Cancer and the GI Biome

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Sterilization and Obesity in Dogs

The study examined the relationship between sterilization (gonadectomy) and overweight/obesity (O/O) in companion dogs in the US. It aimed to determine whether sterilization is associated with an increased risk of O/O compared to intact dogs, whether the age at the time of sterilization influences the risk of O/O, and whether the risk varies depending on the age at the time of surgery among sterilized dogs. The study used Cox proportional hazards models to analyze data from a large sample of sterilized and intact dogs, considering factors such as sex, breed size category, age at sterilization, and other variables. The findings of the study were consistent with previous research and indicated that, overall, gonadectomy increased the risk of O/O in dogs compared to intact dogs. However, the degree to which sterilization increased the risk varied based on factors such as sex, age at sterilization, and breed size. Neutered males had a higher relative risk of O/O compared to spayed females across all ages and size categories. The study also suggested that the timing of gonadectomy played a role in the risk of O/O, with the elevated risk peaking among dogs sterilized at 1.5 to 3 years of age. Additionally, breed size influenced the relative risk, with toy/small dogs having the highest hazard ratios for O/O and giant dogs having the lowest. The analysis found that dogs sterilized at 6 months or younger generally had a similar or lower risk of developing O/O compared to those sterilized at 1 year. However, among large dogs, gonadectomy at 6 months carried a significant increased risk of subsequent O/O for both sexes. These findings highlight the complex relationship between sterilization, age at surgery, and the risk of O/O in dogs. The findings of this study provide valuable insights into the relationship between sterilization and O/O in dogs, highlighting the importance of considering factors such as sex, age at sterilization, and breed size when assessing the risk. Veterinarians can use this information to provide personalized guidance to dog owners regarding the timing of sterilization and measures to prevent O/O. It is crucial to consider the overall risks and benefits of sterilization on a case-by-case basis, taking into account other potential outcomes associated with age at surgery.

Benka, V. A., Scarlett, J. M., Sahrmann, J., Rieke, K., Briggs, J. R., Ruple, A., Zawistowski, S., Morrison, J. A., Spofford, N., & Romagnoli, S. (2023). Age at gonadectomy, sex, and breed size affect risk of canine overweight and obese outcomes: a retrospective cohort study using data from United States primary care veterinary clinics, Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.22.12.0596 

Bottom line — No surprise but large breed at 6 months was the worst…

Cancer and the GI Biome

Microbes, including bacteria, viruses, protozoans, archaea, and fungi, form a diverse ecosystem known as the microbiota, which has a significant impact on the host, including animals. The microbiota and its host have a symbiotic and pathobiont relationship that plays a crucial role in various aspects of health and disease. The microbiota metabolizes substances in the animal body, such as epithelial cells, mucus, and undigested substrates, through fermentation, leading to the production of short-chain fatty acids (SCFA). SCFA provides energy for the growth of epithelial cells and bacterial metabolism. Studies have shown that germ-free animals require more caloric consumption than conventional animals to maintain their energy levels. A balanced microbial population is essential for immune homeostasis and the training of the immune system. When the microbiota's balance is disrupted, it can lead to chronic inflammation, breakdown of the epithelial barrier, and overgrowth of harmful bacteria, all of which have been linked to the development of cancer. Dysbiosis, characterized by decreased bacterial diversity, reduced stability of microbial communities, and an imbalance between anaerobic and facultative anaerobic bacteria, has been identified as a hallmark of dysbiosis in various species. Cancer is a leading cause of death in adult dogs and humans. Microorganisms are believed to be involved in 15%–20% of cancers, particularly those associated with chronic inflammation processes, such as colorectal and gastric carcinomas. Bacteria can be found in tumor tissue, normal adjacent tissue, and distant tumor sites, suggesting their involvement in cancer development. In vivo models have demonstrated that intestinal bacteria can have a causative role in colorectal cancer. Helicobacter pylori is a well-known example of a bacterium associated with gastric carcinoma in humans and mice. Microorganism-associated molecular patterns (MAMPs) recognized by Toll-like receptors (TLRs) can trigger reactive oxygen and nitrogen species release, leading to gene mutations, including those involved in tumorigenesis. MAMPs can also activate inflammasomes and autophagy through TLRs, contributing to carcinogenesis. Studies comparing microbial populations in healthy and diseased individuals, both animals and humans, have revealed significant differences, suggesting that microbes living in the host can influence cancer development and treatment efficacy. Advances in sequencing technologies and bioinformatics have enabled the molecular characterization of microbial populations in animals and humans. The similarities between the microbiota of humans, cats, and dogs have led to increased interest in translational medicine. The immune-regulatory and anti-inflammatory effects of gut and tumor microbiota are crucial in cancer defense. However, the understanding of microbiota function during disease states is still limited, and further research, particularly clinical studies involving both humans and animals, is necessary. Such comparative strategies require interdisciplinary collaboration between human and veterinary medicine, emphasizing the interconnectedness of human health, animal health, and the environment. 

