Surgical modeling of Chiari-like malformation in rats: Insights from canine morphology.

BACKGROUND: Chiari-like malformation in dogs and Chiari malformation type 1 in humans are conditions characterized by a relatively small caudal cranial fossa, leading to cerebellar herniation. This study aimed to develop a rat model of Chiari-like malformation using surgical techniques based on morphological characteristics observed in dogs. METHODS: Endocranial magnetic resonance images of both normal dogs and dogs diagnosed with Chiari-like malformation were retrospectively analyzed. Measurements of the caudal cranial fossa volume, rostral and medial fossa volume, and volume index were taken. The differences in caudal cranial fossa volume and volume index between normal dogs and those diagnosed with Chiari-like malformation were then utilized to create a rat model of Chiari-like malformation through surgical intervention. The measurements were conducted on both the rat Chiari-like malformation models and normal rats, with each measurement taken twice and the mean values calculated. RESULTS: Significant differences were found between normal dogs and dogs diagnosed with Chiari-like malformation in terms of the volume of the caudal cranial fossa (27.62% reduction) and the volume index (23.36% reduction) (p<0.05). These differences were used to develop a rat model, which also showed significant reductions in both caudal cranial fossa volume (29.52%) and volume index (28.30%) compared to normal rats (p<0.05). The condition in the rat model was confirmed through magnetic resonance imaging, which revealed cerebellar herniation into the foramen magnum. CONCLUSIONS: The study successfully established a rat model of Chiari-like malformation that accurately reproduces the morphological features observed in dogs. This model potentially serves as a valuable tool for investigating the pathological mechanisms and potential therapeutic approaches for Chiari-like malformation in veterinary medicine.

Comprehensive comparative study of Chiari-like malformation in veterinary and human medicine.

This review aims to enrich our understanding of Chiari-like malformation (CLM) by combining human and veterinary insights, and providing a detailed cross-species overview. CLM is a developmental abnormality characterised by caudal displacement of the hindbrain into the foramen magnum due to an entire brain parenchymal shift caused by insufficient skull volume. This malformation leads to a progressive obstruction at the craniocervical junction, which disrupts the normal cerebrospinal fluid flow, leading to secondary syringomyelia. The clinical signs of CLM and syringomyelia include phantom scratching, head tilt, head tremor, ataxia, tetraparesis, pain, muscle atrophy, and scoliosis or torticollis. Magnetic resonance imaging remains the gold standard for diagnosing CLM, since it allows the visualisation of abnormal findings such as the caudal cerebellar herniation, caudal cerebellar compression from occipital dysplasia, and attenuated cerebrospinal fluid cisternae. Although various medical and surgical interventions, including foramen magnum decompression, can provide temporary symptomatic/clinical sign relief, current literature shows a lack of sustained long-term efficacy. Therefore, additional research is needed to evaluate the long-term effects of existing treatment strategies and to compare different techniques utilised in conjunction with foramen magnum decompression.

Intrahepatic Duct Incision and Closure for the Treatment of Multiple Cholelithiasis in a Dog.

This report describes the successful intrahepatic duct incision and closure for the treatment of multiple cholelithiasis in a dog with untreated hypothyroidism. A 12-year-old spayed female Spitz dog weighing 11.3 kg was diagnosed with multiple cholelithiasis, and a quadrate liver lobectomy and cholecystectomy were performed. Large gallstones were located in the left liver lobe's intrahepatic duct distal to the anastomosis of the intrahepatic ducts of the left medial and lateral lobes. The dilated intrahepatic duct was packed off with wet gauze, and incision and closure were performed on the most dilated section, which was proximal to the largest gallstone. After surgery, the patient showed normal liver function and was discharged with normal total bilirubin and C-reactive protein levels. On postoperative day 83, no stones were observed in the dilated common bile duct (CBD), and the degree of dilatation of the CBD had decreased from 9 mm to 4 mm, with no obstructions. Right intrahepatic gallstones were confirmed without dilatation. Hypothyroidism was managed medically. Hepatic duct incision and closure can be performed in dogs with multiple cholelithiasis. Although not the first option, intrahepatic bile duct incision proves to be a new alternative for the successful treatment of cholelithiasis in dogs.

