Double Freeze-thaw Cycle Research Articles

Feline distichiasis treated with cryoepilation: Aretrospective study of 15 cats (27 eyes).

To describe the clinical features of cats diagnosed with distichiasis and report on the outcomes following cryoepilation. Fifteen cats (27 eyes). Medical records of domestic cats with distichiasis that underwent a double freeze-thaw cycle with a -80°C cryoprobe applied to the palpebral conjunctiva, with hair then epilated were retrospectively studied. The patient signalment, distichiae locations, concurrent ocular diseases, recurrences, complications, and outcomes were recorded. The mean (std dev) age at the time of diagnosis and treatment was 2.2 years (2.8 years). All (15/15) cats were of the domestic shorthair (DSH) breed. Concurrent ocular findings at the initial examination were observed in 17/27 (63%) eyes, with upper lateral eyelid hypoplasia the most prevalent, present in 9/27 (33.3%) eyes. Recurrence of distichiae occurred in 8/27 (29.6%) eyes. The clinical presentation in the instances of recurrence was judged as asymptomatic and not of a clinical concern in 3/27 (11.1%) eyes, with a second procedure deemed necessary to alleviate symptoms in 5/27 (18.5%) eyes. All eyes treated with a second procedure had no recurrence of distichiae or symptoms. Complications following cryoepilation occurred in 4/27 (14.8%) eyes, with two cats developing bilateral entropion post-procedure. Treatment of distichiasis in cats utilizing cryoepilation was effective at alleviating symptoms, though some cats needed a second procedure. The development of post-procedural entropion was seen occasionally.

PD51-12 COMPARISON OF MID-TERM ONCOLOGICAL OUTCOMES OF ACTIVE SURVEILLANCE AND PERCUTANEOUS CRYOABLATION OF SMALL RENAL MASSES

You have accessJournal of UrologyKidney Cancer: Localized: Active Surveillance1 Apr 2018PD51-12 COMPARISON OF MID-TERM ONCOLOGICAL OUTCOMES OF ACTIVE SURVEILLANCE AND PERCUTANEOUS CRYOABLATION OF SMALL RENAL MASSES Paolo Umari, Michele Rizzo, Michele Billia, Nicola Pavan, Gaetano Chiapparrone, Giovanni Liguori, Fulvio Stacul, Monica Zacchero, Paolo De Angelis, Alessandro Volpe, and Carlo Trombetta Paolo UmariPaolo Umari More articles by this author , Michele RizzoMichele Rizzo More articles by this author , Michele BilliaMichele Billia More articles by this author , Nicola PavanNicola Pavan More articles by this author , Gaetano ChiapparroneGaetano Chiapparrone More articles by this author , Giovanni LiguoriGiovanni Liguori More articles by this author , Fulvio StaculFulvio Stacul More articles by this author , Monica ZaccheroMonica Zacchero More articles by this author , Paolo De AngelisPaolo De Angelis More articles by this author , Alessandro VolpeAlessandro Volpe More articles by this author , and Carlo TrombettaCarlo Trombetta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2352AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Partial nephrectomy (PN) is considered the standard approach for small renal masses (SRMs). Active surveillance (AS) and ablative therapies represent emerging strategies for older and comorbid patients due to the indolent behaviour of most SRMs and to the high competing risk mortality. Aim of this study was to compare the mid-term oncological outcomes of AS and percutaneous cryoablation (PCA) of small renal masses (SRMs). METHODS Data regarding PCA and AS in patients with a single T1a renal tumors were collected prospectively at two large academic centers. 60 patients underwent PCA and 77 were enrolled in a AS protocol. The minimum follow-up period was 6 months. The most frequent indications for AS were severe comorbidities (48,1%), <15 mm renal masses (23,4%) and advanced age (15,6%). All patients in AS were followed with a standardized protocol including serial imaging (US, CT or MRI) every 6 months during the first 3 years and yearly thereafter. Tumor progression was defined as the reach of a 4 cm threshold in maximum diameter or a tumor volume doubling time <12 months. All PCA procedures were performed with a percutaneous approach. A double freeze-thaw cycle was performed using a mean of 2 sealed argon 17G cryoprobes per patient. Tumor progression after PCA was defined as a new nodular enhancement in the ablation zone or the enlargement of the ablated tumor 3 months after the treatment. RESULTS 14 masses showed dimensional progression during AS and 9 were surgically removed after a median follow-up of 30 months. 3 patients in the PCA group experienced progression and underwent a repeat ablation with a median follow-up of 24 months. Progression free survival (PFS) at 2 years was 94,8% and 95,0% for AS and PCA group, respectively. None of the patients progressed to metastatic disease. Overall survival at 2 years was 93,5% and 95,0% in the AS and PCA group, respectively. In the PCA group the complication rate was 5% (Clavien grade 1-2). CONCLUSIONS There are no good quality studies comparing the oncological outcomes of AS and PCA. Comparing AS to an active treatment is not an easy task due to the different definitions of the oncological endpoints such as PFS. With these limitations this study shows that both AS and PCA represent viable and safe treatment options for elderly and comorbid patients with SRMs. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e980 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Paolo Umari More articles by this author Michele Rizzo More articles by this author Michele Billia More articles by this author Nicola Pavan More articles by this author Gaetano Chiapparrone More articles by this author Giovanni Liguori More articles by this author Fulvio Stacul More articles by this author Monica Zacchero More articles by this author Paolo De Angelis More articles by this author Alessandro Volpe More articles by this author Carlo Trombetta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

