Comparison of abdominal ultrasound and magnetic resonance imaging for detection of abdominal lymphadenopathy in dogs with metastatic apocrine gland adenocarcinoma of the anal sac

Imaging studies in humans with anal and rectal cancer indicate that magnetic resonance imaging (MRI) is a more sensitive technique than abdominal ultrasound (AUS) for the detection of abdominal lymphadenopathy. The purpose of this retrospective study was to directly compare the efficacy of these two techniques in detecting abdominal lymphadenopathy in dogs with apocrine gland adenocarcinoma of the anal sac (AGAAS). Six dogs with histologically confirmed AGAAS and histopathologic confirmation of metastasis to abdominal lymph nodes (LNs) had AUS and abdominal MRI. AUS identified lymphadenopathy in two of six dogs, whereas MRI identified lymphadenopathy in all the six dogs. Lymphadenopathy was predominantly sacral in location, with involvement of the medial iliac and hypogastric LNs in only two cases. These data suggest that MRI is more sensitive than AUS for detecting sacral abdominal lymphadenopathy in dogs with AGAAS. As such, MRI could be considered in any patient with AGAAS for initial staging of this disease.     

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.     

Breed, gender and neutering status of British dogs with anal sac gland carcinoma

This study details the breed, gender and neutering status of a large cohort of British canine patients suffering from histologically confirmed anal sac gland carcinoma. Estimates of the relative risk for the development of this disease attributable to these factors are calculated. To reduce the impact of sampling errors, cases were selected from veterinary histopathology laboratories rather than referral hospital databases, and multiple estimates of the general British canine population were used. The weaknesses of the statistical assumptions made are discussed. There was no evidence to support a gender predisposition for the development of this condition. English cocker spaniels are significantly over‐represented, with a mean relative risk estimate of 7.3. The mean relative risk estimate associated with being neutered was 1.4; the effect of neutering appeared to be more significant in male dogs compared with that in female dogs.     

Oral malignant melanoma – the effect of coarse fractionation radiotherapy alone or with adjuvant carboplatin therapy

A retrospective study was undertaken of dogs presented to the Animal Health Trust for treatment of oral malignant melanoma, without radiographic evidence of pulmonary metastases. Group 1 (n = 13) received radiotherapy of the primary and any lymph node metastases (4 weekly fractions of 9 Gy); and group 2 (n = 15) were treated the same but additionally received between two and six doses carboplatin at 300 mg m^?2 every 3 weeks. Median survival times for the two groups were 307 and 286 days, respectively (P > 0.05). In addition, carboplatin therapy did not significantly reduce the proportion of dogs dying due to metastases (three from group 1 and four from group 2). We found no evidence of a beneficial effect of carboplatin therapy over radiotherapy alone.     

Surgery of metastatic anal sac adenocarcinoma in five dogs

OBJECTIVE: To identify survival and morbidity information after surgery for metastases from apocrine gland anal sac adenocarcinomas (AGACA). STUDY DESIGN: Retrospective study. ANIMALS: Five dogs with AGACA. METHODS: Medical records of dogs that had surgery for treatment of metastatic AGACA between 1993 and 2003 were reviewed. Criteria for inclusion required that dogs had lymphadenectomy, with or without further debulking, as part of their treatment for metastatic AGACA and that the tissue was histologically confirmed as consistent with the primary AGACA. Signalment, history, physical examination findings, clinicopathologic data, imaging findings, surgical complications, number of surgeries, survival times, and cause of death were recorded. All dogs had a complete blood count, serum biochemical profile, serum electrolytes, 3-projection thoracic radiographs, abdominal radiographs and/or abdominal ultrasonography, and histologic confirmation of metastatic AGACA invading the regional lymph nodes and caudal abdomen. RESULTS: No surgical complications occurred. Three dogs were euthanatized; median survival, 20.6 months. One dog was alive for 19 months postoperatively. One dog had 5 sequential surgical procedures: 1 iliac lymphadenectomy and 4 debulking procedures of metastatic neoplastic tissue around and dorsal to the iliac vessels extending into the pelvic cavity, and was alive 54 months after initial surgery. CONCLUSION: Dogs with anal sac adenocarcinoma metastases to the iliac lymph nodes can experience long-term survival after surgical excision of the metastatic lesion. CLINICAL RELEVANCE: Lymphadenectomy may afford long-term survival to patients with metastatic anal sac adenocarcinoma.     

Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory lymphoma (2000–2013)

Medical records of 22 dogs treated with carboplatin (n = 8) or carboplatin and cytarabine (n = 14) chemotherapy for relapsed or refractory lymphoma between 2000 and 2013 were retrospectively reviewed. The clinical response rate was 18.2% (4/22). Median time to progression was 18 days (56 for responders; 12 for non‐responders, P = 0.0006). Median overall survival time was 28 days (109 for responders; 21 for non‐responders, P = 0.0007). Thrombocytopenia and neutropenia occurred in 84.2% (16/19) and 52.6% (10/19), respectively. Grade IV thrombocytopenia and neutropenia occurred in 56.3% (9/16) and 60.0% (6/10), respectively. Dogs that received both drugs were more likely to become neutropenic (P = 0.022) or thrombocytopenic (P = 0.001) than dogs receiving carboplatin alone. All responders received both drugs giving a 28.6% (4/14) response rate for the combination. Although some dogs responded to the combination, toxicity was high and the responses were not durable. With adequate supportive care, this protocol may be an acceptable rescue option for some dogs.     

A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3 cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2 cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5-year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2 cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2 cm. The association between tumour size group (<2 vs. ≥2 cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9–15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2 cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.     

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.     

Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer‐bearing dogs

Rosiglitazone is an FDA‐approved peroxisome proliferator‐activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m² to seven dogs. Carboplatin was administered at 240–300 mg/m² in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose‐limiting toxicity was hepatic at a dose of 8 mg/m². Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ‐glutamyltranspeptidase values were noted.     

Three‐dimensional conformal versus non‐graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002–2007)

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non‐graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under‐dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.     

Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985-1995)

OBJECTIVE: To characterize the signalment, clinical signs, biological behavior, and response to treatment of carcinoma of the apocrine glands of the anal sac in dogs. DESIGN: Retrospective study. ANIMALS: 113 dogs with histologically confirmed carcinoma of the apocrine glands of the anal sac. PROCEDURE: Data on signalment, clinical signs, and staging were reviewed and analyzed along with treatment modality for potential association with survival time. RESULTS: Sex distribution was approximately equal (54% female, 46% male). One hundred four dogs underwent treatment consisting of surgery, radiation therapy, chemotherapy, or multimodal treatment. Median survival for treated dogs was 544 days (range, 0 to 1,873 days). Dogs treated with chemotherapy alone had significantly shorter survival (median, 212 days) than those receiving other treatments (median, 584 days). Dogs not treated with surgery had significantly shorter survival (median, 402 days) than those that underwent surgery as part of their treatment (median, 548 days). Dogs with tumors > or = 10 cm2 had significantly shorter survival (median, 292 days) than dogs with tumors < 10 cm2 (median, 584 days). Hypercalcemia was identified in 27% (n = 29) of dogs, and those dogs had significantly shorter survival (median, 256 days), compared with those that were normocalcemic (median, 584 days). Dogs with pulmonary metastasis had significantly shorter survival (median, 219 days) than dogs without evidence of pulmonary metastasis (median, 548 days). CONCLUSIONS AND CLINICAL RELEVANCE: Unlike most previous reports, this study revealed an approximately equal sex distribution, and results suggest a more favorable prognosis.     

