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  • Author or Editor: Michael O. Childress x
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Abstract

OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas.

DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial.

ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment.

PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO). The primary outcome of interest was progression-free survival time. Veterinary caregivers and assessors of outcome were not blinded to treatment assignment. Treatment assignment was concealed from the owners of study dogs prior to enrollment, but was revealed after written informed consent was provided.

RESULTS The trial was terminated early because of slow enrollment. The 40 dogs successfully enrolled in the study were randomly assigned to the L-CHOP (n = 18) or L-CHO (22) group; results for all 40 dogs were analyzed with respect to the primary outcome. Median progression-free survival time was 142.5 days for dogs receiving L-CHO and 292 days for dogs receiving L-CHOP (hazard ratio, 1.79; 95% confidence interval, 0.85 to 3.75). Serious adverse events were more common among dogs receiving L-CHO. However, this difference was not significant.

CONCLUSIONS AND CLINICAL RELEVANCE The exclusion of prednisone from the L-CHOP protocol did not appear to result in improved progression-free survival time for dogs with peripheral nodal lymphomas. However, the present trial was likely underpowered to detect a clinically meaningful difference in progression-free survival time between groups.

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in Journal of the American Veterinary Medical Association

Abstract

Case Description—2 dogs were referred for surgical removal of cutaneous tumors that had previously been treated by intratumoral injection of a herbal preparation containing blood-root (Sanguinaria canadensis) extract.

Clinical Findings—11 days following injection of bloodroot extract into a small dermal tumor, dog 1 developed a large, soft, fluctuant cutaneous mass at the site of injection. Ultrasonographic evaluation of the mass revealed a fluid-filled central cavity with increased echogenicity of the surrounding subcutaneous tissues. Dog 2 had a small dermal tumor under the left mandible that had been treated in similar fashion. However, an exuberant reaction was not observed following injection of bloodroot extract in this dog.

Treatment and Outcome—Both dogs underwent surgical excision of the cutaneous tumors. Histologic evaluation revealed severe necrosis and inflammation in the excised tissues from dog 1. This dog experienced postsurgical wound complications and had a prolonged postsurgical recovery. Similar, although less severe, histopathologic findings were apparent in the excised tissues from dog 2; this dog recovered without complications.

Clinical Relevance—Various products containing bloodroot are marketed on the Internet for topical and parenteral treatment of cutaneous neoplasms in domestic animals. However, the antineoplastic properties, therapeutic efficacy, and adverse effects of these products are poorly described in the veterinary literature. Clinicians should be aware of the potential for harm caused by the use of these products.

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in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To measure programmed cell death ligand-1 (PD-L1) mRNA expression in archived primary nodal diffuse large B-cell lymphoma (DLBCL) specimens of dogs and determine whether that expression was associated with progression-free survival time (PFST).

SAMPLE Archived tumoral lymph node specimens from 42 dogs with DLBCL and lymph node specimens from 10 healthy dogs (controls).

PROCEDURES Archived tumoral and control lymph node specimens underwent multiplex qPCR analysis with probes and primers against canine PD-L1 and glyceraldehyde 3-phosphate dehydrogenase (housekeeping gene) to determine PD-L1 mRNA expression. The 2−ΔΔCt method was used to calculate the fold change in PD-L1 expression in DLBCL specimens relative to that in control lymph nodes. Kaplan-Meier and Cox proportional hazard analyses were used to evaluate the association of various tumoral and clinical factors with PFST.

RESULTS The fold change in PD-L1 mRNA expression in DLBCL specimens relative to control specimens ranged from 0.21 to 7.44. Twenty-one of 42 (50%) DLBCL specimens had a PD-L1-fold change > 1, which suggested PD-L1 was overexpressed in those specimens. Median PFST was 249 days for dogs with DLBCL. The PFST was not associated with PD-L1 mRNA expression but was associated with thrombocytopenia at the time of diagnosis (hazard ratio, 2.56; 95% confidence interval, 1.28 to 5.15).

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that tumoral PD-L1 mRNA expression varied among dogs with DLBCL and that PD-L1 MRNA was overexpressed in half the study population. Therefore, anti–PD-L1 therapies may be clinically beneficial for some dogs with DLBCL.

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in American Journal of Veterinary Research

Abstract

Case Description—An 8-year-old 12.2-kg (26.9-lb) spayed female American Cocker Spaniel was referred for evaluation of abdominal discomfort and a suspected intra-abdominal lipoma with possible invasion into the thorax.

Clinical Findings—Physical examination revealed a tense abdomen, and the margins of a large abdominal mass could be appreciated. Abdominal imaging revealed a mass of fat opacity in the abdominal and thoracic cavities. Computed tomography with precontrast and postcontrast peritoneograms was used to determine whether the masses connected via a diaphragmatic defect.

Treatment and Outcome—Exploratory laparotomy revealed a retroperitoneal lipomatous mass that had focally invaded the hypaxial musculature and had extended across the dorsolateral aspect of the diaphragm via the lumbocostal trigone into the intrathoracic extrapleural space. Surgical resection required transdiaphragmatic thoracotomy. Histologic examination of excised tissue confirmed the preoperative diagnosis of a lipoma. The dog recovered from surgery with no complications and had no disease recurrence for at least 32 months after surgical resection.

Clinical Relevance—The defect of the lumbocostal trigone is also called the foramen of Bochdalek in humans, and it is recognized as a common location for congenital diaphragmatic hernia. A lumbocostal trigone hernia may be considered as a differential diagnosis for bicavitary masses in dogs, particularly in the absence of a history of trauma.

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in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To evaluate effects of substituting mitoxantrone for doxorubicin in a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapeutic protocol for first-line treatment of dogs with multicentric intermediate- to large-cell lymphoma.

