According to a PubMed search of articles indexed for MEDLINE using the terms scrotal or cutaneous, pain or ulceration, and HIPEC or hyperthermic intraperitoneal or mitomycin C, 4 cases of scrotal necrosis as a suspected complication of HIPEC have been reported.1-3 In 2015, Abdul Aziz et al2 reported a case of scrotal eschar presenting 67 days after HIPEC. Silva et al3 presented a similar case 9 days after HIPEC. Akhavan et al1 reported 2 cases of scrotal eschar presenting at 3 and 4 months following HIPEC. All cases involved the anterior scrotum with erythema and pain progressing to an eschar. No fever or other systemic signs or symptoms were reported, cultures were negative, and treatment with antibiotics was ineffective. Conservative managements failed, and excision of the necrotic area with primary closure produced resolution of pain. Histology showed epidermal and dermal necrosis.1,3 The remarkably similar presentation of these patients following HIPEC with MitC in the absence of an identifiable alternative etiology supports an extravasation reaction.
Hyperthermic intraperitoneal chemotherapy involves installation of high-concentration chemotherapeutics into the peritoneal cavity at the conclusion of surgical cytoreductive therapy. Cell cycle–nonspecific agents such as MitC commonly are used for this procedure.4 It is classified as a vesicant, which is the designation given to drugs known to produce the most severe extravasation reactions of skin ulceration and necrosis.5,6 Symptoms typically include an early area of localized edema, erythema, and severe pain that progresses to superficial soft tissue and skin necrosis.7 Unfortunately, no well-studied antidote exists for MitC, though empirical guidelines suggest therapeutic management with DMSO and ice packs.6,8
Dimethyl sulfoxide is thought to work as a free radical scavenger as well as a solvent that facilitates diffusion of chemotherapeutics through tissues and thus down a concentration gradient, ideal in the circumstance of an extravasation reaction.8 Topical DMSO has been studied as a nonsurgical treatment in a small number of patients to prevent progression to necrosis following MitC extravasation.5,7 However, these cases only report extravasation reactions from IV infiltration.5,7,9 Dimethyl sulfoxide is rapidly absorbed and acts as a theoretical carrier for MitC as well as other topical substances.5,10,11 Caution is advised when using topical lidocaine or steroids in combination with DMSO, as they will be rapidly absorbed systemically. Patients also should be informed about a mild local burning sensation after DMSO application and a garliclike odor of the breath, which have occurred in 5.5% and 27.5% of patients, respectively (N=144).5 Dimethyl sulfoxide has no known toxic side effects but can cause erythema, pruritus, and very rarely allergic contact dermatitis.5,12 Abdul Aziz et al2 postulated that DMSO might be used as a method to prevent the progression of necrosis in symptomatic patients following HIPEC with MitC. Reports of its use on the scrotum are absent in the current available literature.
Treatment with DMSO was attempted in our patient with limited success secondary to delayed recognition and lack of supporting literature for DMSO treatment of scrotal necrosis. Treatment was delayed by 11 days after the onset of symptoms, which is far beyond the recommendation of starting within 10 minutes.8 Irreversible tissue necrosis had already occurred as evidenced by the presence of eschar. However, it seems apparent that DMSO provided some benefit given the clear improvement in erythema and pain 7 hours after application (Figure 2). It is unknown to what extent the necrosis would have progressed if not treated with DMSO.
Scrotal necrosis following HIPEC with MitC is a rare and incompletely understood but important chemotherapy reaction. The presentation is fairly specific with the presence of intractable and constant scrotal pain along with erythema and induration progressing to eschar. Although DMSO has been found to be effective for certain vesicant extravasation reactions at IV sites, it is not well studied for MitC, and no reports exist regarding its use on the scrotum. The presented characterization and explanation of the pathophysiology of this entity will aid in early recognition and timely institution of topical mitigating agents such as DMSO, which may prevent progression to scrotal necrosis and need for surgical debridement. More effective strategies may be geared toward prevention with thorough washout following HIPEC, preprocedural radiologic imaging or intraoperative visualization of the patent processus vaginalis, internal inguinal canal plugs, and patient education with anticipatory guidance should a reaction occur.2