Surgical Punctal Occlusion; Combined Lacrimal Canaliculi Cauterization and Punctal Suturing for Severe Dry Eye.

Purpose: To evaluate the treatment outcome of surgical punctal occlusion with combined canaliculi ablation and punctal suturing in patients with severe dry eye. Methods: Eleven eyes of seven patients were diagnosed with severe dry eye with decreased lacrimal secretion and were refractory to treatment with various eye drops and/or had repeatedly experienced loss of punctal plugs, and continued to experience subjective symptoms received surgical punctal occlusion. In 20 puncta, lacrimal canaliculi ablation was performed along the entire length of the lacrimal canaliculus where a diathermy needle could be inserted. After resection of the annulus fibrosus in the peri-punctal area, tight cross-stitch suturing of the puncta was performed with 8-0 absorbent thread. Visual acuity, corneal staining score according to the area (A) and density (D) classification, and Schirmer tear test (STT); tear break up time (tBUT); and subjective symptoms assessed by the University of North Carolina (UNC) and Dry Eye Management Scale were compared before and one year after surgery. Results: Recanalization occurred in 1/20 puncta (5.0% at month 5) in 1/11 eyes. Student's t-test showed significant improvement at one year compared with preoperative values for LogMAR value (P = 0.019), corneal staining score A (P = 0.00003) and D (P = 0.0003), STT (P = 0.004), and subjective symptoms (P = 0.015). No change was shown in tBUT and no serious adverse event occurred. Conclusion: This improved, minimally invasive surgical procedure has a low recanalization rate and achieves both objective and subjective improvements at one year.

[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.

Surgical Treatment of a Retropharyngeal Abscess in a Japanese Black Cow.

A 17-month-old Japanese Black cow presented with inappetence, wheezing, dysphagia, and drooling. Radiography and ultrasonography revealed an oval, dorsal, pharyngeal mass, with an internal horizontal line demarcating the radiolucent area from the radio-opaque area. Upper airway endoscopy revealed pus-like deposits in the dorsal nasal passage, hyperemia, and edema in the dorsal pharynx, leading to swelling and airway obstruction. Manual palpation, after sedation, revealed a thickened mass surface, which was difficult to rupture with manual pressure. After inserting a linear sonographic probe through the mouth to establish the vascularity surrounding the mass and to identify a relatively thin-walled area, a trocar was pierced into the mass under endoscopic guidance, and the opening was enlarged manually. The mass was filled with stale pus-like material, which was removed manually. The abscess cavity was washed using saline and povidone-iodine. Day 1 post-surgery, dysphagia and wheezing disappeared. Day 16 post-surgery, endoscopy showed significant improvement in the airway patency. One year postoperatively, the owner reported that the cow had an uneventful recovery. For deep abscesses, such as bovine pharyngeal abscesses, it is important to perform a preoperative transoral Doppler ultrasonography to assess the vascularity and thickness of the abscess wall for safe trocar insertion and abscess drainage.

Intra-abdominal mass containing controlled internal drug release (CIDR) devices detected by CT in a Japanese Black cow.

This report describes an intra-abdominal mass caused by progesterone-containing controlled internal drug release (CIDR) devices in the abdominal cavity of a 28-month-old Japanese Black heifer presenting with infertility. Rectal examination revealed a mass containing a cartilage-like object in the pelvic cavity. Computed tomography revealed a mass containing two T-shaped foreign bodies. Laparotomy was performed to remove the mass containing the foreign bodies. The heifer was healthy at discharge seven days post-surgery. This case adds CIDR device as a new etiology for intra-abdominal masses. Furthermore, it highlights the usefulness of CT in diagnosing deep abdominal lesions.

Decellularized Organ-Derived Scaffold Is a Promising Carrier for Human Induced Pluripotent Stem Cells-Derived Hepatocytes.

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research.

Identification of domestic cat hepadnavirus from a cat blood sample in Japan.