CASE REPORT: EXCISION, AMNIOTIC MEMBRANE GRAFT, CRYOTHERAPY AND INTRALESIONAL MITOMYCIN C INJECTION FOR THE TREATMENT OF A LIMBAL MELANOMA IN A DOG

A four-year-old, female neutered, Shih-Tzu dog was presented with a one-year history of limbal masses on both eyes (OU, oculi utrque). The masses arose from the corneoscleral limbus with marked corneal involvement. An en bloc excision of the involved meridians with human amniotic membrane grafting was performed at the left eye (OS, oculus sinister) limbal masses. A double freeze-thaw cycles of cryotherapy and intralesional mitomycin-C (MMC) injection was performed on both eyes two weeks later. Histopathology provided the definitive diagnosis of limbal melanoma. After 6 months of follow-up, OU limbal masses recurred without intraocular invasion, and 2 cycles of cryotherapy and intralesional MMC injection was then performed on recurrent sites. Despite that both cryotherapy and intralesional injection were applied the lesions recurred at an interval of 4–6 months for 18 months. At the end only a small corneal scar was present on OS, and there was no recurrence for 3 years until now. The cryotherapy combined with intralesional MMC injection was able to control the recurrence of limbal melanoma after tumor excision while maintaining the ocular surface integrity.

Effects of Triple Cryoenergy Application on Lesion Formation and Coronary Arteries in the Developing Myocardium.

To improve long-term outcome after cryoablation of substrates of supraventricular tachycardia, application of two and three consecutive freeze-thaw cycles has been performed. The effect of triple freeze-thaw cycles on lesion formation within developing myocardium and coronary arteries, however, has not been studied yet. In eight piglets (mean age 15 weeks, weight 15-20kg), 30 cryolesions (three consecutive freeze-thaw cycles) were applied to the atrial aspect of both AV valve annuli (n = 18) as well as to ventricular myocardium below the valves (n = 12). Coronary angiography was performed before and after cryoenergy application. The animals were reevaluated by coronary angiography and intracoronary ultrasound (ICUS) after 48h. All hearts were removed for histological examination of the lesions subsequently. After staining (hematoxylin-eosin, desmin immunohistochemistry), lesions was measured by planimetry with a digital virtual miscroscope analysis system and volumes of the cryolesions were calculated. Mean atrial lesion volume was 190.68 ± 167.53 mm3 (n = 18), and mean ventricular lesion volume was 184.34 ± 107.42 mm3 (n = 12). Compared with previously reported data on lesion volumes after single and double freeze-thaw cycles, lesions were significantly larger. Coronary arteries were unaffected on coronary angiography as well as on ICUS. No affection of coronary arteries was found on histological examination. Application of three consecutive freeze-thaw cycles resulted in increased lesion volume compared with single and double freeze-thaw cycles. No affection of the coronary arteries was evident. To evaluate the clinical benefit and safety of triple cryoenergy application for catheter ablation, prospective randomized trials are required.

