Imatinib mesylate treatment in a dog with gastrointestinal stromal tumors with a c-kit mutation

A 13-year-old spayed mixed-breed dog was diagnosed with a gastrointestinal stromal tumor (GIST) after histopathological examination of an abdominal mass. Five months after surgical resection of the tumor, we detected the recurrence of GIST with multiple disseminated abdominal lesions. A sequence analysis of cDNA obtained from a biopsy of the recurrent tumors revealed a mutation within exon 9 of the c-kit gene (1523A>T, Asn⁵⁰⁸Ile), which has been shown to cause ligand-independent phosphorylation of the KIT protein in GISTs and canine mast cell tumors (MCTs). Upon detection of the recurrent tumors, we initiated treatment with imatinib mesylate (10 mg/kg, q 24 hr). After 2 months, the dog achieved complete remission. Our findings indicate that canine GIST, and possibly MCT, may be responsive to molecular-targeted therapy.     

Computed tomographic findings may be useful for differentiating small intestinal adenocarcinomas,lymphomas, and spindle cell sarcomas in dogs

An improved understanding of the CT characteristics for histologically confirmed primary intestinal tumors would be helpful for guiding prognosis and treatment plans in affected dogs. This retrospective, multi-center, analytical study aimed to evaluate the CT characteristics for the differentiation of adenocarcinoma, lymphoma, and spindle cell sarcoma (SCS) in dogs. Thirty-seven dogs who underwent contrast CT and histopathological examinations were included (adenocarcinomas, n = 11; lymphomas, n = 12; SCS, n = 14). Quantitative and qualitative CT parameters, including tumor morphology, contrast enhancement pattern, Hounsfield unit (HU) value, and presence or absence of intraabdominal lymphadenopathy, were evaluated for each included small intestine tumor CT case. Adenocarcinomas tended to show endophytic growth, intestinal obstruction, and a heterogeneous enhancement pattern. Lymphomas tended to show exophytic growth, contrast enhancement of the intestinal tumor mucosal layer, a homogeneous enhancement pattern, and the presence of lymphadenopathies in the abdominal cavity. SCSs tended to show lobulated growth, a large cystic portion within the tumor, a heterogeneous enhancement pattern, a large size with fat stranding sign, and lower HU values in postcontrast images. Cut-off values of the minimum diameter/fifth lumbar vertebral mid-body height (≥5.80; area under the curve [AUC] = 0.97, P < 0.001) and minimum HU value/HU value of the aorta (≤0.26; AUC = 0.96, P < 0.001) were derived to discriminate SCS from the two other tumor types. In conclusion, contrast CT characteristics may be useful in differentiating small intestinal adenocarcinomas, lymphomas, and SCSs in dogs.     

Outcome in dogs with surgically resected oral fibrosarcoma (1997-2008)

Oral fibrosarcoma (FSA) is a common oral tumour in dogs, and historically reported survival times after surgical excision range from 7.0 to 12.2 months with local recurrence rates of 32-57%. The purpose of this retrospective study was to report outcome in a cohort of dogs with oral FSA treated with surgical excision with or without adjuvant radiation therapy. Twenty-nine dogs with a histological diagnosis of FSA arising from the oral cavity that underwent surgical resection of their oral FSA were included in this study. Twenty-one dogs were treated with surgical excision alone and eight dogs with both surgery and radiation therapy. The median progression-free interval was >653 days. The median survival time was 743 days. The 1- and 2-year survival rates were 87.7 and 57.8%, respectively. Seven (24.1%) dogs developed local recurrence. Seven dogs (24.1%) developed metastasis.     

A retrospective multi‐center study of treatment,outcome, and prognostic factors in 34 dogs with disseminated aspergillosis in Australia

