Immunohistochemical Expression of Human Epidermal Growth Factor Receptor 2 and Ki67 in Apocrine Gland Anal Sac Adenocarcinoma.

Apocrine gland anal sac adenocarcinoma is an aggressive neoplasm, and surgery remains the treatment of choice, although it is controversial in advanced cases. The prognostic factors are not well established. Human Epidermal Growth Factor Receptor 2 (HER2) is a membrane protein related to tumorigenesis, whereas Ki67 is a nuclear protein related to cell proliferation. Both are potential prognostic markers and therapeutic targets. This study aimed to evaluate the expression of HER2 and Ki67 markers in canine apocrine gland anal sac adenocarcinoma. The tumor samples were divided into four groups: largest tumor diameter less than 2.5 cm, largest tumor diameter greater than 2.5 cm, metastatic lymph nodes, and control group of non-neoplastic anal sacs. Each contained 10 samples. Immunohistochemistry was performed to verify the expression of HER2 and Ki67 markers. Positive HER2 staining was observed in 45% of the neoplastic cases and negative HER2 staining in 100% of the control group. The Ki67 expression had a median of 25% in all groups, except for the control group, which had a median of 8%. The HER2 and Ki67 expression was present in apocrine gland anal sac adenocarcinoma, making them potential therapeutic targets. However, it was not possible to determine the clinical value of either marker.

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

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CLINICAL SIGNIFICANCE: 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.

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

OBJECTIVE: To evaluate short- and long-term outcomes for dogs undergoing anal sacculectomy for massive (> 5 cm) apocrine gland anal sac adenocarcinoma (AGASACA). ANIMALS: 28 client-owned dogs with massive AGASACA. PROCEDURES: 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). RESULTS: 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. CLINICAL RELEVANCE: 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 1.3 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.

Immunolabelling of SCF and c-KIT in canine perianal gland tumours.

c-KIT and its ligand stem cell factor (SCF) play a direct role in the oncogenesis of various cancers by regulating the cell fate. Recent evidence indicates that an increased expression of c-KIT/SCF, driven by hormonal imbalances, is an important step in the development of hormone-dependent cancers. We investigated the possible role of the c-KIT/SCF system in the carcinogenesis in 44 perianal gland tumours (16 adenomas, 15 epitheliomas and 13 carcinomas) and 10 normal perianal gland tissues by assessing the percentage and type of cells that expressed c-KIT and SCF as well as the cellular localization of immunoreactivity. No differences in immunolabelling of SCF were found between normal glands and neoplastic cells of any histotype. The highest expression of c-KIT was seen in carcinomas and a positive correlation was found between c-KIT labelling score and mitotic index (R = 0.876; P <0.01). c-KIT labelling patterns in hepatoid cells varied among the tumour histotypes with adenomas having only membranous labelling. Three labelling patterns (membranous only, membranous and cytosolic, and cytosolic only) were seen in the other tumour histotypes. Cytosolic labelling was statistically more frequent in carcinomas than in adenomas (P <0.001). These findings suggest that c-KIT expression and its cellular localization may play a role in the development and progression of perianal gland tumours by influencing cell proliferation.

[Radiation therapy for the treatment of macroscopic canine anal gland tumors - a retrospective study]. / Strahlentherapie zur Behandlung makroskopischer Analbeuteltumoren des Hundes ­ eine retrospektive Studie.