Editorial Comment

The authors report on a retrospective series of patients who underwent laparoscopic cryoablation of solid renal masses presumed to be renal cell carcinoma. The explicit goal of the study was to examine the “long-term” oncologic outcomes of laparoscopic cryoablation in a large cohort of patients. Selection criteria was limited to those with clinical stage I disease and >5 years of follow-up. Treatment logistics were consistent with best practice recommendations including a double freeze-thaw cycle and ablation under real-time sonographic guidance.

OP3-05 LONG-TERM ONCOLOGIC OUTCOMES OF LAPAROSCOPIC RENAL CRYOABLATION: 10 YEARS RESULTS FROM A SINGLE INSTITUTION

INTRODUCTION AND OBJECTIVES: Laparoscopic renal cryoablation [LRC] is an effective minimally invasive treatment option for small renal masses [SRMs], but evidences regarding long-term oncologic safety are still lacking. The aim of this study is to evaluate the longterm oncological outcomes of LCR in patients with at least one SRM. METHODS: The study design is an observational, retrospective analysis of prospectively collected data of 189 consecutive patients who underwent LRC between 2000 and 2013. Overall, 214 cT1a contrast enhanced SRMs were diagnosed on CT or MRI scan and subsequently treated with LRC. Surgery consisted of transperitoneal or retroperitoneal access to the renal cavity, kidney mobilization, laparoscopic ultrasound evaluation, ultrasound-guided biopsy of the lesion, puncture of the SRM with the cryoprobes and double freeze-thaw cycle extending the ice ball approximately 1 cm beyond the tumor edge. Patients were evaluated on post-operative day 1 with MRI to assess the treatment efficacy: residual disease was defined as persistent enhancing tissue in the treated area. Follow-up was determined using serial MRI at 1, 6, 12, 24, 36, 48, 60, 72 and 120 months. Local recurrence after LRC was defined as the presence of an enhancing nodule in the treated area increasing in size. The outcome of the study was to evaluate the 5 years disease free survival, cancer specific survival and overall survival. RESULTS: Mean follow up was 55.6 months (range 1-156). Mean patient age was 63.42 (range 25 88). Median tumor size was 21 mm (range 7 40). The mean ice-ball diameter after surgery was 44.8 mm (range 18 80), and it decreased over time: MRI showed a mean iceball diameter of 35.0, 23.3, 18.5, 13.5, 11.7, 9.5, 6.4, 5.8 and 2.4 mm at 1, 6, 12, 24, 36, 48, 60, 72 and 120 months, respectively (p<0.001). Histologic examination revealed 135 renal cell carcinoma, 57 benign lesions and 22 non-diagnostic tissues. Overall 10 patients patients developed a metachronous renal neoplasm located in a different site than the cryoablated area. Among patients diagnosed with a renal malignancy, only one showed residual disease after surgery and was effectively treated with a 2nd look LRC, while 4 patients developed a local recurrence. Median time to local recurrence was 18 months (range 6 48). Five-years disease free survival, cancer specific survival and overall survival were 96.91%, 100% and 95.1%, respectively. CONCLUSIONS: Laparoscopic renal cryoablation ensures optimal cancer control outcomes at long term follow-up. These results should be taken into account in patients with small renal masses.

Contemporary technique of intraoperative 3-dimensional ultrasonography–guided transperineal prostate cryotherapy

Successful cryotherapy of the prostate for neoplasms relies on imaging to achieve good oncological outcomes with minimal complications. Traditional prostatic cryotherapy relies on 2-dimensional ultrasonography (2DUS) guidance, which often makes it difficult to track the passage of needles in an oblique plane. We describe our initial 3-dimensional ultrasonography (3DUS) system, and the subsequent improvements that have been made during the last 10 years. Our imaging system uses a Philips HDI 5000 ultrasonography unit, a standard PC, a Matrox Meteor II video frame grabber and 3DUS developed at Robarts Research Institute. For the cryotherapy we use ultrathin (17-gauge) IceRod needles. After image acquisition, preplanning is performed using the 3-dimensional (3D) software, and then the IceRod needles are inserted into the prostate. As the freezing process commences, continuous 3DUS images are taken and analyzed during the double freeze-thaw cycles to monitor the progress of the ice ball formation. Real-time intraoperative 3D imaging of the prostate during cryotherapy has allowed us to accurately preplan and then monitor the progression of ice ball formation, which represents a significant advantage over conventional 2DUS.

