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.

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

OBJECTIVE: 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. STUDY DESIGN: Observational clinical retrospective study. ANIMAL POPULATION: Forty-seven client-owned dogs histologically diagnosed with AGASACA. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL SIGNIFICANCE: 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.

Stereotactic radiotherapy for advanced canine anal sac adenocarcinoma: an exploratory study.

For dogs with anal sac adenocarcinoma (ASAC), metastasis to intra-abdominal and pelvic lymph nodes occurs early in the disease course. Death is usually related to locoregional progression. Surgical excision is the treatment of choice, but may not be possible in advanced cases. Dogs treated with RT in the gross disease setting showed a 38%-75% overall response rate, but side effects to organs at risk in this area (especially the colon, bladder, and spinal cord) were reported. Stereotactic radiation therapy (SRT) utilizes highly conformal treatment planning with rapid dose fall-off and hypofractionation. SRT may help to reduce the risk of late side effects of radiation while also creating a larger biological effect on ASACs. A primary aim of this prospective, descriptive, exploratory study was to describe the safety and feasibility of an SRT protocol in a small sample of dogs with ASAC, using objective and subjective measures to monitor acute and late side effects. A secondary aim was to describe the anti-tumor response of the SRT protocol using CT at 3- and 6 months posttreatment. Five dogs completed the radiation protocol. Four had follow-up CT characteristics of complete response (1), partial response (2), and stable disease (1). Minimal acute side effects were observed. Despite some large tumor volumes, constraints for OAR were achieved in all but the spinal cord for one patient. Findings indicated that SRT is a safe and feasible treatment for dogs with ACAC. Future studies are warranted to compare patient outcomes for SRT versus other treatments.

A retrospective study of treatment, outcome, recurrence and concurrent diseases in 190 dogs with anal sacculitis.

BACKGROUND: Few studies report the treatment and recurrence rate in anal sacculitis (AS). OBJECTIVES: Retrospective study reporting the management, recurrence and concurrent diseases in dogs with AS in a primary care practice. ANIMALS: One hundred and ninety privately owned dogs in Sweden. MATERIALS AND METHODS: Clinical records of dogs diagnosed with AS between 2018 and 2021 were reviewed, and management, time until clinical resolution, number of recurrent episodes and comorbidites were recorded. RESULTS: The 190 dogs developed 290 episodes of AS. The most common management, in 235 of 290 (81.0%) episodes, was flushing ± infusion of an antimicrobial product into the sacs ± prescription of a nonsteroidal anti-inflammatory drug (NSAID), providing resolution in 213 of 235 (90.6%) episodes. Median time to resolution was one week (range 1-16 weeks), with resolution seen within one week in 205 of 290 (70.7%) episodes. A single episode of AS developed in 126 of 190 (66.3%) dogs. Dogs with concurrent cutaneous allergic disease were more likely (p < 0.001) to have recurrence of AS when compared to dogs with other comorbidities. Cutaneous allergic disease occurred more often (p < 0.001) in dogs with AS than in the practice population. CONCLUSIONS AND CLINICAL RELEVANCE: Local treatment of the anal sacs ± systemic NSAID was the most common treatment, inducing clinical resolution in the majority of dogs. Cutaneous allergic disease was the most common concurrent diagnosis, with higher recurrence rate of AS compared to other diseases and occurring in higher prevalence than in the practice population. Further studies are needed to determine if management of cutaneous allergic disease would reduce the risk of AS.

Anal sac mast cell tumor in a dog.

An 11-year-old castrated mixed-breed dog was diagnosed with a unilateral anal sac mass. Anal sacculectomy was performed without complication. Histopathology of the mass was consistent with a well-differentiated mast cell tumor. Analyses for the Ki-67 protein, KIT expression pattern, and the presence of c-kit mutations were done. Recovery from surgery was unremarkable and repeat staging revealed no evidence of mast cell disease at 4, 8, and 12 mo after surgery. To the authors' knowledge, primary mast cell neoplasia of the anal sac has not previously been reported in the veterinary literature. Key clinical message: Although mast cell tumors of the perineal region are commonly encountered in veterinary practice, the anal sac represents a novel location for this disease. Cytology of anal sac masses can be a useful diagnostic tool to confirm the diagnosis, guide staging, and assist in treatment decisions.