Treatment and outcome of four cats with apocrine gland carcinoma of the anal sac and review of the literature

Anal sac adenocarcinoma is uncommon in cats. We report the outcome of multi-modality therapy in two cats (surgery, definitive radiotherapy and systemic chemotherapy) and surgery alone in two cats. All received surgical excision of the primary tumour followed by radiotherapy and carboplatin chemotherapy in two cases. Both cats that underwent multimodal therapy developed distant metastatic disease and one developed recurrence of the primary tumour. One cat that underwent surgery alone with incomplete margins also developed rapid recurrence. Overall survival times were 89, 161 and 169 days. One cat that had complete surgical excision is still alive without recurrence 425 days postoperatively. Whilst the role of radiation in the local control of this disease is yet to be defined, clearly a more effective systemic therapy is required before such aggressive local treatment can be routinely recommended.     

Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy

This study aimed to evaluate the analgesic efficacy of gabapentin as an adjuvant for postoperative pain management in dogs. Twenty dogs undergoing mastectomy were randomized to receive perioperative oral placebo or gabapentin (10 mg/kg). All dogs were premedicated with intramuscular acepromazine (0.03 mg/kg) and morphine (0.3 mg/ kg). Anesthesia was induced with propofol (4 mg/kg) intravenously and maintained with isoflurane. Intravenous meloxicam (0.2 mg/kg) was administered preoperatively. Postoperative analgesia was evaluated for 72 hr. Rescue analgesia was provided with intramuscular morphine (0.5 mg/kg). Dogs in the Placebo group received significantly more morphine doses than the Gabapentin group (P=0.021), despite no significant differences in pain scores. Perioperative gabapentin reduced the postoperative morphine requirements in dogs after mastectomy.     

Ultrasound and computed tomography of the iliosacral lymphatic centre in dogs with anal sac gland carcinoma

In this prospective study, we hypothesized that computed tomography (CT) would identify more normal and abnormal iliosacral lymph nodes (LNs) than abdominal ultrasound in dogs with anal sac gland carcinoma (ASGC). Twelve client‐owned dogs with ASGC but without distant metastasis were enrolled. Abdominal ultrasound and contrast‐enhanced CT scans of the abdomen were obtained. Iliosacral LNs were counted and assessed for location, laterality and size. Significantly (P < 0.00001) more iliosacral LNs were identified with CT (61) than ultrasound (30), including significantly (P = 0.00012) more medial iliac LNs with CT (33) than ultrasound (19). There was no difference in number of internal iliac LNs identified with CT versus ultrasound. Significantly (P = 0.000061) more sacral LNs were identified with CT (15) than ultrasound (0). Ultrasound identified slightly more (7) abnormal iliosacral LNs than CT (5). Contrast CT was able to identify more normal but not more abnormal LNs than ultrasound.     

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour‐bearing dogs: A phase I dose finding study

Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low‐dose metronomic and/or anti‐angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose‐finding clinical trial assumed an open‐label 3 + 3 cohort design. Client‐owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled. No preference for tumour histology, grade or stage was expressed. Toceranib was administered at a dose of 2.75 mg kg^?1 by mouth (PO) every other day (EOD), and carboplatin administered intravenously (IV) every 21 days at a starting dose of 200 mg m^?2. A total of 25% dose escalation was proposed for carboplatin, to a maximum of 300 mg m^?2. AEs were graded according to the Veterinary Cooperative Oncology Group's common terminology criteria for AEs (VCOG‐CTCAE). Grade 3 haematologic or gastrointestinal AEs were nominated dose‐limiting. Response to therapy was evaluated according to the VCOG's revised RECIST criteria. Eleven dogs were enrolled. Tumour histologies included sinonasal carcinoma, osteosarcoma, thyroid carcinoma, melanoma and apocrine gland anal sac adenocarcinoma. MTDs of carboplatin and toceranib were identified as 200 mg m^?2 IV every 21 days and approximately 2.75 mg kg^?1 PO EOD, respectively. The dose‐limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well‐tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials.     

Association between weight change during initial chemotherapy and clinical outcome in dogs with multicentric lymphoma

The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased‐ or decreased‐weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained‐weight group. The median progression‐free survival (PFS) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 226, 256 and 129 days, respectively. The decreased‐weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox‐regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.