Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs.

BACKGROUND: There is no widely accepted standard medical treatment for apocrine gland anal sac adenocarcinoma (AGASACA) in dogs. Targeted agents such as toceranib may be effective in treatment of AGASACA, but the number of clinical reports investigating its efficacy is limited. HYPOTHESIS/AIM: To evaluate the efficacy of toceranib treatment of AGASACA in dogs, and to assess prognostic factors in the study population. Our hypothesis was that toceranib would provide a clinical benefit in the treatment of dogs with AGASACA. ANIMALS: Thirty-six client-owned dogs with either a cytologic or histologic diagnosis of AGASACA that were treated with toceranib alone or in combination with surgery, nonconcurrent chemotherapy or both. METHODS: Retrospective study. RESULT: The median progression-free survival (PFS) and overall survival time (OST) for the study population was 313 days and 827 days, respectively. A clinical benefit from toceranib treatment was observed in 69% of dogs, with 20.7% of dogs experiencing partial response and 48.3% of dogs experiencing stable disease. Dogs that responded to toceranib treatment had significantly prolonged PFS and OST. Hypercalcemia was a negative prognostic factor for clinical outcomes. CONCLUSIONS: Toceranib is effective in the treatment of AGASACA in dogs. Prospective, controlled clinical trials are needed to determine the efficacy of toceranib in comparison to other treatment protocols for dogs with AGASACA.

Prognostic significance of histopathology in canine anal sac gland adenocarcinomas: Preliminary results in a retrospective study of 39 cases.

Metastatic rates and survival times of canine anal sac gland adenocarcinomas (ASGACs) vary among studies, making prognostication difficult. Little is known about the prognostic significance of histopathology of ASGACs. This retrospective study investigated associations between histological features, clinical presentation and outcome for 39 ASGACs. Most tumours were incompletely excised (62%) and had moderate to marked peripheral infiltration (74%). The predominant growth pattern was solid, tubules/rosettes/pseudorosettes and papillary in 49%, 46% and 5% of the cases, respectively. Nuclear pleomorphism was either moderate (77%) or mild (23%). Necrosis and lymphovascular invasion were present in 54% and 10% of the cases, respectively. All histological features except mitotic count and necrosis were associated with nodal metastasis at presentation. A statistically significant poorer outcome was identified for tumours with a solid growth pattern, moderate or marked peripheral infiltration, necrosis and lymphovascular invasion. These results need further validation in a larger cohort of dogs.

Outcome and clinical, pathological, and immunohistochemical factors associated with prognosis for dogs with early-stage anal sac adenocarcinoma treated with surgery alone: 34 cases (2002-2013).

OBJECTIVE To determine survival time and metastatic rate for dogs with early-stage anal sac adenocarcinoma (ASACA) treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for those dogs. DESIGN Retrospective case series. ANIMALS 34 dogs with early-stage, nonmetastatic ASACA that were treated with surgery only. PROCEDURES Medical record databases of 2 referral hospitals were searched to identify dogs examined between 2002 and 2013 that had a diagnosis of nonmetastatic ASACA that was < 3.2 cm at its largest diameter. Only dogs that received surgical treatment alone were included in the study. For each dog, information extracted from the medical record included signalment, clinical and diagnostic test findings, tumor characteristics, and outcome. When available, archived tumor specimens were histologically reviewed and tumor characteristics were described; Ki-67 and E-cadherin expressions were evaluated by use of immunohistochemical methods. Clinical, pathological, and immunohistochemical factors were assessed for associations with survival time and tumor recurrence and metastasis rates. RESULTS Median survival time was 1,237 days. Seven dogs had tumor recurrence and 9 dogs developed metastatic disease at a median of 354 and 589 days, respectively, after primary tumor removal. Cellular pleomorphism was positively associated with development of metastatic disease. No other factors evaluated were associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated dogs with early-stage nonmetastatic ASACA generally had a favorable outcome following surgical removal of the primary tumor alone. Routine rectal examination may be a simple and useful method for detection of dogs with early-stage ASACA.

Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999-2013).

Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252-448 days). Median progression free survival was 289 days (range: 224-469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC.

Anal sac gland carcinoma in 64 cats in the United kingdom (1995-2007).

