Utility of a multiple serum biomarker test to monitor remission status and relapse in dogs with lymphoma undergoing treatment with chemotherapy.

A blinded retrospective study was conducted to investigate remission and recurrence of lymphoma in dogs receiving chemotherapy. The objective was to compare clinicians' assessment using palpation and cytology to the results of serum biochemical tests for haptoglobin (Hapt) and C-reactive protein (C-RP). These biochemical test results were combined using a diagnostic algorithm developed using data from 344 individual dogs. This multivariate approach, termed the canine lymphoma blood test (cLBT), was used to follow 57 dogs during and after treatment. cLBT of remission and recurrence compared well with clinicians' assessment and differentiated dogs in remission and those with recurring disease before appearance of lymphadenopathy (P < 0.001). The cLBT demonstrated prognostic potential based on pre-treatment values on dogs with shorter survival times and on those achieving the lowest cLBT score during treatment that showed longer survival times. The test, therefore, demonstrates potential to assist in monitoring treatment of canine lymphoma.

Survey of UK-based veterinary surgeons' opinions on the use of surgery and chemotherapy in the treatment of canine high-grade mast cell tumour, splenic haemangiosarcoma and appendicular osteosarcoma.

The objective of this study was to determine the frequency of recommendation of adjuvant chemotherapy by UK-based general veterinary practitioners (GVPs) for canine patients with high-grade mast cell tumours (HGMCTs), splenic haemangiosarcomas (SHSs) and appendicular osteosarcomas (AOSs); to determine which chemotherapeutic protocols are used by GVPs; and to evaluate reasons why chemotherapy may or may not be recommended postoperatively. An internet survey was created in 2013 using an online programme and was distributed to GVPs. Questions relating to the use of adjuvant chemotherapy for three tumours were selected. In total, 300 responses were generated. Surgery was seen as primary therapy by most GVPs for HGMCT (91 per cent) and SHS (88 per cent), but less frequently for AOS (59 per cent). Also, 90, 40 and 57 per cent of respondents recommended adjuvant chemotherapy for HGMCT, SHS and AOS, respectively. Of these, an appropriate chemotherapy protocol was not known by 25, 51 and 36 per cent of GVPs for HGMCT, SHS and AOS, respectively. From the GVPs not recommending chemotherapy, 29, 64 and 66 per cent did not believe chemotherapy to be efficacious for these tumours. The frequency of recommendation regarding postoperative chemotherapy is variable by tumour type. Reasons given why postoperative chemotherapy is not recommended also vary by tumour type.

A retrospective review of treatment and response of high-risk mast cell tumours in dogs.

This retrospective case series evaluates survival outcome of 94 dogs with high metastatic risk mast cell tumours (MCT). Patients were treated with a cytotoxic chemotherapy protocol or the tyrosine kinase inhibitor masitinib, in the presence of gross disease or as an adjunct to surgical resection of the primary tumour. In patients presenting with metastatic disease, surgical resection of the primary tumour with adjunctive therapy with any chemotherapy incurred a significant survival advantage [median survival time (MST): 278 days] compared to patients receiving chemotherapy without surgical excision of the primary tumour (MST: 91 days, P < 0.0001). Patients with a surgically excised Patnaik grade II tumour and high Ki-67 in the absence of metastatic disease treated with vinblastine and prednisolone showed a significantly longer survival (MST: 1946 days) than those treated with masitinib (MST: 369 days, P = 0.0037). Further prospective case-controlled clinical trials of high-risk MCTs are required to make precise evidence-based treatment decisions for individual patients.

Comparison between Ki-67 index and mitotic index for predicting outcome in canine mast cell tumours.

OBJECTIVES: To assess correlation between Ki67 index and mitotic index and determine which more accurately predicts survival in canine mast cell tumours. METHODS: Retrospective analysis of cases from three UK referral hospitals. Correlation between Ki67 index and mitotic index was assessed and survival analysis performed. RESULTS: A total of 162 dogs were included: 57 dogs died with 37 due to mast cell tumour. Correlation between Ki67 index and mitotic index was moderate, while the agreement was poor. A high Ki67 index was considered sensitive (86 · 5%) at predicting mast cell tumour-related death, but poorly specific (57 · 9%). Mitotic index(>5) was poorly sensitive (32 · 4%), but highly specific (96%). A mitotic index of ê2 had a 75 · 7% sensitivity and an 80 · 0% specificity. Ki67 index showed a statistically significant survival difference within the mitotic index <2 (P = 0 · 009) group. Ki67 index did not predict survival rate in tumours with mitotic index of ê2. CLINICAL RELEVANCE: Correlation between Ki67 and mitotic index is moderate. High mitotic index accurately predicted death, but many dogs with low mitotic index also died. Low Ki67 accurately predicted survival, but high Ki67 should not be considered a poor prognostic indicator. A three-tier mitotic index assessment may more accurately predict death due to mast cell tumour.

