Retroperitoneoscopic assisted cryoablation for small renal tumors. The first cases treated in Romania

Introduction
Cryoablation for small renal tumors is a safe and effective minimal invasive, nephron-sparing treatment alternative (1, 2, 3, 4).
Renal cell carcinoma (RCC), the most common adult kidney neoplasm, is relatively resistant to non-surgical treatment modalities and therefore is primarily managed by surgery. The growing and widespread application of ultrasonography and computed tomography has resulted in the increased recognition of small renal tumors (5).
Nephron-sparing surgery (NSS), has been demonstrated to be a safe and effective alternative to radical nephrectomy not only for RCC arising in a solitary functioning kidney but also for tumors in patients with a normal contralateral kidney, thus facilitating preservation of renal function and management of metachronous contralateral pathology (6, 7).
Laparoscopic approach gives reduced postoperative pain, shortened length of hospitalization and duration of convalescence, improved cosmesis, similar complication rates, and similar medium-term oncologic outcomes compared with open surgery. Laparoscopic NSS combine the benefits of minimal invasiveness of the laparoscopy with the advantage of preserving renal function of the nephron sparing surgery, but the procedure remains challenging (8).
In the past years, cryoablation, has also been used to treat RCC due to its ability to percutaneously or laparoscopically treat small exophytic tumors (1, 3, 4, 9).
Renal tumors less than 4 cm in diameter are potential candidates for renal cyroablation. Renal cryoablation is especially useful for those patients with single kidney, comorbidities who may not tolerate the longer operative times or increased blood loss usually associated with laparos-copic partial nephrectomy. Cryoablation is also an important treatment alternative for patients with familial renal tumor patterns such as von Hippel-Lindau syndrome or tuberous sclerosis, who are at greater risk of developing multiple renal tumors during their lifetime.
Cryotherapy for renal masses may be performed through an open incision, laparoscopically, or percutaneously with real-time ultrasound, computed tomography, or magnetic resonance imaging (MRI) guidance.
Renal cryoablation technology currently relies on the application of multiple 17-Gauge (1.47-mm) cryoprobes in a template configuration.
To date, the medium term oncological results of cryo-ablation for RCC are encouraging.
Major drawback is the risk of gaining limited informations about tumor type. In one series, only in 10 of 14 cases the pathologic type could be assessed by peroperative biopsy. Even if the tumors are benign, surgical approach is adequate (1, 3, 4, 9).
Objective
The aim of our study was to present the initial results with retroperitoneoscopic cryoablation of small renal tumors.

Material & Method
Patients characteristics
Since January 2007 we have used a retroperitoneoscopy assisted cryoablation for small renal tumors at our institution. All consecutive patients with solitary small peripheral renal tumors were considered for cryotherapy. The patients were assessed using: clinical exam, lab exam, ultrasound, CT scan and IVP. All the patients have given informed consent.
Twelve patients, 7 male and 5 female, with mean age 52.35 (34-71) years underwent retroperitoneoscopy-assisted cryoablation of the renal tumor. The mean tumor size on CT scan was 3.89 (2.16-6.01) cm. The left kidney was affected in 7 cases and the right kidney was affected in 5 cases. Five tumors were located on the anterior aspect of the kidney, four on the posterior aspect and three laterally. tumor pozition was on the upper pole in 2 cases, medial in 7 cases and on the lower pole in 3 cases. Two patients had single kidney due to previous nephrectomy. In one case, the nontumoral kidney was hypoplazic. (Table 1)
Surgical technique
The patient under general anesthesia is placed in an overextended flank position. Retroperitoneoscopic access is gained through a 1.5-cm incision at the tip of the 12th rib. The flank muscle fibers are sequentially split with S-retractors, and the lumbodorsal fascia is opened, gaining entry into the retroperitoneum. Finger dissection creates a space for placement of the balloon dilator between the psoas muscle and Gerota's fascia. After balloon dilation to 800 mL and removal, a 12-mm Bluntip canula is secured.
Pneumoretroperitoneum is established (15 mm Hg), and a 12-mm, 35° laparoscope is inserted. Two secondary trocars are placed: a 12-mm port in the midaxillary line 3 cm superior to the iliac crest and a posterior 5-mm port at the lateral border of the psoas muscle just below the 12th rib (Fig. 1).
For anterior or posterior located tumors, another 5-mm port may be placed at the anterior axillary line, employed to retract the peritoneum anteriorly.
For cryoablation, we used the Galil Medical SeedNetTM with 17 Gauge cryoprobes. The cryomachine and cryoprobes are checked for adequate functioning and absence of leak by a test freeze (Fig. 2).

