Serum thymidine kinase 1 activity as a prognostic biomarker in dogs with chemotherapy-treated diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is frequently treated with chemotherapy incorporating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), which induces remission in 80% to 95% of cases. However, not all dogs derive meaningful benefit from CHOP, and prognostic factors for dogs with DLBCL are poorly defined. Serum thymidine kinase 1 (TK1) activity, a marker of tumour cell proliferation, has shown promising initial results as a prognostic biomarker in dogs with multicentric lymphomas. The purpose of this study was to determine if baseline serum TK1 activity is associated with clinical outcome in dogs with CHOP-treated DLBCL. Baseline serum TK1 activity was measured in banked sera from 98 dogs with CHOP-treated DLBCL using a commercially available ELISA kit. Data on other potential prognostic factors were abstracted retrospectively from electronic medical records. Multivariable statistical methods were used to identify associations between TK1 and other potential prognostic factors with progression-free survival (PFS) and attainment of complete remission. TK1 activity at baseline was not associated with PFS (p = .299) or attainment of complete remission (p = .910) following CHOP chemotherapy. Of the other prognostic factors analysed, only purebred (vs. mixed breed) status (HR 8.81, 95% CI 1.68–46.30, p = .010), attainment of complete (vs. partial) remission (HR 0.09, 95% CI 0.02–0.49, p = .006), and baseline serum C-reactive protein concentration (HR 1.19, 95% CI 1.07–1.32, p = .001) were independently associated with PFS. Based on these findings, baseline serum TK1 activity does not appear to be a useful prognostic biomarker in dogs with CHOP-treated DLBCL.     

Timely adjuvant chemotherapy improves outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy

Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included. Median StoC was 20 days (range: 4–70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with non-metastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.     

Adjuvant anthracycline‐based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi‐institutional retrospective study of the Italian Society of Veterinary Oncology

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin‐based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum‐tolerated‐dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39‐61) and 55 days (95% CI, 43‐66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment‐related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment‐related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma.     

Comparison of mitotic index and Ki67 index in the prognostication of canine cutaneous mast cell tumours

Proliferation markers are commonly used for prognostication of mast cell tumours. The aim of the study is to compare the relative abilities of Ki67 and mitotic index to predict survival in the same cohort of dogs with cutaneous MCTs. Histological grade, mitotic index and Ki67 index were performed in all samples and clinical information was obtained by a follow‐up questionnaire. Ninety‐five dogs were included in the study with a median follow‐up of 1145 days. Survival times varied significantly between categories of histological grade, mitotic index and Ki67 index. Multivariable analyses showed that the risk of dying due to MCT was similar in dogs with increased Ki67 index [hazard ratio, HR: 3.0 (95% CI 1.3–6.8)] or increased mitotic index [HR: 2.7 (95% CI 1.1–6.5)]. In conclusion, both mitotic index and Ki67 index were able to independently differentiate MCTs with worse prognosis. This distinction is particularly meaningful in selecting intermediate grade MCTs that may benefit from more aggressive local or systemic treatment.     

Retrospective analysis of factors affecting clinical outcome following CHOP‐based chemotherapy in dogs with primary nodal diffuse large B‐cell lymphoma

Numerous factors are known to affect the prognosis of dogs with chemotherapy‐treated lymphomas. However, prognostic factors for dogs with specific subtypes of lymphoma are less clearly defined. The objective of this study was to identify prognostic factors for dogs receiving CHOP‐based chemotherapy for primary nodal diffuse large B‐cell lymphoma (DLBCL). Medical records of dogs treated for DLBCL at the Purdue Veterinary Teaching Hospital (PUVTH) from 2006 to 2016 were reviewed. Factors potentially related to prognosis were analysed using multivariable statistical methods. Ninety‐eight dogs were included in the study. Best overall response to chemotherapy was complete remission in 80 dogs (81.6%) and partial remission in 18 dogs (18.4%). Median progression‐free survival (PFS) for the entire population was 252 days (range 19‐1068). Factors significantly associated with achieving partial (rather than complete) remission following CHOP included presence of thrombocytopenia at diagnosis (OR 6.88; 95% CI 1.98‐23.93; P = .002), baseline serum globulin concentration (OR 2.63; 95% CI 1.03‐6.75; P = .044), and age at diagnosis (OR 1.36; 95% CI 1.08‐1.71; P = .009). Factors significantly associated with PFS in the lowest quartile (≤93 days) included presence of thrombocytopenia at diagnosis (OR 8.72; 95% CI 1.54‐49.33; P = .014), age at diagnosis (OR 1.47; 95% CI 1.12‐1.94; P = .005), and baseline neutrophil count (OR 1.18; 95% CI 1.02‐1.37; P = .025). Presence of thrombocytopenia, greater age, higher neutrophil count, and higher serum globulin concentration all may be associated with a particularly poor outcome in dogs receiving CHOP‐based chemotherapy for DLBCL.     

