Cryotherapy with liquid nitrogen versus topical salicylic acid application for cutaneous warts in primary care: randomized controlled trial

Background

Cryotherapy is widely used for the treatment of cutaneous warts in primary care. However, evidence favours salicylic acid application. We compared the effectiveness of these treatments as well as a wait-and-see approach.

Methods

Consecutive patients with new cutaneous warts were recruited in 30 primary care practices in the Netherlands between May 1, 2006, and Jan. 26, 2007. We randomly allocated eligible patients to one of three groups: cryotherapy with liquid nitrogen every two weeks, self-application of salicylic acid daily or a wait-and-see approach. The primary outcome was the proportion of participants whose warts were all cured at 13 weeks. Analysis was on an intention-to-treat basis. Secondary outcomes included treatment adherence, side effects and treatment satisfaction. Research nurses assessed outcomes during home visits at 4, 13 and 26 weeks.

Results

Of the 250 participants (age 4 to 79 years), 240 were included in the analysis at 13 weeks (loss to follow-up 4%). Cure rates were 39% (95% confidence interval [CI] 29%–51%) in the cryotherapy group, 24% (95% CI 16%–35%) in the salicylic acid group and 16% (95% CI 9.5%–25%) in the wait-and-see group. Differences in effectiveness were most pronounced among participants with common warts (n = 116): cure rates were 49% (95% CI 34%–64%) in the cryotherapy group, 15% (95% CI 7%–30%) in the salicylic acid group and 8% (95% CI 3%–21%) in the wait-and-see group. Cure rates among the participants with plantar warts (n = 124) did not differ significantly between treatment groups.

Interpretation

For common warts, cryotherapy was the most effective therapy in primary care. For plantar warts, we found no clinically relevant difference in effectiveness between cryotherapy, topical application of salicylic acid or a wait-and-see approach after 13 weeks. (ClinicalTrial.gov registration no. ISRCTN42730629)Cutaneous warts are common.^1–3 Up to one-third of primary school children have warts, of which two-thirds resolve within two years.^4,5 Because warts frequently result in discomfort,⁶ 2% of the general population and 6% of school-aged children each year present with warts to their family physician.^7,8 The usual treatment is cryotherapy with liquid nitrogen or, less frequently, topical application of salicylic acid.^9–12 Some physicians choose a wait-and-see approach because of the benign natural course of warts and the risk of side effects of treatment.^10,11A recent Cochrane review on treatments of cutaneous warts concluded that available studies were small, poorly designed or limited to dermatology outpatients.^10,11 Evidence on cryotherapy was contradictory,^13–18 whereas the evidence on salicylic acid was more convincing.^19–23 However, studies that compared cryotherapy and salicylic acid directly showed no differences in effectiveness.^24,25 The Cochrane review called for high-quality trials in primary care to compare the effects of cryotherapy, salicylic acid and placebo.We conducted a three-arm randomized controlled trial to compare the effectiveness of cryotherapy with liquid nitrogen, topical application of salicylic acid and a wait-and-see approach for the treatment of common and plantar warts in primary care.     

Renal Impairment in Hepatic Cryotherapy

Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following cryotherapy, and its etiology is unknown. The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Ten of 204 patients with renal impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2 days postprocedure) were identified. One patient had postoperative pancreatitis with late renal impairment (20 days) and was excluded. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19). Two patients required temporary hemodialysis. Only one patient, who had significant cardiac disease, had associated pulmonary injury and shock. Demographic data in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194). Patients in the renal impairment group had a greater number of lesions than those of the nonrenal impairment group (3.4 vs 2.1,P< 0.01), as well as larger lesion diameter (2.9 vs 1.9,P< 0.01), increased freezing time (74.7 vs 44.3,P< 0.01), and a higher aspartate transaminase (AST) (2254 vs 1157,P< 0.01). This study suggests that renal impairment is more likely to be seen in patients undergoing more extensive cryotherapy. The number and diameter of lesions together with AST data link renal injury with magnitude of liver injury—all renal impairment patients had an AST > 1000, compared with only 28% of patients who did not.     

Human papillomaviruses and DNA ploidy in anal condylomata acuminata

Previous studies have emphasized the usefulness of DNA ploidy measurement and Human Papillomavirus (HPV) detection as prognostic markers in low grade cervical lesions. We addressed the eventual relationship between HPV type, DNA profile, and p53 tumor suppressor protein expression in anal condylomata acuminata to eventually determine parameters which may be considered as predictive risk factors for the development of cancer. DNA ploidy was assessed by image cytometry after Feulgen staining of contiguous serial sections of 45 anal condylomata acuminata without atypia containing HPV detected by in situ hybridization and Polymerase Chain Reaction (PCR). p53 expression was detected by immunohistochemistry. DNA aneuploidy was found in 53.3% of these lesions, 48.9% containing non oncogenic HPV types 6 and/or 11 and 4.4% harbouring HPV types 11 and 18. The DNA diploid lesions were all associated with non oncogenic HPV types 6 and/or 11 and one case also contained HPV type 33. There was no significant correlation between the detection of DNA aneuploidy and the presence of immuno-detected p53. DNA aneuploidy was not related to the presence of oncogenic HPV in anal condylomata acuminata. The DNA aneuploid profile frequently observed, especially in lesions associated with non oncogenic HPV types, is not yet well explained and cannot be considered as a prognostic factor. In contrast, a more intensive clinical follow-up should be proposed in patients with oncogenic HPV associated to DNA aneuploidy.     

Cryotherapy for advanced carcinoma of the trachea and bronchi.

Cryotherapy was used to relieve symptoms in 75 patients suffering from advanced carcinoma of the trachea or bronchi. In all patients surgical resection, radiotherapy, or chemotherapy had been tried and been unsuccessful or had been thought to be unsuitable because of the patients'' poor general condition. In cryotherapy the intraluminal tumour was frozen through a Stortz bronchoscope. Localised necrosis increased the patency of the lumen of the trachea or bronchi, resulting in relief of symptoms. Cryotherapy is effective and easily performed and causes the patient little discomfort.     

Cryotherapy of the liver: A histological review

Introduction

Cryotherapy has been largely used in the past for palliation of unresectable liver tumors, but high local recurrence rates and peculiar systemic complications have determined its progressive abandonment. This review analyzes the histological changes produced to provide the basis for the local recurrences.

Materials and methods

A detailed literature search was performed on studies focusing on liver cryotherapy. Included were only those that described the histological characteristics in detail.

Results

A total of 22 studies were found, one clinical and the others in-vivo animal studies. Similar to other ablative techniques, cryotherapy produces a lesion which is composed by a central zone of coagulative necrosis surrounded with a transitional inflammatory zone. The lesion’s dimensions and morphology are influenced by numerous factors including the probe temperature, diameter, the duration of freezing time, fast cooling rate, slow thawing rate, the number of freezing cycles and the inflow occlusion (Pringle maneuver). The temporal evolution is consistent across studies and leads to a progressive inflammatory invasion of the necrosis with definitive fibrotic substitution.

Conclusions

Lesions obtained after cryotherapy seem similar and behave as those obtained after other techniques of liver ablation. However, controversial areas still exist and include the optimum number of freeze thaw cycles, the place of inflow occlusion, the potential corrupting effects of intra-lesional or proximal blood vessels on ablation morphology. The influence of these factors on the local recurrences are still not fully understood.