INTRODUCTION: Canine anal gland tumors are locally invasive and early metastasize to the loco-regional pelvic lymph nodes. Radiation therapy is a good method for loco-regional tumor control, especially in inoperable tumors. Since the organs in the pelvic area are sensitive to both acute and late radiation damage (chronic diarrhea, bleeding, strictures or intestinal perforations) and such damage mainly depends on the fraction size, we examined the radiation protocol used in this study with a reduced number of fractions (hypofractionated) regarding effectiveness and side effects. This retrospective study describes 13 dogs with macroscopic anal gland carcinoma that were irradiated with imaging-guided, intensity-modulated radiation therapy with a hypofractionated curative protocol of 12 × 3,8 Gy. Gross pathology was either in the region of the anal gland and/or in the sublumbar lymph nodes. Ten of the 13 dogs had advanced tumor diseases (stage 3a or 3b). The acute radiation reactions were mild to moderate and had been reported for some of the dogs in a previous study. The mean study time was 572 days (range 105-1292 days). Disease progression was observed or suspected in 7/13 dogs during the study period: local or loco-regional progression occurred in 3 dogs (23 %) and distant metastases in 4 dogs (31 %). Median progression-free survival was 480 days (95 %CI, 223-908), median survival was 597 days (95 %CI, 401-908). One year after treatment, 76,9 % (95 %CI, 53,5-100) of the dogs were still alive. The likelihood of tumor progression was lower with increasing age, otherwise none of the examined tumor or patient factors showed a prognostic influence on progression or survival time. No clinically relevant late side effects were observed apart from slight alopecia, pigmentation changes or dry, scaly skin, Medium to long-term tumor control can be expected in dogs with macroscopic anal gland tumors treated with a moderately hypofractionated radiation therapy protocol (12 × 3,8 Gy). During long-term monitoring no serious side effects or side effects requiring treatment were observed.

INTRODUCTION: Les tumeurs des glandes anales canines sont localement invasives et métastasent rapidement dans les ganglions lymphatiques loco-régionaux pelviens. La radiothérapie est une bonne méthode de contrôle des tumeurs loco-régionales, en particulier pour les tumeurs inopérables. Étant donné que les organes de la région pelvienne sont sensibles aux dommages aigus et tardifs de la radiation (diarrhée chronique, saignements, sténoses ou perforations intestinales) et que ces dommages dépendent principalement de la taille des fractions, nous avons étudié le protocole de radiations utilisé dans cette étude avec un nombre réduit de fractions (hypofractionné) en terme d'efficacité et d'effets secondaires. Cette étude rétrospective décrit 13 chiens atteints de carcinome macroscopique de la glande anale qui ont été traités par une radiothérapie à modulation d'intensité guidée par imagerie avec un protocole curatif hypofractionné de 12 × 3,8 Gy. La pathologie macroscopique se trouvait soit dans la région de la glande anale et/ou dans les ganglions lymphatiques sublombaires. Dix des 13 chiens présentaient des pathologies tumorales avancées (stade 3a ou 3b). Les réactions aiguës aux radiations étaient légères à modérées et avaient été signalées pour certains des chiens dans une étude précédente. La durée moyenne de l'étude était de 572 jours (fourchette 105­1292 jours). Une progression de la maladie a été observée ou suspectée chez 7/13 chiens au cours de la période d'étude : une progression locale ou loco-régionale est survenue chez 3 chiens (23 %) et des métastases à distance chez 4 chiens (31 %). La survie médiane sans progression était de 480 jours (95 %CI, 223­908), la survie médiane était de 597 jours (95 %CI, 401­908). Un an après le traitement, 76,9 % (95 %CI, 53,5­100) des chiens étaient encore en vie. La probabilité de progression de la tumeur était plus faible avec l'âge, mais aucun des facteurs examinés concernant la tumeur ou le patient n'a montré d'influence pronostique sur la progression ou la durée de survie. Aucun effet secondaire tardif cliniquement pertinent n'a été observé, hormis une légère alopécie, des changements de pigmentation ou une peau sèche et squameuse, On peut s'attendre à un contrôle tumoral à moyen et long terme chez les chiens atteints de tumeurs macroscopiques de la glande anale traités par un protocole de radiothérapie modérément hypofractionnée (12 × 3,8 Gy). Au cours du suivi à long terme, aucun effet secondaire grave ou nécessitant un traitement n'a été observé.

Complications associated with iliosacral lymphadenectomy in dogs with metastatic apocrine gland anal sac adenocarcinoma.

