Eighty percent of all breast biopsies reveal benign lesions,in which,the most common benign tumor is a fibroadenoma. Approximately 10% of women will experience a breast fibroadenoma in their lifetime. Despite their benign nature, many women eventually choose to have their bothersome lumps surgically removed. An estimated 500 000 fibroadenomas are still surgically excised in United States. Factors that may lead patients to choose removal of a benign mass include palpable prominence, localized discomfort, interval growth, and peace of mind. For certain patient groups, multiple growing masses are more problematic.
Overview of treatment
Resection has been the standard, but nonsurgical options for benign or malignant breast masses include vacuum-assisted biopsy, radiofrequency ablation, laser therapy, and cryoablation. Newer 8-gauge vacuum-assisted biopsy devices may achieve visual removal for some masses up to 2 cm in maximal diameter, but complete resection may still be limited by targeting and/or visualization difficulties due to local hemorrhage as multiple cores are obtained . Heat-based treatments are difficult to monitor with ultrasonography (US) and are limited by potential skin damage if masses are less than 1 cm from the chest wall or skin surface.
Cryoablation has been developed since the 1960s to destroy benign and malignant tissues and is well established to treat a variety of neoplasms with minimal surgical risk. Recent studies have demonstrated that, as a primary therapy for breast fibroadenoma, cryoablation is safe and effective with durable results that can be reproduced in community practices.
Indication of cryoablation
Biopsy-confirmed breast fibroadenoma less than 4 cm in dimension .
Procedure of cryoablation
Pre-procedure
Real-time US guidance is used to document fibroadenoma sizes and to guide thermocouple and probe placements, as well as to monitor iceball formation and associated safety measures (ie, sterile saline injections). US monitoring is often performed with a high-frequency (10–13 MHz) linear-array probe. Each fibroadenoma should be characterized with respect to its general location within the breast (ie, quadrant) and its width, height, and length. Note is also made of tumor blood supply by using power Doppler estimates of internal, or "feeder," vascularity.
Procedure
A multiple port system (Cryocare; Endocare, Irvine, Calif) is often used so that two or more probes could be used simultaneously.
The patients are prepped and draped in sterile fashion. The angle of approach is chosen along the longest axis of the fibroadenoma to use the longer freeze length of the cryoprobe. A lateral or inferior puncture site is selected when possible for best cosmetic results. The overlying skin is infiltrated with buffered 2% lidocaine and is extended around all tumor margins. After a 3-mm skin nick is made, a 12-gauge coaxial trocar needle is advanced through the center of the fibroadenoma. Transverse US scanning (Fig 1) allow to verify central placement. Once the trocar needle tip penetrate the distal margin of the mass(Fig 2), the stylet is removed and is replaced with the 2.4-mm cryoprobe. The needle sheath is then retracted to expose the distal 4 cm of the cryoprobe. The coaxial sheath also help insulate the insertion tract from freezing damage.
The Cryocare units have adjustable duty cycles, which can be used to alter the length of time that argon gas expands to cool the probe. At "100% duty cycle" argon flows continuously, while at "10% duty cycle" argon flows for 1 second and is stopped for 9 seconds of every 10-second period. For all tumors 1 cm in diameter or larger, each 100% duty cycle freeze is followed by a maintenance freeze at 10% duty cycle; this process is designed to maintain cold temperatures within the tumor while slowing the expansion of the iceball beyond its borders. A freeze-thaw-freeze technique is used. The passive thaw between the first and second freeze is continued until the probe warmed to about –1°C. Typically, the time required for such warming is about the same as the total time of each freeze. However, the thaw with helium is often used. Switching from argon to helium gas by means of the thaw switch on the systems actively warm the probe after the final freeze cycle. This "active thawing" phenomenon facilitate prompt removal (ie, <2 min) of the probe from the iceball.
For monitoring temperature, a thermocouple is placed through an 18-gauge arterial needle. The thermocouple tip is lodged beneath the outer rim of the fibroadenoma, which prevent it from subsequently being pushed laterally by the advancing iceball in the loose breast fat (Fig 3,4). Thermocouple distance from the cryoprobe vary between 4 to 12 mm, depending on the fibroadenoma diameter and the depth of insertion of the thermocouple beneath the capsule. Temperatures from thermocouples within the fibroadenoma and along the skin surface were recorded at 1-minute increments throughout the procedure.

