Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model.

Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.

[A case of rectovaginal metastasis 6 years after initial resection of extra-gastrointestinal stromal tumor of vulvar origin].

A 53-year-old woman who had undergone excision of KIT-positive extra-gastrointestinal stromal tumor (EGIST) of the vulva 6 years ago presented to our hospital due to a positive fecal occult blood test. Colonoscopy revealed a submucosal tumor in the rectum ventral side. In addition, computed tomography and magnetic resonance imaging revealed a tumor in the rectovaginal septum. For diagnostic and therapeutic purposes, the tumor was resected via the perineal approach. The resected specimen analysis revealed a KIT-positive gastrointestinal stromal tumor (GIST). Following immunopathological and genetic mutation identifications, GIST of the rectovaginal septum from vulva EGIST metastasis was diagnosed. It is important to consider primary GIST and metastatic GIST as differential diagnoses in the case of a rectal submucosal tumor detected by endoscopy.

[A case of upper gastrointestinal bleeding due to a ruptured gastric aneurysm caused by arteriosclerosis derived from primary aldosteronism-induced hypertension].

A 77-year-old woman with a history of hypertension underwent upper gastrointestinal endoscopy for hematemesis, and vasodilation with erosion was detected. Contrast-enhanced computed tomography and abdominal angiography revealed a gastric aneurysm penetrating the stomach wall. Endoscopic hemostasis was thought to be not applicable to a ruptured aneurysm. Transcatheter arterial embolization was not performed because of technical difficulties. Therefore, local gastric resection was performed. It was later determined that the cause of the persistent hypertension was primary aldosteronism, which was thought to cause arteriosclerotic obstruction of the celiac, common hepatic, and splenic arteries, resulting in the formation of the gastric arterial aneurysm. In the case of upper gastrointestinal bleeding, keeping primary aldosteronism in mind as a differential diagnosis is important to make a precise diagnosis and suitable treatment selection.

Transplantation of a decellularized mitral valve complex in pigs.

PURPOSE: Conventional mitral valve replacement is associated with the loss of natural continuity of the mitral valve complex. This study evaluated the morphologic/histological characteristics and function of a decellularized mitral valve used as a transplantable graft. METHODS: Hearts excised from pigs were decellularized by perfusion using detergent. Grafts with the mitral annulus, valve, chordae, and papillary muscle isolated from the decellularized heart were then transplanted into recipient pigs. After transplantation, the function of the graft was analyzed through echocardiography. A histological analysis was performed to evaluate the postoperative features of the decellularized graft. RESULTS: The decellularized graft was successfully transplanted in all cases but one. The remaining grafts maintained their morphology and function. They did not exhibit mitral regurgitation or stenosis. Only one animal survived for 3 weeks, and a histological analysis was able to be performed in this case. The transplanted valve was re-covered with endothelial cells. The microvessels in the papillary muscle were recellularized with vascular endothelial cells, and the papillary muscle was completely attached to the papillary muscle of the recipient. CONCLUSION: The early outcome of decellularized mitral graft transplantation was acceptable. This native organ-derived acellular scaffold is a promising candidate for the replacement of the mitral valve complex.

[Hematemesis due to rupture of splenic artery pseudoaneurysm in association with segmental arterial mediolysis:a case report].

A gastric ulcer was detected in a 54-year-old man who underwent upper gastrointestinal endoscopy for hematemesis. An abdominal contrasted computed tomography scan detected a splenic artery aneurysm adjacent to the gastric wall. Endoscopic hemostasis was thought to be risky owing to possible rupture of the aneurysm. Rupture of a splenic artery pseudoaneurysm due to segmental arterial mediolysis (SAM) was diagnosed by abdominal angiography, and subsequently transcatheter arterial embolization was performed. In cases of upper gastrointestinal hemorrhage, hemostasis is often performed during the emergency endoscopic examination. However, in cases of massive gastrointestinal bleeding, the possibility of a splenic artery aneurysm, in association with SAM, should be recognized. The risk of rupturing the aneurysm should be considered in selecting the most suitable treatment.

Efficacy of New Polylactic Acid Nonwoven Fabric as a Hemostatic Agent in a Rat Liver Resection Model.

BACKGROUND: During minimally invasive surgery, efficient and nontoxic hemostats are important for difficult to access bleeding areas. Polylactic acid is an ecofriendly hemostatic agent and we aimed to evaluate the efficacy of a polylactic acid nonwoven fabric (PLAF) developed by Toray Industries, Inc, on liver hemostasis in a preclinical study. MATERIALS AND METHODS: PLAF consists of both 1-µm diameter fibers and 100-µm diameter beaded fibers. Four rats were used, and 2 trough-shaped resections of the liver parenchyma were performed (n = 8 lobes). Immediately after the resection, PLAF (PLAF group: n = 4 lobes) or rayon gauze (Rayon group: n = 4 lobes) were applied on the resected plane and compressed manually. We compared the mean time to hemostasis and blood loss per lobe, as well as histological findings between the groups. RESULTS: The PLAF group had a significantly shorter bleeding time ( P = .006), and showed lower blood loss compared with the Rayon group ( P = .076). Histopathological evaluation showed a large amount of beads on the liver surface in the PLAF group. Aggregated red blood cells evident by electron microscopy and von Willebrand factor immunofluorescence were seen surrounding the beads. The PLAF group showed significantly greater von Willebrand factor expression than the Rayon group ( P = .004). DISCUSSION: This new PLAF showed superior outcomes thanks to its unique characteristic of forming beaded nanofibers, and it has the potential to be an efficient hemostat in minimally invasive surgery in the human body.