Whole blood manganese concentrations in dogs with primary hepatitis.

OBJECTIVES: Increased whole blood manganese concentrations have been reported in humans with primary liver disease. Due to the neurotoxic effects of manganese, altered manganese homeostasis has been linked to the development of hepatic encephalopathy. Whole blood manganese concentrations are increased in cases of canine congenital portosystemic shunts, but it remains unclear whether dogs with primary hepatopathies also have altered manganese homeostasis. METHODS: Whole blood manganese concentrations were measured by graphite furnace atomic absorption spectrometry in 21 dogs with primary hepatitis, 65 dogs with a congenital portosystemic shunt, 31 dogs with non-hepatic illnesses and 18 healthy dogs. RESULTS: The whole blood manganese concentrations were significantly different between dogs with primary hepatitis, dogs with non-hepatic illnesses and healthy dogs (P=0·002). Dogs with primary hepatitis had significantly increased whole blood manganese concentrations compared with healthy dogs (P<0·05) and dogs with non-hepatic illnesses (P<0·01). Dogs with primary hepatitis had significantly lower whole blood manganese concentration compared with dogs with congenital portosystemic shunts (P=0·0005). CLINICAL SIGNIFICANCE: Dogs with primary hepatopathies have increased concentrations of whole blood manganese although these concentrations are not as high as those in dogs with congenital portosystemic shunts. The role of altered manganese homeostasis in canine hepatic encephalopathy is worthy of further study.

Management of 13 cases of canine respiratory disease using inhaled corticosteroids.

OBJECTIVES: To determine the value of inhaled corticosteroids in the management of chronic inflammatory airway disease in dogs. METHODS: Medical records of dogs that were presented for the investigation of respiratory disease were reviewed retrospectively. Criteria for inclusion were knowledge of previous medical treatment including side effects, diagnosis of the underlying disease, use of inhaled corticosteroids and at least two-months follow-up data. RESULTS: Thirteen dogs that fulfilled the criteria were identified. Ten dogs were diagnosed with chronic bronchitis and three with eosinophilic bronchopneumopathy. Four dogs had not previously received corticosteroid treatment for their respiratory disease, and all these showed a reduction or a resolution of clinical signs without obvious side effects after inhaled corticosteroid therapy. Nine dogs had previously received oral or parenteral corticosteroids for treatment of their respiratory disease, and all had exhibited side effects. Five of these dogs were treated with inhaled corticosteroids alone, and all exhibited an improvement in clinical signs without observable side effects. The remaining four dogs were treated with a combination of inhaled and oral corticosteroids, and all showed improvement in clinical signs and reduction in side effects. Inhaled medication was well tolerated in all dogs. CLINICAL SIGNIFICANCE: Inhaled corticosteroids were used for the management of chronic bronchitis and eosinophilic bronchopneumopathy in 13 dogs, and these may have the advantage of reducing side effects associated with oral corticosteroids.

Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay.

OBJECTIVE: To assess the haemodynamic effect of simultaneously adjusting atrioventricular (AV) and interventricular (VV) delays. METHOD: 35 different combinations of AV and VV delay were tested by using digital photoplethysmography (Finometer) with repeated alternations to measure relative change in systolic blood pressure (SBP(rel)) in 15 patients with cardiac resynchronisation devices for heart failure. RESULTS: Changing AV delay had a larger effect than changing VV delay (range of SBP(rel) 21 v 4.2 mm Hg, p < 0.001). Each had a curvilinear effect. The curve of response to AV delay fitted extremely closely to a parabola (average R2 = 0.99, average residual variance 0.8 mm Hg2). The response to VV delay was significantly less curved (quadratic coefficient 67 v 1194 mm Hg/s2, p = 0.003) and therefore, although the residual variance was equally small (0.8 mm Hg2), the R2 value was 0.7. Reproducibility at two months was good, with the SD of the difference between two measurements of SBP(rel) being 2.5 mm Hg for AV delay (2% of mean systolic blood pressure) and 1.5 mm Hg for VV delay (1% of mean systolic blood pressure). CONCLUSIONS: Changing AV and VV delays results in a curvilinear acute blood pressure response. This shape fits very closely to a parabola, which may be valuable information in developing a streamlined clinical protocol. VV delay adjustment provides an additional, albeit smaller, haemodynamic benefit to AV optimisation.

