Serum insulin-like growth factor-1 as a marker of improved liver function and surgical outcome in dogs with congenital extrahepatic portosystemic shunts.

Serum insulin-like growth factor-1 concentration (sIGF-1c) is reduced in various hepatopathies in humans and dogs. This work aimed to evaluate sIGF-1c in dogs before and after congenital extrahepatic portosystemic shunt (cEHPSS) attenuation, in relation to surgical outcome (closed vs. persistent shunting). Secondarily, it aimed to assess if sIGF-1c can discriminate between cEHPSS and portal vein hypoplasia (PVH) and finally compare sIGF-1c ratio (postoperative/preoperative sIGF-1c) to pre-prandial serum bile acids (preBA), post-prandial bile acids (postBA), bile acid stimulation test (BAST) and fasting ammonia (FA), regarding surgical outcome. Thirty-nine dogs were included: 15 with closed cEHPSS, 15 with persistent shunting and nine with PVH. Transplenic portal scintigraphy was used to classifiy surgical outcome. There was no significant difference in sIGF-1c between dogs with cEHPSS and those with PVH (P > 0.05). Postoperative sIGF-1c increased in all dogs (P < 0.001 and P = 0.023 for closed and persistent shunting, respectively) and the increase was more pronounced in closed cEHPSS than in persistent shunting (P = 0.006). Using an optimal sIGF-1c ratio cut-off of 2.23, the sensitivity was 93.3% and the specificity was 66.7% for differentiation between surgical outcomes. Serum pre-prandial bile acids, postBA BAST and FA had sensitivities of 80%, 86.7%, 86.7%, 60%; and specificities of 100%, 93.3%, 93.3%, 100%, respectively. There was a greater increase in sIGF-1c after shunt closure than during persistent shunting; nevertheless sIGF-1c ratio was inferior to advanced imaging to assess surgical outcome.

Serum hyaluronic acid, a marker for improved liver perfusion after gradual surgical attenuation of extrahepatic portosystemic shunt closure in dogs.

Current liver function tests used in dogs do not consistently normalise after successful surgical attenuation of portosystemic shunts (PSS). Serum hyaluronic acid (sHA) concentrations in dogs with PSS are reported to be higher at diagnosis than in healthy dogs. The objective of this study was to assess sHA as a marker of liver perfusion by measuring sHA concentrations in dogs before and after gradual surgical attenuation of extrahepatic (EH)PSS and by determining whether sHA concentrations could differentiate closed EHPSS from persistent shunting. Specificity of sHA was assessed by comparing sHA concentrations in dogs with EHPSS to those in dogs with other liver diseases. Twenty dogs with EHPSS had sHA concentrations measured at diagnosis, 1, 3, and 6 months postoperatively. In addition, sHA concentrations were determined in 10 dogs with other liver diseases. At EHPSS diagnosis, median sHA concentration was 335.6 ng/mL (43.0-790.7 ng/mL). All dogs had a significant decrease in sHA concentrations from 1 month postoperatively onwards (P < 0.05), regardless of surgical outcome. At all postoperative follow-up visits, there was a significant difference between the median sHA concentration in dogs with closed EHPSS vs. those with persistent shunting (P < 0.05). Median sHA concentration in dogs with other liver diseases was 89.8 ng/mL (22.9-160.0 ng/mL), which was significantly lower than dogs with EHPSS at diagnosis (P < 0.001). In conclusion, sHA is a promising non-invasive biomarker that can help to determine liver perfusion after surgical attenuation of EHPSS. In addition, sHA could potentially be used to differentiate dogs with EHPSS from dogs with other liver diseases.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers.

Combretastatin A4-phosphate (CA4P) is an anti-tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m-2 intravenous CA4P. The dogs were screened and monitored before and after injection. Pre- and post-treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post-treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti-vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12).

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 µSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients.

A dose-escalation study of combretastatin A4-phosphate in healthy dogs.

Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m-2 . At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m-2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m-2 , low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m-2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m-2 , although transient, does not invite to use this dose in canine oncology patients.

Congenital lobar emphysema in a kitten.

A five-month-old ragdoll cat presented with severe respiratory signs, unresponsive to medical therapy. Hyperinflation of the right middle lung lobe was diagnosed with radiography and computed tomography. Lung lobectomy following a median sternotomy led to full recovery. Histopathological analysis revealed lobar emphysema and, based on the animal's age, congenital lobar emphysema was considered the most likely diagnosis.

