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Journal of Veterinary Internal Medicine 2007Reports of canine anal sac gland carcinoma (ASGC) describe varied clinical presentations and management and differing responses to therapy. A unifying approach to... (Clinical Trial)
Clinical Trial
BACKGROUND
Reports of canine anal sac gland carcinoma (ASGC) describe varied clinical presentations and management and differing responses to therapy. A unifying approach to clinical stage determination and management of this disease has yet to be presented.
HYPOTHESIS
An ordinal clinical staging scheme for canine ASGC can be devised on the basis of responses to therapy for a retrospective cohort of affected dogs.
ANIMALS
130 dogs with naturally occurring ASGC.
METHODS
A simplified clinical stage system and a management algorithm for canine ASGC were derived from retrospective evaluation of a cohort of 80 dogs; applicability of both was then prospectively evaluated in a cohort of 50 dogs.
RESULTS
Retrospective evaluation revealed 4 statistically significant negative prognostic indicators for survival: lack of therapy, presence of distant metastases, presence of lymph node metastases, and primary tumor size. Lymph node extirpation was a statistically significant positive prognostic indicator by bivariate analysis. In both retrospective and prospective analyses, the modified clinical stage scheme revealed a significant association with survival time.
CONCLUSIONS AND CLINICAL IMPORTANCE
The clinical staging scheme permits differentiation between groups in terms of prognosis and, therefore, decisions on therapy. This will facilitate application of appropriate therapy and enhanced communication and collaboration in further investigations of ASGC.
Topics: Algorithms; Anal Sacs; Animals; Antineoplastic Agents; Dog Diseases; Dogs; Female; Male; Neoplasms; Radiotherapy; Retrospective Studies; Survival Rate
PubMed: 17427388
DOI: 10.1892/0891-6640(2007)21[274:cstapi]2.0.co;2 -
Journal of Veterinary Internal Medicine May 2020Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.
BACKGROUND
Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.
OBJECTIVES
To 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.
ANIMALS
Ninety-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.
METHODS
Retrospective, 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.
RESULTS
Median 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 IMPORTANCE
Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.
Topics: Adenocarcinoma; Animals; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Dog Diseases; Dogs; Female; Indoles; Male; Neoplasm Recurrence, Local; Neoplasms; Pyrroles; Retrospective Studies; Treatment Outcome; Tumor Microenvironment; Vascular Endothelial Growth Factor Receptor-2
PubMed: 32267594
DOI: 10.1111/jvim.15768 -
Journal of Veterinary Internal Medicine Mar 2020There is no widely accepted standard medical treatment for apocrine gland anal sac adenocarcinoma (AGASACA) in dogs. Targeted agents such as toceranib may be effective...
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.
Topics: Adenocarcinoma; Anal Gland Neoplasms; Anal Sacs; Animals; Apocrine Glands; Disease-Free Survival; Dog Diseases; Dogs; Female; Indoles; Male; Pyrroles; Retrospective Studies; Treatment Outcome; Wisconsin
PubMed: 31977135
DOI: 10.1111/jvim.15706 -
Animals : An Open Access Journal From... Dec 2021Limited data are available on canine and feline non-neoplastic anal sac disease. Therefore, the aim of this study was to obtain observational data on the incidence,...
Limited data are available on canine and feline non-neoplastic anal sac disease. Therefore, the aim of this study was to obtain observational data on the incidence, predisposing factors, diagnosis, treatment, and recurrence rate of canine and feline anal sac disease. To this end, a questionnaire was distributed among veterinarians. The incidence of non-neoplastic anal sac disease was estimated at 15.7% in dogs and 0.4% in cats. Predisposing factors were diarrhea, skin problems, several dog breeds, and particularly small breed dogs, male cats, British shorthairs, and obesity in dogs. Diagnosis was made based on the presence of clinical signs and characteristics of the anal sac content. Manual expression and treating any potential underlying disease were the most important treatments for all three types of non-neoplastic anal sac disease. Anal sacculectomy was performed in refractory cases. The most recurrent anal sac disease condition was impaction. Diagnosis of anal sac disease should be based on clinical signs and rectal examination, as the evaluation of the anal sac content is not reliable. Surgical outcomes of anal sacculectomy can be improved when surgery is performed after medical management. Future studies should investigate these findings in prospective trials.