Dobutamine-induced hyperaemia inversely correlates with coronary artery stenosis severity and highlights dissociation between myocardial blood flow and oxygen consumption.

OBJECTIVES: To compare the relationship between dobutamine myocardial blood flow (MBF), rate-pressure product (RPP) and stenosis severity in patients with coronary artery disease (CAD). METHODS: 27 patients with single-vessel CAD were allocated to three groups based on stenosis severity: group 1, 50-69% (n = 9); group 2, 70-89% (n = 9); and group 3, >or= 90% (n = 9). Nine normal volunteers served as controls. Resting and dobutamine MBF were measured by positron emission tomography in the territory subtended by the stenosis (Isc) and remote myocardium (Rem). Mean left ventricular MBF was used for controls. RESULTS: In group 1, mean dobutamine MBF-Isc (2.48 (SD 0.48 ml/min/g)) and dobutamine MBF-Rem (2.70 (0.50) ml/min/g, NS) were comparable. In groups 2 and 3, dobutamine MBF-Isc (1.91 (0.44) and 1.22 (0.21) ml/min/g) was significantly lower than dobutamine MBF-Rem (2.27 (0.28) and 1.98 (0.25) ml/min/g, p < 0.02 and p < 0.005, respectively). An inverse relation between dobutamine MBF and stenosis severity existed both in Isc (r = 0.79, p < 0.001) and in Rem territories (r = 0.71, p < 0.001). For any given RPP, dobutamine MBF was greater in controls than in Rem (p < 0.05), which in turn was greater than in Isc (p < 0.05). CONCLUSION: Dobutamine MBF inversely correlated with stenosis severity and achieved significant flow heterogeneity for coronary stenoses > 70%. Dobutamine MBF and RPP were dissociated in both Isc and Rem segments in patients compared with controls.

Pancreatic mixed acinar-endocrine carcinoma in a dog.

A 10.5-year-old crossbreed dog was presented with a history of hypoglycaemic episodes and elevated serum insulin concentration. A pancreatic mass was removed at surgery along with an enlarged draining lymph node. An unresectable hepatic nodule was also present. Immunohistochemistry confirmed the pancreatic and lymph node masses as functional mixed acinar-endocrine carcinoma, previously unreported in domestic species. Persistent hypoglycaemia and hyperinsulinaemia post-operatively was highly suggestive of the hepatic mass being a functional metastasis. The dog was managed on prednisolone and remained asymptomatic 9 months post-operatively. This tumour type has only been rarely reported in human patients and may highlight the need for more rigorous immunohistochemical staining of pancreatic masses in veterinary species to identify the prevalence of this tumour type.

A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery.

OBJECTIVES: To compare the clinical- and cost-effectiveness of minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery (LAD). DESIGN: Multi-centre randomised trial without blinding. The computer-generated sequence of randomised assignments was stratified by centre, allocated participants in blocks and was concealed using a centralised telephone facility. SETTING: Four tertiary cardiothoracic surgery centres in England. PARTICIPANTS: Patients with ischaemic heart disease with at least 50% proximal stenosis of the LAD, suitable for either PTCA or MIDCAB, and with no significant disease in another vessel. INTERVENTIONS: Patients randomised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure. Patients randomised to MIDCAB had general anaesthetic. The chest was opened through an 8-10-cm left anterior thoracotomy. The ribs were retracted and the left internal thoracic artery (LITA) harvested. The pericardium was opened in the line of the LAD to confirm the feasibility of operation. The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD. All operators were experienced in carrying out MIDCAB. MAIN OUTCOME MEASURES: The primary outcome measure was survival free from cardiac-related events. Relevant events were death, myocardial infarction, repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up. Secondary outcome measures were complications, functional outcome, disease-specific and generic quality of life, health and social services resource use and their costs. RESULTS: A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001. Of the 1091 patients with proximal stenosis of the LAD, 127 were eligible and consented to take part; 100 were randomised and the remaining 27 consented to follow-up. All randomised participants were included in an intention-to-treat analysis of survival free from cardiac-related events, which found a non-significant benefit from MIDCAB. Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2% for MIDCAB and PTCA, respectively. There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life. The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA, respectively. The costs of resources used during 1 year of follow-up were 1033 British pounds and 843 British pounds, respectively. CONCLUSIONS: The study found no evidence that MIDCAB was more effective than PTCA. The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA. Given these findings, it is unlikely that MIDCAB represents a cost-effective use of resources in the reference population. Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB. At the same time, cardiologists are treating more patients with multi-vessel disease by PTCA. Future primary research should focus on this comparison. Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review.