Objective: To report intraoperative and immediate postoperative complications associated with removal of metastatic iliosacral lymph nodes in dogs with apocrine gland anal sac adenocarcinoma. Animals: There were 136 client-owned dogs in the study. Procedure: Retrospective multi-institutional study. The database of collaborating institutions was searched for dogs with metastatic apocrine gland anal sac adenocarcinoma that underwent lymphadenectomy for removal of one or more iliosacral lymph nodes. Information of signalment, hematological abnormalities, abdominal computed tomography or ultrasound findings, number and size of enlarged lymph nodes, intraoperative and postoperative complications, treatment and outcome were collected. Results: The overall complication rate associated with metastatic iliosacral lymphadenectomy was 26.1%. The only intraoperative complication recorded was hemorrhage and was reported in 24 (17.6%) surgeries, 11 (45.8%) of which received a blood transfusion. Postoperative complications were reported in 10.4% of surgeries, and included edema formation (n = 4, 2.6%), unilateral or bilateral paraparesis (n = 4, 2.6%), hypotension (n = 3, 2.0%), surgical site infection (n = 2, 1.3%), abdominal incision dehiscence (n = 1, 0.6%), urinary incontinence (n = 1, 0.6%), and death (n = 1, 0.6%). The size of the iliosacral lymph nodes was significantly associated with a greater risk of complications, hemorrhage, and the need of transfusion during lymphadenectomy for metastatic apocrine gland anal sac adenocarcinoma. Conclusion: Complications associated with iliosacral lymphadenectomy for metastatic apocrine gland anal sac adenocarcinoma are relatively common and mostly relate to hemorrhage. These complications are significantly associated with the size of the extirpated metastatic lymph nodes. Clinical relevance: This retrospective study provides information for the clinician regarding the potential surgical complications for extirpation of metastatic iliosacral lymph nodes. These complications, although not common, can be severe and should be discussed with owners before surgery.

Objectif: Rapporter les complications peropératoires et postopératoires immédiates associées à l'ablation des ganglions lymphatiques ilio-sacrés métastatiques chez les chiens atteints d'un adénocarcinome des glandes apocrines des sacs anaux. Animaux: Il y avait 136 chiens appartenant à des clients dans l'étude. Procédure: Étude multi-institutionnelle rétrospective. La base de données des institutions collaboratrices a été recherchée pour les chiens atteints d'un adénocarcinome métastatique des glandes apocrines des sacs anaux qui ont subi une lymphadénectomie pour l'ablation d'un ou plusieurs ganglions lymphatiques ilio-sacrés. Des informations sur le signalement, les anomalies hématologiques, les résultats de la tomodensitométrie abdominale ou de l'échographie, le nombre et la taille des ganglions élargis, les complications peropératoires et postopératoires, le traitement et les résultats ont été recueillis. Résultats: Le taux global de complications associées à la lymphadénectomie ilio-sacrée métastatique était de 26,1 %. La seule complication peropératoire enregistrée était une hémorragie et a été rapportée dans 24 (17,6 %) chirurgies, dont 11 (45,8 %) ont reçu une transfusion sanguine. Des complications postopératoires ont été signalées dans 10,4 % des interventions chirurgicales et comprenaient la formation d'oedème (n = 4, 2,6 %), la paraparésie unilatérale ou bilatérale (n = 4, 2,6 %), l'hypotension (n = 3, 2,0 %), l'infection du site opératoire (n = 2, 1,3 %), la déhiscence de l'incision abdominale (n = 1, 0,6 %), l'incontinence urinaire (n = 1, 0,6 %) et le décès (n = 1, 0,6 %). La taille des ganglions ilio-sacrés était significativement associée à un risque accru de complications, d'hémorragie et à la nécessité d'une transfusion lors d'une lymphadénectomie pour un adénocarcinome métastatique des glandes apocrines des sacs anaux. Conclusion: Les complications associées à la lymphadénectomie ilio-sacrée pour l'adénocarcinome métastatique des glandes apocrines des sacs anaux sont relativement fréquentes et concernent principalement l'hémorragie. Ces complications sont significativement associées à la taille des ganglions lymphatiques métastatiques retirés. Pertinence clinique: Cette étude rétrospective fournit des informations au clinicien concernant les complications chirurgicales potentielles pour le retrait des ganglions lymphatiques ilio-sacrés métastatiques. Ces complications, bien que rares, peuvent être graves et doivent être discutées avec les propriétaires avant la chirurgie.(Traduit par Dr Serge Messier).

