BackgroundPrognostic markers for dogs with thyroid tumors are limited.Hypothesis/ObjectivesTo identify clinical, pathologic, and immunohistochemical prognostic factors for dogs with thyroid tumors.AnimalsSeventy dogs with thyroid neoplasia.MethodsRetrospective study. Dogs with thyroid neoplasia were included when follow‐up information and formalin‐fixed paraffin‐embedded tumor samples were available. Immunohistochemistry (IHC) was performed for thyroglobulin, calcitonin, Ki‐67, and E‐cadherin. Correlation of tumor variables (diameter, volume, localization, scintigraphic uptake, thyroid function, IHC) with local invasiveness and metastatic disease was performed on all tumor samples. Forty‐four dogs treated by thyroidectomy were included in a survival analysis.ResultsFifty dogs (71%) had differentiated follicular cell thyroid carcinoma (dFTC) and 20 (29%) had medullary thyroid carcinoma (MTC). At diagnosis, tumor diameter (P = .007; P = .038), tumor volume (P = .020), tumor fixation (P = .002), ectopic location (P = .002), follicular cell origin (P = .044), and Ki‐67 (P = .038) were positively associated with local invasiveness; tumor diameter (P = .002), tumor volume (P = .023), and bilateral location (P = .012) were positively associated with presence of distant metastases. Forty‐four dogs (28 dFTC, 16 MTC; stage I–III) underwent thyroidectomy. Outcome was comparable between dogs with dFTC and MTC. Macroscopic (P = .007) and histologic (P = .046) vascular invasion were independent negative predictors for disease‐free survival. Although time to presentation, histologic vascular invasion and Ki‐67 were negatively associated with time to metastases, and time to presentation was negatively associated with time to recurrence, no independent predictors were found. E‐cadherin expression was not associated with outcome.Conclusions and Clinical ImportancePrognostic factors have been identified that provide relevant information for owners and clinicians.

Background Acute pancreatitis (AP) is associated with a high death rate in dogs, but accurate predictors of early death are still lacking. Objectives To develop a scoring system for prediction of short‐term case fatality in dogs with AP. Animals One hundred sixty‐nine dogs with AP including 138 dogs in the training cohort and 31 dogs in the validation cohort. Methods Multicenter, retrospective cohort study. Survival analysis was used to assess the associations with short‐term death (within 30 days after admission). Independent predictors of death were identified by a stepwise selection method and used for the score calculation. Results Death rate within 30 days after admission was 33% in the training cohort. Four independent risk factors for short‐term death were identified in the training cohort: presence of systemic inflammatory response syndrome, coagulation disorders, increased creatinine and ionized hypocalcemia. Canine Acute Pancreatitis Severity (CAPS) score was developed to predict short‐term death, integrating these 4 factors in a weighted way. A simplified version of CAPS score (sCAPS) including respiratory rate instead of SIRS was also assessed. The area under the receiver‐operating characteristic curve (AUC) of CAPS and sCAPS scores was 0.92 in the training cohort with an optimal cutoff of 11 (sensitivity, 89%; specificity, 90%) and 6 (sensitivity, 96%; specificity, 77%), respectively. CAPS and sCAPS score were validated in the validation cohort with respective AUC of 0.91 and 0.96. Conclusions and Clinical Importance We propose 2 scoring systems that allow early and accurate prediction of short‐term death in dogs with AP.

BackgroundThyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease.Hypothesis/ObjectivesTo investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors.Animals74 dogs with thyroid neoplasia.MethodsImmunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase‐2 (cox‐2), and P‐glycoprotein (P‐gp).ResultsFifty‐four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76–100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox‐2. Seven percent of FTCs and 70% of MTCs expressed P‐gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox‐2 (P = .013), and P‐gp (P < .001) was significantly higher in MTCs compared to FTCs.Conclusions and Clinical Importance VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox‐2 and P‐gp may be useful molecular targets in canine MTC.