Establishment and characterization of six canine hepatocellular carcinoma cell lines.

Background: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. Methods: The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). Results: We established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial-mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Conclusion: Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model.

IMPORTANCE: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). OBJECTIVE: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. METHODS: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2 × 106 cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5 × 106 cells, group C with 3 × 106 cells, group D with 1 × 106 cells, group E with 1 × 106 cells injected twice with a one-day interval, group F with 2 × 106 cells in 100 µL of suspension, and group G with 2 × 106 cells in 300 µL of suspension. RESULTS: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). CONCLUSIONS AND RELEVANCE: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Clinical evaluation and surgical intervention for diaphragmatic eventration mimicking peritoneopericardial hernia in a cat.

A 2-year-old spayed female British Shorthair cat presented with an increased frequency and duration of cough since infant period. Based on radiographic, ultrasonographic, and computed tomography findings, peritoneopericardial diaphragmatic hernia was considered so that repair surgery was planned. During celiotomy, lax diaphragm was identified instead of defect. Transabdominal diaphragmatic plication was performed to resolve lax diaphragm and to prevent recurrence by overlapping relatively normal part of diaphragm. Diagnosed with diaphragmatic eventration postoperatively, the cat showed improvement in clinical signs and imaging results. Transabdominal diaphragmatic plication is a suitable treatment; the patient maintained normally during a 14-month follow-up period.

Double-wire woven nitinol stent for treating dogs with refractory tracheal collapse: A case series.

This retrospective case series describes the signalments, clinical signs, diagnostic test results, and postoperative complications obtained from the medical records of 10 client-owned dogs that underwent treatment for grade IV tracheal collapse using double-wire woven nitinol stents between October 2017 and September 2021. Respiratory signs resolved in all dogs immediately after tracheal stent placement. Mild to moderate stent fractures were identified in five dogs, of which two showed concurrent respiratory distress necessitating re-stenting after several months. Minor complications, such as stent migration, were absent. The double-wire woven nitinol stent optimised for the canine trachea showed favourable outcomes and minimal complications.

Fatigue analysis of canine tracheal stents using the finite element method.

This study aimed to evaluate fatigue of three stent designs when various forces are applied and perform a comparative analyses. A computer simulation using the finite element method was performed. In particular, we constructed a three-dimensional finite element model of nitinol stents with three designs (S6: single-woven wire, wire diameter: 0.006 inch; D6: double-woven wire, wire diameter: 0.006 inch, and D7: double-woven wire, wire diameter: 0.007 inch) that are used to treat canine tracheal collapse (TC). The stents were subjected to a 200 mmHg compression force, a pure torsion force in a perpendicular direction, and a bending-torsion force combining perpendicular and axial forces. The von Mises stress was calculated to evaluate the extent of stent displacement, and Goodman diagrams were plotted to compare fatigue life cycles. D7 exhibited a longer fatigue life compared to S6 and D6. Under compression, pure torsion, and bending-torsion forces, displacement was the smallest for D7, followed by D6 and S6. Similarly, the fatigue life was the longest for D7, followed by D6 and S6. S6 showed the greatest displacement when subjected to external forces; among stents designed using the same wire, D6 displayed less displacement than S6, and D7 exhibited superior fatigue life when subjected to varying degrees of force. This study showed that the structural stability and fatigue life of stents could be effectively compared using finite element method D7 has the greatest stability and structural rigidity under cyclic load.

Reconstructive surgery with an autologous bone graft in a dog with presumptive chronic non-bacterial osteomyelitis.