[Intraductal papillary neoplasm of bile duct developed in a patient with IgG4-related sclerosing cholangitis, autoimmune pancreatitis, and myasthenia gravis].

In the course of treatment for myasthenia gravis, enlargement of a cystic mass in the liver with peripheral bile duct dilation, diffuse pancreatic enlargement, and serum IgG4 level elevation was identified in a 65-year-old man. Following the diagnosis of autoimmune pancreatitis, a left hepatectomy was performed because of suspected malignancy of the cystic lesion. Analysis of the resected specimen revealed the cystic lesion to be a dilated bile duct. Intraductal papillary tumor comprising fibrovascular stalks covered by neoplastic epithelium was identified in the lesion. Infiltration of IgG4-positive plasma cells was discovered around the cystic lesion. Finally, a diagnosis of intraductal papillary neoplasm of bile duct with IgG4-related sclerosing cholangitis was made. Autoimmune diseases, including IgG4-related diseases, require careful observation because of their potential for malignancy.

The Safety and Anti-Tumor Effects of Ozonated Water in Vivo.

Ozonated water is easier to handle than ozone gas. However, there have been no previous reports on the biological effects of ozonated water. We conducted a study on the safety of ozonated water and its anti-tumor effects using a tumor-bearing mouse model and normal controls. Local administration of ozonated water (208 mM) was not associated with any detrimental effects in normal tissues. On the other hand, local administration of ozonated water (20.8, 41.6, 104, or 208 mM) directly into the tumor tissue induced necrosis and inhibited proliferation of tumor cells. There was no significant difference in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL)-positive cells following administration of ozonated water. The size of the necrotic areas was dependent on the concentration of ozonated water. These results indicate that ozonated water does not affect normal tissue and damages only the tumor tissue by selectively inducing necrosis. There is a possibility that it exerts through the production of reaction oxygen species (ROS). In addition, the induction of necrosis rather than apoptosis is very useful in tumor immunity. Based on these results, we believe that administration of ozonated water is a safe and potentially simple adjunct or alternative to existing antineoplastic treatments.

[Successful resection of a gastric aberrant pancreas causing gastrointestinal bleeding by laparoscopy and endoscopy cooperative surgery].

A man in his 50s was admitted to our hospital for treatment of hematemesis. Endoscopy revealed arterial bleeding from a gastric submucosal tumor and endoscopic hemostasis was successful. However, surgical resection was contemplated to prevent recurrent bleeding and for making a definitive diagnosis. Surgical resection was eventually performed by laparoscopy and endoscopy cooperative surgery (LECS), and the tumor was pathologically diagnosed to be a gastric aberrant pancreas. We think that LECS is suitable for a gastric aberrant pancreas causing gastrointestinal bleeding, because the procedure is effective for tumor resection with minimal removal of the stomach wall.

A fundamental study of cryoablation on normal bone: diagnostic imaging and histopathology.

Cryoablation is a minimally invasive cancer treatment. In this study, the effects of cryoablation on normal rabbit bone were evaluated using imaging and histopathological examinations. Cryoablation was performed using a Cryo-Hit (Galil Medical, Yokneam, Israel). Under anesthesia, one cryoablation needle was inserted at the center of the femur (day 0). To create an ice ball (2 x 3 cm), two 10-min freeze cycles were performed, separated by a 5-min thaw cycle. During cryoablation, changes in the bone and regional tissue were monitored using magnetic resonance imaging (MRI). MRI scans, computed tomography (CT) scans, and collections from the femur (for histopathological evaluation) were performed on days 7, 14, 28, and 56. In terms of the all rabbits' general conditions, we did not observe lameness, decreased appetite, or any other side effects during the experimental periods. Histopathological evaluations of the femur were performed using hematoxylin and eosin staining. MRI indicated inflammation around the ice ball on day 7. Subsequently, the area of inflammation gradually decreased from days 14 to 56. In the histopathological examination, necrosis of bone marrow cells and endosteum were observed from days 7 to 56. No regeneration of bone marrow cells was observed during the experimental period. On the other hand, cryoablation did not influence osteoblasts. Furthermore, there was no pathologic fracture during the experimental period. Our results suggest that cryoablation does not induce severe adverse effects on normal bone, and therefore has potential as a therapeutic option for bone tumors, including metastatic tumors to bone.