Dog’s chemotherapy wound heals without surgery after delayed epirubicin extravasation

A severe chemotherapy injection-site ulcer in a dog has healed completely without surgery, according to a case report published in Frontiers in Veterinary Science on 28 October 2026. The 9-year-old spayed female Poodle, being treated for suspected stage IV multicentric lymphoma, developed a progressive ulcerative lesion 17 days after suspected epirubicin extravasation — an event well beyond the recommended treatment window for the standard interventions dexrazoxane, topical dimethyl sulfoxide (DMSO), and cold compresses. Despite the delay and the severity of the injury, complete re-epithelialization was achieved by day 93, and the wound remained fully healed until the dog died of progressive lymphoma on day 138.

The report, authored by Chaeyeon Gloria Kim and Soon-Wuk Jeong of Konkuk University’s Department of Veterinary Surgery and Ji-Hwan Park of Leaders Animal Medical Center in South Korea, describes how the lesion was managed with a multimodal conservative strategy. The principal adjunctive modality was hyperbaric gaseous cryotherapy (HGC), a technique that delivers high-pressure carbon dioxide gas to affected tissues and had not previously been reported for anthracycline extravasation in veterinary medicine. Dexrazoxane, topical DMSO, and ice-pack application were also incorporated despite the elapsed therapeutic window, because few alternative treatment options remained at that stage.

The case began when the Poodle was diagnosed with stage IV multicentric lymphoma on the basis of generalized peripheral lymphadenopathy and fine-needle aspiration cytology of an enlarged submandibular lymph node. Abdominal ultrasonography revealed diffuse, heterogeneous splenic echogenicity with a honeycomb-like pattern suggestive of splenic involvement, although this was not cytologically confirmed. With no systemic clinical signs present, the disease was classified as substage a, and a modified L-CHOP chemotherapy protocol consisting of L-asparaginase, cyclophosphamide, epirubicin, vincristine, and prednisolone was initiated. Epirubicin was chosen as the anthracycline component because of its reported lower cardiotoxicity compared with doxorubicin.

Epirubicin hydrochloride at 30 mg/m2 was diluted in 0.9% normal saline to a total volume of 14.4 mL and administered manually over 20 minutes through a 24-gauge catheter placed in the left cephalic vein. The catheter was assessed every minute by flushing with saline and confirming blood return. After approximately one-third of the drug had been given, mild swelling was noted proximal to the catheter site. Administration was stopped immediately and aspiration was attempted, but catheter function remained intact, with unobstructed saline flow and persistent blood return. No pain response had been observed during administration. These findings made extravasation appear less likely at the time, although the authors note that preserved blood return does not exclude the possibility. The remaining dose was given through a new catheter in the right lateral saphenous vein, and ice packs were recommended at home.

At the 7-day follow-up, the owner reported no abnormalities and ice packs had been used only intermittently because no local changes had developed. Thirteen days after the suspected event, subtle erythema and reduced weight-bearing of the left forelimb appeared at the same site. Given the clinical history, the lesion location, the absence of any subsequent catheterization at that site, and a delayed course consistent with reported anthracycline extravasation cases, the injury was considered most consistent with epirubicin extravasation. Because the lesion was recognized well beyond the recommended treatment window for dexrazoxane and DMSO and the signs were relatively mild, HGC was applied twice for symptomatic management. Two days later, mild erythema with early superficial skin erosion developed, and by day 17 the erythema had worsened, with early ulceration, exudation, and increasing pain.

At that point a single dose of dexrazoxane at 300 mg/m2 intravenously was administered, and topical 70% DMSO gel containing 30% aloe vera together with ice-pack application was prescribed for home care. By day 20 the lesion had progressed to more extensive ulceration with increased yellow exudation and crusting. Physical examination revealed marked hyperemia of the affected limb, with surrounding tissue warm and moist; the dog refused to bear weight on the limb and vocalized even with gentle manipulation near the lesion. Surgical debridement was considered after surgical consultation. However, the dog’s poor response to antineoplastic treatment — complete remission had never been achieved during the initial L-CHOP cycle, a lomustine rescue trial had produced only a limited response, and intermittent hematologic toxicity had caused treatment delays — combined with the owner’s preference to prioritize quality of life, led the team to pursue conservative management instead.

