Apocrine Gland Anal Sac Adenocarcinoma Research Articles

Radiotherapy for Canine Apocrine Gland Anal Sac Adenocarcinoma: Survival Outcomes and Side Effects of a Palliative Treatment Protocol of 20 Gy in Five Consecutive Fractions.

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198-569) and 628 days (95% CI 579-676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282-391 days), and 402 days (95% CI 286-517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs.

Histopathological diagnosis and surgical complications following bilateral anal sacculectomy for the treatment of unilateral canine apocrine gland anal sac adenocarcinoma: 35 cases (2019-2023).

To report the histopathological diagnosis of both anal sacs in dogs undergoing bilateral anal sacculectomy for the treatment of unilateral apocrine gland anal sac adenocarcinoma and to compare the surgical complication rate associated with this procedure in this population with previously published literature. Records were retrospectively reviewed for dogs that underwent bilateral anal sacculectomy for the treatment of apparently unilateral apocrine gland anal sac adenocarcinoma, at a single institute between 2019 and 2023. Clinical staging, surgical treatment, histological findings, intra- and postoperative complications were evaluated. Thirty-five dogs were included. Only five of 35 (14%) dogs were found to have histologically normal contralateral anal sacs. Non-neoplastic anal sac disease was found in 23 of 35 (66%) dogs and bilateral apocrine gland anal sac adenocarcinoma was seen in seven of 35 (20%) dogs. None of the dogs diagnosed with bilateral neoplasia had evidence of bilateral neoplasia before surgery despite a thorough work-up. Complications attributable to the primary tumour removal were seen in 9% of dogs intraoperatively and 14% of dogs postoperatively, commonly tumour capsule disruption and surgical site infection, respectively. Bilateral anal sac disease was diagnosed histologically in the majority of presumed normal anal sacs, with 20% of cases being found to have bilateral apocrine gland anal sac adenocarcinoma. The surgical complication rates of this cohort were comparable to those reported for unilateral anal sacculectomy alone. These findings promote and encourage the use of bilateral anal sacculectomy in cases of suspected unilateral anal sac neoplasia.

Outcomes of dogs with apocrine gland anal sac adenocarcinoma treated via modified closed anal sacculectomy (2015-2022).

To evaluate the postoperative complication rate and local recurrence rate of apocrine gland anal sac adenocarcinoma (AGASACA) in dogs surgically treated with a modified closed anal sacculectomy technique between 2015 and 2022. Observational clinical retrospective study. Forty-seven client-owned dogs histologically diagnosed with AGASACA. Medical records were evaluated for patient demographics and history, physical examination findings, diagnostic imaging, incidence of concurrent neoplasia, postoperative complications, and incidence and time to local recurrence. Dogs with at least 150 days of follow-up were included in evaluation of local recurrence. Two dogs were euthanized at 4 and 11 days after surgery. Forty-five dogs were included for long-term local recurrence evaluation, with a median of 364 days of follow-up (range 156-2156 days). Only one dog (2.2%) developed local recurrence with a time to recurrence of 90 days. Postoperative complications were reported in 15 dogs (31.9%) and were considered minor in 14 dogs (93.3%) and major in one dog (6.7%). Mean survival time for the 20 dogs that were deceased as of November 1, 2022 was 521 days (range 156-1409 days) and the median survival time was 388 days. The modified closed anal sacculectomy technique resulted in a lower AGASACA local recurrence rate than previously reported in the veterinary literature with a comparable postoperative complication rate. Given the low recurrence rate found in this study, the modified closed anal sacculectomy technique may reduce the need for adjuvant radiation therapy and potentially chemotherapy in AGASACA patients.

Short- and long-term outcomes associated with anal sacculectomy in dogs with massive apocrine gland anal sac adenocarcinoma.