BioGlue Iceball Stabilization to Minimize the Risk of Hemorrhage During Laparoscopic Renal Cryoablation

To evaluate the application of a BioGlue adhesive shell to minimize iceball fracture. Iceball fracture and hemorrhage is common with laparoscopic cryoablation (LCA) of larger (>4 cm) renal tumors. Twenty large iceballs were created in porcine kidneys using 3 cryoablation probes in a nonsurvival study. Each kidney underwent an upper and lower pole ablation. One pole in each kidney was covered with 5 mL of BioGlue and the opposite pole served as a control. A double freeze-thaw cycle was performed (10 minutes freeze and 5 minutes active thaw) in both renal poles simultaneously. The probes were removed and the sites were monitored for 20 minutes under direct vision. Fracture length (mm), severity of fracture depth, severity of bleeding (absent, mild, moderate, severe), and estimated blood loss (EBL) (mL) were recorded. In the control group, the mean fracture length was 1.9 mm (range, 0-3 mm). Blood loss was absent in 10%, mild in 60%, and moderate in 30% of ablations. The mean EBL was 20.5 mL (range, 0-50 mL). For the BioGlue ablations, there were no parenchymal fractures. Blood loss was mild in 30% and absent in 70% of sites with an average EBL of 5 mL (range, 0-20). Two bleeding sites occurred as a result of subcapsular hematomas caused by initial probe placement. BioGlue application minimized the frequency and magnitude of renal fracture. EBL was lower with BioGlue application and most sites demonstrated no postablation bleeding. Further clinical study of the BioGlue shell should be performed to confirm these results.

Retroperitoneoscopic cryoablation for small renal tumors: a preliminary report

Objective To present the technique and short-term results of retroperitoneal laparoscopic renal cryoablation for small renal tumors. Methods Ten selected patients cases with 11 renal tumors were included in present study. There were 3 cases of left renal tumor, 6 cases of right renal tumor and 1 case of bilateral renal tumors. Tumors were located at the upper pole (2), middle (6), or lower pole (3). All tumors were located distant from the collecting system, without evidence of metastatic disease. Mean tumor size was 2. 8 cm (range: 1.5-4.0). All the patients were managed with a double freeze-thaw cycle of retroperitoneal laparoscopic renal cryoablation. The preoperative Hb was (137± 21)g/L, ESR was (27±12)mm/1 h, SCr was (92±41)μmol/L, GFR was (42±10)ml/min.All the patients were taken routine biopsies. Results Cryoablation was technically successful in all 10 patients (11 tumors). The mean time of the operations was (101 ± 31) min, and the mean blood loss was (42±21) ml. None of the cases received blood transfusion post-operation. No operative complication was seen. The postoperative hospital stay was (4±2) d. The postoperative Hb was (129 ±18)g/L,ESR was (31±14)mm/1 h,SCr was (95±39)μmol/L,GFR was (40±11)ml/min. There was no statistic change of Hb, ESR, SCr and ECT-GFR after operations(P＞0. 05). The biopsy results revealed that 8 tumors were renal clear cell carcinomas, and 2 tumors were papillary renal cell carcinomas, and 1 tumor was renal angiomyolipoma. All the patients had a minimum follow-up of 6 months (mean 16, range 6 to 21). Follow-up magnetic resonance imaging at 1, 3, and 6 months identified the punched-out, nonenhancing, spontaneously resorbing, renal cryolesions. Follow-up biopsie of the cryoablated tumor site was negative in the only patient who have undergone the biopsy. No evidence of local or port-site recurrence was found, and no metastatic disease. Conclusions Retroperitoneal laparoscopic renal cryoablation for small renal tumors could be an accurate and effective intervention with a relatively low incidence of complications. Critical long-term data regarding laparoscopic renal cryoablation are awaited. Key words: Kidney neoplasms; Laparoscopes; Cryosurgery

The effects of cryosurgery upon the pulmonary parenchyma with single or double freeze-thaw cycles in rabbits

Objective The aim of our study was to observe the different effects including diameter of cryosurgery region and incidence of pneumothorax and pleural effusion when cryosurgery upon the pulmonary parenchyma with single or double freeze-thaw cycles in rabbits.