HGC was selected as the principal adjunctive modality based on the clinicians’ prior experience in wound management and pain control. On day 20, two sessions were performed roughly 3 to 4 hours apart, each consisting of two 1.5-minute applications separated by a 30-second rest interval. The nozzle was held approximately 2 to 3 centimeters from the wound surface and moved continuously in a circular pattern over the ulcerated area and surrounding skin to avoid prolonged cooling of any single spot. The procedure was well tolerated with manual restraint and without sedation, and no new local tissue injury was observed. Immediately after the first session, local heat appeared subjectively reduced and the dog appeared more comfortable, with fewer attempts to lick the lesion and less resistance to handling of the limb. Subsequent sessions followed on days 23, 30, 41, 51, 72, and 93, with intervals determined clinically according to wound progression and lengthening as the lesion improved.

Healing progressed steadily under this regimen. By day 23 the dog showed improved limb use, though it still intermittently avoided weight-bearing, and yellow exudation had decreased. By day 30, limb use had further improved and exudation was minimal, although local heat, moisture, and pain persisted in diminished form. Pain-related signs progressively decreased throughout conservative multimodal management, and no systemic analgesics were needed during the subsequent course. By day 41, erythema and pain had further reduced and granulation tissue with progressive wound contraction was evident. Advancing re-epithelialization with mild post-inflammatory hyperpigmentation appeared by day 51, at which point topical DMSO and ice packs were discontinued because local warmth and inflammation had substantially decreased. By day 72 the wound bed was largely covered with newly formed epithelium, and complete epithelialization with partial hair regrowth was observed by day 93, when HGC was stopped.

The authors place the case in the context of the known biology of anthracycline injury. Anthracyclines intercalate DNA and inhibit topoisomerase II, producing persistent double-stranded DNA breaks, and their strong DNA affinity means they remain bound within cells until cell death, when they are released and taken up by adjacent viable cells. This self-propagating cycle of uptake, death, and re-release allows prolonged intracellular retention and redistribution within tissues, offering a biological explanation for delayed clinical progression and ulcer formation. Persistent epirubicin concentrations have been detected in affected tissues weeks after extravasation despite DMSO and cold compress treatment, with progressive necrosis ultimately requiring surgical excision. Anthracyclines also undergo redox cycling that generates reactive oxygen species, contributing to oxidative stress, endothelial damage, microvascular thrombosis, and progressive tissue necrosis, and experimental models confirm that injury may continue to evolve for days after the initial event.

The authors are careful to frame the limitations of a single-case report. According to the Veterinary Cooperative Oncology Group Common Terminology Criteria for Adverse Events, the presence of ulceration is consistent with a Grade 3 extravasation injury, defined as severe local tissue damage for which surgical intervention is indicated, and earlier surgical intervention has been associated with more favorable recovery than delayed surgery after established necrosis. Dexrazoxane is the only FDA-approved agent for anthracycline extravasation in human medicine, with a recommended administration window within 6 hours of the event and additional doses at 24 and 48 hours; evidence supporting its use at a markedly delayed stage is lacking, and the individual contributions of dexrazoxane, DMSO, and ice packs to this dog’s wound resolution remain uncertain. Similarly, the relevance of rapid cooling to restrict drug distribution at a delayed stage is uncertain, and no objective tissue temperature monitoring was performed during HGC application. Wound measurements were not obtained, and changes in pain and limb use were assessed subjectively without standardized scoring systems. Nonetheless, the authors conclude that the favorable course adds to the limited veterinary evidence on conservative management of delayed anthracycline extravasation and provides a clinical basis for further investigation of HGC as an adjunctive modality in presentations where surgery is not feasible or a conservative approach is preferred.

Subject of Research: Conservative management of delayed epirubicin extravasation ulceration in a dog using adjunctive hyperbaric gaseous cryotherapy

Article Title: Case Report: Delayed epirubicin extravasation-induced ulceration in a dog managed without surgical intervention using adjunctive hyperbaric gaseous cryotherapy

Article References: Kim, C. G., Park, J.-H., & Jeong, S.-W. (2026). Case Report: Delayed epirubicin extravasation-induced ulceration in a dog managed without surgical intervention using adjunctive hyperbaric gaseous cryotherapy. Frontiers in Veterinary Science, 13, Article 1939525. https://doi.org/10.3389/fvets.2026.1939525

Image Credits: AI Generated

DOI: 10.3389/fvets.2026.1939525

Keywords: epirubicin, extravasation, anthracycline, hyperbaric gaseous cryotherapy, dexrazoxone, DMSO, wound healing, veterinary oncology, case report, chemotherapy complication, dog, lymphoma