Cryotherapy :: adverse effects
Stephen B Williams, Yin Lei, Paul L Nguyen, Xiangmei Gu, Stuart R Lipsitz, Hua-Yin Yu, Keith J Kowalczyk, Jim C Hu
Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. email@example.com
UNLABELLED Despite the increased popularity of emerging therapies for localised prostate cancer, such as cryotherapy and brachytherapy, outcomes data remains sparse beyond single-centre comparative studies. The present study identified that although less costly, cryotherapy was associated with more urinary and ED complications and a greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer. OBJECTIVE To compare prostate cryotherapy vs brachytherapy outcomes and costs, as despite the greater popularity of these emerging therapies for localised prostate cancer, outcomes data remains sparse beyond single-centre comparative studies. PATIENTS AND METHODS Observational study of 10 928 men who underwent primary cryotherapy (943 patients) or brachytherapy (9985) with ≥2 years of follow-up using USA Surveillance, Epidemiology, and End Results (SEER-) Medicare linked data. Weighted propensity score methods were used. RESULTS Use of cryotherapy increased four-fold whereas brachytherapy utilization remained the same from 2001 to 2005 (P < 0.001). Men who underwent cryotherapy vs brachytherapy were older (P < 0.001), more likely to be Black (P < 0.001), less likely to live in areas of higher education (P < 0.001), less likely to live in areas with greater income (P < 0.001), and were more likely to live in urban vs rural areas (P = 0.007). In propensity score-weighted analyses, cryotherapy was associated with more urinary (41.4% vs 22.2%, P < 0.001) and erectile dysfunction (ED) complications (34.7% vs 21.0%, P < 0.001) while brachytherapy was associated with more bowel complications (19.0% vs 12.1%, P < 0.001). Cryotherapy was associated with greater use of salvage androgen deprivation therapy (ADT; 1.4 vs 0.5 per 100 person-years, P < 0.001), suggesting worse cancer control. Finally costs were significantly greater for brachytherapy vs cryotherapy ($16 887 vs $12 629 USA dollars, P < 0.001). CONCLUSIONS Although less costly, cryotherapy was associated with more urinary and ED complications and greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer.
Most cited papers:
University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Sydney, Australia.
Published results of hepatic cryotherapy are now available for almost 900 patients. Its safety is well established and its clinical role in treating patients with unresectable hepatoma or liver metastases from colorectal carcinoma is well supported by tumour marker and survival data; the results in the treatment of neuroendocrine liver metastases are promising. Its role as an alternative to liver resection is not yet well supported by long-term data. Although different adjuvant treatment protocols have been used following the cryotherapy of colorectal liver metastases, the effect of adjuvant treatment on recurrence or survival has not been assessed in prospective studies. Laparoscopic hepatic cryotherapy is feasible in selected patients with suitable tumour locations. However, the proportion of patients who might be usefully treated with this technique is not yet well established. The mechanisms of tissue destruction by freezing are reviewed.
A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix.
University of Texas Health Science Center, the University of Texas M.D. Anderson Cancer Center, and Memorial Clinical Associates, Houston 77030, USA. firstname.lastname@example.org
OBJECTIVE: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). METHODS: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using chi2 statistics, logistic regression analysis, and the Cox proportional hazards model. RESULTS: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6-37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). CONCLUSION: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.
University Department of Dermatology, Western Infirmary, Glasgow, U.K.
The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.
Departments of Radiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
PURPOSE To describe the cryoablation of liver tumors by using a percutaneous approach and intraprocedural magnetic resonance (MR) imaging monitoring and to assess the feasibility and safety of the procedure. MATERIALS AND METHODS Fifteen hepatic tumors (mean diameter, 2.9 cm) in 12 patients were treated (18 total cryoablations). Fourteen were metastases and one was a hemangioma; all were proved at biopsy. By using a 0.5-T open MR imaging system, cryoneedles were placed and lesions ablated by using real-time monitoring. Clinical signs and symptoms were assessed and laboratory tests performed. Intraprocedural depictions of iceballs were compared with contrast material-enhanced MR imaging-based estimates of cryonecrosis that were obtained 24 hours after cryoablation. RESULTS MR imaging-guided percutaneous cryotherapy resulted in no serious complications and no clinically important changes in serum liver enzymes or creatinine or myoglobin levels. Intraprocedural MR imaging demonstrated iceballs as sharply marginated regions of signal loss that expanded and engulfed tumors. The maximal iceball size was 4.9 x 2.2 x 2.2 cm with the use of one cryoneedle and 6.0 x 5.6 x 4.9 cm with three cryoneedles. Intraprocedural iceball depictions correlated well with postprocedural cryonecrosis estimates. CONCLUSION MR imaging-guided percutaneous cryotherapy of liver tumors is feasible and safe. MR imaging can be used to estimate cryotherapy effects and guide therapy intraprocedurally.
