Boosting immune response with GM-CSF optimizes primary cryotherapy outcomes in the treatment of prostate cancer: a prospective randomized clinical trial.

OBJECTIVE: We explored the association of prostate cryotherapy and immunomodulation with granulocyte-macrophage colony-stimulating factor (GMCSF) in the generation of detectable tumor-specific T- and B-cell responses in men with prostate cancer. MATERIALS AND METHODS: A randomized pilot study of patients assigned to either cryotherapy alone (Control group) or in combination with GMCSF (Treatment group). The impact of therapy on the development of T- and B-cell responses against tumor-related antigens was studied using enzyme-linked immune absorbent spot (ELISpot) and protein microarray panels (Sematrix) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISpot values against the mean pre-cryoablation response. Student t tests between treatment and control groups at 4 weeks and 12 weeks across all the antigens were performed. RESULTS: A total of 20 patients were randomized to either control or treatment arm. At 4 weeks after cryotherapy, the treatment group demonstrated an average fold change in cancer antigen-related antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% change below mean baseline (p < 0.05). At 12 weeks, antibody response in treatment group increased to 25% above baseline, while the average of control group patients remained 9% below baseline (p < 0.05). Patients in treatment group displayed, on average, higher ELISPOT readings for the 4- and 12-week times points (527 vs 481 for PSA and 748 vs 562 for PAP). CONCLUSIONS: GMCSF appeared to broadly elevate antibodies against prostate-specific and nonspecific antigens. Prostate antigen-specific T-cell responses were more enhanced over non-prostate-specific responses, preferentially in the treatment group. Our findings suggest a possible therapeutic effect of adjuvant immunotherapy in association with cryotherapy for the treatment of prostate cancer.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason

Cold water immersion: kill or cure?

NEW FINDINGS: What is the topic of this review? This is the first review to look across the broad field of 'cold water immersion' and to determine the threats and benefits associated with it as both a hazard and a treatment. What advances does it highlight? The level of evidence supporting each of the areas reviewed is assessed. Like other environmental constituents, such as pressure, heat and oxygen, cold water can be either good or bad, threat or treatment, depending on circumstance. Given the current increase in the popularly of open cold water swimming, it is timely to review the various human responses to cold water immersion (CWI) and consider the strength of the claims made for the effects of CWI. As a consequence, in this review we look at the history of CWI and examine CWI as a precursor to drowning, cardiac arrest and hypothermia. We also assess its role in prolonged survival underwater, extending exercise time in the heat and treating hyperthermic casualties. More recent uses, such as in the prevention of inflammation and treatment of inflammation-related conditions, are also considered. It is concluded that the evidence base for the different claims made for CWI are varied, and although in most instances there seems to be a credible rationale for the benefits or otherwise of CWI, in some instances the supporting data remain at the level of anecdotal speculation. Clear directions and requirements for future research are indicated by this review.

Outcomes after cryoballoon or radiofrequency ablation for persistent atrial fibrillation: a multicentric propensity-score matched study.

PURPOSE: Recent data show no benefit of additional ablation beyond pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF). Evidence suggests that radiofrequency energy (RF) and cryoballoon (CRYO) have comparable efficacy for PVI. We aimed to assess the outcomes after a single catheter ablation procedure, comparing PVI using CRYO vs. RF ablation for PVI plus additional ablation in a cohort of patients with persistent AF. METHODS: In this prospective multicenter propensity score-matched comparison, 59 consecutive patients undergoing CRYO ablation of persistent AF were matched to 59 patients treated with RF from November 2010 to June 2012. RESULTS: During a mean follow-up of 15.6 ± 11.5 months, 43.2 % of patients presented atrial arrhythmia relapse after a blanking period of 3 months, which was comparable between the two groups (40.7 % in CRYO vs. 45.8 % in RF, Log rank P = 0.14; HR = 0.67, 95 %CI 0.38-1.16, P = 0.15), despite the fact that 52.5 % of RF patients add additional complex fractionated atrial electrogram ablation, as well as left atrial linear ablation in over two-thirds (roof line in 67.8 % and mitral isthmus in 32.2 %). On multivariate Cox regression, only AF duration in years (HR = 1.10, 95 %CI 1.01-1.10, P = 0.04) was a predictor of relapse. Patients undergoing RF ablation presented a numerically, but non-significantly, lower complication rate (6.8 vs 10.2 %, P = 0.51). CONCLUSION: In our multicenter experience, freedom from atrial arrhythmias was comparable among matched patients treated with CRYO and RF, despite non-significant trends in favor of RF in terms of complications, at the cost of longer procedure times.

Endobronchial Treatment of Carcinoid Tumors of the Lung.