Figure 1. US images showed transverse view of developing iceball (<1 cm in diameter; straight arrows) in 2.3-cm-diameter fibroadenoma (arrowheads) at initiation of freeze. Thermocouple tip (curved arrow) is 7 mm from the cryoprobe (from Peter J et al. Radiology 2005;234:63-72).

 
Figure 2. US images showed transverse view of developing iceball (<1 cm in diameter; straight arrows) in 2.3-cm-diameter fibroadenoma (arrowheads) at initiation of freeze(from Peter J et al. Radiology 2005;234:63-72).

.

Figure 3. US images showed transverse view of developing iceball (<1 cm in diameter; straight arrows) in 2.3-cm-diameter fibroadenoma (arrowheads) at initiation of freeze. Thermocouple tip (curved arrow) is 7 mm from the
cryoprobe(from Peter J et al. Radiology 2005;234:63-72).

Figure 4. US images. (a) Transverse view of developing iceball (<1 cm in diameter; straight arrows) in 2.3-cm-diameter fibroadenoma (arrowheads) at initiation of freeze. Thermocouple tip (curved arrow) is 7 mm from the cryoprobe. (b) Longitudinal view of fibroadenoma (arrowheads) with a 12-gauge trocar placement needle (arrows) prior to removal of the stylet and replacement with the cryoprobe(from Peter J et al. Radiology 2005;234:63-72).

At the time of cryoablation, cryoprobes had air-gap insulation and allowed freezing temperatures to propagate up the probe shaft. Skin protection at the cryoprobe insertion site included the dripping of sterile room-temperature saline on the skin and the placement of moist gauze between the probe (or sheath) and the skin. US-guided sterile saline injections (range, 10–40 mL) were used between the iceball and the skin surface (Fig 5) or chest wall, when needed, throughout both freeze cycles to keep the advancing ice at least 5 mm from either surface. However,it is suggested that saline injection was not necessary between the iceball and chest wall as long as gentle to-and-fro movement of the iceball within the breast was maintained. This motion prevented ice from propagating posteriorly but needed to be initiated before the ice margin came close to the pectoralis muscle.


Figure 5. US views show progress of saline injection. The needle (arrowheads) is increasing the distance (arrows) from the skin surface to the fibroadenoma, from less than 3 mm (left image in both a and b) to more than 8 mm (right image in both a and b) (from Peter J et al. Radiology 2005;234:63-72).

After finishing cryoablation procedure,manual pressure is then applied for at least 20 minutes to decrease the risk of hematoma formation.

Clinical comment

Peter et al[1]. reported that 29 patients (mean age, 27 years) biopsy-confirmed fibroadenomas received treatment by using a 2.4-mm cryoprobe inserted into the fibroadenoma with US guidance. The first seven patients underwent conscious sedation, but the other 22 patients required only local anesthesia. US and thermocouple monitoring of the procedure were performed to evaluate freeze protocols based on tumor size. No significant complications were noted, and patients were very pleased with the resolution of palpable mass effect and cosmetic results. The average pretreatment fibroadenoma volume of 4.2 cm3± 4.7 (standard deviation) was reduced to 0.7 cm3± 0.8 at 12-month follow-up (73% reduction, P < .001). US produced excellent ice visualization beyond tumor margins, while thermocouples confirmed cytotoxic temperatures approximately 5 mm behind the visible leading edge. Two patients elected to undergo either removal or biopsy of a residual mass, which revealed a shrunken hyaline matrix with preserved collagenous architecture. Mammograms showed comparable resolution of mass effects with mild surrounding parenchymal reaction.
Kaufman et al[2] has made a lot of work on cryoablation of breast fibroadenoma. In 2002,they reported a table-top cryoablation system employing a 2.4-mm cryoprobe to treat biopsy-proven benign fibroadenomas up to 4 cm in maximum diameter in a prospective nonrandomized fashion. Fifty patients with 57 core biopsy-proven benign fibroadenomas were treated. Seven early cases were treated in an ambulatory surgery center setting. The remaining procedures were completely office-based using only local anesthetic. Tumor diameter varied from 7 mm to 42 mm (mean 21 mm). Transient postoperative side effects were local swelling and ecchymosis. Postoperative discomfort rarely required medication beyond acetaminophen or ibuprofen. Lesions showed progressive shrinkage and disappearance over 3 to 12 months. No skin injury was noted and appearance remained excellent. Patient satisfaction was excellent.