Comparison of a 5-mm and 10-mm vessel sealing device in an open ovariectomy model in dogs.

The objectives of this study were to compare (1) the extent of thermal damage and (2) the time between the 5-mm LigaSure V (LS5) and 10-mm LigaSure Atlas (LS10) vessel sealing devices (VSD) when performing open ovariectomy in dogs. A prospective, randomised, clinical trial was performed in 40 client-owned sexually entire female dogs. In each dog, one ovary was randomly assigned to be surgically removed using LS5 and the contralateral using LS10. The depth of thermal spread, measured on histopathological preparations, was significantly larger for LS10 (LS10 1.35±0.23 mm v LS5 0.82±0.10 mm; P<0.001). Mean ovariectomy time was significantly faster when using LS10 (LS5 2.58±1.32 minutes v LS10 2.07±1.27 minutes; P=0.008). Bodyweight was positively correlated with the time required for ovariectomy using LS5 (P=0.004), but no such correlation was present for LS10 (P=0.611). In conclusion, during open ovariectomy using VSD, LS10 causes significantly more thermal spread but surgical time is shorter compared with LS5. When using LS5, the ovariectomy time increases with increasing bodyweight.

Combretastatin A4-phosphate and its potential in veterinary oncology: a review.

For many years, research on anticancer therapy has focussed almost exclusively on targeting cancer cells directly, to selectively kill them or restrict their growth. But limited advances in this strategy have led researchers to shift their attention to other potential targets. Active research is now on-going on targeting tumour stroma. Vascular disrupting agents (VDAs) appear a promising class of anticancer drugs that are currently under investigation as a sole or combined therapy in human cancer patients. This article will briefly touch on the history and biology of combretastatin A4-phosphate (CA4P) as a typical example of VDAs and will concentrate on the side effects that can be expected when used in veterinary patients. Particularly, the pathogenesis of these side effects and how they may be prevented and/or treated will be discussed. The purpose of this article is to illustrate the potentials of CA4P as anticancer therapy in veterinary oncology patients.

Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients.

Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4 weeks after treatment with metronomic temozolomide (6.6 mg m-2 ), cyclophosphamide (12.5 mg m-2 ) or cyclophosphamide and temozolomide. The percentage of circulating CD25+ Foxp3+ CD4+ Tregs and the plasma levels of TSP-1 and VEGF were measured. There was a significant difference in the percentage of Tregs between cancer patients and healthy dogs. A significant decrease in Tregs was noted in patients treated with metronomic cyclophosphamide and the combination. Treatment with temozolomide had no effect on the percentage of Tregs. TSP-1 and VEGF levels were, respectively, significantly lower and higher in cancer patients than in healthy dogs, but they were not influenced by any of the studied metronomic treatment regimens.

Transdiaphragmatic pericardiectomy in dogs.

In patients with recurrent pericardial effusions, pericardiectomy is indicated. The purpose of this study was to describe a transdiaphragmatic approach for subtotal pericardiectomy in dogs and to evaluate its feasibility. In total, 20 canine cadavers weighing less than 10 kg (group S) and 20 weighing more than 20 kg (group L) were used. Within each group, half underwent a subphrenic pericardiectomy via an intercostal approach and half via a transdiaphragmatic approach. For each approach and within each weight group, the percentage of resected pericardium was calculated and compared. Additionally, a case series of nine consecutive client-owned dogs that underwent a transdiaphragmatic pericardiectomy for pericardial effusion was reported. Exposure of pericardium and associated phrenic nerves was excellent in cadavers and clinical patients. In group S, the percentage of resected pericardium was not significantly different between the two approaches. In group L, on the other hand, the percentage of resected pericardium was lower with the transdiaphragmatic approach compared with the intercostal approach (P=0.001). In the clinical patients, no intraoperative complications were encountered and no recurrence of pericardial effusion was seen. Subtotal pericardiectomy via a transdiaphragmatic approach is straightforward and a safe surgical procedure to obtain permanent pericardial drainage in small and large breed dogs.

Embryonal Rhabdomyosarcoma of the Oesophagus in a Young Dog.

A 15-month-old great Dane dog, showing clinical signs related to hypertrophic osteopathy, was diagnosed radiographically with a mass in the region of the thoracic oesophagus. Exploratory thoracotomy revealed an extensive, highly vascularized and locally invasive oesophageal mass and the presence of nodules in adjacent lung lobes. The dog was humanely destroyed intra-operatively. Histological examination revealed that the mass was an embryonal rhabdomyosarcoma. This is the first report of rhabdomyosarcoma of the oesophagus of a dog. Rhabdomyosarcoma should be considered a differential diagnosis when a mass adjacent to the oesophagus is diagnosed.

Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer.

Interleukin 12 (IL-12) is a powerful immunostimulatory cytokine with a strong antitumoural activity. In this work, the immunological, anti-angiogenic and clinical effects of three consecutive intratumoural IL-12 electrogene therapy (EGT) treatments were evaluated in nine dogs with spontaneous cancer. In all the dogs, tumour biopsies and blood samples were taken prior, during and after the intratumoural IL-12 EGT (on days 1, 8, 35 and 1, 3, 8, 15, 35, respectively). An initial decrease in immune cells was followed by an increase above baseline 1-3 weeks after treatment initiation. Interestingly, the decrease in peripheral leukocytes 2 days after the first intratumoural IL-12 EGT coincided with erythema and tumour swelling. Transient increases of IL-12 and interferon γ were measured in the serum and the tumour tissue, whereas IL-10 transiently increased only in the serum. The effect of intratumoural IL-12 EGT on the levels of IL-24 and vascular endothelial growth factor in the sera and tumour biopsies differed per dog. Via contrast-enhanced ultrasound (US) (on days 1, 8 and 35), we demonstrated that intratumoural IL-12 EGT resulted in a significant decrease of the relative blood volume and blood flow speed in the tumour compared with baseline. Metastases were present in two dogs. In one of these dogs, IL-12 EGT of the primary tumour caused a transient partial regression of the metastases, but not of the primary tumour. The second dog with metastases did not survive long enough to complete the entire treatment cycle. Despite encouraging immunostimulatory and anti-angiogenic effects after intratumoural IL-12 EGT, no clinically relevant outcomes were observed in this study, as persistent tumour regression could not be obtained. On the other hand, the laboratory and US results hold great promise for combinatorial strategies of intratumoural IL-12 EGT with conventional antitumour (immuno)therapies.

No evidence that medicinal honey reduces bacterial skin colonisation at a peripheral catheter insertion site in dogs.

OBJECTIVES: To determine whether topical exit-site application of medicinal honey at the catheter insertion place reduces bacterial skin colonisation. MEASUREMENTS AND RESULTS: Dogs were selected at random and divided into the honey or the control group. When the catheter was removed, an area of approximately 3×3 cm of the skin at the insertion site was sampled with a sterile cotton swab. The catheter stayed in place for a median of 84 hours. Out of 46 patients, 6 patients in the honey group and 5 out of 54 patients in the control group had a positive skin culture at the time of catheter removal (P=0·547). Infection was clinically suspected in 1 of those 11 dogs; catheter-associated complications were observed in 8 additional dogs that did not have a positive skin culture. CLINICAL SIGNIFICANCE: Few catheter-associated complications were observed. Extra attention to hygiene by working with a standardised catheter placement and handling protocol might have resulted in this low incidence. In this study topical application of a medicinal honey did not reduce bacterial skin colonisation at the insertion site of peripheral catheters in dogs.

The Microscopic Structure of the Omentum in Healthy Dogs: The Mystery Unravelled.

The canine omentum has many valuable properties but is still an underestimated organ. It contributes in many ways to the protection of the peritoneal cavity through its versatility on immunological level, but also through its role during angiogenesis, absorption, adhesion and fat storage. Despite a wide range of applications, the basic structure of the omentum is not well documented. This study provides an insight in the microscopic structure of the canine omentum through both light microscopic and electron microscopic investigations. Two regions could be distinguished in the canine omentum: translucent and adipose-rich regions. The translucent regions were composed of two different layers: a continuous flattened mesothelium on top of a submesothelial connective tissue matrix. The adipose-rich regions consisted of a substantial layer of adipocytes on which a flattened continuous mesothelium was present. Between those two layers, a few strands of collagen fibres could be detected. Large aggregates of immune cells, the so-called milky spots, were not observed in the omentum of healthy dogs. Only a limited number of leucocytes, macrophages and neutrophils were found, scattered throughout the connective tissue in the translucent regions. At the level of the adipose-rich regions, the immunological population was virtually non-existent.

Morphology of the Canine Omentum Part 2: The Omental Bursa and its Compartments Materialized and Explored by a Novel Technique.