DESIGN Retrospective cohort study.

ANIMALS 44 dogs treated with cyclophosphamide, mitoxantrone, vincristine, and prednisone (CMOP) and 51 dogs treated with CHOP at 12 referral institutions.

PROCEDURES Medical records were reviewed to determine response to treatment, progression-free survival time, and overall survival time. For dogs treated with CMOP, adverse events were also recorded.

RESULTS All 44 (100%) dogs treated with CMOP and 37 of 38 (97.4%) dogs treated with CHOP had a complete or partial response. Median progression-free survival time for dogs treated with CMOP was 165 days (95% confidence interval [CI], 143 to 187 days), and median overall survival time was 234 days (95% CI, 165 to 303 days). For dogs treated with CHOP, median progression-free survival time was 208 days (95% CI, 122 to 294 days), and median overall survival time was 348 days (95% CI, 287 to 409 days). Progression-free and overall survival times were not significantly different between groups. Overall, 9 of the 44 (20%) dogs treated with CMOP had adverse events likely or probably related to mitoxantrone, but all of these adverse events were mild.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that mitoxantrone may be a reasonable substitution in a CHOP protocol for treatment of dogs with multicentric intermediate- to large-cell lymphoma when doxorubicin is contraindicated.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs.

Sample—10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma.

Procedures—Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis.

Results—FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild.

Conclusions and Clinical Relevance—This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.

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in American Journal of Veterinary Research

Abstract

Objective—To determine uroplakin III expression, potential etiologic factors, biological behavior, and treatment response of transitional cell carcinoma (TCC) in the abdominal wall (ABWTCC) in dogs.

Design—Retrospective case series.

Animals—24 dogs with TCC of the urinary tract that also had histopathologic confirmation of ABWTCC.

Procedures—Medical records, histologic slides, radiographs, and ultrasonographic images of dogs with ABWTCC between July 1, 1985, and December 31, 2010, were reviewed. In available tissue specimens, immunohistochemistry was used to detect uroplakin III expression in the ABWTCC and in the primary tumor.

Results—The ABWTCC lesions ranged from < 2 to > 20 cm in diameter. Uroplakin III was expressed in 19 of 20 primary tumors and 17 of 17 ABWTCCs. Transitional cell carcinoma in the abdominal wall developed significantly more often in dogs that had undergone cystotomy (18/177 [10.2%]) than in those that had not (6/367 [1.6%]). In 1 dog that had not undergone cystotomy, TCC had invaded through the urinary bladder wall and spread down the median ligament to the abdominal wall. None of 18 dogs that received anticancer drugs had remission of the ABWTCC once clinically detected; median survival time after ABWTCC detection was 57 days (range, 0 to 324 days).

Conclusions and Clinical Relevance—Results suggested that ABWTCC is uncommon, but once TCC becomes established and clinically detectable in the abdominal wall, it carries a poor prognosis. It is crucial to minimize risk of TCC seeding at surgery. Percutaneous sampling of TCC should be avoided. Uroplakin III is commonly expressed in ABWTCC.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To assess the diagnostic utility of transurethral cystoscopic biopsy in dogs with histologically confirmed transitional cell carcinoma (TCC) of the urinary bladder and urethra.

Design—Retrospective case series.

Animals—92 dogs with histologically confirmed TCC.

Procedures—Information on sex, breed, neuter status, body weight, tumor location, biopsy method, number of biopsy procedures, experience level of clinician performing biopsy, and quality of biopsy sample was obtained from medical records. The association of variables with likelihood of achieving a diagnostic-quality biopsy sample was evaluated by use of logistic regression.

Results—If used as the initial biopsy method, cystoscopic biopsy samples were of diagnostic quality in 65% of male dogs and 96% of female dogs with histologically confirmed TCC. Cystoscopic biopsy samples were significantly more likely to be of diagnostic quality in female dogs than in male dogs.

Conclusions and Clinical Relevance—Cystoscopic biopsy is an effective method to obtain biopsy samples in dogs with TCC of the bladder and urethra. Cystoscopy is more likely to produce a diagnostic-quality biopsy sample in female dogs with TCC than in male dogs with TCC. Cystoscopy should be considered as a primary means of biopsy in male and female dogs with masses of the urinary bladder or urethra.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the antitumor effects and toxicoses of metronomic oral administration of a low dose of chlorambucil in dogs with transitional cell carcinoma (TCC).

Design—Prospective clinical trial.

Animals—31 client-owned dogs with TCC for which prior treatments had failed or owners had declined other treatments.

Procedures—Chlorambucil (4 mg/m2, PO, q 24 h) was administered to dogs. Before and at scheduled times during treatment, evaluations of dogs included physical examination, CBC, serum biochemical analyses, urinalysis, thoracic and abdominal imaging including cystosonography for measurement of TCCs, and grading of toxicoses.

Results—29 of 31 dogs had failed prior TCC treatment. Of the 30 dogs with available data, 1 (3%) had partial remission (≥ 50% reduction in tumor volume), 20 (67%) had stable disease (< 50% change in tumor volume), and 9 (30%) had progressive disease (≥ 50% increase in tumor volume or development of additional tumors); 1 dog was lost to follow-up. The median progression-free interval (time from the start of chlorambucil treatment to the day progressive disease was detected) for the dogs was 119 days (range, 7 to 728 days). The median survival time of dogs from the time of the start of chlorambucil treatment was 221 days (range, 7 to 747 days). Few toxicoses were detected; chlorambucil administration was discontinued because of toxicoses in only 1 dog.

Conclusions and Clinical Relevance—Metronomic administration of chlorambucil was well tolerated, and 70% of dogs had partial remission or stable disease. Metronomic administration of chlorambucil may be a treatment option for dogs with TCC.

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in Journal of the American Veterinary Medical Association