To evaluate short- and long-term outcomes for dogs undergoing anal sacculectomy for massive (> 5 cm) apocrine gland anal sac adenocarcinoma (AGASACA). 28 client-owned dogs with massive AGASACA. A retrospective multi-institutional study was performed. Pre-, intra-, and post-operative data was collected, and variables were statistically analyzed for associations with progression-free interval (PFI) and overall survival (OS). At the time of anal sacculectomy, 19 (68%) dogs underwent concurrent iliosacral lymph node extirpation, including 17 of 18 (94%) dogs with suspected nodal metastasis preoperatively. Five (18%) dogs experienced grade 2 intraoperative complications. Ten (36%) dogs experienced postoperative complications, including 1 grade 3 and 1 grade 4 complication. No dogs had permanent fecal incontinence, tenesmus, or anal stenosis. Nineteen dogs received adjuvant chemotherapy, radiation, or both. Local recurrence occurred in 37% of dogs. Dogs with lymph node metastasis at surgery were more likely than dogs without metastasis to develop new/progressive lymph node metastasis (10/17 [59%] vs 0/10 [0%]; P = .003) and distant metastasis (7/17 [41%] vs 0/10 [0%]; P = .026). Median PFI was 204 days (95% CI, 145 to 392). Median OS was 671 days (95% CI, 225 to upper limit not reached). Nodal metastasis at the time of surgery was associated with shorter PFI (P = .017) but not OS (P = .26). Adjuvant therapy was not associated with outcome. Dogs with massive AGASACA experienced prolonged survival following anal sacculectomy despite a high incidence of local recurrence and metastasis. Lymph node metastasis at the time of surgery was a negative prognostic indicator for PFI but not OS.

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 1.3cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2cm 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 <2cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2cm. The association between tumour size group (<2 vs. ≥2cm) 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 <2cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.

Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma.

Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor, particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and a few recent reports have suggested the activation of the immune checkpoint axis in canine AGASACA. In our study, we developed canine-specific monoclonal antibodies targeting PD-1 and PD-L1. A total of 41 AGASACAs with complete clinical and follow-up information were then analyzed by immunohistochemistry for the expression of the two checkpoint molecules (PD-L1 and PD-1) and the presence of tumor-infiltrating lymphocytes (CD3 and CD20), which were evaluated within the tumor bulk (intratumor) and in the surrounding stroma (peritumor). Seventeen AGASACAs (42%) expressed PD-L1 in a range between 5% and 95%. The intratumor lymphocytes were predominantly CD3+ T-cells and were positively correlated with the number of PD-1+ intratumor lymphocytes (ρ = 0.36; p = 0.02). The peritumor lymphocytes were a mixture of CD3+ and CD20+ cells with variable PD-1 expression (range 0-50%). PD-L1 expression negatively affected survival only in the subgroup of dogs treated with surgery alone (n = 14; 576 vs. 235 days). The presence of a heterogeneous lymphocytic infiltrate and the expression of PD-1 and PD-L1 molecules support the relevance of the immune microenvironment in canine AGASACAs and the potential value of immune checkpoints as promising therapeutic targets.

Quantification of Canine Apocrine Gland Anal Sac Adenocarcinoma (AGASACA) Tumor Specimen Shrinkage after Formalin Fixation.

The aim was to prospectively measure the shrinkage of primary apocrine gland anal sac adenocarcinoma (AGASACA) tumors after 24 and 48 h of formalin fixation. Dogs that were diagnosed with AGASACA pre-operatively by aspiration cytology were prospectively enrolled in the study. Tumor extirpation was performed in a closed technique. The tumor and associated tissues were examined on the back table away from the patient and the widest dimension of the tumor was measured using a sterile ruler (Medline®; Northfield, IL, USA). This measurement was recorded in mm (t0). The tissue was placed in 10% buffered formalin and stored at room temperature. Two further measurements were taken after 24 (t24) and 48 (t48) hours of formalin fixation. Once the 48 h measurement was taken, the tissue was submitted for histopathology. The percentage of shrinkage between time points was calculated by using the following equation: (1 - [time b/time a]) × 100. Overall, 23 dogs with 23 tumors were enrolled. The mean percentage of shrinkage after 24 and 48 h of formalin fixation was 4.8% and 7.2%, respectively. The median diameter of the tumors reduced by 1 mm over 48 h and was not significantly different at any time point. These data will aid clinicians in interpreting measurements of AGASACA tumors following formalin fixation and shows that minimal change in tumor size is expected following 48 h.

Minimal complications observed with a modified surgical approach for treatment of canine anal sac neoplasia.