Immunolabelling of c-KIT and CAM5.2 in Canine Anal Sac Gland Adenocarcinoma.

The role of c-KIT receptor in anal sac gland adenocarcinoma (ASGAC) is unclear despite its importance in the development of tumours. In this preliminary study, the expression of c-KIT was investigated in rarely observed canine ASGAC. The potential use of CAM5.2 in distinguishing ASGAC from perianal gland tumours was also evaluated. ASGAC was diagnosed in five out of 25 examined perianal tumours. By immunohistochemistry, cytosolic (abnormal) c-KIT expression was seen in four of the five cases. CAM5.2 immunoreactivity was detected in neoplastic cells of all ASGAC cases examined, whereas it was not evident in any case of perianal gland tumour. The findings suggest that c-KIT expression and its cellular localization may be important in the oncogenesis of ASGAC and CAM5.2 can be used to distinguish between ASGAC and perianal gland tumours.

Canine Apocrine Gland Anal Sac Adenocarcinoma: A Review.

Apocrine gland anal sac adenocarcinoma (AGASAC) is a relatively uncommon tumor in the dog and comprises approximately 17% of perianal malignancies; however, it is one of the most common causes of paraneoplastic hypercalcemia. Clinical signs in affected dogs most commonly are associated with mechanical obstruction caused by the primary tumor or enlarged regional metastatic lymph nodes and the effects of paraneoplastic hypercalcemia when present. Surgical excision of the primary tumor and metastasectomy of affected locoregional lymph nodes is the preferred initial treatment option for most dogs, although radiation therapy and adjuvant chemotherapy are commonly incorporated into multi-modality treatment plans. A significant role for the use of adjuvant chemotherapy has not been clearly demonstrated. Prolonged survival times are possible, especially for dogs with smaller primary tumors and for dogs that undergo further treatments for recurrent disease. In this article, we review the clinical signs, diagnosis, staging, treatment, and prognosis of AGASAC in the dog.

Updated Concepts in Oncologic Surgery: Apocrine Gland Anal Sac Adenocarcinoma and Mast Cell Tumors.

Advancements within the field of veterinary surgical oncology are constantly presenting themselves, especially with continued development of comprehensive cancer programs. With the use of more advanced imaging techniques within veterinary medicine, tumor staging is improving and techniques novel to veterinary medicine are being evaluated for potential clinical application. Recommended tumor staging and treatment approach for apocrine gland anal sac adenocarcinoma in dogs has evolved, with the anticipation of good long-term patient outcomes. Preoperative staging for mast cell tumors and recommendations for surgical margins to obtain for wide surgical excision is being reassessed by surgeons.

Computed tomographic staging of dogs with anal sac adenocarcinoma.

OBJECTIVES: To describe the CT appearance of anal sac adenocarcinoma lesions in a population of dogs including the relations between primary tumour, and locoregional and distant metastasis. MATERIALS AND METHODS: Retrospective review of dogs with confirmed anal sac adenocarcinoma and available CT images of the thorax, abdomen and pelvis. RESULTS: A population of 70 dogs were included in the study. No association was found between anal sac mass size and presence or absence of iliosacral lymph node enlargement. The prevalence of local metastatic disease characterised by iliosacral lymphadenomegaly in this study was 71%, with pulmonary metastases identified in 11% of cases. There were no cases of distant pulmonary metastasis without concurrent locoregional lymphadenomegaly. CLINICAL SIGNIFICANCE: In our population of dogs local metastatic spread of anal sac adenocarcinoma was common, with a relatively low prevalence of pulmonary metastasis. The study demonstrates the importance of thorough rectal examination and/or imaging to assess the iliosacral lymph centre in this disease irrespective of the size of the anal sac mass.

