A randomised clinical trial of loop electrosurgical excision procedure (LEEP) versus cryotherapy in the treatment of cervical intraepithelial neoplasia. Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial. Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis. Laser or cryotherapy for cervical intraepithelial neoplasia: a randomized study to compare efficacy and side effects. Benefit of aggressive multimodality therapy with autologous stem cell support for intra-abdominal desmoplastic small round cell tumor. [Cutaneous cryosurgery in family medicine: dimethyl ether-propane spray versus liquid nitrogen]. Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. Cryotherapy with liquid nitrogen versus topical salicylic acid application for cutaneous warts in primary care: randomized controlled trial. A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-related stomatitis. Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial. Cryotherapy temperature differences after total knee arthroplasty: a prospective randomized trial.
The objective of the treatment of cervical intraepithelial neoplasia (CIN) is the prevention of invasive carcinoma of the cervix, which still remains the most common cancer in Zimbabwean women, as in most other low-resource countries where screening facilities are grossly inadequate. We conducted a randomised prospective study to compare CIN treatment outcome after cryotherapy and loop electrosurgical excision procedure (LEEP) in 400 women with histologically confirmed high grade squamous intra-epithelial lesions (HGSIL). Treatment outcome measures were immediate complications, persistent disease and recurrent disease evaluated at follow-up visits. Eighty-two per cent of the women (159 cryotherapy, 168 LEEP) completed their 6-month and 12-month follow-up visits. LEEP had a significantly higher overall cure rate of 96.4% (absence of persistent or recurrent disease) compared to 88.3% cryotherapy (P=0.026). Although cryotherapy was not superior to LEEP, its cure rate (88.3%) is acceptable and therefore provides a viable treatment option for low resource countries such as Zimbabwe where the majority of women at risk for cervical cancer reside in rural areas. To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts.
                A multicentre, open, two arm randomised controlled trial.
                University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland.
                240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid.
                Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks.
                Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment.
                There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI -8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients' preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference -3.15% (-16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar warts at 12 weeks (incident rate ratio 1.08 (0.81 to 1.43), P=0.62).
                Salicylic acid and the cryotherapy were equally effective for clearance of plantar warts.
                Current Controlled Trials ISRCTN18994246, National Research Register N0484189151. Recently, a randomised study demonstrated the utility of oral cooling (cryotherapy) in the prevention of 5-fluorouracil (5FU)-induced stomatitis. In order to verify these results a confirmatory study, using identical treatment regimen, was initiated. 84 patients treated with a 5-FU-containing regimen were randomised to a control arm or to receive oral cryotherapy. End point evaluation was obtained by a global assessment of the physician's judgement and patients' description of mucositis severity graded 0-4. Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy (the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group, P < or = 0.05) and all the chemotherapeutic courses (the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group, P < or = 0.05). In conclusion, the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens. A randomized study was performed to compare efficacy and side effects of laser and cryotherapy: 51 patients were treated with laser vaporization and 50 patients with cryotherapy. Success rates for laser and cryotherapy were not significantly different. Success rates were significantly related to lesion size. Grade of CIN, positive endocervical curettage, parity, and age at treatment were not found to be related. Vaginal discharge, both in duration and amount, was significantly less in patients treated with laser vaporization, compared with cryotherapy, but pain and bleeding occurred more often in patients treated with laser vaporization. A brief review of possible sources of bias in comparative studies on laser and cryotherapy is given, indicating the preference for a randomized study. It is concluded that widespread introduction of laser facilities in smaller centers is not justified, because the success rates are not better than those of cryotherapy, and because the advantages of less discharge are outweighed by the high cost. A case is described of a 19-year-old man with poor prognosis intra-abdominal desmoplastic small round cell tumor, who achieved a durable complete remission after aggressive multimodality treatment. He was diagnosed with a large peri-rectal mass and bulky metastases to the peritoneum, omentum and liver. He achieved a partial response to six courses of chemotherapy with VAC (vincristine, adriamycin, actinomycin, cyclophosphamide) and VIP (VP-16, ifosfamide, cisplatin). This was followed by resection of the omentum and cryotherapy to six of the liver lesions. He then achieved a complete response following high-dose busulfan 16 mg/kg and melphalan 140 mg/m2 with autologous stem cell support. Finally, pelvic radiotherapy was given to consolidate the remission. Twenty-six months following his diagnosis, and 19 months after the transplant, he remains well with no clinical or radiologic evidence of recurrent disease. This case report suggests a role for autologous stem cell transplantation as part of multimodality therapy for this unusual and aggressive malignancy. To compare the efficacy, tolerance and safety of two types of cryotherapy, performed by family physicians, for benign cutaneous lesions: low freezing (-59 degrees C) with dimethyl either-propane cryogenic spray (DMEP) and intense freezing (196 degrees C) with conventional liquid nitrogen (LN).
