Development and validation of a multivariable model and online decision-support calculator to aid in preoperative discrimination of benign from malignant splenic masses in dogs.

OBJECTIVE: To develop a multivariable model and online decision-support calculator to aid in preoperative discrimination of benign from malignant splenic masses in dogs. ANIMALS: 522 dogs that underwent splenectomy because of splenic masses. PROCEDURES: A multivariable model was developed with preoperative clinical data obtained retrospectively from the records of 422 dogs that underwent splenectomy. Inclusion criteria were the availability of complete abdominal ultrasonographic examination images and splenic histologic slides or histology reports for review. Variables considered potentially predictive of splenic malignancy were analyzed. A receiver operating characteristic curve was created for the final multivariable model, and area under the curve was calculated. The model was externally validated with data from 100 dogs that underwent splenectomy subsequent to model development and was used to create an online calculator to estimate probability of splenic malignancy in individual dogs. RESULTS: The final multivariable model contained 8 clinical variables used to estimate splenic malignancy probability: serum total protein concentration, presence (vs absence) of ≥ 2 nRBCs/100 WBCs, ultrasonographically assessed splenic mass diameter, number of liver nodules (0, 1, or ≥ 2), presence (vs absence) of multiple splenic masses or nodules, moderate to marked splenic mass inhomogeneity, moderate to marked abdominal effusion, and mesenteric, omental, or peritoneal nodules. Areas under the receiver operating characteristic curves for the development and validation populations were 0.80 and 0.78, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The online calculator (T-STAT.net or T-STAT.org) developed in this study can be used as an aid to estimate the probability of malignancy in dogs with splenic masses and has potential to facilitate owners' decisions regarding splenectomy.

Toxic tacrolimus levels after application of topical tacrolimus and use of occlusive dressings in two bone marrow transplant recipients with cutaneous graft-versus-host disease.

Tacrolimus, a macrolide immunosuppressant, is used topically for the treatment of cutaneous manifestations of graft-versus-host disease (GVHD) for rapid, symptomatic relief of pruritus and erythema. Despite the manufacturer's product information reporting minimal systemic effects of topical tacrolimus, this has not been evaluated in patients with cutaneous GVHD and with occlusive dressings. We describe two patients with cutaneous GVHD who developed toxic tacrolimus levels after receiving several applications of tacrolimus ointment along with occlusive dressings to enhance skin effectiveness. The first patient was a 62-year-old woman with a history of acute myelogenous leukemia (AML) who underwent allogeneic bone marrow transplantation and developed chronic GVHD involving 70% of her body surface area. Her GVHD treatment plan consisted of oral corticosteroids, oral tacrolimus, topical corticosteroids, topical tacrolimus 0.1% ointment twice/day, emollient creams, intravenous rituximab, and photopheresis. The patient's tacrolimus trough levels rose rapidly over the course of 6 days from less than 2 ng/ml to 23 ng/ml, despite oral tacrolimus dosage adjustments. The second patient was a 25-year-old man who developed severe, chronic skin GVHD after undergoing allogeneic sibling bone marrow transplantation for AML. In addition to intravenous corticosteroids, corticosteroid creams, and oral tacrolimus, the patient also received topical tacrolimus twice/day with occlusive dressings. Over the course of 2 days, his tacrolimus trough levels increased from 7.10 ng/ml to 22.10 ng/ml. Although improvement was noted in both patients' skin GVHD with application of the occlusive dressings, the practice was discontinued due to increased and erratic systemic tacrolimus absorption. These case reports suggest that substantial use of topical tacrolimus with occlusive dressings in patients with cutaneous GVHD may contribute to increased systemic absorption resulting in toxic tacrolimus levels. Based on the findings from our two patients as well as published case reports, systemic absorption appears to increase with greater skin permeability, skin barrier dysfunction, amount of body surface area applied, and use of occlusive dressings. When one or more of these factors are present, it may be prudent to monitor tacrolimus levels.