A retrospective study was performed to characterize 64 cases of anal sac gland carcinoma (ASGC) in cats. All ASGCs diagnosed between 1995 and 2007 at a private diagnostic laboratory in the UK were reviewed. Apocrine gland origin was confirmed in a subset of these tumors by immunohistochemistry and the use of the glandular cytokeratin antibody (CAM 5.2). Associated clinical, gross, and histologic features were compared with those of canine ASGC. Anal sac gland carcinoma accounted for 0.5% of all feline skin neoplasms. Thirty-nine of the cats with ASGC were female, with a female male ratio of 1.56. Fifty-two (81.1%) of the 64 tumors were in Domestic Shorthair cats, 5 (7.8%) in Siamese, 3 (4.8%) in Domestic Longhair, 2 (3.1%) in Burmese, and 1 (1.6%) each in a Birman and a Persian cat. Significant differences in prevalence of ASGC among breeds were not detected. Cats ranged in age from 6 to 17 years (median and mean age, 12 years). More than three quarters of the affected cats for which postsurgical outcome was known were euthanatized or died as a direct consequence of the neoplasm, with a median survival of 3 months. Survival rates at 1 and 2 years were 19 and 0%, respectively.

Anal sac tumours of the dog and their response to cytoreductive surgery and chemotherapy.

A retrospective study of anal sac tumours without pulmonary metastases, from the author's clinical records for the period July 1989 to July 2002, was conducted to establish the response to treatment with surgery and melphalan chemotherapy. Of 21 dogs with tumours of the anal sacs 19 had apocrine gland adenocarcinomas of anal sac origin, one had a benign papillary cystadenoma and another had a malignant melanoma. Two of the 19 dogs had bilateral anal sac adenocarcinomas. Ten of the 19 dogs with apocrine gland adenocarcinomas of anal sac origin had sublumbar lymphadenopathy. Five dogs were excluded by their owners from recommended treatment. Fourteen dogs with apocrine gland adenocarcinomas of anal sac origin were treated by surgical cytoreduction and chemotherapy with melphalan. Seven of the 14 dogs had regional lymph node metastases. Cytoreduction was by local excision of the anal sac in all 14 dogs and concurrent removal of the sublumbar retroperitoneal lymph nodes in the seven dogs with regional lymph node metastases. The median survival time of dogs with sublumbar nodal metastasis was 20 months and for dogs with tumour localised to the anal sac the median survival time was 29.3 months. There was no difference in median survival of those dogs with sublumbar metastases compared to those without. This study suggests there is a role for melphalan in the treatment of dogs with anal sac adenocarcinoma when combined with cytoreductive surgery, with treatment survival times and the local recurrence rate of the primary tumour comparing favourably with previously published treatment regimes.

Long-term outcome of patients with perianal Paget's disease.

BACKGROUND: Perianal Paget's disease (PPD) is a rare intraepithelial adenocarcinoma with a significant rate of recurrence after treatment and high risk of progression to an invasive cancer. PATIENTS AND METHODS: Fourteen patients with a mean follow-up longer than 5 years were studied to determine the outcome after surgical treatment. The immunohistochemical accumulation of p53 protein also was assessed in tissue specimens to evaluate its prognostic role in patients with PPD. RESULTS: Four patients were excluded because of progression to invasive malignancy at the time of diagnosis. Two patients underwent local excision (LE) with macroscopic clearance of the surgical margins; the remaining eight patients underwent wide local excision (WLE), i.e., > 1 cm microscopic clearance of the surgical margins. The actuarial 8-year recurrence rate for patients treated with LE and WLE was 100% and 50% (SE = 17.7), respectively. Progression to invasive carcinoma occurred after a median time of 56 months (range 23-72) in two patients treated with LE and in one of eight patients treated with WLE. All four patients with recurrence after WLE were successfully treated (no further recurrence) with a second WLE. Actuarial 8-year survival was 0% in the LE group and 40% (SE = 21.9) in the WLE group. There was no p53 protein accumulation in any of the ten patients with PPD. CONCLUSIONS: Survival of patients with PPD treated by WLE was higher than that for those treated with LE. Thus, wide local excision is recommended over limited local excision as a preferred treatment for PPD. Follow-up longer than 5 years seems to be indicated because of the risk of late progression to invasive cancer. When PPD does recur, a second WLE may be curative. The absence of accumulated p53 protein suggests that this marker may not have a prognostic role in PPD.