To describe a modified approach to closed anal sacculectomy and report the short-term outcomes of dogs that underwent the procedure for treatment of neoplasia. 16 client-owned dogs. Medical records of 1 referral hospital were reviewed to identify dogs that underwent modified closed anal sacculectomy for treatment of anal sac neoplasia between January 2018 and September 2020. Data collected included signalment, examination and diagnostic imaging findings, surgical details, intraoperative and postoperative complications, cytologic and histologic findings, adjuvant treatments, duration of follow-up, and short-term outcome. 15 dogs had apocrine gland anal sac adenocarcinoma, and 1 had a collision tumor. No dogs had intraoperative complications; 1 dog had a minor postoperative complication (paraparesis) that resolved. The median duration of postoperative follow-up was 286 days (range, 67 to 777 days). One dog had confirmed local disease recurrence 290 days after surgery, and 1 had suspected local disease recurrence 203 days after surgery and was euthanized because of systemic disease progression. The modified closed anal sacculectomy was well tolerated in this sample of dogs, with minimal short-term complications. This study provided evidence to justify evaluation of the procedure in a larger number of dogs and assessment of the effects of procedural modifications on postoperative complication rates and time to local recurrence.

Minimal late radiation toxicity and transient early toxicity following postoperative definitive intent conformal radiation therapy (20×2.5Gy) for canine apocrine gland anal sac adenocarcinoma.

Postoperative radiation therapy (RT) may be beneficial for dogs with anal sac apocrine gland adenocarcinoma (ASAC). Clinically significant late toxicities have been reported in up to 65% of dogs with perianal tumors following non-conformal definitive RT, particularly when fractions of 3Gy or higher are prescribed. The primary objective of this prospective, descriptive study was to evaluate tolerability of a novel 3D conformal RT (3DCRT) protocol in a group of dogs. Dogs with ASAC were prospectively enrolled if clients elected RT following surgery. The planning target volume was prescribed 50Gy in 2.5Gy fractions using 6 MV photons and administered over 26 days. Early and late radiation toxicities were graded according to standardized criteria. Thirteen dogs were initially enrolled but 1 was excluded due to a high risk of anesthesia-related mortality. Seven dogs presented with early stage disease. Median follow up time was 771 days (91-2223). Transient grade 3 dermatitis and anusitis developed in all dogs, with resolution within 4weeks. Two dogs developed transient grade 2 late colitis. Locoregional failure in the irradiated field was documented in one dog at 738 days. All-cause median survival time was 771 days (95% confidence interval: 510→2223 days). Findings indicated that this fractionation may be safely administered to the canine anus and pelvic canal using 3DCRT, although acute toxicity should be anticipated. Further prospective studies are needed in order to confirm long-term tolerability and efficacy.

A Retrospective Study of Clinical and Histopathological Features of 81 Cases of Canine Apocrine Gland Adenocarcinoma of the Anal Sac: Independent Clinical and Histopathological Risk Factors Associated with Outcome.

Simple SummaryDogs can be affected by a tumour arising from the glands of the anal sacs. These tumours can grow aggressively and spread to other organs, resulting in disruption of bowel movements and/or organ function, ultimately leading to death or euthanasia. The reason why some tumours grow or spread more quickly is not well understood, and veterinarians are not able to distinguish between dogs likely to have better or worse survival times at the time of initial diagnosis. This study evaluates clinical, imaging, and tumour features of dogs with anal sac tumours and examines which features were linked to improved survival times. Smaller tumour size, smaller lymph node size, surgical removal, and treatment with radiotherapy were associated with better survival times. When examining the tumour tissue, the presence of closely packed tumour cells, dead tumour tissue, and invasion of vessels by tumour cells were each associated with worse survival times. Features that impacted survival were used to create two checklists that, when applied to an individual case, may indicate prognosis and therefore help clinicians and owners make more informed clinical decisions.Canine apocrine gland anal sac adenocarcinoma (AGASAC) is a malignant tumour with variable clinical progression. The objective of this study was to use robust multivariate models, based on models employed in human medical oncology, to establish clinical and histopathological risk factors of poor survival. Clinical data and imaging of 81 cases with AGASAC were reviewed. Tissue was available for histological review and immunohistochemistry in 49 cases. Tumour and lymph node size were determined using the response evaluation criteria in the solid tumours system (RECIST). Modelling revealed tumour size over 2 cm, lymph node size grouped in three tiers by the two thresholds 1.6 cm and 5 cm, surgical management, and radiotherapy were independent clinical variables associated with survival, irrespective of tumour stage. Tumour size over 1.3 cm and presence of distant metastasis were independent clinical variables associated with the first progression-free interval. The presence of the histopathological variables of tumour necrosis, a solid histological pattern, and vascular invasion in the primary tumour were independent risk factors of poor survival. Based upon these independent risk factors, scoring algorithms to predict survival in AGASAC patients are presented.