Tumeur mastocytaire du sac anal chez un chien. Un chien de race mixte castré âgé de 11 ans a reçu un diagnostic de masse unilatérale du sac anal. La sacculectomie anale a été réalisée sans complication. L'histopathologie de la masse était compatible avec une tumeur mastocytaire bien différenciée. Des analyses de la protéine Ki-67, du modèle d'expression KIT et de la présence de mutations c-kit ont été effectuées. La récupération après la chirurgie était sans particularité et la répétition de la stadification n'a révélé aucun signe de maladie mastocytaire à 4, 8 et 12 mois après la chirurgie. À la connaissance des auteurs, la néoplasie primitive des mastocytes du sac anal n'a pas été signalée auparavant dans la littérature vétérinaire.Message clinique clé:Bien que les tumeurs mastocytaires de la région périnéale soient couramment rencontrées en pratique vétérinaire, le sac anal représente une nouvelle localisation pour cette maladie. La cytologie des masses du sac anal peut être un outil de diagnostic utile pour confirmer le diagnostic, guider la stadification et aider aux décisions de traitement.(Traduit par Dr Serge Messier).

Local treatment for canine anal sacculitis: A retrospective study of 33 dogs.

BACKGROUND: Little information has been published regarding treatment of canine anal sacculitis (AS). OBJECTIVES: Primary objective: determine the outcomes of AS local treatment at the referral dermatology service of the authors' institution. SECONDARY OBJECTIVE: determine signalment, body condition score (BCS), stool quality and comorbidities associated with AS. ANIMALS: Thirty-three dogs with AS presented to the referral dermatology service between 1 January 2010 and 31 March 2021. MATERIALS AND METHODS: An electronic medical record search was conducted. Information regarding sex, breed, age at disease onset, weight, BCS, stool quality, comorbidities, treatment and treatment outcome were collected. Treatment outcome was categorised as "resolved clinically", "clinical signs resolved per owner", "did not complete treatment" or "failed". Dogs were excluded if seen by another service, not treated for AS, or if perianal sinuses (fistulae), anal sac masses, or anal sac abscesses were identified. RESULTS: Nineteen dogs were male and 14 female. Twenty-four breeds were included. Average age at disease onset was 4.4 years. Average BCS was 5.8 of 9. Stool quality was "poor" in seven of 33 and normal in 23 of 33 cases. Atopic dermatitis was the most common comorbidity (12 of 33). Treatment typically consisted of anal sac flushing with saline followed by infusion using a commercially available steroid/antibiotic/antifungal ointment. Treatment was repeated on average 2.9 times. Resolution of AS was obtained in 24 of 33 cases, clinical signs resolved per owner in four of 33, five of 33 cases did not complete treatment, and no cases failed treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Local treatment with flushing and infusion is effective for treating AS in dogs.

Contexte - Peu d'informations ont été publiées concernant le traitement de la sacculite anale canine (SA). Objectifs - Objectif principal : déterminer les résultats du traitement local de la SA au service de dermatologie des auteurs. Objectif secondaire : déterminer le signalement, le score d'état corporel (BCS), la qualité des selles et les comorbidités associées à la SA. Animaux - Trente-trois chiens SA présentés au service de dermatologie entre le 1er janvier 2010 et le 31 mars 2021. Matériels et méthodes - Une recherche dans le dossier médical électronique a été effectuée. Des informations concernant le sexe, la race, l'âge au début de la maladie, le poids, le BCS, la qualité des selles, les comorbidités, le traitement et les résultats du traitement ont été recueillies. Le résultat du traitement a été classé comme « résolu cliniquement ¼, « signes cliniques résolus par le propriétaire ¼, « n'a pas terminé le traitement ¼ ou « échec ¼. Les chiens ont été exclus s'ils étaient vus par un autre service, non traités pour la SA, ou si des sinus périanaux (fistules), des masses du sac anal ou des abcès du sac anal étaient identifiés. Résultats - Dix-neuf chiens étaient des mâles et 14 des femelles. Vingt-quatre races ont été incluses. L'âge moyen au début de la maladie était de 4,4 ans. Le BCS moyen était de 5,8 sur 9. La qualité des selles était « mauvaise ¼ dans sept cas sur 33 et normale dans 23 cas sur 33. La dermatite atopique était la comorbidité la plus fréquente (12 sur 33). Le traitement consistait généralement en un rinçage du sac anal avec une solution saline suivi d'une perfusion à l'aide d'une pommade stéroïde/antibiotique/antifongique disponible dans le commerce. Le traitement a été répété en moyenne 2,9 fois. La résolution de la SA a été obtenue dans 24 des 33 cas, les signes cliniques ont disparu dans quatre des 33 cas, cinq des 33 cas n'ont pas terminé le traitement et aucun cas n'a échoué au traitement. Conclusions et pertinence clinique - Le traitement local par rinçage et perfusion est efficace pour traiter la SA chez le chien.