Retrospective outcome evaluation for dogs with surgically excised,solitary Kiupel high‐grade,cutaneous mast cell tumours

Published outcomes for dogs with specifically high‐grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high‐grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2‐year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow‐up 980 days) and 2 dogs were lost to follow‐up. Death was considered MCT‐related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.     

A phase II study to evaluate the toxicity and efficacy of alternating CCNU and high‐dose vinblastine and prednisone (CVP) for treatment of dogs with high‐grade,metastatic or nonresectable mast cell tumours

Safety and efficacy of a protocol of alternating 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea (CCNU; 70 mg m^?2) and vinblastine (3.5 mg m^?2), and prednisone (1–2 mg kg^?1; CVP) in dogs with mast cell tumours (MCT) were evaluated. A total of 17 dogs had nonresectable MCTs and 35 received CVP as adjunctive treatment to locoregional control of metastatic MCTs or grade III MCTs. Neutropenia with fever occurred in 8% of dogs after treatment with vinblastine and in 2% after treatment with CCNU. Persistent elevation of serum alanine transaminase, suggestive of hepatotoxicity, occurred in 9% of the dogs. Response rate in dogs with nonresectable MCTs was 65%; five achieved a complete response (median, 141 days) and six achieved a partial response (median, 66 days). Overall median progression‐free survival (PFS) time in dogs treated in the adjuvant setting was 489 days. Dogs with grade III MCTs had shorter PFS compared with dogs with metastatic grade II MCTs (190 days versus 954 days; P < 0.001). Phase III studies are needed to provide reliable information about the comparative efficacy of this protocol.     

Retrospective Evaluation of the Effect of Heart Rate on Survival in Dogs with Atrial Fibrillation

Background

Atrial fibrillation (AF) usually is associated with a rapid ventricular rate. The optimal heart rate (HR) during AF is unknown.

Hypothesis/Objectives

Heart rate affects survival in dogs with chronic AF.

Animals

Forty‐six dogs with AF and 24‐hour ambulatory recordings were evaluated.

Methods

Retrospective study. Holter‐derived HR variables were analyzed as follows: mean HR (meanHR, 24‐hour average), minimum HR (minHR, 1‐minute average), maximum HR (maxHR, 1‐minute average). Survival times were recorded from the time of presumed adequate rate control. The primary endpoint was all‐cause mortality. Cox proportional hazards analysis identified variables independently associated with survival; Kaplan‐Meier survival analysis estimated the median survival time of dogs with meanHR <125 bpm versus ≥125 bpm.

Results

All 46 dogs had structural heart disease; 31 of 46 had congestive heart failure (CHF), 44 of 46 received antiarrhythmic drugs. Of 15 dogs with cardiac death, 14 had CHF. Median time to all‐cause death was 524 days (Interquartile range (IQR), 76–1,037 days). MeanHR was 125 bpm (range, 62–203 bpm), minHR was 82 bpm (range, 37–163 bpm), maxHR was 217 bpm (range, 126–307 bpm). These were significantly correlated with all‐cause and cardiac‐related mortality. For every 10 bpm increase in meanHR, the risk of all‐cause mortality increased by 35% (hazard ratio, 1.35; 95% CI, 1.17–1.55; P < 0.001). Median survival time of dogs with meanHR<125 bpm (n = 23) was significantly longer (1,037 days; range, 524‐open) than meanHR ≥125 bpm (n = 23; 105 days; range, 67–267 days; P = 0.0012). Mean HR was independently associated with all‐cause and cardiovascular mortality (P < 0.003).