Unilateral anal sacculectomy for anal sac apocrine gland adenocarcinoma with urethral involvement

The patient presented to a veterinary hospital with a month-long history of ‘scooting’ and a right-sided anal gland mass. A diagnosis of a stage 2 anal sac apocrine gland adenocarcinoma was confirmed, and the patient underwent a right-sided anal sacculectomy. There was involvement of the urethra and adherence to the rectum and a subsequent urethral incision was necessary, which was surgically repaired at the time of surgery. The patient was hospitalised for several weeks postoperatively for urinary catheter care and further nursing interventions. The patient was discharged from hospital 3 weeks after surgery once the urethra had healed sufficiently enough to enable normal micturition and subsequently made a full recovery.

Post-operative complications following apocrine gland anal sac adenocarcinoma resection in dogs.

Describe the complications associated with surgical resection of primary apocrine gland anal sac adenocarcinoma (AGASACA) tumours study design multi-institutional retrospective cross-sectional cohort study Animals Client owned dogs with spontaneous disease using the Clavien-Dindo classification system, post-operative events were assigned and described. Logistic regression analysis was used to analyse for risk factors for a significant association with complications. One hundred sixty-one dogs were included in the analysis. The post-operative sequelae, complication, and failure to cure rates specific to the anal sac site was 14%, 17% and 1%, respectively. The majority (68%) of complications were grade II or higher, therefore requiring some form of intervention. Intra-operative complications were identified in 11 cases (7%) with anorectal wall perforation being most common. An intra-operative complication was significantly associated with post-operative complications (p < 0.001; OR 7.4) while anorectal wall perforation was the only significant risk factor on regression analysis (p < 0.001; OR 19). Surgical site infection was identified in 20 of 161 (12%) of cases. Local recurrence (LR) occurred in 18% of cases at a median of 374 days (95% CI: 318-430). The only risk factor significantly associated with LR was the presence of vascular or lymphatic invasion (p=0.008; OR 3). Post-operative complications were relatively infrequent but the risk was significantly increased when there was an intraoperative complication during resection of a primary AGASACA tumour. This study provides information for the clinician regarding risk factors for post-operative complications.

Prognostic Value of Ki67 and Other Clinical and Histopathological Factors in Canine Apocrine Gland Anal Sac Adenocarcinoma.

Simple SummaryApocrine gland anal sac adenocarcinoma (AGASACA) is a locally aggressive tumor with a high metastatic rate to the regional ileo-sacral lymph nodes and later to distant sites. Clinical signs depend on the tumor and regional lymph nodes size or on the paraneoplastic hypercalcemia. Therefore, dogs are often referred for perineal swelling, tenesmus, constipation and/or polyuria, polydipsia. Surgical excision of both the neoplastic anal sac and the metastatic regional lymph nodes represents the standard of care. Adjuvant chemotherapy and/or radiotherapy are also indicated. Prognostic factors include tumor size, hypercalcemia, regional lymph nodes metastasis and tumor histologic features. The aim of the study was to retrospectively evaluate the prognostic significance of tumor Ki67 expression. The authors’ hypothesis was that higher Ki67 index correlated with decreased disease-free interval and overall survival time. Clinical data such as tumor size, regional lymph nodes metastasis and hypercalcemia at presentation and histological features such as tumor pattern, mitotic count, necrosis, inflammatory infiltration, vascular invasion, anisokaryosis, and anisocytosis were also investigated and correlated to the oncologic outcome in the dogs included in the study.Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.

Apocrine Gland Anal Sac Adenocarcinoma in Dogs: 22 Cases (2015-2020)