Introducción- se ha publicado poca información sobre el tratamiento de la saculitis anal canina (AS). Objetivos - Objetivo primario: determinar los resultados del tratamiento local de la AS en el servicio de referencia dermatológica de la institución de los autores. Objetivo secundario: determinar la presentación clínica, la puntuación de la condición corporal (BCS), la calidad de las heces y las comorbilidades asociadas a la AS. Animales - Treinta y tres perros con AS presentados al servicio de dermatología de referencia entre el 1 de enero de 2010 y el 31 de marzo de 2021. Materiales y métodos - Se realizó una búsqueda en la historia clínica electrónica. Se recopiló información sobre sexo, raza, edad de inicio de la enfermedad, peso, BCS, calidad de las heces, comorbilidades, tratamiento y resultado del tratamiento. El resultado del tratamiento se clasificó como "resuelto clínicamente", "signos clínicos resueltos por propietario", "no completó el tratamiento" o "fracasó". Los perros fueron excluidos si fueron vistos por otro servicio, no tratados por AS, o si se identificaron senos perianales (fístulas), masas en los sacos anales o abscesos en los sacos anales. Resultados- diecinueve perros eran machos y 14 hembras. Se incluyeron veinticuatro razas. La edad promedio de inicio de la enfermedad fue de 4,4 años. BCS promedio fue 5.8 de 9. La calidad de las heces fue "mala" en siete de 33 y normal en 23 de 33 casos. La dermatitis atópica fue la comorbilidad más común (12 de 33). El tratamiento generalmente consistía en enjuagar el saco anal con solución salina seguido de una infusión usando un ungüento de esteroide/antibiótico/antifúngico disponible en el mercado. El tratamiento se repitió un promedio de 2,9 veces. La resolución de AS se obtuvo en 24 de 33 casos, los signos clínicos se resolvieron por propietario en cuatro de 33, cinco de 33 casos no completaron el tratamiento y ningún caso fracasó en el tratamiento. Conclusiones y relevancia clínica- el tratamiento local con lavado e infusión intrasacular es eficaz para tratar la AS en perros.

Contexto - Poucas informações foram publicadas sobre o tratamento da saculite anal (SA) canina. Objetivos - Objetivo primário: determinar os desfechos do tratamento tópico localizado da SA em um serviço especializado de dermatologia veterinária da instituição do autor. Objetivo secundário: determinar as manifestações clínicas, escore de condição corporal (ECC), qualidade das fezes e comorbidades associadas à SA. Animais - Trinta e três cães com SA apresentados ao serviço de dermatologia entre 1° de janeiro de 2010 e 39 de março de 2021. Materiais e métodos - Realizou-se um levantamento de prontuários eletrônicos. Foram coletadas informações sobre sexo, raça, idade no surgimento da doença, peso, ECC, qualidade das fezes, comorbidades, tratamentos e desfecho do tratamento. O desfecho do tratamento foi categorizado como "resolvido clinicamente", "sinais clínicos resolvidos de acordo com o tutor", "não completou o tratamento" ou "falhou". Os cães foram excluídos do estudo se tivessem sido tratados em outro serviço, não tivessem sido tratados para SA, ou se fossem identificados abscessos, massas ou fístulas nos sacos anais. Resultados - Dezenove cães eram machos e 14 fêmeas. Vinte e quatro raças foram incluídas. A idade média no surgimento da doença foi de 4,4 anos. O ECC médio foi 5,8 em 9. A qualidade das fezes foi ruim em sete de 33 cães e normal em 22 de 33 casos. A dermatite atópica foi a comorbidade mais comum (12 de 33). O tratamento tipicamente consistiu de lavagem dos sacos anais com solução salina seguido de infusão de uma solução comercial contendo esteroide/antibiótico/antifúngico. O tratamento foi repetido em média 2,9 vezes. Resolução da SA foi alcançada em 24 de 33 casos, os sinais clínicos se resolveram de acordo com o tutor em quatro de 33 casos, cinco de 33 casos não completaram o tratamento e em nenhum caso houve falha terapêutica. Conclusões e relevância clínica - Tratamento tópico com lavagem e infusão é eficaz para tratar SA em cães.