A 15-year-old Cocker Spaniel was referred to for the evaluation of left forelimb lameness. Radiographic and computed tomography examinations revealed osteolysis of the proximal left third, fourth and fifth metacarpal bones and pathological fractures of the proximal left fourth metacarpal bone. Histopathological examination via bone biopsy did not provide a definitive diagnosis, and the owner elected limb-sparing surgery. The fourth metacarpal bone and digits were amputated. Subsequently, autologous bone grafts were performed on the lytic area of the third and fifth metacarpal bones. The dog showed improvement in gait 7 weeks after reconstructive surgery. Chronic non-bacterial osteomyelitis (CNO) was diagnosed by exclusion. To the best of our knowledge, CNO has not been previously reported in dogs.

Long-term adjuvant metronomic chemotherapy in a dog with recurrent maxillofacial osteosarcoma.

Osteosarcoma (OSA) is the most common malignant bone tumour in dogs; however, OSA of the maxilla is uncommon compared to appendicular OSA. Oral melanoma also commonly occurs in dogs with frequent distant metastasis. The role of adjuvant chemotherapy has been questioned in maxillary OSA and melanoma. A 17-year-old English Cocker Spaniel was referred with a growing mass on the right maxilla and a right lower lip mass. Osteosarcoma was diagnosed after partial maxillectomy, and the right lower lip mass was diagnosed as oral melanoma. Metronomic chemotherapy (MC) was performed, and the number of doses was tapered due to side effects at 5 weeks after initiation of MC. After 130 weeks of MC, chemotherapy was suspended due to kidney disease. After the suspension of chemotherapy, findings suggesting recurrence and metastasis were detected. The dog suddenly died 193 weeks after surgery, which was 8-14 times longer than the expected survival time. To the best of our knowledge, this is the first case report of successful long-term combination therapy, including surgery and MC, in a dog with maxillary OSA and lip melanoma. Our results show that the survival time can be greatly extended if MC is performed with proper management.

Case report: Adjuvant therapy with toceranib for an incompletely resected renal cell carcinoma with suspected pulmonary metastasis in a dog.

Primary renal neoplasia is rare in humans and dogs, with renal cell carcinoma (RCC) being the most common form of this cancer. As RCC is often diagnosed at an advanced stage, pulmonary metastasis is frequently observed. Tyrosine kinase inhibitors (TKIs) are the standard adjuvant treatments for metastatic RCC in humans. Similarly, in veterinary medicine, recent trials have employed TKIs for early-stage RCC patients who underwent complete surgical resection and showed no distant metastasis. However, the use of TKIs has not yet been reported commonly in cases of advanced RCC with metastasis. This case study presents the first clinical outcomes of TKI therapy in a dog with incompletely resected RCC and metastasis. A 5-year-old spayed female Chihuahua was referred to our hospital with a right renal mass and multiple pulmonary nodules suspected to be metastases. A portion of the renal mass was surgically removed, and histopathological examination revealed RCC with a high mitotic index. Adjuvant chemotherapy was administered, owing to incomplete resection with suspected pulmonary metastasis. An anticancer drug response prediction test was conducted using patient tissues. Since toceranib showed the most favorable responsiveness, it was selected as a therapeutic agent. Toceranib was orally administered at a dosage of 2.27 mg/kg every 48 h. Regular medical records for potential adverse effects were obtained, including systemic blood pressure, complete blood count, serum biochemical examination, and urinalysis. After 2 weeks of toceranib therapy, partial remission of pulmonary nodules continued for 2 months. The patient did not experience any adverse effects of the anticancer drug during the 4-month follow-up period. However, the patient died from an unidentified cause 6 months after the initial detection of the renal mass. This report describes the use of toceranib in dogs with RCC. In the present case, the patient showed an initial response to chemotherapy, and despite the presence of several poor prognostic factors, the dog survived beyond the expected 3-month lifespan to 6 months. Notably, no adverse events were observed during treatment.

The biomechanical and biological effect of supercooling on cortical bone allograft.