Treatment response to eribulin and anlotinib in lung metastases from rare perianal adenoid cystic carcinoma: a case report.

Adenoid cystic carcinoma (ACC) is a rare salivary glands tumor and often displays aggressive behavior with frequent relapse and metastasis. The terminal ACC lacks standard treatment guidelines and is always accompanied by poor prognosis. Here, we report a case of rare perianal ACC who received resection and palliative adjuvant radiation. Five years later, PET-computed tomography (CT) showed perianal recurrence and multiple pulmonary metastases. Combined chemotherapy with doxorubicin, carboplatin and cyclophosphamide was applied for two cycles but ineffective. Further next-generation sequencing analysis of perianal tissue demonstrated the v-myb avian myelobastosis viral oncogene homolog and nuclear factor I/B fusion gene and two novel BCL-6 corepressor (BCOR) mutations (p.F1106Tfs*5 and p.L1524Hfs*8). The therapy was switched to eribulin and anlotinib and has been performed for eight cycles. At recent follow-ups, MRI and CT examinations revealed the diminishing perianal and pulmonary lesions. This study presented the first case of perianal ACC with multiple pulmonary metastases and particular BCOR mutations, who presented a durable response to eribulin and anlotinib, providing a potential therapeutic option for advanced refractory ACC.

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.

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.

Gene expression of prostaglandin EP4 receptor in three canine carcinomas.

BACKGROUND: Chronic 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. RESULTS: In 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. CONCLUSIONS: These 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.

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.

Comparison of methods to determine primary tumour size in canine apocrine gland anal sac adenocarcinoma.

OBJECTIVES: To assess agreement between measurement of primary apocrine gland anal sac adenocarcinoma tumours using digital palpation, CT and formalin-fixed tissue and to look for associations with metastasis at presentation. MATERIALS AND METHODS: Retrospective study of different methods of measuring primary tumour size in histopathologically-confirmed canine apocrine gland anal sac adenocarcinoma. RESULTS: One hundred sixteen tumours from 107 dogs were included. There was moderate agreement between maximal dimension of the primary tumour measured by CT compared to formalin-fixed tissue and digital palpation. There was no significant difference in median maximum dimension between the measurement methods. Vascular invasion, CT stage, digital rectal examination stage and formalin-fixed tissue stage were significantly associated with metastasis at presentation, while mitotic index of the primary tumour was not. Dogs with tumours >2.5 cm (tumour-stage 2) were significantly more likely to present with metastatic disease. CLINICAL SIGNIFICANCE: In canine apocrine gland anal sac adenocarcinoma, primary tumour size, tumour-stage and vascular invasion are strong predictors of metastasis at presentation.

Evaluation of Serum Acute Phase Protein Concentrations in Dogs with Circumanal Gland Tumours.

The aim of this study was to determine the serum concentrations of acute phase proteins (APPs), including C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hp) in dogs with circumanal gland tumours. Investigations were conducted on 39 male dogs of mixed breed. The animals were divided into four groups depending on the degree of tumour malignancy and type of hormones that were dominant in the bloodstream. All measurements of serum APPs were conducted by the use of commercial diagnostic kits. In dogs with benign tumours, the concentrations of each APP decreased during therapy, while in dogs with malignant tumours, despite anti-tumour therapy, concentrations of APPs in serum increased markedly. The results of this study suggest that changes in serum concentrations of CRP, SAA and Hp during anti-hormone therapy may be a reliable marker for differentiating tumour grade and degree of malignancy. Including APPs in routine diagnostics may assist with formulating a prognosis for the outcome of the disease, before implementing anti-tumour therapy. Moreover, monitoring the effectiveness of therapy may be possible based on the determination of serum APP concentrations.