Kaufman et al[3]. reported the result of a prospective nonrandomized trial in 2004. Ultrasound-guided cryoablation of core biopsy-proven benign fibroadenomas, other benign breast nodules, or nodular fibrocystic change was performed on 78 lesions in 63 patients. Eighty-five percent of lesions treated were benign fibroadenomas. Sixty-four of 78 lesions (mean size 2.0 cm [range 0.8 to 4.2]) were followed-up for at least 12 months after cryoablation per protocol, which included 53 fibroadenomas. At 1 year, ultrasound tumor volume resorption was 88.3% overall (87.3% for fibroadenomas), and 73% of the entire group became nonpalpable to both clinician and patient (75% for fibroadenomas)(Figure 6). Two of the fibroadenoma patients had their palpable residual nodule excised, both revealing necrotic debris and no viable tumor in the treated volume. Serial mammograms showed resorption of the lesion leaving minimal residual density without calcifications(Figure 7). Cosmesis was excellent with only a small scar remaining at the probe insertion site(Figure 8)[4,5]. There was no report of visual or palpable volumetric deficit. Patient satisfaction was good to excellent in 92% of cases.

  
a                                                     b

   
c                                              d
Figure 6 Ultrasound a) pretreatment and b) at 1 week, c) 3 months and d)
12 months post cryosurgery. Progressive resolution of early edema hypoechoic
necrotic debris is seen over time. (From Kaufman CS et al)

Figure 7 Mammograms pre and post cryosurgery.
Each left picture is pre-treatment and each right picture
is mirror image view 12 months post treatment. Varied
amounts of background breast density makes visualization
of treated sites difficult(From Kaufman CS et al).

Figure 8 Serial photographs of fibroadenoma patient
treated with cryosurgery at a) one week, b) six weeks
and c) over a year post treatment (marked with ink to
show site of puncture) (From Kaufman CS et al).

In 2005,Kaufman et al[6] evaluated long-term (2-3 years) efficacy, safety, and satisfaction of the cryoablation for breast fibroadenoma. Thirty-seven treated fibroadenomas were available for assessment with an average follow-up period of 2.6 years. Of the original 84% that were palpable prior to treatment, only 16% remained palpable to the patient as of this writing. Of those fibroadenomas that were initially < or = 2.0 cm in size, only 6% remained palpable. A median volume reduction of 99% was observed with ultrasound. Ninety-seven percent of patients and 100% of physicians were satisfied with the long-term treatment results. They showed that cryoablation should be a preferred option for those patients desiring definitive therapy for their fibroadenomas without surgical intervention.