Department of Orthopaedics, Ostra University Hospital, Göteborg, Sweden.
The use of cryotherapy, i.e. the application of cold for the treatment of injury or disease, is widespread in sports medicine today. It is an established method when treating acute soft tissue injuries, but there is a discrepancy between the scientific basis for cryotherapy and clinical studies. Various methods such as ice packs, ice towels, ice massage, gel packs, refrigerant gases and inflatable splints can be used. Cold is also used to reduce the recovery time as part of the rehabilitation programme both after acute injuries and in the treatment of chronic injuries. Cryotherapy has also been shown to reduce pain effectively in the post-operative period after reconstructive surgery of the joints. Both superficial and deep temperature changes depend on the method of application, initial temperature and application time. The physiological and biological effects are due to the reduction in temperature in the various tissues, together with the neuromuscular action and relaxation of the muscles produced by the application of cold. Cold increases the pain threshold, the viscosity and the plastic deformation of the tissues but decreases the motor performance. The application of cold has also been found to decrease the inflammatory reaction in an experimental situation. Cold appears to be effective and harmless and few complications or side-effects after the use of cold therapy are reported. Prolonged application at very low temperatures should, however, be avoided as this may cause serious side-effects, such as frost-bite and nerve injuries. Practical applications, indications and contraindications are discussed.
Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
OBJECTIVES: Cryotherapy of the prostate represents a potential treatment for localized recurrent prostate cancer after radiation therapy. We report our experience and evaluate the predictive factors for prostate-specific antigen (PSA) recurrence. METHODS: Between October 1994 and April 1999, 43 patients underwent salvage cryoablation. All patients had biopsy-proven recurrent prostate cancer without seminal vesicle invasion, negative bone scans, and negative lymph node dissection. Patients had received 3 months of combined hormonal therapy before cryosurgery. Biochemical recurrence-free survival (bRFS) was defined as a PSA value less than 0.1 ng/mL. RESULTS: Complications included incontinence (9%), obstruction (5%), urethral stricture (5%), rectal pain (26%), urinary infection (9%), scrotal edema (12%), and hematuria (5%). The mean follow-up was 21.9 months (range 1.2 to 54). Twenty-six patients (60%) reached a serum PSA nadir less than 0.1 ng/mL, 16 (37%) had a PSA less than 4 ng/mL, and 1 (3%) had a PSA less than 10 ng/mL. The bRFS rate was 79% at 6 months and 66% at 12 months. The bRFS rate was higher for patients who had an undetectable postcryotherapy PSA than for patients who did not reach a PSA less than 0. 1 ng/mL (73% versus 30%, P = 0.0076). Using multivariate analysis, a PSA nadir greater than 0.1 ng/mL was an independent predictor of PSA recurrence. CONCLUSIONS: Current salvage cryotherapy of the prostate can result in undetectable serum PSA levels with low morbidity. Our data support the current safety and efficacy profile. We believe that cryotherapy is a viable option in the treatment of patients who have biopsy-proven local failure after radiation therapy for prostate cancer. Further refinements in technique and equipment may enhance cryosurgical results.
Cryotherapy is used for endoscopic management of tracheobronchial obstruction (TBO). This study describes the use of a flexible cryoprobe for cryotherapy using nitrous oxide as a cryogen through a fiberoptic bronchoscope. The study group consisted of 22 patients, ages ranging from 28 to 82 years. Twenty patients had malignant TBO and two had bronchial obstruction (BO) following lung transplantation. Benign BO was first dilated with a balloon and followed with cryotherapy. Eighteen of the 20 malignant endobronchial lesions were completely removed. In three of these patients, the airway remained occluded due to extrinsic compression. Cryotherapy offers an alternative to Nd:YAG laser in the management of TBO. Cryotherapy offers other advantages such as being inexpensive, safe for the operator, and safe for other members of the team. Similarly for the patient, there is no danger of bronchial wall perforation or endobronchial fires, cryotherapy can be done under local anesthesia with conscious sedation, and it can be performed in an endoscopy suite.
Thoracic masses treated with percutaneous cryotherapy: initial experience with more than 200 procedures.
Tumor Targeted Cryotherapy Center, PLA General Navy Hospital, Beijing, China.