PubMed: 35011201
DOI: 10.3390/ani12010095 -
Animals : An Open Access Journal From... Jun 2021Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the...
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.
PubMed: 34199347
DOI: 10.3390/ani11061649 -
Cancers Dec 2022Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant...
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 ( = 0.36; 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 ( 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.
PubMed: 36551672
DOI: 10.3390/cancers14246188 -
PloS One 2022Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived...
Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.
Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.
Topics: Animals; Biomarkers, Tumor; Dogs; Early Detection of Cancer; Hemangiosarcoma; Hematologic Tests; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Osteosarcoma
PubMed: 35471999
DOI: 10.1371/journal.pone.0266623 -
Journal of Ethology 2018Scent emitted from anal sac secretions provides important signals for most Carnivora. Their secretions emit a variety of volatile compounds, some of which function as...
Scent emitted from anal sac secretions provides important signals for most Carnivora. Their secretions emit a variety of volatile compounds, some of which function as chemical signals with information about the scent owners. The domestic cat has a pair of anal sac glands to secrete a pungent liquid. Their anal sac secretions may give information about sex, reproductive state, and recognition of individuals. However, little is known about the volatile compounds emitted from anal sac secretions and their biological functions in cats. In this study, we examined the volatile chemical profiles of anal sac secretions in cats and their olfactory ability to discriminate intraspecific anal sac secretions. Analysis with gas chromatography-mass spectrometry showed that the major volatile compounds were short-chain free fatty acids, whose contents varied among individuals, as well as other carnivores. There was no sex difference in the volatile profiles. In temporal analyses of individual anal sac secretions performed 2 months apart, the profiles were highly conserved within individuals. Habituation-dishabituation tests showed that cats can distinguish individual differences in the odor of anal sac secretions. These results suggest that cats utilize short-chain free fatty acids emitted from anal sac secretions to obtain scent information for individual recognition rather than species or sex recognition.
PubMed: 30636835
DOI: 10.1007/s10164-017-0532-x -
Veterinary Dermatology Oct 2022Little information has been published regarding treatment of canine anal sacculitis (AS).
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.
Topics: Anal Sacs; Animals; Dermatitis, Atopic; Dog Diseases; Dogs; Female; Male; Rectal Fistula; Retrospective Studies
PubMed: 35866443
DOI: 10.1111/vde.13102 -
Canadian Journal of Veterinary Research... Jan 2021The aim of the present study was to characterize the bacterial microbiota of anal sacs in healthy dogs using NGS. Swabs were used to sample the rectum and secretions...
The aim of the present study was to characterize the bacterial microbiota of anal sacs in healthy dogs using NGS. Swabs were used to sample the rectum and secretions from each anal sac in 15 healthy dogs. DNA was extracted from swabs and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced with Illumina MiSeq. Overall, 14 different bacterial phyla were identified in the rectum and in both anal sacs, the 5 main ones being Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria. The rectum had higher microbial diversity and richness than the left and right anal sacs. Community membership and structure significantly differed between the rectum and both anal sacs, but not between the right and the left anal sacs. This study showed that the diversity and richness of the bacterial microbiota of the anal sacs in dogs is greater than what has been reported in previous studies with culture-based methods. In conclusion, the bacterial microbiota of the anal sacs in dogs varies between individuals and differs from the rectal bacterial microbiota.
Topics: Anal Sacs; Animals; Bacteria; DNA, Bacterial; Dogs; Microbiota; RNA, Bacterial; RNA, Ribosomal, 16S; Rectum
PubMed: 33390648
DOI: No ID Found