                A randomised, multi-centered, controlled clinical trial, with single-blind assessment.
                Three primary care teaching teams in the Community of Madrid.
                Ten MIR from family & community medicine intervened. There were 124 patients, who had 174 benign cutaneous lesions, suitable for cryotherapy. There were 3 voluntary withdrawals, none because of an adverse reaction. Interventions, in each case there was local application for a standard time of the randomised agent. Control-group intervention, 81 cases: swab soaked in LN. Study-group intervention, 93 cases: swab saturated with DMEP spray. Maximum of three freezings per case, at weekly intervals.
                A doctor made a blind assessment of the results (elimination, adverse reaction, aesthetic result) 15 days after treatment.
                No clinically relevant differences between the efficacy, tolerance and safety of the two cryogenic agents used in primary care were found. The low freezing of DMEP was sufficient for the cryotherapy of benign lesions. A prospective randomised trial to compare radiotherapy and cryotherapy in the treatment of basal-cell carcinomas was carried out in 93 patients. Two years after treatment, 4% of tumours treated with radiotherapy and 39% of those treated with cryotherapy had recurred. It is concluded that cryotherapy does not offer a satisfactory alternative to radiotherapy in the treatment of basal-cell carcinomas. 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.
                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.
                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.
                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). The authors previously reported that 30 minutes of oral cryotherapy inhibits 5-fluorouracil (5-FU)-induced stomatitis. The current trial was designed to determine whether a longer duration of cryotherapy would provide additional protection.
                This trial involved patients who were receiving their first course of a 5-FU plus leucovorin chemotherapy regimen, for which stomatitis is a major dose-limiting toxicity. These patients were randomized to receive either 30 or 60 minutes of oral cryotherapy given at around the same time as the 5-FU therapy.
                A total of 178 evaluable patients were studied. Both cryotherapy groups had similar degrees of mucositis.
                The authors continue to recommend the use of 30 minutes of oral cryotherapy for patients receiving bolus intensive courses of 5-FU-based chemotherapy. Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT).
                The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT.
                Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts.
                This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids.
                Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT. In spite of its widespread use after orthopaedic procedures, the literature evaluating the clinical efficacy of cryotherapy is controversial. The purpose of this prospective randomized trial was to compare two different temperatures for administering cryotherapy after total knee arthroplasty with regards to short-term postoperative outcomes. Sixty-four subjects were assigned either the 45 degrees F group or the 75 degrees F group. Subjects in the 45 degrees group were as likely to report a lower pain score at the time of follow-up compared to the 75 degrees group. Our results demonstrate no additional analgesic effect associated with the lower temperature of cryotherapy. Postoperative narcotic consumption, postoperative drainage, self-reported knee function, and range of motion were not affected by the different cryotherapy temperatures. No adverse effects were reported with the cryotherapy treatment.
On the basis of one randomised clinical trial with high risk of bias, there is insufficient evidence to conclude if in patients with liver metastases from various primary sites cryotherapy brings any significant benefit in terms of survival or recurrence compared with conventional surgery. In addition, there is no evidence for the effectiveness of cryotherapy when compared with no intervention. At present, cryotherapy cannot be recommended outside randomised clinical trials.