Background: Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly malignant disease mostly invading regional lymph nodes at the time of disease diagnosis.Methods: Twenty- two cases of Apocrine gland anal sac adenocarcinoma (AGASACA) were treated during five years. Contrast radiography with Iohexol and Lipidol were carried out to detect primary anal sac mass and regional lymph node through indirect lymphography technique. For clinical staging, ultrasonography, fine-needle aspiration cytology, histopathology of both primary tumor mass and regional lymph node were performed. Closed anal Sacculectomy was performed as curative therapy for anal sac adenocarcinoma.Result: The median age and weight of dogs at presentation were 8.4 years and 20.9 kg, respectively. Diagnostic radiology, histopathology and biochemical assay confirm twenty-two cases of anal sac adenocarcinoma and medial iliac lymph node to be sentinel lymph node. Carcinoma was of unilateral occurrence in all the dogs. Four (18%) dogs had hypercalcemia and twelve (54%) had metastases to the regional lymph nodes with clinical signs of tenesmus or constipation, polyuria -polydipsia and anorexia. Apocrine gland Adenocarcinoma of anal sac was found to initially metastasize to the medial iliac lymph node. Survival times of dogs treated with the surgical procedure only (8 out of 22 dogs) were appreciably longer than the dogs with therapeutic only. Animals with metastasis to regional lymph nodes or lymphadenopathy had poor prognosis.

Evaluation of electrochemotherapy in the management of apocrine gland anal sac adenocarcinomas in dogs: A retrospective study.

Background:Electrochemotherapy (ECT) combines the administration of anticancer drugs with the delivery of electric pulses, thus increasing the drug uptake through the cell membranes, resulting in increased efficacy.Aim:The aim of our study was to describe the tolerability and efficacy of ECT alone or in association with other treatment modalities for the management of apocrine gland anal sac adenocarcinoma (AGASAC).Methods:Medical records of dogs with a diagnosis of AGASAC that were treated with ECT alone or in combination with surgery/chemotherapy were retrospectively evaluated. Each dog received 20 mg/m2 of bleomycin intravenously. Based on the clinician’s decision, the primary tumor or tumor bed was also infiltrated with cisplatin at the dose of 0.5 mg/cm2. Trains of permeabilizing biphasic electric pulses were then applied under general anesthesia.Results:Ten dogs were enrolled in the study. Of those 10 dogs, only one received ECT for treatment of microscopic local disease, while in six cases ECT was the only treatment modality. In three dogs, ECT was followed by systemic medical treatment. Six dogs (60%) had a partial response (PR), three dogs (30%) had stable disease, and one dog treated for microscopic disease did not show any sign of local relapse for 305 days after treatment, being still alive and in complete remission at the time of writing this article. The median time to progression was 303 days and the median survival time was 365 days. The treatment was well tolerated and local side effects were minimal. No systemic effects were documented.Conclusion:This preliminary study suggests that ECT may be beneficial for dogs with AGASAC and could be a useful addition to the current therapeutic options in consideration of its low cost, limited toxicity, and ease of administration.

Computed tomography and magnetic resonance imaging findings in a dog with apocrine gland anal sac adenocarcinoma with vertebral canal metastasis

A 10-year-old male neutered cocker spaniel was presented for further investigation of an enlarged sublumbar lymph node, which was cytologically consistent with epithelial cell malignancy. CT revealed marked left medial and internal iliac and mild lumbo-aortic lymphadenomegaly. Surgical extirpation of the lymph nodes was performed, and histopathology was consistent with poorly differentiated carcinoma. Despite the absence of a discernible primary lesion, metastatic apocrine gland anal sac adenocarcinoma (AGASAC) was suspected and chemotherapy was started. Six days after starting chemotherapy, the patient developed acute-onset paraparesis and trembling. MRI revealed a left-sided extradural mass at the level of T11–T13. CT imaging revealed mild enlargement of multiple left sided lumbo-aortic lymph nodes. The dog was euthanised 3 days later due to neurological deterioration. Postmortem examination confirmed a diagnosis of left AGASAC with local lymph node and T11–T13 vertebral canal metastasis.

Optical coherence tomography imaging of excised canine apocrine gland anal sac adenocarcinoma tumours.

Optical coherence tomography (OCT) is an optical imaging modality that has been investigated for real-time surgical margin evaluation in human breast cancer patients. Previous veterinary OCT studies have been limited to surgical margin imaging for soft tissue sarcoma (STS) tumours. To the authors knowledge, OCT has never been used to characterize or evaluate other types of neoplasia in dogs. The goal of this study was to characterize the OCT imaging appearance of apocrine gland anal sac adenocarcinoma (AGASACA) in excised ex vivo specimens from five client-owned dogs. All excised tissue surgical margins were imaged using a clinical spectral domain OCT system and two to four areas suspicious for incomplete surgical margins were selected. These areas were inked and sections were trimmed for histopathology. This enabled OCT imaging from each area of interest to be compared with corresponding H&E stained histology imaging from the same location. OCT was able to identify the presence of AGASACA at or within 1 mm of the surgical margin in all areas of interest. AGASACA, similar to the previously described canine STS, generated a dense, highly scattering image without any specific textural architecture. This study was able to validate the ability of OCT to accurately identify another type of tumour presence at or close to the surgical margin in the dog. Further study is needed to assess OCT accuracy at identifying other tumour types in dogs to understand its potential clinical applications.