Aluai-Cunha, CS, Pinto, CA, Correia, IADFL, dos Reis Serra, CA, Santos, AAF. The animal's microbiome and cancer: A translational perspective. Vet Comp Oncol. 2023; 21( 2): 166- 183. doi:10.1111/vco.12892 

Bottom line — Dysbiosis can lead to Inflammation and then tumorigenesis

Anal sac tumors and metastasis

Apocrine gland anal sac adenocarcinoma (AGASACA) is a malignant tumor that originates from the glandular epithelium of the anal gland in dogs. It is responsible for approximately 17% of perianal malignancies in dogs. This type of cancer tends to be aggressive, with a high likelihood of local invasion and metastasis to regional lymph nodes and distant sites. Clinical staging and identification of metastatic disease are important for determining prognosis and treatment recommendations. Metastasis to regional lymph nodes, particularly the iliosacral lymph nodes, is common in AGASACA. Various diagnostic imaging modalities, such as ultrasound and computed tomography, can be used for staging, but limitations exist for each method. The behavior of AGASACA tumors and the response to different treatments vary among patients. Therefore, a clinical staging system has been proposed to guide treatment decisions. Factors considered for staging include the size of the primary tumor, presence and size of metastatic lymph nodes, and presence of distant metastatic disease. Studies have shown that larger primary tumor size is associated with a higher risk of metastatic disease. However, there are cases where small tumors have a significant volume of metastatic disease in regional lymph nodes. Therefore, staging dogs with small tumors is still important to identify metastasis. The aim of one study was to determine the proportion of dogs with primary tumors smaller than 2 cm or 1.3 cm that had metastatic disease. The study found that 20% of dogs with tumors smaller than 2 cm and 21% of dogs with tumors smaller than 1.3 cm had evidence of lymph node metastasis. Additionally, 19% of dogs with tumors smaller than 2 cm developed metastasis after the initial diagnosis. The overall presence of regional metastatic disease at the time of diagnosis was 46%, which is consistent with previous studies. The study also noted variations in age of disease onset and breed representation, with certain breeds being more commonly affected. The gender predisposition in this study differed from previous reports. Hypercalcemia, a condition where calcium levels in the blood are elevated, was observed in 33% of patients. It is a common occurrence in AGASACA and has been associated with various clinical manifestations. However, its association with metastatic disease and survival is still debated. The study also assessed the rate of progressive regional metastatic disease in patients without metastasis at the time of diagnosis. The rate of disease progression was 19%, and the majority of patients with progressive disease had small primary tumors at diagnosis. This finding emphasizes the importance of serial clinical staging in patients with stage 1 disease and challenges the assumption that primary tumor size alone determines the potential for metastatic burden. In summary, this study highlights the significance of staging the locoregional lymph nodes in AGASACA patients, even those with small primary tumors. A relatively high proportion of dogs with small tumors had evidence of lymph node metastasis at diagnosis, and a significant number of them developed metastasis after treatment. Thorough clinical staging is crucial for prognosis and treatment decisions. The study also suggests that primary tumor size alone may not be sufficient for determining treatment strategies, and further research is needed to investigate molecular markers for risk assessment and treatment stratification. 

Jones, AE, Wustefeld-Janssens, BG. A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis. Vet Comp Oncol. 2023; 21( 2): 327- 331. doi:10.1111/vco.12890 

Bottom line — 46% had metastatic disease at the time of diagnosis

Just putting things in perspective …