PURPOSE To perform and report initial experience with percutaneous cryotherapy (PCT) of the thorax. MATERIALS AND METHODS A human investigation committee approved the study protocol, and all patients gave informed consent. One hundred eighty-seven patients who were not surgical candidates underwent computed tomography (CT)-guided PCT for treatment of thoracic cancer masses. CT-visualized low-attenuating ice formation after PCT was compared with initial tumor size and location. At 1 week and at 1, 3, 6, and 12 months after PCT, the various findings seen on available CT scans and any complications were noted. chi(2) and Student t tests were used to identify significant differences in frequencies and mean values of imaging observations, respectively. RESULTS Ice formation was identified at CT as reduced attenuation values (in Hounsfield units) within soft-tissue masses, the mean sizes of which were 4.3 cm +/- 0.2 (standard deviation) in peripheral locations and 6.4 cm +/- 0.3 in central locations. Tumor size and location were independent predictors of tumor coverage by low-attenuating ice: Mean coverage was 99% for peripheral masses 4 cm or smaller (n = 101) and 80% for central masses larger than 4 cm (n = 58)(P <.001). An area of necrotic cavitation larger than the original mass developed in 80%(77 of 96) of masses within 1 week and was nearly resolved by 3 months in 7%(five of 76) of masses. By 6 months, minimal pulmonary scarring was noted in 56 patients and 86% of masses showed reduced or stable size. The overall rate of pneumothorax was only 12%(22 of 187 patients), and other side effects appeared to be self limited. No major bleeding or bronchial damage was noted. Two deaths in debilitated patients were temporally related, and two complications involved brachial and recurrent laryngeal nerve damage. The patient with laryngeal nerve damage regained speech within 2 months. CONCLUSION CT-guided PCT yielded low procedural morbidity given the extent of freezing, even near mediastinal structures. Ongoing advances in cryotechnology, imaging guidance, and treatment planning may help to avoid the degree of undertreatment of larger central masses observed in this study.
Institute of Postgraduate Medicine and Health Science University of Ulster, Northern Ireland. DC.Macauley@ulst.ac.uk
Ice, compression and elevation are the basic principles of acute soft tissue injury. Few clinicians, however, can give specific evidence based guidance on the appropriate duration of each individual treatment session, the frequency of application, or the length of the treatment program. The purpose of this systematic review is to identify the original literature on cryotherapy in acute soft tissue injury and produce evidence based guidance on treatment. A systematic literature search was performed using Medline, Embase, SportDiscus and the database of the National Sports Medicine Institute (UK) using the key words ice, injury, sport, exercise. Temperature change within the muscle depends on the method of application, duration of application, initial temperature, and depth of subcutaneous fat. The evidence from this systematic review suggests that melting iced water applied through a wet towel for repeated periods of 10 minutes is most effective. The target temperature is reduction of 10-15 degrees C. Using repeated, rather than continuous, ice applications helps sustain reduced muscle temperature without compromising the skin and allows the superficial skin temperature to return to normal while deeper muscle temperature remains low. Reflex activity and motor function are impaired following ice treatment so patients may be more susceptible to injury for up to 30 minutes following treatment. It is concluded that ice is effective, but should be applied in repeated application of 10 minutes to be most effective, avoid side effects, and prevent possible further injury.
Service de pneumologie et d'oncologie thoracique, Hôpital Nord, Saint-Etienne, France.
BACKGROUND Treatment of early superficial bronchogenic carcinoma (ESBC) is under debate, and no consensus has been achieved. Different therapeutic methods have been proposed, including surgical resection and endoscopic methods. STUDY OBJECTIVE To assess the efficacy of cryotherapy in patients with ESBC. Patients and methods: Patients included in the study had histologically proven ESBC after fiberoptic bronchoscopy. Cryotherapy was performed through a rigid bronchoscope. Efficacy was assessed by endoscopy with multiple biopsies 1 month after treatment and during the follow-up period. Parameters studied were response to treatment, adverse effects, and survival. RESULTS We included 35 patients (34 men and 1 woman). The mean age was 61 +/- 9 years. Multiple locations of ESBC were observed in seven patients (20%). Complete response rate at both 1 month and 1 year was 91%(32 patients). No severe adverse effects were noted. Local recurrence was observed within 4 years in 10 patients (28%). A follow-up period of at least 4 years was available in 22 patients; of them, 11 patients (50%) were long-term survivors. CONCLUSION Our results suggest that cryotherapy is an effective method of treatment in patients with ESBC. Due to its relative tolerance compared to surgery, cryotherapy could be proposed as a first-line therapy in this population with high carcinogenic risk.