Minimal late radiation toxicity and transient early toxicity following postoperative definitive intent conformal radiation therapy (20 × 2.5 Gy) 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 3 Gy 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 50 Gy in 2.5 Gy 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 4 weeks. 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 â†’ 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.

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).

Anal sacculiths may be an incidental finding in dogs.

Mineral-attenuating material is occasionally seen in the anal sacs of dogs during abdominal CT studies. This retrospective, descriptive study was performed to estimate the prevalence and CT appearance of this mineral-attenuating material. A total of 357 abdominal CTs were reviewed retrospectively. The mineral-attenuating material was most easily identifiable using the brain window setting (window width: 120 HU; window level: 40 HU). In the current study, the prevalence of mineral-attenuating material in the anal sacs was 7.6% (95% confidence interval, 5.0-10.8%) with 48.1% bilateral involvement and equal distribution in the right and left in dogs with unilateral involvement. Successful collection and material analysis were performed in three dogs. The material was determined to be 100% dried blood, 100% waxy matter, and a "small amount of fat enmeshed in unidentified noncrystallined material." Given the CT appearance and the Hounsfield unit of these mineral-attenuating material within the anal sacs, the term "anal sacculiths" is proposed. All dogs with anal sacculiths within this study population did not have any reported disease of the anal sacs.

Pilot study evaluating the feasibility of stereotactic body radiation therapy for canine anal sac adenocarcinomas.

The use of stereotactic body radiation therapy (SBRT) to treat many canine tumors is rapidly expanding. However, published studies are lacking regarding use of SBRT for management of canine anal sac adenocarcinoma (ASAC), primarily due to concerns regarding intolerable late effects. The objective of this retrospective, pilot study was to describe the efficacy and safety profile of coarse fractions administered with an SBRT regime to manage a group of dogs with ASAC. A total of 12 dogs with ASAC that received SBRT as a component of their treatment were sampled. Three patients had macroscopic primary tumors irradiated, while nine patients received SBRT following incomplete surgical resection. Seven patients also received metastatic regional lymph node irradiation. Primary tumor and nodal irradiation sites received three fractions totaling 22-24 Gy and 22.5-24 Gy, respectively, over three consecutive days. All patients developed acute effects including mild colitis, alopecia, and erythema. Late effects included alopecia, variable dermal pigmentation and leuko- or melanotrichia within radiation fields, and rectal stricture in one patient. A median progression free survival time of 549 days and median survival time of 991 days were achieved in this study. These results should be considered preliminary data suggesting that coarse fractionation administered with an SBRT technique is a safe and effective treatment regime for the management of canine ASAC, with the aim to conduct prospective studies in the future.

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®.

Sentinel lymph node mapping of the canine anal sac using lymphoscintigraphy: A pilot study.