Conclusions and Clinical Importance

Holter‐derived meanHR affects survival in dogs with AF. Dogs with meanHR <125 bpm lived longer than those with meanHR ≥ 125 bpm.     

Efficacy of stereotactic radiation therapy for the treatment of confirmed or presumed canine glioma

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non-modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy-confirmed glioma or a presumptive diagnosis of intra-cranial glioma based on MRI characteristics that were treated with SRT. Twenty-three client-owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty-one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162–584). Median disease specific survival time was 413 days (95% CI, 217–717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable.     

c‐Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine

Background

KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c‐kit mutations.

Hypothesis/Objectives

To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c‐kit mutated MCT would have a better response to TOC than VBL.

Animals

Eighty‐eight client‐owned dogs with macroscopic MCT.

Methods

Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m² weekly × 4 then EOW) by KIT localization and c‐kit mutation status using an adaptive randomization scheme.

Results

Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c‐kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62–3.92]; P = 0.28). Median progression‐free survival (PFS) for dogs receiving VBL was 78 days (7–1,521) and for TOC 95.5 (14–990); hazard ratio (HR) = 1.34 [0.72–2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10–1,521) for the VBL group and 159 (20–990) for the TOC group; HR = 0.80 ([0.45–1.41]; P = 0.44).

Conclusions and Clinical Importance

Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c‐kit mutations was not different between treatment groups in this population of dogs, c‐kit mutation status did not predict treatment response.     

Vinblastine and prednisolone chemotherapy for surgically excised grade III canine cutaneous mast cell tumours

The effect of treatment with vinblastine and prednisolone chemotherapy in dogs undergoing only surgical excision of Patnaik grade III cutaneous mast cell tumours is reported. Potential explanatory variables were explored using Kaplan–Meier survival analysis with log‐rank tests. During a median follow‐up period of 429 days, the overall median survival time (MST) was not reached (lower 95% CI = 322 days). The 1‐year survival probability was 0.71 (standard error 0.1), remaining unchanged at 2 years. Secondary disease at presentation was an independent risk factor for survival (P= 0.045). The MST of dogs presenting with secondary disease was 322 days, with a lower 95% confidence interval of 142 days and a 1‐year survival of probability of 0.47 (standard error 0.19). Adverse effects were recorded in 6 of the 108 (5.6%) vinblastine doses given. This chemotherapy regimen is a well‐tolerated adjunct to surgery for grade III mast cell tumours and appears to prolong survival compared with that expected with surgery alone.     

Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m^?2 (range, 150–300 mg m^?2) and 4 (range, 2–11), respectively. The overall median progression‐free survival for all dogs was 259 days [95% confidence interval (CI₉₅), 119–399 days]. The first progression‐free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI₉₅, 247–633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia.     

Idiopathic Canine Laryngeal Paralysis as One Sign of a Diffuse Polyneuropathy: An Observational Study of 90 Cases (2007–2013)

Objective

To determine survival and incidence of complications in dogs with idiopathic laryngeal paralysis (ILP) and concurrent neurologic signs.

Study Design

Observational study.

Animals

Dogs (n = 90) with ILP.

Methods

Medical records (January 2007–June 2013) of dogs with ILP were reviewed. Neurologic comorbidities, including pelvic limb neurologic abnormalities and esophageal abnormalities were identified. Using medical record information and client interviews, the relationship between these comorbidities and postoperative survival (primary outcome measure) and postoperative complications (secondary outcome measure) was identified.

Results

Dogs that had surgical correction of ILP had a 2.6‐fold reduction in the hazard of death throughout the study period (HR = 2.6; 95% CI: 1.34–4.84, P = .006). Owner assessed patient quality of life (10‐point scale) increased by an average of 4.1 ± 1.4 units immediately postoperatively, and 4.9 ± 0.9 units until death or followup compared with preoperative values. Thirty‐five of 72 dogs available for followup had evidence of diffuse neurologic comorbidities. Overall complication rate for dogs with neurologic comorbidities was 74%, compared with 32% for dogs without neurologic comorbidities. Presence of any neurologic comorbidity was associated with a significantly greater odds of any complication (OR = 4.04; 95% CI: 1.25–13.90, P = .019) as well as recurring complications (OR = 8.00; 95% CI: 1.49–54.38; P = .015).