Efficacy of lamellar resection, cryotherapy, and adjunctive grafting for the treatment of canine limbal melanoma

To evaluate the efficacy and complication rate of partial lamellar resection followed by cryotherapy for the management of canine limbal melanoma. Fourteen dogs with unilateral canine limbal melanoma which were managed surgically by partial lamellar resection, cryotherapy (1,1,1,2-tetrafluoroethane) and an adjunctive graft procedure. The clinical records of dogs treated between June 1998 and June 2008 were reviewed. The signalment, approximate size and location of the melanoma, variation in surgical technique, recurrence rate, short-term (< three months) and long-term (> three months) complications were assessed. Follow-up information was collected by patient re-examination or telephone interview. The mean age at diagnosis was 6.3 years, with a range from 3.2 to 12 years. Seven breeds were affected, including five cross-breed dogs and four Golden Retrievers. The tumour involved the dorsal arc (from the dorsomedial to the ventrolateral quadrant) in 12 eyes and the ventral arc in two eyes. The size of the tumour ranged from 30 to 180 degrees of the limbal circumference. A double freeze-thaw cycle of cryotherapy was performed in 7/14 eyes and a triple freeze-thaw cycle in 7/14 eyes. An adjunctive conjunctival graft was performed in 13/14 eyes (free graft n = 3, posterior nictitans conjunctiva/cartilage n = 4, advancement graft n = 5, small intestinal submucosa/advancement graft n = 1) and a frozen homologous graft in 1/14 eyes. The duration of follow-up ranged from 6 months to 8.5 years with a median of 2.1 years. Recurrence was not clinically detected in any of the 14 eyes. Early complications occurred in 8/14 eyes and included anterior uveitis (7/14), corneal ulceration (5/14), marked corneal granulation tissue at the graft margin (2/14), dyscoria (2/14), corneal lipidosis (1/14) and corneal oedema (1/14). Intra-operative globe perforation had occurred in 5/7 eyes with anterior uveitis and 2/2 eyes with transient dyscoria. Late complications occurred in 3/14 eyes and included corneal lipidosis which was either mild (< 2mm in diameter, 1/14) or marked (>1cm in diameter, 2/14). Marked lipidosis only occurred following the treatment of extensive limbal melanomas which involved approximately 50% of the limbal circumference. Surgical management comprising partial lamellar resection, cryotherapy and adjunctive graft placement is technically straightforward, minimally invasive, well tolerated and highly effective. Marked corneal lipidosis is most likely to occur as a post-operative complication when the limbal melanoma is extensive.

Crioterapia renal laparoscópica: experiencia inicial

Objective Renal cryotherapy has been described as a minimally invasive procedure that represents an alternative for selected patients with small renal tumors. Our preliminary experience with this procedure is reported. Material y methods Eighteen patients with 21 tumors with a mean tumor size of 2.2 cm (1-4) in the preoperative CT scan underwent renal cryotherapy using a double freeze-thaw cycle. The group consisted of 14 males (64%) and 4 females (18% with a mean age of 68 years (32-84). All patients had undergone prior surgery for renal tumor in the treated or the opposite kidney. A transperitoneal laparoscopic approach was used in all patients. Results Mean operating time was 196 minutes (120-140), and no patient received transfusions during or after surgery. No complications occurred in 14 patients (64%). Perirenal abscess, splenic laceration, ureteral lesion, and polar artery lesion occurred in one patient each. Peroperative biopsy was performed in 5 patients (22.7%) and was positive for renal cancer in two cases, while material was insufficient in three patients. Mean hospital stay was 6 days (2-16). Creatinine levels were 106 mg% (48-230) before surgery and 123 mg/% (52-270) 6 months after surgery. A CT scan was performed in all patients one and six months after surgery, showing a residual enhancement area in two of them. Sixteen patients (88.8%) are disease-free after a mean follow-up time of 46 months (6-116). Metastatic disease occurred in two patients (11%) in the setting of a prior renal tumor in the same or the opposite kidney and required treatmet with antiangiogenic agents. Conclusions This is the largest series reporting renal cryosurgery in Spain, in complex cases and with adequate follow-up. Results are encouraging and allow for considering renal cryotherapy among the minimally invasive procedures for nephron-sparing surgery.

Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy

Though not in regular practice, intralesional (IL) bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Our aim was to assess the evidence for the efficacy of IL bleomycin, in comparison with a control group of similar sample receiving cryotherapy, in the treatment of cutaneous warts. Patients were randomized using computer-generated codes to receive either cryotherapy (double freeze-thaw cycle) or IL bleomycin (0.1% solution with concurrent anesthesia) for a maximum of four treatments 3 weeks apart and a maximum of five warts treated in each visit for both groups. Patients had their warts measured at base-line and with each return visit including a post treatment follow-up that was 8 weeks apart from last treatment taken. Of the 73 patients completing the study, 39 (53%) were treated with IL bleomycin and 34 (47%) were treated with cryotherapy. Out of 155 treated warts, 87 (56%) were treated with IL beomycin and 68 (44%) were treated with cryotherapy. The clearance rates in context of number of patients and number of warts were 94.9% and 97% for bleomycin and 76.5% and 82% for cryotherapy respectively (P < 0.05 by x(2) analysis and RR = 7.67). IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

Comparison of the Histologic Accuracy of Needle Biopsy Before and After Renal Cryoablation: Laboratory and Initial Clinical Experience

To minimize the risk of needle biopsy, including tumor seeding and hemorrhage, we examined the feasibility of needle biopsy after renal cryoablation. Four cryolesions were created bilaterally on normal porcine renal tissue with an 8-minute double-freeze cycle using a single 17-gauge cryoprobe. Biopsies were obtained with a 16G biopsy needle before and after cryoablation under direct vision. Each biopsy specimen was evaluated for the number of glomeruli and arterioles. We used a two-sample t-test to analyze the data. Subsequently, 10 patients with small renal masses underwent laparoscopic cryoablation using a standard double freeze-thaw cycle. We used an 18G biopsy needle to sample the renal mass with a single core taken before and after cryoablation. A blinded pathologist evaluated the specimens for the histologic accuracy of the two sampling techniques. We used chi-square statistic to determine an association between the diagnostic quality of the core specimens. Two hundred biopsies were obtained from porcine renal tissue. The average number of glomeruli for the pre- and postcryoablation sample was 9.6, and 7.8, respectively (P = 0.04). The average number of arterioles for the pre- and postcryoablation group was 2.3 and 1.9, respectively (P = 0.04). During clinical application, seven of 10 precryoablation and seven of 10 postcryoablation biopsies were diagnostic (P = 0.639). Histopathology was established in all 10 cases. There was no significant bleeding from any needle biopsy. The porcine model established the feasibility of histologic diagnosis after cryoablation. Our preliminary clinical experience demonstrates that postcryoablation biopsy has similar diagnostic yields to precryoablation biopsy.

Surgical Excision versus Curettage plus Cryosurgery in the Treatment of Basal Cell Carcinoma

BACKGROUND Both cryosurgery, with and without prior curettage, and surgical excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC). OBJECTIVE The objective was to compare the efficacy between curettage plus cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck. MATERIALS AND METHODS A randomized controlled trial was carried out, in which tumors were assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double freeze–thaw cycle after prior curettage of the tumor. SE was performed with a margin of 3 mm and with delayed histologic examination. RESULTS Recurrences occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5-year recurrence probability was 19.6% for C&C and 8.4% for SE (p = .10). A hazard ratio of 2.57 (95% CI, 0.79–8.34) indicated a putative, but not statistically significant, advantage of SE. CONCLUSION These data reflect the outcome of the first randomized controlled trial with long-term follow-up in the treatment of BCC, comparing C&C with SE. Although not statistically significantly different, the observed differences could still be of clinical relevance. Owing to the trend toward lower recurrence rates, better cosmetic results, and reduced wound healing time, we believe that SE should be preferred to C&C in the treatment of primary, nonaggressive BCC of the head and neck.

