Long-term Survival In Dogs Research Articles

Conventionally fractionated radiation therapy is associated with long-term survival in dogs with infiltrative lipomas.

To describe radiotherapy outcomes for canine infiltrative lipomas and provide detailed radiotherapy planning data. 24 dogs from 2000 to 2020. In this retrospective study, dogs received 1 to 3 surgeries prior to conventionally fractionated radiotherapy for gross (18) or microscopic (8) infiltrative lipomas. Dogs received 45 to 51 Gray (Gy) in 15 to 20 daily fractions, with 71% of dogs receiving 48 Gy in daily 3-Gy fractions. Masses were regionally located as follows: limbs (7), trunk (13), head/neck (4). At analysis, 16/24 dogs were deceased, 5/24 were alive (median follow-up for alive dogs: 1,216 days [range, 741 to 1,870 days]), and 3/24 were lost to follow-up. One living dog had progressive disease 923 days after completing conventionally fractionated radiotherapy and received another surgery. The estimated median overall survival (OS) after completing radiotherapy was 4.8 years (1,760 days; 95% CI, 1,215 to 2,777 days; range, 23 to 3,499 days) for any cause of death, and no patients were reported to have been euthanized or died from their tumor. No statistically significant difference was found for dogs based on gross versus microscopic disease (gross OS, 4.8 years vs microscopic OS, 3.6 years; P = .45). Furthermore, the number of surgeries before radiotherapy did not impact survival (P = .96). The survival difference between females (median OS, 7.6 years; 95% CI, 963 days to not reached) versus males (median OS, 4.6 years; 95% CI, 335 to 2,245 days; P = .05) was statistically significant, although 4/5 living dogs were female. This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas.

Examination of tracheal allografts after long-term survival in dogs.

Little is known on the outcome of tracheal allografts after long-term survival. This study aimed to explore the changes in structure and composition by evaluating the status of the mucosa and cartilage of allografts with long-term survival in dogs. Eight tracheal allografts that survived for ˃9 months were enrolled in our study. Epithelium, revascularization, monocyte infiltration and fibrosis were evaluated histologically. The fluorescent dye 4'-6-diamidino-2-phenylindole was used to evaluate the presence of chondrocyte nuclei. Glycosaminoglycan was detected using safranin-O staining and collagen II was evaluated using immunohistochemistry. The 8 animals survived from 277 to 783 days. Bronchoscopy demonstrated that 6 allografts showed no stenosis; 2 cases developed slight stenosis, but could maintain airway patency. Histological examination showed that the epithelium covered the surface of the allografts. In comparison to fresh tracheal controls, allografts demonstrated mild monocyte infiltration, evident revascularization and mild fibrosis in the mucosa or submucosa (all P < 0.05). There were a few viable chondrocytes scattered in the cartilage after long-term survival. Moreover, glycosaminoglycan and collagen II were significantly decreased in the allografts compared with fresh trachea (all P < 0.05). For tracheal allografts with long-term survival after transplantation, only a few viable chondrocytes were retained, and the extracellular matrix of the cartilage demonstrated degeneration. Despite this, the airway could maintain patency. Notably, the significance of monocyte infiltration in the mucosa or submucosa at different time points warrants further study.

Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (−/−) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (−/−) mice. Untreated G6pase (−/−) mice also demonstrated severe delay of growth plate ossification at 12days of age; those treated with AAV2/8-G6Pase at 14days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia.

Predictors of long-term survival in dogs with high-grade multicentric lymphoma

To determine factors predicting survival in dogs with high-grade multicentric lymphoma. Design-Retrospective cohort study. Animals-127 dogs with high-grade multicentric lymphoma evaluated at 4 veterinary hospitals from 2000 to 2009. Records were reviewed to identify dogs with completely staged high-grade multicentric lymphoma treated with chemotherapy. Data collected included signalment, history, hematologic findings, tumor characteristics, treatment, and outcome. Long-term survival was defined as surviving > 2 years after diagnosis. Variables were analyzed for associations with dogs living > 2 years. Among the 127 enrolled dogs, 13 (10%) survived > 2 years with a median survival time of 914 days (range, 740 to 2,058 days). Survival rates at 3, 4, and 5 years were 4%, 3%, and 1 %, respectively. At diagnosis, 11 of the 13 long-term survivors had a body weight ≥ 10 kg, PCV ≥ 35%, absence of ionized hypercalcemia, centroblastic lymphoma, immunophenotype B, absence of bone marrow involvement, and lymphoma stages I through IV and were not previously treated with corticosteroids. The same combination of factors was present in 26 of 114 (23%) dogs surviving ≤ 2 years, yielding a negative predictive value of 97.8% for long-term survivors. Four of the 6 long-term survivors that died during the study died of another cancer; 3 of them had osteosarcoma. Absence of the aforementioned combination of variables at diagnosis may help identify dogs with lymphoma that will not survive > 2 years. Other types of neoplasia, in particular osteosarcoma, may develop in long-term-surviving dogs.

Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors

To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment. 132 dogs with nonresectable grade 2 or 3 MCTs. Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time. In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib. Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

Physiologic studies following canine lung homotransplantation: Long-term survival of dogs

Physiologic studies following canine lung homotransplantation: Long-term survival of dogs

Long-term survival of dogs after experimental pulmonary reimplantation and staged contralateral pneumonectomy.

Sixteen dogs which survived left pulmonary reimplantation were subjected to staged contralateral pneumonectomy. Complete excision of the right lung was achieved in nine of these animals. There were three long-term survivors, of which two lived for more than three years on the single reimplanted lung. Stenosis of the pulmonary veins at the level of the atrial anastomosis was the commonest post-mortem finding. In the first week after reimplantation, the ventilation and oxygen uptake of the reimplanted lung invariably fell to low levels. These usually rose slowly but to a variable extent over the next six to eight weeks, after which there was little further improvement while the normal lung remained intact. In all three long-term survivors the ventilation and oxygen uptake of the reimplanted lung were more than doubled after contralateral pneumonectomy; the rise in oxygen uptake was less and occurred later than the rise in ventilation. Pulmonary hypertension and pulmonary oedema did not occur except in association with organic obstruction to the pulmonary venous drainage.