Left ventricular myxosarcoma in a dog.

An entire male Neopolitan mastiff, aged two years and eight months, presented with a history of chronic diarrhoea and weight loss. The diarrhoea had been present for approximately 12 months and had progressively worsened, with weight loss developing over an eight-week period prior to presentation. No primary gastrointestinal or metabolic cause for the diarrhoea could be identified. Echocardiography revealed a large, multilocular, cyst-like structure within the pericardium compressing the heart and displacing it to the right. The mass was surgically excised from the left ventricular myocardium. Histopathological examination showed it to be a low-grade malignant myxosarcoma. The dog made a full recovery and was still clinically normal nine months postoperatively, with no evidence of tumour recurrence or metastases. However, 11 months postsurgery, the clinical signs of diarrhoea and weight loss returned. Tumour recurrence with local metastasis was diagnosed and the dog was euthanased 358 days after the original surgery.

Retrospective study of 25 young weimaraners with low serum immunoglobulin concentrations and inflammatory disease.

Twenty-five weimaraners with recurrent infections or inflammatory disease were investigated; their median age was four months (range two to 36 months), and 11 of them were male and 14 female. Twenty of them showed signs of lethargy, anorexia or pyrexia, 13 had been vomiting or had diarrhoea, 12 had shown signs of pain in the joints or bones and been lame, five had had reactions at the site of an injection, five had generalised lymphadenopathy, three had urinary tract infections and two had recurrent or severe pyoderma. They all had a lower concentration of one or more classes of serum immunoglobulin (IgG, IgM and IgA) than the standard control ranges, and their mean concentration of IgG was significantly lower (P<0.005) than the mean concentration of IgG in 15 clinically normal weimaraners. Of 10 cases for which a complete vaccination history was available, nine had developed clinical signs within five days of being vaccinated. Follow-up data were available from 21 of the 25 dogs for a median period of 24.5 months. One dog died during a symptomatic episode, three were euthanased, six were alive at follow-up but had continued to show clinical signs and 11 had made a full recovery.

Anal sac adenocarcinoma in a Siamese cat.

A 12-year-old male neutered Siamese cat presented with a history of inappetance and lethargy and an enlarged left anal sac. The anal sac was surgically excised and histopathology confirmed the diagnosis of anal sac adenocarcinoma. Perianal tumours are rare in the cat and anal sac adenocarcinoma has not been previously reported. This is in contrast to the dog where anal sac adenocarcinoma is a well recognised albeit uncommon tumour.

Canine and feline pyothorax: a retrospective study of 50 cases in the UK and Ireland.

Fifty cases (36 dogs and 14 cats) with a confirmed diagnosis of pyothorax were evaluated from five referral institutions in the UK and Ireland. Aetiology, clinical presentation, diagnosis, treatment and outcome of all cases were examined. The underlying cause of pyothorax was determined in 18 per cent of cases. Positive bacteriological cultures of the pleural fluid were obtained in 68.7 per cent of the animals. Treatment modalities included surgery and medical management, involving thoracostomy tube placement, thoracic aspiration, thoracic lavage and antimicrobial therapy. A successful outcome was achieved in 86 per cent of patients.

Cardiac investigation and intervention prior to thoraco-abdominal aneurysm repair: coronary angiography in 35 patients.