Cryoablation of Renal Cancer: Variables Involved in Freezing-Induced Cell Death

The detection of renal tumors has increased significantly over recent years resulting in a greater demand for novel, minimally invasive techniques. Cryoablation has emerged as a valuable treatment modality for the management of renal cancer. In an effort to detail the effects of freezing in renal cancer, the human renal cancer (RCC) cell line, 786-O, was evaluated in vitro. 786-O cells were exposed to a range of freezing temperatures from -5 to -40 degrees C and compared to non-frozen controls. The data show that freezing to -5 degrees C did not affect 786-O cell viability, while -10 degrees C, -15 degrees C, and -20 degrees C results in a significant loss of viability (23, 70, and 91%, respectively). A complete loss of cell viability was evident at temperatures of -25 degrees C and colder. Following this analysis, variables involved in the success of cryoablation were investigated. For each of the temperatures tested, extended freeze hold times and passive thawing rates resulted in more extensive cell damage. Additionally, a double freeze-thaw cycle significantly increased cell death compared to a single cycle (62% vs. 22% at -10 degrees C; 89% vs. 63% at -15 degrees C, respectively). While these variables play an important part in the effective application of cryoablation, a molecular understanding of the cell death involved is critical to improving efficacy. Apoptotic inhibition afforded 12% (-10 degrees C), 25% (-15 degrees C), and 11% (-20 degrees C) protection following freezing. Using fluorescence microscopy analysis, the results demonstrated that apoptosis peaked at six hours post-thaw. Next, apoptotic initiating agents including 5-FU and resveratrol (RVT) applied prior to freezing exposure resulted in a significant increase in cell death compared to either application alone. Importantly, the combination of RVT and freezing was noticeably less effective when applied to normal renal cells. The results herein demonstrate the efficacy of freezing and describe a novel therapeutic model for the treatment of renal cancer that may distinguish between cancer and normal cells.

Surgical Excision versus Curettage plus Cryosurgery in the Treatment of Basal Cell Carcinoma

Both cryosurgery, with and without prior curettage, and surgical excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC). The objective was to compare the efficacy between curettage plus cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck. A randomized controlled trial was carried out, in which tumors were assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double freeze-thaw cycle after prior curettage of the tumor. SE was performed with a margin of 3 mm and with delayed histologic examination. Recurrences occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5-year recurrence probability was 19.6% for C&C and 8.4% for SE (p=.10). A hazard ratio of 2.57 (95% CI, 0.79-8.34) indicated a putative, but not statistically significant, advantage of SE. These data reflect the outcome of the first randomized controlled trial with long-term follow-up in the treatment of BCC, comparing C&C with SE. Although not statistically significantly different, the observed differences could still be of clinical relevance. Owing to the trend toward lower recurrence rates, better cosmetic results, and reduced wound healing time, we believe that SE should be preferred to C&C in the treatment of primary, nonaggressive BCC of the head and neck.

Intermediate-Term Results of Retroperitoneoscopy-Assisted Cryotherapy for Small Renal Tumours Using Multiple Ultrathin Cryoprobes

ObjectivesTo evaluate outcome after retroperitoneoscopic cryotherapy for small renal tumours. MethodsFourteen patients underwent cryoablation performed with six ultrathin 1.5-mm cryoprobes. Retroperitoneoscopic access was used for any tumour location. A double freeze–thaw cycle was performed under simultaneous retroperitoneoscopic visual control and real-time ultrasound monitoring. ResultsMean tumour size was 2.8cm (range: 2.0–4.0), mean patient age was 68 yr (range: 49–83), and six left and eight right kidneys were treated.The mean operative time was 167min (range: 120–200); mean blood loss was 93ml (range: 0–300). Cryosurgery was successfully performed in all 14 patients, with 13 patients undergoing assisted retroperitoneoscopy and one patient, after previous open nephropexy, undergoing an open approach. Intraoperative biopsy specimens revealed renal cell cancer (RCC) in 10 (71%) patients.The only intraoperative complication was bleeding after removal of the cryoprobes in four (29%) patients, necessitating one intracorporeal stitch in each. Two (14%) of the first four patients presented postoperatively with superficial skin frostbite, which healed with conservative treatment.During mean follow-up of 21 mo (range: 2–42), 2 (14%) patients died from unrelated disease, and 12 patients remained without evidence of local recurrence. One patient with previous contralateral nephrectomy for RCC developed retroperitoneal lymph node metastasis on that side without recurrence in the cryoablated kidney. ConclusionsRetroperitoneoscopic cryotherapy using multiple ultrathin cryoprobes is safe and effective with encouraging oncologic results on intermediate-term follow-up. Prospective clinical trials and long-term oncologic data are needed to define its definitive role in treatment of renal tumours.