BackgroundDisseminated aspergillosis (DA) in dogs has a guarded prognosis and there is a lack of a gold standard treatment protocol.ObjectiveTo retrospectively assess survival times and factors influencing survival times.AnimalsDogs diagnosed with DA from January 2007 to June 2017.MethodsDisseminated aspergillosis case data were retrieved from 13 Australian veterinary referral centers, with a diagnosis confirmed with culture or PCR. Factors influencing survival time after diagnosis were quantified using a Cox proportional hazards regression model.ResultsThirty‐four dogs met the study inclusion criteria. Twenty‐two dogs were treated with antifungal treatment and 12 dogs received no antifungal treatment. Accounting for censoring of dogs that were either still alive on the date of data collection or were loss to follow‐up, dogs treated with itraconazole alone (n = 8) had a median survival time (MST) of 63 (95% CI: 20−272) days compared to 830 (95% CI: 267‐1259) days for the n = 14 dogs that received multimodal antifungal therapy (χ2 test statistic 8.6; df = 1; P < .01). The daily hazard of death (DHOD) for dogs with abnormally high serum creatinine concentration at the time of diagnosis was 7.4 (95% CI: 1.9‐29) times that of dogs with serum creatinine within the reference interval.Conclusion and Clinical ImportanceSerum creatinine concentration at the time of diagnosis is a useful prognostic indicator for survival after a diagnosis of DA. The MST for dogs treated with multimodal antifungal therapy is longer than itraconazole alone and warrant further investigation (P < .01).     

Prognostic value of small intestinal dilatation in dogs with protein-losing enteropathy

To date, little is known about the prognostic significance of ultrasonographic findings in dogs with protein-losing enteropathy (PLE). The aim of this retrospective study was to examine the prognostic value of ultrasonographic findings in dogs with PLE. A total of 26 dogs with PLE were included: 20 dogs with chronic enteropathy and 6 dogs with gastrointestinal lymphoma. The presence of small intestinal dilatation was associated with shorter survival time in dogs with PLE (P=0.003). The presence of hyperechoic intestinal mucosal striations was associated with longer survival time in dogs with PLE (P=0.0085). The results of the current study indicate that the presence of small intestinal dilatation might be associated with poor prognosis in dogs with PLE.     

ULTRASONOGRAPHIC FEATURES OF CANINE GASTROINTESTINAL STROMAL TUMORS COMPARED TO OTHER GASTROINTESTINAL SPINDLE CELL TUMORS

Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of gastrointestinal spindle cell tumor recognized with the increasing use of immunohistochemistry. To our knowledge, no imaging features have been described in immunistochemically confirmed canine GISTs. The objective of this retrospective, cross‐sectional study was to describe ultrasonographic features of canine GISTs compared with other spindle cell tumors. Thirty‐seven dogs with an ultrasonographically visible gastrointestinal mass and a histopathologic diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining was performed for retrieved tissue samples to further differentiate the tumor type and each sample was interpreted by a single veterinary pathologist. Ultrasonographic features recorded examined included mass echogenicity, homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and loss of wall layering, location, size, vascularity, and evidence of perforation or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were significantly more likely to be associated (P < 0.03) with abdominal effusion than other tumor types. There was overlap between the anatomical locations of all tumors types with the exception of the cecum where all eight tumors identified were GISTs. Besides location, there were no unique ultrasound features of GISTs that would allow distinction from other gastrointestinal spindle cell tumors. Similar to previous studies, GISTs appeared to be the most common spindle cell tumor associated with the cecum in our sample of dogs. The high frequency of abdominal effusion with GIST's was of unknown etiology could possibly have been due to septic peritonitis.     

Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation‐volvulus: 84 dogs (2003–2007)

Objective – To test whether an initial plasma lactate≥6.0 mmol/L is associated with the presence of macroscopic gastric wall necrosis and overall survival in dogs presenting with gastric dilatation‐volvulus (GDV). Additionally, if no association was identified we sought to identify a different predictive initial plasma lactate concentration and to examine whether serial plasma lactate concentrations provide better prediction of survival. Design – Retrospective study over a 5‐year period (2003–2007). Setting – Urban private referral small animal teaching hospital. Animals – Eighty‐four client‐owned dogs with a diagnosis of GDV and plasma lactate measurements. Interventions – None. Measurements and Main Results – There was no statistically significant relationship found between survival and the presence of macroscopic gastric wall necrosis with the initial plasma lactate≥6 mmol/L. There was a significant relationship between the initial plasma lactate >2.9 mmol/L for predicting necrosis and <4.1 mmol/L for predicting survival to discharge. Forty dogs that had an increased initial plasma lactate (>2.5 mmol/L) also had a subsequent plasma lactate measured within 12 hours of presentation, with 37/40 dogs surviving and 70% of these surviving dogs having the subsequent lactate decrease by≥50% within 12 hours. The 3/40 that died failed to decrease their plasma lactate by≥50% from the initial blood lactate. Conclusion – The results of this study indicate that an initial presenting plasma lactate concentration≥6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations≥50% within 12 hours may be a good indicator for survival. Limitations to the study include its retrospective nature, the small number of patients, and the number of dogs that were euthanized rather than allowed to progress to a natural outcome.     