Nurko et al[7] assessed the intermediate- (6 months) and longer-term (12 months) follow-up of patients with breast fibroadenomas treated by cryoablation,and summarized the experience from 55 different practice settings across the United States. Data from 444 treated fibroadenomas were analyzed. The mean tumor diameter was 1.8 cm. Before cryoablation, 75% of fibroadenomas were palpable by the patient. Follow-up at 6- and 12-month intervals revealed palpability of the treated site in 46% and 35%, respectively. When fibroadenomas were grouped by size, for lesions </=2 cm, residual cryoablation induce changes were visible by ultrasound in 35% of patients at 6 months. The treatment area was palpable in 31% of cases at this time. Visibility by ultrasound was 27%, and palpability was 28% at 12 months follow-up in these patients with smaller fibroadenomas. For lesions >2 cm, residual cryoablation induce changes were visible by ultrasound in 39% of the patients at 6 months. The treatment area was palpable in 78% of the cases at the same time. Visibility by ultrasound was 32%, and palpability was 59% at 12 months follow-up. Patient satisfaction with the procedure was rated as high at 91% and 88% at 6 and 12 months follow-up, respectively.

Discussion
Nonsurgical treatments for benign breast masses have clinical goals of stopping growth and/or reducing (removing) palpable mass effect without leaving a surgical scar (ie, good cosmesis).Cryoablation is a new treatment that combines the better attributes of the current standards: surveillance and surgery. It is a minimally invasive office-based procedure that is administered without the use of general anesthesia, involving minimal patient discomfort and little to no scarring. If cryoablation could accomplish these goals, substantial psychologic and economic benefits could be realized for many of the 1.3 million women who undergo breast biopsy each year according to estimation in USA. Cryoablation is easily visualized with high-frequency (ie, high-spatial-resolution) ultrasound as the ice margin extends beyond the tumor, is virtually painless, and can be used for masses near the skin[8].

Conclusion
With use of ultrasound-guided cryoablation for fibroadenomas there is little or no pain, target lesions are reduced in size or eliminated, scarring is minimal, cosmesis outstanding, and patient satisfaction is excellent. Cryoablation of fibroadenomas is a safe, effective, and virtually painless clinic-based (ie, outpatient) treatment option with good cosmesis[6].
Reference
1.Peter J. Littrup, MD, Laurie Freeman-Gibb, RN, NP, Aleodor Andea, MD, Michael White, MD, Kathy Carolin Amerikia, MD, David Bouwman, MD, Ted Harb, MD and Wael Sakr, MD Cryoablation for Breast Fibroadenomas. Radiology 2005;234:63-72.

2.Kaufman CS, Bachman B, Littrup PJ, White M, Carolin KA, Freman-Gibb L, Francescatti D, Stocks LH, Smith JS, Henry CA, Bailey L, Harness JK, Simmons R.Office-based ultrasound-guided cryoablation of breast fibroadenomas. Am J Surg.
2002;184(5):394-400.

3.Kaufman CS, Bachman B, Littrup PJ, Freeman-Gibb LA, White M, Carolin K, Francescatti D, Stocks LH, Smith JS, Henry CA, Bailey L, Harness JK, Simmons R.Cryoablation treatment of benign breast lesions with 12-month follow-up. Am J Surg. 2004;188(4):340-8.
4.Kaufman, C. S., Bachman, B., Jacobson, L., Kaufman, L. B. Cryoablation
of Benign and Malignant Breast Tumors: Lessons Learned
and Future Implications. Ann Surg Onc200310 Supp:S56-S57

5.Kaufman, C. S. Mammographic Appearance of Fibroadenoma
Disappears After Cryoablation. Presented at RSNA 2002, Annual
Meeting of the Radiologic Society of North America, Chicago,
Illinois, December 4, 2002
6.Kaufman CS, Littrup PJ, Freeman-Gibb LA, Smith JS, Francescatti D, Simmons R, Stocks LH, Bailey L, Harness JK, Bachman BA, Henry CA.
Office-based cryoablation of breast fibroadenomas with long-term follow-up. Breast J. 2005;11(5):344-50.

7. Nurko J, Mabry CD, Whitworth P, Jarowenko D, Oetting L, Potruch T, Han L, Edwards MJ.Interim results from the FibroAdenoma Cryoablation Treatment Registry. Am J Surg. 2005;190(4):647-51;