BACKGROUND: The need for a storage method capable of preserving the intrinsic properties of bones without using toxic substances has always been raised. Supercooling is a relatively recently introduced preservation method that meets this need. Supercooling refers to the phenomenon of liquid in which the temperature drops below its freezing point without solidifying or crystallizing. OBJECTIVES: The purpose of this study was to identify the preservation efficiency and applicability of the supercooling technique as a cortical bone allograft storage modality. METHODS: The biomechanical effects of various storage methods, including deep freezing, cryopreservation, lyophilization, glycerol preservation, and supercooling, were evaluated with the three-point banding test, axial compression test, and electron microscopy. Additionally, cortical bone allografts were applied to the radial bone defect in New Zealand White rabbits to determine the biological effects. The degree of bone union was assessed with postoperative clinical signs, radiography, micro-computed tomography, and biomechanical analysis. RESULTS: The biomechanical properties of cortical bone grafts preserved using glycerol and supercooling method were found to be comparable to those of normal bone while also significantly stronger than deep-frozen, cryopreserved, and lyophilized bone grafts. Preclinical research performed in rabbit radial defect models revealed that supercooled and glycerol-preserved bone allografts exhibited significantly better bone union than other groups. CONCLUSIONS: Considering the biomechanical and biological superiority, the supercooling technique could be one of the optimal preservation methods for cortical bone allografts. This study will form the basis for a novel application of supercooling as a bone material preservation technique.

Anti-Staphylococcal Activity of Ligilactobacillus animalis SWLA-1 and Its Supernatant against Multidrug-Resistant Staphylococcus pseudintermedius in Novel Rat Model of Acute Osteomyelitis.

Osteomyelitis caused by staphylococcal infection is a serious complication of orthopedic surgery. Staphylococcus pseudintermedius is the main causative agent of osteomyelitis in veterinary medicine. Methicillin-resistant S. pseudintermedius (MRSP) has been reported in companion animals, especially dogs. Multidrug-resistant S. pseudintermedius is an emerging pathogen and has acquired antibiotic resistance against various commercial antimicrobial agents. New antimicrobial compounds are urgently needed to address antibiotic resistance, and the development of novel agents has become an international research hotspot in recent decades. Antimicrobial compounds derived from probiotics, such as bacteriocins, are promising alternatives to classical antibiotics. In this study, the antibacterial activities of Ligilactobacillus animalis SWLA-1 and its concentrated cell-free supernatant (CCFS) were evaluated in vitro and in vivo. The CCFS of this bacterium showed no toxicity against osteoblast and myoblast cells in vitro, while significantly inhibiting the multidrug-resistant S. pseudintermedius KUVM1701GC strain in a newly established rat model. The CCFS significantly inhibited multidrug-resistant staphylococci both in vitro and in vivo. This suggests that CCFS derived from L. animalis SWLA-1 has potential as an alternative to classic antibiotics for staphylococcal infections in dogs.

Application of Bifurcated Semitendinosus Muscle Transposition for Treatment of Fecal Incontinence in Two Dogs.

A 4-year-old mixed breed dog and a 19-year-old English cocker spaniel dog were evaluated for fecal incontinence. The second dog's fecal incontinence was associated with the anal mass. In both dogs, reconstruction of the external anal sphincter was required to gain fecal continence. Especially in the dog with an anal mass, the whole musculature involved in fecal continence was removed with the affected anorectum. Conventional surgical treatments for fecal incontinence have limitations in terms of muscle flap length and complexity of the surgical procedure. A modified surgical technique using the semitendinosus muscle was devised in the present study to overcome these limitations. The distal part of the semitendinosus muscle was bifurcated to make two muscle bundles, used to completely encircle the anorectum. These muscle bundles were sutured to the surrounding rectal muscle and the pelvic diaphragm to simulate the function of the external anal sphincter. Three months after surgery, both dogs showed significantly improved fecal continence without severe complications, such as infection, dehiscence, or lameness of the limb where the semitendinosus muscle was harvested. The outcomes of the two dogs supported the acceptability of the bifurcated muscle flap for anal sphincter augmentation. In addition, this report showed the possibility of more diverse applications of semitendinosus muscle in dogs.

A rabbit model of tracheal collapse for optimal self-expanding metal stents.