The canine omental bursa is a virtual cavity enclosed by the greater and lesser omentum. While previous representations of this bursa were always purely schematic, a novel casting technique was developed to depict the three-dimensional organization of the omental bursa more consistently. A self-expanding polyurethane-based foam was injected into the omental bursa through the omental foramen in six dogs. After curing and the subsequent maceration of the surrounded tissues, the obtained three-dimensional casts could clearly and in a reproducible way reveal the omental vestibule, its caudal recess and the three compartments of the splenic recess. The cast proved to be an invaluable study tool to identify the landmarks that define the enveloping omentum. In addition, the polyurethane material can easily be discerned on computed tomographic images. When the casting technique is preceded by vascular injections, the blood vessels that supply the omentum can be outlined as well.

Morphology of the Canine Omentum Part 1: Arterial Landmarks that Define the Omentum.

Although the omentum remains an enigmatic organ, research during the last decades has revealed its fascinating functions including fat storage, fluid drainage, immune activity, angiogenesis and adhesion. While clinicians both in human and veterinary medicine are continuously exploring new potential omental applications, detailed anatomical data on the canine omentum are currently lacking, and information is often retrieved from human medicine. In this study, the topographic anatomy of the canine greater and lesser omentum is explored in depth. Current nomenclature is challenged, and a more detailed terminology is proposed. Consistent arteries that are contained within folds of the superficial omental wall are documented, described and named, as they can provide the anatomical landmarks that are necessary for unambiguous scientific communication on the canine omentum. In an included dissection video, the conclusions and in situ findings described in this study are demonstrated.

Relationship between age at gonadectomy and health problems in kittens adopted from shelters.

Prepubertal gonadectomy (PPG) is promoted as a way of managing overpopulation in cats, but concerns about PPG and potential health issues still exist. The objective of the present study was to evaluate short-term and long-term health problems in cats subjected to PPG in comparison to gonadectomy at traditional age (TAG). In a prospective clinical trial, 800 shelter kittens aged between approximately 8 weeks and 12 weeks were recruited before adoption and randomly assigned to either the PPG group (gonadectomy performed immediately) or the TAG group (gonadectomy delayed until six months to eight months of age). Short-term health issues included mortality between when kittens arrived at the clinic and up to seven days after they returned to the shelter, as well as the occurrence of various other health issues arising in the first month following adoption. Kittens were followed-up until 24 months of age specifically for feline lower urinary tract disease, urethral obstruction (male cats), lameness, fractures and hypersensitivity disorders with dermatological presentation. In the short term, there were no significant differences between health problems in PPG and TAG kittens. Similarly, no significant differences were observed between treatment groups in terms of the type or number of health issues in the long term. In conclusion, there are no health-related contraindications to advocating PPG strategies in shelter cats. Ideally, PPG should be performed at the shelter facility itself as long as excellent infectious disease control and postoperative clinical observation before adoption are guaranteed.

Use of greater omentum in the surgical treatment of a synovial cyst in a cat.

A 13-year-old cat was diagnosed with a synovial cyst originating from the glenohumeral joint. The cat presented with severe front limb lameness and a non-painful fluctuating swelling on the medial aspect of the humerus. Radiographic examination showed severe bilateral shoulder osteoarthritis with osteophyte formation. The mass was surgically resected and histopathology confirmed the diagnosis of a synovial cyst. Three weeks postoperatively the cyst recurred. Surgical resection was repeated followed by omentalisation of the defect. Throughout the following 3 months the cyst did not recur. Unfortunately, for reasons unrelated to the presented disease, the cat was euthanized shortly afterwards, therefore making a long-term follow-up impossible.

Pedicle digital pad transfer and negative pressure wound therapy for reconstruction of the weight-bearing surface after complete digital loss in a dog.

A young Labrador Retriever was presented for treatment of severe distal hindlimb necrosis caused by bandage ischemia. During digit amputation at the metatarsophalangeal joints, the third and fourth digital pads were salvaged and transferred to the metatarsal stump to create a weight-bearing surface. Negative pressure wound therapy (NPWT) was utilized for flap immobilization and to promote granulation tissue in the remaining wound defect. Sturdy adherence of the digital pads was achieved after only four days. The skin defect healed completely by second intention and the stump was epithelialized with a thin pad after three months. At the nine month follow-up examination, the stump had a thick hyperkeratinized pad. The dog walked and ran without any apparent signs of discomfort and compensated for the loss of limb length by extending the stifle and tarsocrural joints. Despite a challenging wound in a difficult anatomical location, digital pad flap transfer and NPWT proved successful in restoring long-term ambulation in an active large breed dog.