinus fistula (PSF), it has recently been suggested that chemocauterization via the internal orifice of the fistula could be an effective non‐invasive treatment for the condition. The present report describes the details of our experience with and the efficacy of endoscopic chemocauterization for pediatric PSF.

Fluorescence Visualization of the Enteric Nervous Network in a Chemically Induced Aganglionosis Model.

Gastrointestinal motility disorders, severe variants in particular, remain a therapeutic challenge in pediatric surgery. Absence of enteric ganglion cells that originate from neural crest cells is a major cause of dysmotility. However, the limitations of currently available animal models of dysmotility continue to impede the development of new therapeutics. Indeed, the short lifespan and/or poor penetrance of existing genetic models of dysmotility prohibit the functional evaluation of promising approaches, such as stem cell replacement strategy. Here, we induced an aganglionosis model using topical benzalkonium chloride in a P0-Cre/GFP transgenic mouse in which the neural crest lineage is labeled by green fluorescence. Pathological abnormalities and functional changes in the gastrointestinal tract were evaluated 2–8 weeks after chemical injury. Laparotomy combined with fluorescence microscopy allowed direct visualization of the enteric neural network in vivo. Immunohistochemical evaluation further confirmed the irreversible disappearance of ganglion cells, glial cells, and interstitial cell of Cajal. Remaining stool weight and bead expulsion time in particular supported the pathophysiological relevance of this chemically-induced model of aganglionosis. Interestingly, we show that chemical ablation of enteric ganglion cells is associated with a long lifespan. By combining genetic labeling of neural crest derivatives and chemical ablation of enteric ganglion cells, we developed a newly customized model of aganglionosis. Our results indicate that this aganglionosis model exhibits decreased gastrointestinal motility and shows sufficient survival for functional evaluation. This model may prove useful for the development of future therapies against motility disorders.

Application of nuclear medicine to achieve less invasive surgery for malignant solid tumors in children

The use of nuclear medicine for the management of malignant tumor, such as radioguided surgery and sentinel lymph node biopsy (SLNB), has been widely accepted in the adult practice. However, there are very few studies to apply those techniques for pediatric diseases. The aim of this study was to investigate the feasibility of application of nuclear medicine in surgery for neuroblastoma (NB) or rhabdomyosarcoma (RMS) in children.

Basic Study of Appropriate Knot-Tying Force in the Gastrointestinal Tract for Development of Haptic Surgical Robot

While endoscopic surgery has frequently been performed as minimally invasive surgery in recent years, it is more difficult to perform than open surgery. Our experience with endoscopic surgery using the latest surgical robot daVinci at our hospital has shown that robotic surgery is beneficial in terms of the safe and easy performance of difficult surgical techniques, however, one of its drawbacks use of the robot does not impart a feeling that the surgeon’s hands are touching the tissues, making meticulous procedures rather difficult (Anthony et al., 2004). In ordinary open surgery or endoscopic surgery, surgeons apply knot-tying force spontaneously based on their experience and the feel of the tissues being handled. In robotic surgery, on the other hand, the force exerted is decided on the basis of visual information alone, such as the tautness of the thread and degree of deformation of the tissue. We therefore thought that objective data should be obtained to determine the optimal knottying force to apply when suturing during robotic surgery. To achieve this goal we developed forceps for robotic surgery whose tips have six degrees of freedom ( Matsuhira et al., 2003) and a new system at our hospital that displays information about force at the tip of the forceps measured by a sensor to the surgeons on monitor or via auditory signals. No studies have ever been conducted to investigate the relationship between knot-tying force and the efficiency of wound healing in the operated tissue, or to estimate the optimal knot-tying force for tissues. We thought that knowing the optimal knot-tying force for tissues in terms of the efficiency of wound healing would make it possible to tie knots based on the information concerning the force at the tip of the forceps displayed during robotic surgery, and to provide basic data in vivo for the development of robotic forceps that impart a feeling that the surgeon’s hands are touching the sutures and tissues. The purpose of this study was to estimate the optimal knot-tying force by investigating the relationship between the force applied assessed on the basis of the information displayed on the surgeon’s monitor and the efficiency of wound healing in the gastrointestinal tract in canine models. O pe n A cc es s D at ab as e w w w .ite ch on lin e. co m