Radiographic findings and clinical factors in dogs with surgically confirmed or presumed colonic torsion

Colonic torsion is a life‐threatening condition in dogs and radiographic findings for this condition have not been well described. The purpose of this retrospective case series was to describe radiographic findings and clinical signs in a group of dogs with colonic torsion. Inclusion criteria were dogs presenting during the period of 2006 and 2016, and that had abdominal radiography and a surgically confirmed or presumed diagnosis of colonic torsion. For each dog, clinical data were recorded from medical records and imaging findings were recorded from retrieved plain radiographs and positive contrast radiographs in which barium enema was performed. Fourteen dogs met inclusion criteria. Of these, nine dogs had colonic torsion confirmed at surgery, with five dogs having surgical confirmation of colonic congestion or mesenteric torsion. Radiographic findings included segmental distention of the colon (14/14), focal narrowing of the colon (11/14), displacement of cecum (11/14), displacement of descending colon (14/14), and mild to no small intestinal distention (14/14). In cases where barium enema was performed, focal narrowing of the colon and longitudinal striations that course in a helical pattern were identified, termed the “torsion sign.” Vomiting was the most common clinical sign observed (12/14), followed by abdominal pain in a small majority of cases (8/14). Severe abdominal pain and hypovolemic shock were uncommon in the patients reported (3/14). Colonic torsion should be considered as a differential diagnosis for dogs with radiographic segmental colonic distention with displacement of the descending colon and cecum. Barium enema is recommended for more definitive diagnosis.     

Timely adjuvant chemotherapy improves outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy

Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included. Median StoC was 20 days (range: 4–70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with non-metastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.     

Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs

There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post‐operative management of ASAGAC. Seventy‐four dogs with naturally occurring ASAGAC underwent surgery. Forty‐four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC.     

CT findings in five dogs with surgically confirmed colonic torsion

Colonic torsion is a life‐threatening condition that results in colonic ischemia, necrosis, perforation, sepsis, and eventual death. The aim of this multicenter, retrospective case series study was to describe the CT findings in dogs with surgically confirmed colonic torsion. Medical records were searched for dogs with surgically confirmed colonic torsion following abdominal CT. Five dogs met the inclusion criteria. Three had a history of chronic intermittent diarrhea prior to presentation. Two dogs presented with acute vomiting, diarrhea, and abdominal pain and one dog presented with acute vomiting and lethargy. Computed tomographic findings in all dogs with surgically confirmed colonic torsion include: “whirl sign,” displacement and distension of the cecum and colon, focal narrowing of the colon, and distension of the mesenteric vasculature in all dogs (5/5); streaky peritoneal fat and peritoneal effusion (4/5), pneumatosis coli (2/5), small intestinal distension (2/5), portal vein thrombosis (1/5), and reduced colonic wall contrast enhancement (1/5). In all dogs (5/5), the torsion site was the descending colon and demonstrated an anticlockwise rotation. At surgery, three of the five dogs had a partial colonic torsion with hyperemia at the site of obstruction and two of the five dogs had a complete torsion with marked necrosis of the colonic wall. Displacement of the colon and cecum, segmental distension and focal narrowing of the colon, the presence of a “whirl sign” and distension of the mesenteric vasculature are CT findings highly suggestive of colonic torsion.     

Evaluation of the modified Glasgow Prognostic Score to predict outcome in dogs with newly diagnosed lymphoma

The modified Glasgow Prognostic Score (mGPS) assigns a numerical value (0–2) from pre‐treatment serum concentrations of C‐reactive protein (CRP) and albumin to predict patient outcome. CRP and albumin were evaluated in 77 untreated dogs with lymphoma to determine the relationship of mGPS to clinicopathological parameters and whether it could predict progression‐free (PFS) and overall survival (OS) in treated dogs. mGPS distribution was significantly associated with clinical stage, substage b, weight loss, gastrointestinal disturbances and lethargy at presentation. On univariate analysis, mGPS was significantly associated with OS and PFS, with shorter median survival times for mGPS 2 compared to mGPS 0 and 1 combined. Hypoalbuminaemia significantly reduced OS and PFS, however increased CRP had no effect. Only clinical stage was significantly associated with OS and PFS on both univariate and multivariate analysis. mGPS has potential prognostic value for canine lymphoma , but further studies are needed.