The hepatitis B virus (Hepadnaviridae) induces chronic hepatitis and hepatic cancer in humans. A novel domestic cat hepadnavirus (DCH) was recently identified in several countries, however, the DCH infection status of cats in Japan is unknown. Therefore, we investigated the DCH infection rate of 139 cat samples collected in Japan. We identified one positive blood sample (0.78%) from a 17-year-old female cat with chronically elevated alanine aminotransferase. Phylogenetic analysis demonstrated that the DCH strain identified in this study is genetically different from strains in other countries. Further investigations are required to elucidate the evolution of DCH and the impact of DCH infection on hepatic diseases in domestic cats.

An organ-derived extracellular matrix triggers in situ kidney regeneration in a preclinical model.

It has not been considered that nephrons regenerate in adult mammals. We present that an organ-derived extracellular matrix in situ induces nephron regeneration in a preclinical model. A porcine kidney-derived extracellular matrix was sutured onto the surface of partial nephrectomy (PN)-treated kidney. Twenty-eight days after implantation, glomeruli, vessels, and renal tubules, characteristic of nephrons, were histologically observed within the matrix. No fibrillogenesis was observed in the matrix nor the matrix-sutured kidney, although this occurred in a PN kidney without the matrix, indicating the structures were newly induced by the matrix. The expression of renal progenitor markers, including Sall1, Six2, and WT-1, within the matrix supported the induction of nephron regeneration by the matrix. Furthermore, active blood flow was observed inside the matrix using computed tomography. The matrix provides structural and functional foundations for the development of cell-free scaffolds with a remarkably low risk of immune rejection and cancerization.

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.

Decellularized liver scaffolds promote liver regeneration after partial hepatectomy.

The resectable liver volume is strictly limited and this reduces the number of patients who may be treated. Recently, "tissue/organ decellularization", a new approach in bioengineering, has been investigated for its ability to produce a native organ scaffold by removing all the viable cells. Such a scaffold may support the repair of damaged or injured tissue. The purpose of this study was to evaluate the potential contribution of liver scaffolds to hepatic regeneration after hepatectomy. We sutured the partial liver scaffolds onto the surfaces of partially hepatectomized porcine livers and assessed their therapeutic potential by immune histological analysis at various time points. Animals were sacrificed after surgery and the implanted scaffolds were evaluated for the infiltration of various types of cells. Immune histochemical study showed that blood vessel-like structures, covered with CD31 positive endothelial cells and ALB positive cells, were present in all parts of the scaffolds at days 10 and 28. Blood inflow was observed in some of these ductal structures. More interestingly, CK19 and EpCAM positive cells appeared at day 10. These results suggest that the implantation of a decellularized organ scaffold could promote structural reorganization after liver resection.

[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.

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.

Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment.

Tumor hypoxia is a severe problem affecting tumor therapy because it reduces the sensitivity of chemotherapy and radiation therapy. Ozone has been known to improve peripheral blood perfusion and oxygen partial pressure. The effect of ozonated water on tumor hypoxia, alone and in combination with an antitumor drug was studied in the present study. Following intraperitoneal administration of ozonated water to colon-26-bearing mice, the Hoechst 33342-positive area and the intratumoral oxygen partial pressure was significantly increased. The tumor growth rate was more suppressed when ozonated water was combined with cisplatin (CDDP) compared with CDDP treatment alone. The number of Ki-67-positive cells significantly decreased, whereas the number of TUNEL-positive cells significantly increased. The present study showed that ozonated water increased intratumoral blood perfusion and improved tumor hypoxia. In addition, ozonated water increased the therapeutic effect of CDDP. These findings, as well as previous reports, suggest that tumor growth is suppressed after treatment with ozonated water as the amount of CDDP reaching the tumor is increased when the intratumoral blood perfusion is increased due to the ozonated water. Thus, the administration of ozonated water may be a new therapeutic approach to solve current concerns regarding antitumor treatment.

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.

Anti-inflammatory effects of ozonated water in an experimental mouse model.

Previous studies have suggested that ozonated water is safe and possesses antibacterial effects for treatment of experimental peritonitis rats. In this study, we evaluated the anti-inflammatory effects of ozonated water that was intraperitoneally injected into an experimental inflammatory mouse model. The concentrations of dissolved ozone decreased constantly and lineally, while the half-life of dissolved ozone was 36.8±2.7 min (27°C). The 10-ppm ozonated water was injected intraperitoneally into mice with lipopolysaccharide (LPS)-induced acute inflammation. The results showed that the intraperitoneal injection of ozonated water decreased the levels of tumor necrosis factor-α (TNF-α) and increased the activity of superoxide dismutase (SOD). The results suggest that ozonated water has anti-inflammatory properties and is a potential therapeutic option for acute inflammation.