BACKGROUND: Bronchial carcinoid tumors are known as low-grade malignancies. Surgery has been proposed as the best treatment of choice for lung carcinoids. However, less invasive treatment approaches may be considered due to low-grade malignancy potential of such tumors. The aim of this study was to review the results of endobronchial treatments of carcinoid tumors of the lung and to compare with the outcome after surgery. METHODS: Initial complete tumor eradication with an endobronchial treatment was attempted for 29 patients. Diode laser or argon plasma coagulation was used during these treatments. Cryotherapy or laser treatments were applied consecutively in patients for whom there was good bronchoscopic visualization of the distal and basal tumor margins and no evidence of bronchial wall involvement. Surgery was performed in cases of atypical carcinoid and in cases of nonvisualization of the basal and distal part of the tumor. RESULTS: Overall, 29 patients have been included (median age 58 years; range, 23-77 years). Median follow-up has been 49 months (range, 22-94 months). A total of 24 patients (69%) had typical carcinoid tumor, 5 patients (31%) had atypical carcinoid tumor. Initial endobronchial treatment provided complete tumor eradication in 21 of 29 patients (72%). Of the eight other patients (28%), two were atypical carcinoids, and underwent surgical treatment. There was no tumor-related death and no recurrence during the follow-up in both groups. There was no difference for survival or recurrence between the surgical and the endobronchial treatment group of patients (p > 0.05). CONCLUSION: Endobronchial treatment may be considered as safe, effective treatment for typical carcinoid tumors in the central airways. Addition of initial endobronchial treatment had no negative effect on the surgical outcome.

MR imaging-guided percutaneous cryotherapy for lung tumors: initial experience.

PURPOSE: To evaluate prospectively the initial clinical experience of magnetic resonance (MR) imaging-guided percutaneous cryotherapy of lung tumors. MATERIALS AND METHODS: MR imaging-guided percutaneous cryotherapy was performed in 21 patients with biopsy-proven lung tumors (12 men, 9 women; age range, 39-79 y). Follow-up consisted of contrast-enhanced chest computed tomography (CT) scan performed at 3-month intervals to assess tumor control; CT scanning was carried out for 12 months or until death. RESULTS: Cryotherapy procedures were successfully completed in all 21 patients. Pneumothorax occurred in 7 (33.3%) of 21 patients. Chest tube placement was required in one (4.8%) case. Hemoptysis was exhibited by 11 (52.4%) patients, and pleural effusion occurred in 6 (28.6%) patients. Other complications were observed in 14 (66.7%) patients. The mean follow-up period was 10.5 months (range, 9-12 mo) in patients who died. At month 12 of follow-up, 7 (33.3%) patients had a complete response to therapy, and 10 (47.6%) patients showed a partial response. In addition, two patients had stable disease, and two patients developed progressive disease; one patient developed a tumor in the liver, and the other developed a tumor in the brain. The 1-year local control rate was 81%, and 1-year survival rate was 90.5%. CONCLUSIONS: MR imaging-guided percutaneous cryotherapy appears feasible, effective, and minimally invasive for lung tumors.

Five-year follow-up of survival and relapse in patients who received cryotherapy during high-dose chemotherapy for stem cell transplantation shows no safety concerns.

We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for stem cell transplantation. The present study is a 5-year follow-up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high-dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up study gave no support for safety concerns with cryotherapy.

Long-term follow up and prognostic factors for cryotherapy of malignant liver tumors.

BACKGROUND: The aims of this study were to determine the long-term outcomes of cryotherapy in patients with hepatic malignancies and to describe prognostic factors that may affect survival. METHODS: Ninety-eight patients (56 colorectal metastases, 28 noncolorectal metastases, 14 hepatocellular carcinomas) undergoing hepatic cryosurgery were identified in a retrospective review from January 1994 to December 2002. RESULTS: Overall survival rates at 1-, 2-, 3-, and 5- years were 81%, 62%, 48%, and 28%, respectively(median survival, 33 months) compared to a hepatic recurrence-free survival of 76%, 42%, 24%, and 16%, respectively (median hepatic recurrence-free survival, 20 months). Median follow-up was 54 months. Three hundred lesions were cryoablated; the recurrence per cryolesion was 5%. Major complications were the lone factor that significantly reduced overall (P=.0005) and hepatic recurrence-free survival (P=.0005). The number of lesions (TNL) and total estimated area (TEA) cryoablated did not significantly affect overall or hepatic recurrence-free survival. Additionally, outcomes depending on tumor type were not significantly different. CONCLUSIONS: Cryotherapy is an important option for a wide range of unresectable malignant hepatic tumors and provides the potential for long-term survival. Patients with major complications at the time of cryotherapy suffer a decreased overall and hepatic recurrence-free survival.