Investigating the characteristics of tracheas can help the understanding of diseases related to the trachea, particularly tracheal collapse (TC) in dogs. This study aimed to compare the mechanical properties of tracheas from New Zealand White (NZW) rabbits and dogs and to introduce a method for inducing a model of TC in the normal trachea. Tracheal samples were obtained from NZW rabbit cadavers (n=5) weighing 3.62-3.92 kg and from dog cadavers (n=5) weighing 2.97-3.28 kg. Three live NZW rabbits weighing 3.5-4.0 kg were used to establish the model. The radial forces of both sample sets were measured using a digital force gauge and statistically compared. Subsequently, TC was surgically induced in three female NZW rabbits by physically weakening their tracheal cartilage under general anesthesia. Their clinical signs were monitored for 3 months, and radiographic examinations were performed monthly for 3 months. The mean radial forces of the two sample sets were comparable (P>0.05). The clinical signs, radiographic examinations, and macroscopic examinations were all comparable to those of dogs with TC. The cadaveric study between the rabbits and dogs demonstrated that the surgically induced rabbit model of TC is an excellent candidate for the experimental study of dogs with TC. This study also provides a reference of tracheal radial force values to enable selection of appropriate mesh types and wire diameters of self-expanding metal stents.

Adjuvant therapy with toceranib for hepatocellular carcinoma and cholangiocarcinoma in a Pomeranian.

A 10-year-old spayed female Pomeranian dog was referred for hepatic mass evaluation. Blood tests revealed mildly elevated alkaline phosphatase activities. Computed tomography revealed a mass with multiple nodules on the right hepatic medial lobe adjacent to the caudal vena cava; histopathology confirmed mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of incomplete resection, adjuvant therapy was recommended. As tumour cells showed PDGFR-α, c-Kit, and FGFR1 overexpression, the anticancer effect of tyrosine kinase inhibitors was evaluated on the cells; toceranib was the most effective and was administered starting with an extra-labelled dose. The dog remained stable for 2.3 years with mild adverse effects. To our knowledge, this is the first successful clinical application of toceranib in a dog with mixed HCC-CC.

Cystadenocarcinoma of the intrahepatic bile duct in a dog.

A 14-year-old spayed female Shih-Tzu was referred to the Veterinary Medical Teaching Hospital of Konkuk University for evaluation of an abdominal mass. In diagnostic imaging, two large cystic masses were identified. The affected liver lobes were surgically resected, and the specimens were submitted for histopathological evaluation and immunohistochemical staining. The two cystic lesions were diagnosed as biliary cystadenocarcinoma (BCAC). Recurrence and regional invasion were identified on ultrasonography 36 days postoperatively. The patient died on postoperative day 271. To the best of our knowledge, previously reported case studies of BCAC in dogs presented limited clinical information. In this report, we present a detailed picture comprising a range of clinical information and histopathological examination of BCAC in a dog.

Comparison of three different self-expanding metal stents using rabbit models for the treatment of tracheal collapse.

PURPOSE: To identify an optimal self-expandable metallic stent (SEMS) and verify whether a mechanically superior SEMS would result in better clinical outcomes in the treatment of tracheal collapse. METHODS: We selected three SEMS (n = 8 each), including an S-type stent with a wire diameter of 0.006 inches (S6) and two D-type stents with wire diameters of 0.006 (D6) and 0.007 inches (D7). Twenty-four New Zealand White rabbits were divided into three equal groups. After the stents were deployed, the clinical signs were recorded daily, and radiographic examinations were performed monthly. All rabbits were euthanized after three months. RESULTS: Two rabbits with S6 stents and one rabbit with a D7 stent died within three months because of stent migration or pneumonia. All rabbits with D6 stents survived for three months. On histological examination, the D6 group had the lowest inflammation score. CONCLUSIONS: Both clinically and histopathologically, the results with D-type stents with a wire diameter of 0.006 inches were superior to those of the other groups (p = 0.001). The use of an optimal intraluminal stent may improve the long-term clinical outcomes in the treatment of tracheal collapse in dogs.