Diagnostic significance of gently sloping depression and irregular margin in superficial elevated colorectal tumors.

INTRODUCTION: Recently, superficial elevated colorectal tumors have been increasingly diagnosed after improvements in endoscopic instruments and techniques. However, their biological characteristics remain obscure and it is difficult to predict malignant potential. The aim of this study is to clarify the characteristics of superficial elevated tumors in endoscopic examination for the evaluation of malignant potential. MATERIALS AND METHODS: Sixty-three resected superficial elevated colorectal tumors more than 10 mm in diameter were analyzed with regard to their morphological characteristics and histological findings. The samples were classified according to the presence of a gently sloping depression and irregular margin at the edge. Their depth of vertical invasion and the degree of depression were examined. RESULTS: The rate of carcinoma in 27 lesions with a gently sloping depression was significantly higher than in 36 lesions with an even surface. The rate of carcinoma in 46 lesions with irregular margin was significantly higher than in 17 lesions without irregular margin. A multivariate analysis revealed that the coexistence of both IM and GSD was significantly associated with submucosal invasion. Statistical associations of age, tumor location, gender, and pathological grade with submucosal invasion were not observed. CONCLUSIONS: In superficial elevated colorectal tumors, a gently sloping depression and irregular margin at the edge when viewed endoscopically may be a predictor of malignant potential. These characteristics should be given priority when deciding on treatment.

HLA-DQB1 locus and gastric cancer in Helicobacter pylori infection.

BACKGROUND AND AIMS: It has been suggested that the incidence of digestive diseases associated with Helicobacter pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. The authors have previously reported that human leukocyte antigen (HLA)-DQB1*0401 plays an important role in the development of atrophic gastritis in H. pylori infected patients. The aim of the present study was to investigate the relationship between HLA-DQB1 genotype and cancer development. METHODS: HLA-DQB1 genotyping was performed by the PCR-RFLP method on 122 H. pylori-infected non-ulcer dyspepsia (NUD) patients, 53 gastric cancer patients and 28 uninfected controls. To reliably estimate the grade of atrophic gastritis, histological evaluation was performed. RESULTS: The allele frequency of DQB1*0401 was significantly higher in intestinal type cancer patients compared with age- and sex-matched H. pylori-infected NUD patients. There was no significant difference in the mean atrophic scores of the biopsy samples from the lesser curvature of the mid-corpus between these groups. CONCLUSIONS: HLA-DQB1*0401 is a useful marker for determining susceptibility to intestinal type gastric cancer.

Influence of gastritis on cyclooxygenase-2 expression before and after eradication of Helicobacter pylori infection.

OBJECTIVES: Helicobacter pylori infection causes chronic gastritis and induces cyclooxygenase (COX)-2 expression. The relationship between gastritis and COX-2 expression is not well understood, especially long after the organism has been eradicated. We designed a study to elucidate this relationship. METHODS: Four endoscopic gastric biopsies from each of 118 H. pylori-infected subjects were assessed for COX-2 expression immunohistochemically, gastritis, by an updated Sydney System. In the 107 successfully eradicated subjects, the assessment was repeated once yearly, for 3 years. RESULTS: After successful eradication, COX-2 expression was reduced significantly regardless of site. Atrophy improved significantly and intestinal metaplasia improved but not in the antrum greater curvature. After 1 year COX-2 expression was not significantly different in the epithelia with and without intestinal metaplasia. Correlation between COX-2 expression and neutrophil score in the antrum (r = 0.214, P = 0.042) and inflammation in the corpus (r = 0.234, P = 0.025) disappeared after eradication. COX-2 expression correlated well with atrophy and metaplasia before and after eradication. No significant reduction in COX-2 or improvement in gastritis was found in subjects with eradication failure. CONCLUSION: H. pylori infection is associated with the enhancement of COX-2 expression in the gastric mucosa. Eradication therapy reduces COX-2 expression and hence may reduce the risk of cancer development.