Gene expression of prostaglandin EP4 receptor in three canine carcinomas

BackgroundChronic inflammation mediated by the cyclooxygenase enzymes, specifically their product prostaglandin E2 (PGE2), can result in the development of cancer. PGE2 promotes cell proliferation, apoptosis, and angiogenesis through interaction with its specific receptors (EP1 receptor - EP4 receptor [EP1R-EP4R]). In multiple human cancers, the expression of EP4R is associated with the development of malignancy and a poor prognosis. The expression of EP4R has not yet been evaluated in canine tumors. The aim of this study was to characterize the mRNA gene expression of EP4R (ptger4) in canine squamous cell carcinoma (SCC), apocrine gland anal sac adenocarcinoma (AGASACA), and transitional cell carcinoma (TCC). Archived tumor samples of canine cutaneous SCC (n = 9), AGASACA (n = 9), and TCC (n = 9), and matched archived normal tissue controls were evaluated for mRNA expression of canine EP4R using RNA in situ hybridization (RNAscope®). Quantification of RNAscope® signals in tissue sections was completed with an advanced digital pathology image analysis system (HALO). Data was expressed as copy number, H-index, and percent tumor cell expression of EP4R.ResultsIn all canine SCC, AGASACA, and TCC samples evaluated, strong universal positive expression of EP4R was identified. For SCC and AGASACA, mRNA EP4R expression was statistically higher than that of their respective normal tissues. The TCC tissues displayed significantly less mRNA EP4R expression when compared to normal bladder mucosa.ConclusionsThese results confirm the mRNA expression of canine EP4R in all tumor types evaluated, with SCC and AGASACA displaying the highest expression, and TCC displaying the lowest expression. This study also represents the first reported veterinary evaluation of EP4R expression using the novel in situ hybridization technique, RNAscope®.

Adherence to follow-up recommendations for dogs with apocrine gland anal sac adenocarcinoma: A multicentre retrospective study.

Progressive disease is common following anal sacculectomy for apocrine gland anal sac adenocarcinoma (AGASACA); additional therapy may prolong survival. Adherence to medical recommendations influences therapeutic success in humans. The purpose of this study was to assess the adherence to follow-up recommendations in dogs with AGASACA. Medical records of patients that underwent anal sacculectomy for AGASACA, with or without iliosacral lymphadenectomy, between July 2015 and July 2018, were reviewed at eight referral institutions to assess post-operative recommendations and owner adherence to recommendations. One hundred and seventy-four dogs were included, of which 162 underwent unilateral anal sacculectomy, 12 underwent bilateral anal sacculectomy and 39 underwent concurrent iliosacral lymphadenectomy. Seventy-six owners (44%) received recommendations for staging at the time of discharge, histopathology results or at the first follow-up visit. One hundred and forty owners (80%) received recommendations for treatment following the initial surgery. Fifty of seventy-six (66%) owners pursued at least one staging recommendation and 69 of 140 (49%) owners pursued some kind of adjuvant treatment recommendation. Overall, 16 of 76 (21%) were adherent to staging recommendations with 20 adherent for the first year following surgery (26%). Forty-seven of 140 (34%) were adherent to treatment recommendations with 54 (39%) adherent for the first year. Owners that were adherent to restaging recommendations at 1 year following surgery were significantly more likely to pursue treatment for progressive disease (P = .014). Further work is required to assess owner motivation and evaluate strategies to improve adherence, given the potential impact on patient treatment.

Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs

BackgroundToceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.ObjectivesTo investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor‐infiltrating regulatory T cells (Tregs), and intratumoral hypoxia.AnimalsNinety‐two client‐owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma.MethodsRetrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor‐2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia‐inducible factor (HIF)‐1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries.ResultsMedian TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65‐0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF‐1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries.Conclusions and Clinical ImportanceToceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.