Sentinel lymph node mapping and biopsy are important parts of oncologic staging in human medicine. Sentinel lymph node mapping enables identification of the first lymph node to receive lymphatic drainage while avoiding unnecessary lymph node dissection. Anal sac adenocarcinoma is the most common malignant neoplasm of the canine perineal area. For dogs with anal sac adenocarcinoma, lympadenectomy and metastasis to the iliosacral lymphocentrum are negative prognostics indicators. The objectives of this prospective, two by two, crossover pilot study were to establish the feasibility of lymphoscintigraphy using Technetium-99 sulfur colloid of the canine anal sac of healthy dogs, compare two injection techniques, and the time for identification of sentinel lymph nodes using each technique. We hypothesized that both intramural and perimural injections of the canine anal sac would identify similar sentinel lymph node drainage. The sentinel lymph node was identified in all dogs using either technique. Intramural injection of the canine anal sac showed radiopharmaceutical uptake faster than perimural injection technique (P = 0.040). There was concordance between intramual and perimural techniques for the sentinel lymph node identified in 50% of cases. A sacral lymph node was identified as sentinel in three of eight dogs (37.5%). Lymphoscintigraphy of the canine anal sac is safe and feasible in normal dogs; however, the method of injection technique seems to have a significant effect on the sentinel lymph node identified.

Modified balloon-catheter-assisted closed anal sacculectomy in the dog: Description of surgical technique.

The aim of this report is to describe a modified Foley catheter technique for anal sacculectomy. A standard approach used for a closed anal sacculectomy was performed. The duct of the anal sac was then freed from the surrounding tissues and ligated. The duct was transected lateral to the ligature and a purse string suture placed. The anal sac balloon catheter was inserted through the duct into the anal sac and the purse string was tightened. Once inflated, the catheter was then used as a handle to facilitate manipulation and dissection of the anal sac from surrounding tissues. This technique permits circumferential dissection of the anal sac with good visualization, accuracy, and control, especially at the medial portion of the anal sac adjacent to the rectum. This technique can be considered for application to cases of chronic anal sacculitis and small anal gland adenocarcinomas.

Sacculectomie anale fermée assistée par ballon cathéter modifié chez le chien : description de la technique chirurgicale. Le but de ce rapport consistait à décrire une technique de cathéter de Foley modifiée pour la sacculectomie anale. Une approche standard utilisée pour une sacculectomie anale fermée a été réalisée. Le canal du sac anal a ensuite été libéré des tissus environnants et ligaturé. Une dissection transversale du canal a été effectuée latéralement à la ligature et une suture en cordon de bourse a ensuite été réalisée. Le ballon cathéter du sac anal a été inséré par le canal du sac anal et le cordon de bourse a été resserré. Une fois gonflé, le cathéter a ensuite été utilisé comme une poignée pour faciliter la manipulation et la dissection du sac anal des tissus environnants. Cette technique permet la dissection circonférentielle du sac anal avec une bonne visualisation, de l'exactitude et du contrôle, particulièrement à la portion médiale du sac anal adjacent au rectum. Cette technique peut être considérée pour application à des cas de sacculite anale chronique et à de petits adénocarcinomes des glandes anales.(Traduit par Isabelle Vallières).

Clinical hypocalcemia following surgical resection of apocrine gland anal- sac adenocarcinomas in 3 dogs.

Three canine patients were presented with marked hypercalcemia secondary to an apocrine gland anal sac adenocarcinoma (AGASCA). Two of the patients underwent treatment for hypercalcemia before surgical resection of their tumors, including diuresis and the administration of bisphosphonates. All dogs developed clinically symptomatic hypocalcemia 2 to 4 days following surgery. Clinical signs included facial rubbing, muscle fasciculations, lameness, and collapse. The dogs each required calcium supplementation and close monitoring of serum ionized calcium, as inpatients and continuing after discharge. Hypocalcemia and associated clinical signs resolved with treatment in all cases.

Hypocalcémie clinique après la résection chirurgicale d'adénocarcinomes du sac de glandes anales aprocrines chez trois chiens. Trois patients canins ont été présentés avec une hypercalcémie marquée secondaire à un adénocarcinome du sac des glandes anales apocrines (ASGAA). Deux des patients ont subi un traitement pour l'hypercalcémie avant la résection chirurgicale de leurs tumeurs, y compris la diurèse et l'administration de bisphosphonates. Tous les chiens ont développé une hypocalcémie cliniquement symptomatique de 2 à 4 jours après la chirurgie. Les signes cliniques incluaient le frottement de la face, des fasciculations des muscles, la boiterie et le collapsus. Les chiens ont tous exigé de la supplémentation au calcium et une étroite surveillance du calcium ionisé sérique, comme patients à l'interne et après le congé. L'hypocalcémie et les signes cliniques connexes se sont résorbés avec le traitement dans tous les cas.(Traduit par Isabelle Vallières).