OBJECTIVE: retrospective studies indicate a high risk of cardiac events in patients undergoing thoraco-abdominal aneurysm repair. We aimed to determine the prevalence of coronary disease in these patients, define the role of non-invasive cardiac testing and assess the short-term outcome of coronary re-vascularisation. DESIGN: a prospective cohort study of consecutive patients referred to a single surgeon. MATERIALS AND METHODS: forty patients recruited over 16 months (Type I, 6; II, 11; III, 8; IV, 15). Dobutamine stress echocardiography, coronary angiography and coronary re-vascularisation (PTCA or CABG) were performed according to a pragmatic protocol. Main outcome measures were the prevalence of coronary artery disease, sensitivity and specificity of clinical assessment and non-invasive cardiac testing, and adverse events associated with coronary investigation and intervention. RESULTS: seven patients (17.5%) were stratified as having high perioperative cardiac risk. The majority of patients (23, 57.5%) had no cardiac risk factor other than the operation type. Five patients (12.5%) had inducible ischaemia on non-invasive testing. Fourteen patients (40%) had haemodynamically significant coronary artery stenoses, of whom 12 (34%) underwent coronary revascularisation. Dobutamine stress echocardiography demonstrated 100% specificity and 71% sensitivity for the detection of significant coronary artery lesions. Coronary re-vascularisation by three-vessel bypass grafting was complicated by non-fatal stroke in one patient. Thirty-five patients (87.5%) proceeded to aneurysm repair. No patient who had been adequately investigated suffered a cardiac complication. CONCLUSIONS: the 40% prevalence of coronary artery disease in these patients is comparable to that of other patients undergoing arterial surgery. Non-invasive testing proved beneficial, both in screening low-risk patients and planning intervention in patients at higher risk. An aggressive approach to intervention was associated with an acceptable complication rate and favourable short-term outcome.

The effect of adjusting for baseline risk factors and post revascularisation coronary disease on comparisons between coronary angioplasty and bypass surgery.

BACKGROUND: In CABRI at 1 year PTCA was associated with greater repeat revascularisation and angina (but not myocardial infarction or death). We determined whether adjusting for baseline risk factors and post revascularisation coronary disease offsets this disadvantage of PTCA. METHODS: In the CABRI population the crude association of revascularisation mode (i.e. PTCA or CABG) with four clinical outcome (i.e. mortality, myocardial infarction, repeat revascularisation and angina) was adjusted for the baseline risk factors using a logistic regression model for each clinical outcome. A number of measures of angiographic coronary disease were used to assess post revascularisation coronary disease. One at a time, each of these measures was added to each of the four outcome models, to adjust for post revascularisation coronary disease. RESULTS: Comparing adjusted and crude unadjusted association of PTCA with repeat revascularisation there was an increase from 12.8 (P<0.0005) (crude relative risk) to 16.7 (P<0.0005) (adjusted odds ratio), with angina, from 1.89 (P=0.001) to 1.98 (P<0.0019), and with mortality from 1.84 (P=0.092) to 2.15 (P=0.060). PTCA was not significantly associated with myocardial infarction, either crudely or after adjustment. CONCLUSION: Adjusting for baseline risk factors and post revascularisation coronary disease tended to strengthen rather than weaken associations between PTCA and 1 year mortality, repeat revascularisation and angina at 1 year.

Improvement in midwall myocardial shortening with regression of left ventricular hypertrophy.

Despite normal indices of left ventricular (LV) chamber function, patients with LV hypertrophy (LVH) due to hypertension are thought to have depressed midwall systolic shortening compared with normotensives. The aims of the present study were (1) to confirm this observation and (2) to assess the effects of antihypertensive therapy that cause regression of LVH on LV systolic function assessed at both the midwall and endocardium. Thirty-eight previously untreated hypertensive subjects with LVH underwent echocardiography and were compared with 38 normotensive control subjects. Comparisons between the group with LVH and the control group revealed no significant differences in cardiac output (4. 32+/-0.23 versus 4.55+/-0.21 L/min), ejection fraction (62.5+/-2% versus 66.4+/-1.07%), or endocardial fractional shortening (34.5+/-1.45% versus 37.0+/-0.82%), but shortening assessed at the midwall was significantly less in the group with LVH (17.9+/-1.11% versus 21.6+/-0.63%, P<0.01). Subsequently, 32 patients with uncontrolled hypertension (24 previously untreated and 8 on existing antihypertensive therapy) underwent treatment with ramipril, with the addition of felodipine and bendrofluazide if required, to reduce blood pressure to <140/90 mm Hg. These 32 patients underwent echocardiography at baseline, after blood pressure control, and after an additional 6 months of tight blood pressure control. Good blood pressure control was achieved after 6 months compared with baseline (143/86+/-2.8/1.4 versus 174/103+/-4.1/1.9 mm Hg; P<0.01) with significant regression of LV mass index (124+/-3.4 versus 145+/-3.8 g/m(2), P<0.01). LV fractional shortening assessed at the midwall improved with regression of LVH (21.9+/-0.84 and 18.7+/-1. 19%, P<0.05), with posttreatment midwall shortening being similar to that of the normal control subjects evaluated in the first study. Hypertensive patients with LVH have depressed midwall systolic shortening despite normal indices of LV chamber function. Regression of LVH after good blood pressure control improved midwall shortening to normal levels.