BackgroundInformation on the genetic events leading to thyroid cancer in dogs is lacking.Hypothesis/ObjectivesUpregulation of the PI3K/Akt pathway has an important role in the tumorigenesis of thyroid carcinoma in dogs.AnimalsFifty‐nine dogs with thyroid carcinoma and 10 healthy controls.MethodsQuantitative RT‐PCR was performed for VEGFR‐1, VEGFR‐2, EGFR, PIK3CA, PIK3CB, PDPK1, PTEN, AKT1, AKT2, COX‐2, and CALCA. Mutation analysis was performed for known hotspots of RAS (N, K, H), PIK3CA, BRAF, RET, and for the entire coding region of PTEN.ResultsForty‐three dogs (73%) had follicular cell thyroid carcinoma (FTC) and 16 dogs (27%) had medullary thyroid carcinoma (MTC). The relative mRNA expressions of VEGFR‐1 (P < .001), VEGFR‐2 (P = .002), PDPK1 (P < .001), AKT1 (P = .009), and AKT2 (P < .001) were increased in FTC, and those of EGFR (P < .001), VEGFR‐1 (P = .036), and PIK3CA (P = .019) were increased in MTC when compared to normal thyroid glands. Mutation analysis of K‐RAS identified 2 activating missense mutations, which also have been described in thyroid cancer of humans. A G12R substitution was present in 1 FTC and an E63K substitution was present in 1 MTC. No functional mutations were found in the sequenced regions of H‐RAS, N‐RAS, PIK3CA, BRAF, RET, and PTEN.Conclusions and Clinical ImportanceThe increased expression of several genes associated with PI3K/Akt signaling suggests the involvement of this pathway in the pathogenesis of thyroid carcinoma in dogs, warranting further research on pathway activation and gene amplification. The mutations most frequently associated with thyroid cancer in humans are rare in dogs.

No abstract

Gastric inflammatory myofibroblastic proliferation (IMP) is an extremely rare entity in children, which to our knowledge has only been mentioned in case reports. We describe the ninth pediatric case and review the literature concerning the etiology, clinical and laboratory features, pathology, treatment, and outcome. There has been a predominance in preschool females. Abdominal pain, upper gastrointestinal hemorrhage, and an abdominal mass, either isolated or associated, have been the main clinical features. Iron-deficiency anemia has been a constant finding. Lesions are elevated and involve the full thickness of the gastric wall, usually with ulceration of the luminal surface; extragastric extension suggesting malignancy is frequent. Diagnosis is made by histology after surgical excision. There was no mortality directly related to gastric IMP, and only one case recurred after surgical excision. The pathogenesis is controversial, but the finding of Helicobacter pylori in our case may indicate an inflammatory origin. Awareness of this benign lesion and its mimicry of malignancy is important so that inappropriately aggressive therapy can be avoided.

Defective innervation of the neuromuscular junctions (NMJ) was recently described in intestinal neuronal dysplasia type B (IND B). The aim of the present study was to correlate the alterations in NMJs to other classically described parameters in dysganglionoses and to determine the relationship between NMJ abnormalities in IND B and clinical symptoms. The rectal biopsies and full-thickness colonic biopsy specimens of 17 patients were studied applying histochemical (acetylcholinesterase [AChE], lactic dehydrogenase [LDH], and succinic dehydrogenase [SDH] reactions) and immunohistochemical (neuronal-cell adhesion molecule [NCAM] and SY antibodies) methods. Thirteen patients had Hirschsprung's disease (HD). IND B was diagnosed in 11 (associated with HD in 8 cases, isolated in 2, and associated with hypoganglionosis in 1). In the aganglionic segment of HD there was very intense AChE activity; in contrast, NCAM- and SY-immunoreactive nerve fibers were markedly decreased. A spectrum of abnormalities was observed in IND B, usually more severe in the most distal segments: giant and immature ganglia in the submucous plexus were observed in all cases; heterotopic myenteric ganglia were frequent (72.7%); hyperganglionosis was observed in 6 (54.5%) and was not related to the patients' age; thick and tortuous NCAM- and SY-immunoreactive nerve fibers, irregularly distributed in the colonic wall, were observed in 81.8% of the cases. No relationship was observed between abnormalities of NCAM- and SY-immunoreactive nerve fibers and AChE activity, ganglion-cell maturity, heterotopy, or the clinical symptoms presented by the patients with IND B. In hypoganglionism, low AChE activity and a slight decrease in NCAM- and SY-immunoreactive nerves were observed. Thick and tortuous, irregularly-distributed intrinsic NCAM- and SY-immunoreactive nerves were observed in every colon layer in IND B. Our results do not support IND B as a NMJ disorder.

No abstract