Pathology of the Emerging Mycobacterium tuberculosis Complex Pathogen, Mycobacterium mungi, in the Banded Mongoose ( Mungos mungo).

Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion. Similar inflammatory cell infiltrates expanded the dermis of the nasal planum with frequent ulceration. However, even in cases with intact epidermis, acid-fast bacilli were present in variable numbers among dermal infiltrates and on the epidermal surface among desquamated cells and debris, most commonly in small crevices or folds. In general, tissue involvement varied among cases but was highest in lymph nodes (50/54, 93%), liver (39/53, 74%), spleen (37/51, 73%), and anal glands/sacs (6/8, 75%). Pulmonary lesions were present in 67% of sampled mongooses (35/52) but only in advanced disseminated disease. The pathological presentation of M. mungi in the banded mongoose is consistent with pathogen shedding occurring through scent-marking behaviors (urine and anal gland secretions) with new infections arising from contact with these contaminated olfactory secretions and percutaneous movement of the pathogen through breaks in the skin, nasal planum, and/or skin of the snout. Given the character and distribution of lesions and the presence of intracellular acid-fast bacilli, we hypothesize that pathogen spread occurs within the body through a hematogenous and/or lymphatic route. Features of prototypical granulomas such as multinucleated giant cells and peripheral fibrosis were rarely present in affected mongooses. Acid-fast bacilli were consistently found intracellularly, even in regions of necrosis. The mongoose genome has a unique deletion (RD1mon) that includes part of the encoding region for PPE68 (Rv3873), a gene co-operonic with PE35. These proteins can influence the host's cellular immune response to mycobacterial infections, and it remains uncertain how this deletion might contribute to observed patterns of pathology. M. mungi infection in banded mongooses is characterized by both a unique transmission and exposure route, as well as accompanying pathological features, providing an opportunity to increase our understanding of MTC pathogenesis across host-pathogen systems.

INDIRECT COMPUTED TOMOGRAPHIC LYMPHOGRAPHY FOR ILIOSACRAL LYMPHATIC MAPPING IN A COHORT OF DOGS WITH ANAL SAC GLAND ADENOCARCINOMA: TECHNIQUE DESCRIPTION.

Sentinel lymph node mapping can help to direct surgical oncologic staging and metastatic disease detection in patients with complex lymphatic pathways. We hypothesized that indirect computed tomographic lymphography (ICTL) with a water-soluble iodinated contrast agent would successfully map lymphatic pathways of the iliosacral lymphatic center in dogs with anal sac gland carcinoma, providing a potential preoperative method for iliosacral sentinel lymph node identification in dogs. Thirteen adult dogs diagnosed with anal sac gland carcinoma were enrolled in this prospective, pilot study, and ICTL was performed via peritumoral contrast injection with serial caudal abdominal computed tomography scans for iliosacral sentinel lymph node identification. Technical and descriptive details for ICTL were recorded, including patient positioning, total contrast injection volume, timing of contrast visualization, and sentinel lymph nodes and lymphatic pathways identified. Indirect CT lymphography identified lymphatic pathways and sentinel lymph nodes in 12/13 cases (92%). Identified sentinel lymph nodes were ipsilateral to the anal sac gland carcinoma in 8/12 and contralateral to the anal sac gland carcinoma in 4/12 cases. Sacral, internal iliac, and medial iliac lymph nodes were identified as sentinel lymph nodes, and patterns were widely variable. Patient positioning and timing of imaging may impact successful sentinel lymph node identification. Positioning in supported sternal recumbency is recommended. Results indicate that ICTL may be a feasible technique for sentinel lymph node identification in dogs with anal sac gland carcinoma and offer preliminary data to drive further investigation of iliosacral lymphatic metastatic patterns using ICTL and sentinel lymph node biopsy.

Microbes and animal olfactory communication: Where do we go from here?