Percutaneous cryoablation of renal cell carcinoma guided by horizontal open magnetic resonance imaging

Cryoablation is a treatment option for some patients with small exophytic lesions of the kidney. The purpose of this study is to determine the feasibility, safety, and intermediate-term treatment outcome of percutaneous cryoablation of renal cell carcinoma guided by horizontal open magnetic resonance imaging (MRI). We prospectively used cryoablation to treat 13 patients with radiographically confirmed enhancing small, solid renal tumors (< or =4.8 cm). An argon gas-based cryoablation system was used. One to four cryoprobes with 2 or 3-mm diameters were placed percutaneously into the tumor under local anaesthesia and MRI guidance. Ice ball dimensions were monitored by 2-D MR images. Double freeze-thaw cycles were conducted throughout the procedure. After successful cryoablation, patients were followed on a regular basis to evaluate the treatment's clinical outcome. Median follow up from time of procedure is 35 months (range, 28-42). In all cases the entire procedure was accomplished without significant morbidity or complications. A mild retroperitoneal hematoma, which subsided spontaneously, was noted in one patient. Follow-up dynamic computed tomography (CT) at 3 months after operation confirmed the absence of enhancement in resolved tumor masses for 11 of 13 cases. None of these 11 patients had clinical evidence of recurrent disease at last follow up. The remaining two patients had lesions with some enhanced areas. Subsequent partial nephrectomy histologically confirmed the presence of vital tumor in, respectively, the center and the periphery of the residual masses. One of these patients developed multiple lung and ipsilateral adrenal metastases 13 months after surgical resection. Percutaneous cryoablation of small renal cell carcinomas under horizontal open MRI guidance appears to be safe and feasible. An intermediate-term follow up continues to demonstrate efficacy in most patients; however, a few patients experience incomplete ablation with risk of treatment failure. The ideal candidates for this procedure still need to be determined in longer follow up with diligent observation.

Impact of Duration of Cryothermal Application on Clinical Efficacy of Pulmonary Vein Isolation Using Transvenous Cryoablation

Recent studies have demonstrated that transvenous cryoablation is a safe and feasible method for pulmonary vein (PV) isolation for treatment of atrial fibrillation (AF). However, this technique is limited by a much longer ablation time than conventional radiofrequency ablation. The aim of this study was to determine the effect of duration of cryoablation application with double freeze-thaw cycles on clinical efficacy for PV isolation for treatment of AF. We compared the clinical efficacy and procedural time of cryoablation (CryoCorTM, San Diego, CA, USA) for segmental PV isolation in 30 patients (mean age 51 +/- 13, 20 men) with paroxysmal AF using either double 5-minute (n = 15) or double 2.5-minute (n = 15) freeze-thaw cycle delivered with a 10 F deflectable transvenous catheter. Clinical recurrence of AF and the occurrence of PV stenosis as determined by computer tomography of the thorax were performed at 3- and 12-month follow-up. Acute successful electrical isolation of PV was achieved with cryoablation in 96 of 98 (98%) targeted PVs in 30 patients (mean: 3.2 +/- 0.8 PVs per patient). There were no significant differences between the baseline characteristics, the number of PV isolated per patient, the total number and percentage of effective cryoablation and the acute clinical efficacy between using double 5-minute and double 2.5-minute freezes (P > 0.05). However, the fluoroscopy time (107 +/- 43 vs 138 +/- 113 minutes, P = 0.06) and the procedural time (360 +/- 113 vs 510 +/- 115 minutes, P = 0.01) of using double 2.5-minute freezes was reduced by approximately 30% compared with double 5-minute freezes. At a mean of 20 +/- 8 month follow-up, there was no significant difference in the chronic clinical efficacy of cryoablation in terms of freedom from AF in the absence of antiarrhythmic drug therapy between using double 5-minute (6/15, 40%) and double 2.5-minute freezes (7/15, 46%, P = 0.98). As compared with double 5-minute freeze, the use of a shorter double 2.5-minute freeze protocol significantly reduces the procedural time without affecting the acute and long-term clinical efficacy of cryoablation to isolate PV for treatment of AF.