Conclusion

Surgical correction of ILP was positively associated with survival, and dogs with neurologic comorbidities were at greater risk for developing postoperative complications.

     

A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma

Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL‐DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated. No significant difference in survival between the two treatments was found. The calculated median overall survival time for the 34 dogs was 166 days [95% confidence interval (CI) 148–184]. The ½ year and one‐year survival was 41.2% (95% CI 24.8–56.9) and 22.7% (95% CI 9.9–37.4), respectively. In dogs treated with PL‐DOX, a desquamating dermatitis like palmar‐plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions. Cardiotoxicity was not seen in either treatment groups.     

Prognostic significance of CD25 expression in dogs with a noninvasive diagnosis of B-cell lymphoma treated with CHOP chemotherapy

Prior studies have identified high CD25 expression in canine diffuse large B-cell lymphoma as a negative prognostic indicator. The objective of this retrospective study was to evaluate CD25 expression as a prognostic indicator in dogs with B-cell lymphoma (BCL) diagnosed with commonly used noninvasive diagnostics (cytology and flow cytometry [FC]) and treated with CHOP chemotherapy. Lymph node aspirates from 57 dogs with cytologic diagnosis of lymphoma composed of intermediate to large lymphocytes were analysed with FC. Percentage of neoplastic B-cells expressing CD25 and median fluorescence intensity (MFI) of CD25 were measured. Relationships of CD25 percent positivity and MFI to progression free survival (PFS) and survival time were evaluated. Median survival time (MST) of all dogs was 272 days (95% CI, 196–348 days) and median PFS was 196 days (95% CI, 172–220 days). Higher percentage of B-cells positive for CD25 was associated with decreased risk of death in multivariable analysis (p = .02). Dogs with higher CD25 positivity had longer MST and PFS than dogs with lower CD25 positivity (318 days versus 176 days and 212 days versus 148 days, respectively), but these differences were not significant. CD25 MFI was not significantly associated with outcome. Based on the results of this study, the association of CD25 expression and prognosis in dogs with BCL diagnosed using noninvasive methods should be interpreted with caution. Further evaluation, with studies that include histopathologic differentiation of lymphoma subtypes, is needed.     

Survival of horses following strangulating large colon volvulus

Reasons for performing study: The pattern of long‐term survival and specific factors associated with long‐term survival have not previously been evaluated in horses with a strangulating large colon volvulus (LCV). Objectives: To provide data on the long‐term survival of horses with LCV and to identify pre‐, intra‐ and post operative variables associated with survival. Methods: Clinical data and long‐term follow‐up information were obtained from 116 horses with a strangulating LCV (≥360°) undergoing general anaesthesia. Two multivariable Cox proportional hazards models for post operative survival time were developed: Model 1 included all horses and evaluated preoperative variables and Model 2 included horses that survived anaesthesia and evaluated pre‐, intra‐ and post operative variables. Results: The study population comprised 116 horses. Eighty‐nine (76.7%) survived general anaesthesia. Of these, the percentage that survived until discharge, to one year and to 2 years was 70.7%, 48.3% and 33.7%, respectively. Median survival time for horses that survived general anaesthesia was 365 days. In Model 1 increased preoperative packed cell volume (PCV) was significantly associated with reduced post operative survival (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05–1.11). However, this effect changed over time. In Model 2 abnormal serosal colour intraoperatively (HR 3.61, 95% CI 1.55–8.44), increased heart rate at 48 h post surgery (HR 1.04, 95% CI 1.02–1.06), and colic during post operative hospitalisation (HR 2.63, 95% CI 1.00–6.95), were all significantly associated with reduced post operative survival. Conclusions: Survival time in horses with a LCV was associated with preoperative PCV, serosal colour, heart rate at 48 h post operatively and colic during post operative hospitalisation. Potential relevance: This study provides evidence‐based information on the long‐term survival of horses with LCV and identifies parameters that may assist decision‐making by clinicians and owners.     

Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy

Stage 3b anal sac gland carcinoma (ASGC) can be life‐threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression‐free interval (PFI) and median survival time (MST) were compared. Twenty‐eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life‐threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135–184 days) and 182 days (95% CI: 146–218 days), both significantly lower than for RT cases with 347 days (95% CI: 240–454 days) and 447 days (95% CI: 222–672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.     

Cholangitis and Cholangiohepatitis in Dogs: A Descriptive Study of 54 Cases Based on Histopathologic Diagnosis (2004–2014)

Background

Cholangitis in dogs appears to be more common than previously thought, but understanding of the disease remains incomplete.

Objective

To describe a population of dogs with cholangitis or cholangiohepatitis.

Animals

Fifty‐four client‐owned dogs with cholangitis or cholangiohepatitis.

Methods

Medical records of dogs with cholangitis or cholangiohepatitis confirmed by histopathology between January 2004 and December 2014 were identified using a computer‐based search and retrospectively reviewed.

Results

Clinical signs included vomiting (72.2%), lethargy (70.4%), and inappetence (64.8%). Most dogs (49/50) had increased liver enzyme activities, hyperbilirubinemia (32/50), and hypercholesterolemia (24/43). Ultrasonographic abnormalities of the hepatobiliary system were seen in 84% of cases. On histopathology, 53 of 54 affected dogs had neutrophilic cholangitis (NC) or cholangiohepatitis, whereas 1 dog had lymphocytic cholangitis. Most cases (42/54) were chronic. Evidence of concurrent biliary disease (46.2%) and biliary tract obstruction (42.6%) was common. Seventeen of 36 biliary and 11 of 25 liver cultures were positive for bacterial growth; Escherichia coli and Enterococcus spp. were most common. Median patient survival was 671 days (95% confidence interval [CI]: 114–1,426). On Cox regression, dogs that did not have a cholecystectomy performed had a 2.1 greater hazard for death (P = 0.037; 95% CI: 1.0–4.3) compared to cholecystectomized dogs. Dogs >13 years old had a 5.0 greater hazard for death (P = 0.001; 95% CI: 1.9–13.2) compared to younger dogs.

Conclusions and Clinical Significance

Chronic NC or cholangiohepatitis was most common. Cholecystitis and biliary tract obstruction often occurred in conjunction with cholangitis. Cholecystectomized dogs had decreased risk of death; thus, cholecystectomy may improve patient outcome.     

Cyclical 10-day dosing of melphalan for canine multiple myeloma

Canine multiple myeloma (MM) is typically treated with melphalan chemotherapy. A protocol with repeated 10-day cyclical dosing of melphalan has been used at our institution but has not been described in the literature. Our objectives were to describe the outcome and adverse events of this protocol in a retrospective case series. We hypothesised the cyclical 10-day protocol would have similar outcomes compared to other reported chemotherapy protocols. Dogs diagnosed with MM that received melphalan treatment at Cornell University Hospital for Animals were identified through a database search. Records were retrospectively reviewed. Seventeen dogs met inclusion criteria. Lethargy was the most common presenting complaint. The median duration of clinical signs was 53 days (range, 2–150 days). Seventeen dogs had hyperglobulinemia with 16/17 having monoclonal gammopathies. Sixteen dogs had bone marrow aspiration and cytology performed at initial diagnosis and plasmacytosis was diagnosed in all. Based on serum globulin concentrations, 10 of 17 dogs (59%) achieved complete response (CR), and 3 dogs (18%) achieved partial response (PR), for an overall response rate of 76%. The median overall survival time was 512 days (range, 39–1065). Retinal detachment (n = 3) and maximum response of CR/PR (n = 13) were associated with overall survival on multivariate analysis (p = .045 and .046, respectively). Adverse events were minimal with diarrhoea being the most reported (n = 6). This cyclical 10-day protocol was better-tolerated with fewer adverse events than with other reported chemotherapy protocols, but response rate was also lower, likely due to a lower dosing intensity.