We know that microbes contribute to the production of odors that some animals use to communicate, but how common is this phenomenon? Recent studies capitalizing on new molecular technologies are uncovering fascinating associations between microbes and odors of wild animals, but causality is difficult to ascertain. Fundamental questions about the nature of these unique host-microbe interactions also remain unanswered. For instance, do microbes benefit from signaling associations with hosts? How does microbial community structure influence signal production? How do hosts regulate microbes in order to generate appropriate signals? Here, we review the current state of knowledge on microbially produced signals in animals and discuss key research foci that can advance our understanding of microbial-based signaling in the animal world.

Owner assessment of pruritus and gastrointestinal signs in apparently healthy dogs with no history of cutaneous or noncutaneous disease.

BACKGROUND: Determining the cause of pruritus relies on establishing the pattern of abnormal pruritus. The presence of gastrointestinal (GI) disease has also been helpful in determining the cause of pruritus. No study has systematically evaluated typical GI signs and pruritic behaviours in apparently healthy dogs. HYPOTHESIS/OBJECTIVES: To evaluate owners' perceptions of pruritus and GI signs in apparently healthy dogs, and determine if age, breed, activity, diet or supplements affected these signs. ANIMALS: Three hundred and fourteen apparently healthy dogs ≥ 12 months old with an unremarkable physical examination and no history of pruritus, otitis, skin/hair disease, metabolic or GI disease were enrolled. METHODS: Thirty one veterinarians enrolled dogs after establishing their pruritus visual analog scale (PVAS) score and faecal consistency score (FCS); owners completed a comprehensive online survey regarding GI signs, possible pruritic behaviours, ear cleaning and sneezing. RESULTS: A PVAS score of ≤ 1.9 was recorded in 87.6% of dogs and the FCS was 2-3 in 94.9% of dogs. PVAS was positively correlated with paw licking/chewing, facial/muzzle rubbing, head shaking and sneezing. Scooting was positively correlated with sneezing. Over 96% of dogs had 1-3 bowel movements (BM) per day. Age was positively correlated with facial/muzzle rubbing, sneezing, coprophagia and borborygmi. The number of walks/day was positively correlated with paw licking/chewing, head shaking, sneezing, number of BM/day, coprophagia, belching, flatulence and borborygmi. CONCLUSION AND CLINICAL IMPORTANCE: A standard method of asking relevant questions was developed and the frequency of GI signs and many behaviours that may indicate pruritus in apparently healthy dogs was established.

Bacterial microbiota and proinflammatory cytokines in the anal sacs of treated and untreated atopic dogs: Comparison with a healthy control group.

The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.

Association between total hypercalcaemia and iliosacral lymph node metastasis in dogs diagnosed with anal sac adenocarcinoma using abdominal ultrasonography.

BACKGROUND: Anal sac adenocarcinoma (ASACA) in dogs is a malignant perianal tumour that often metastasizes to the iliosacral lymph nodes. Additionally, this tumour can be associated with hypercalcemia of malignancy. To date, no study has looked at the association between increased blood calcium levels and suspected or confirmed lymph node metastasis as a primary objective. OBJECTIVE: The objective of this study was to determine if increased total serum calcium level is associated with iliosacral lymph node metastasis in dogs diagnosed with ASACA. METHODS: Medical records of a single referral hospital were searched to identify dogs examined between 2011 and 2021 that had a diagnosis of ASACA via cytology or histopathology. Only dogs that had serum total calcium recorded and abdominal ultrasound were included in the study. All images were reviewed by a board-certified radiologist blinded to any patient identifiers. RESULTS: Of the 58 dogs, 33% (19/58) had total hypercalcaemia, and of these, 68% had confirmed or suspected iliosacral lymph node metastasis. Total hypercalcaemia was significantly associated with confirmed or suspected iliosacral lymph node metastasis (p < 0.01). However, 46% (11/24) of dogs with confirmed or suspected iliosacral lymph node metastasis were normocalcaemic. CONCLUSIONS: Based on these results, it is suggested that while the presence of total hypercalcaemia may increase the likelihood of concurrent lymph node metastasis, total hypercalcaemia alone cannot be used as a screening tool for lymph node metastasis. Dogs diagnosed with ASACA should undergo full staging regardless of total serum calcium values.