Using laparoscopic techniques, the kidney is completely mobilized within Gerota's fascia (Fig. 3a), then by exposing the entire renal surface, including the tumor (Fig. 3b.).
An endoscopic, ultrasound probe is introduced through the 12-mm trocar at the tip of the 12th rib. With the probe in direct contact with the renal surface, detailed ultrasound examination of the entire kidney is performed to evaluate the following: margins, size of the renal tumor, proximity of the tumor margins to the collecting system, and presence of any satellite tumors in the remainder of the kidney (Fig. 4).

Before inserting the cryoprobes, a needle biopsy was taken in all cases, to document the tumor type.
Four to six 17 Gauge cryoprobes are inserted in the tumor under endoscopic and ultrasound control (Fig. 5). The cryoneedles are placed circumferentially at the same depth using a specially designed grid. A double freeze-thaw cycle was performed under real-time endoscopic ultrasound monitoring. (Fig. 6)

We used high presure argon for freezing and helium gas for thawing. Cryolesions were induced with a core temperature of - 175ºC at the tip of the cryoprobes while the temperature in the tumor reached - 75ºC. A rapid freeze was performed until the advancing, hyperechoic, semilunar edge of the ice ball was noted to circumferentially extend approximately 1 cm beyond the tumor margins on ultrasound. Extreme care was taken to ensure that the entire extent of the ice ball on the renal surface was completely exposed and under clear laparoscopic visualization at all times. It is critically important to prevent the adjacent peritoneum and ureter from coming into even momentary contact with the ice ball or the cryoprobe at any time.
After the rapid initial freeze, a slow complete thaw was performed until the laparoscopically visible ice ball begins to melt. With the cryoprobe maintained in position, a second rapid freeze was performed.
Laparoscopic visualization, the method to monitor the second freeze, confirms that the visible external surface area of the ice ball is similar to the first freeze. Because the cryodestruction created by the initial freeze cycle may render the ablated area anechoic, real-time ultrasound is incapable of visualizing the advancing edge of the second ice ball until it advances beyond the boundary of the initial ice ball. Thus, the ice ball created by the second freeze cycle is monitored by 2 methods: (1) laparoscopic visualization of its external surface, and (2) ultrasonic confirmation that the secondary ice ball does not progress beyond the margins of the initial ice ball.
On completion of the second freeze, slow thawing was performed. Melting of the cryolesion releases the probe, which was removed gently, without any torquing. Forceful or premature removal of the cryoprobe may result in fracture of the cryolesion, with subsequent post-thaw hemorrhage.
On removal of the cryoprobe, haemostatic pressure was maintained on the puncture site with a piece of Surgicel for a period of 10 to 15 minutes. After releasing the haemostatic pressure on the renal puncture site, the pneumo-retroperitoneum was lowered to 5 mm Hg, and haemostasis was confirmed for an additional 5 minutes.
Follow-up
After surgery a baseline contrast-enhanced spiral CT scan was performed in order to assess the cryolesion aspect and size. Follow-up design includes clinical exam, lab exam and contrast-enhanced spiral CT scan scheduled at three, six and 12 months and annually thereafter.
Results
Mean surgical time was 145.42 15.59 (120-165) min. Mean blood loss was 179.17 121.47 (100-550) ml. One hemorrhagic and one urinary complications were resolved by surgery. Three patients presented postoperatively with a superficial skin frostbite, which healed with conservative treatment.
Histological examination of the core biopsy revealed clear cell RCC in 8 patients, papillary RCC in 3 patients and angiomyolipoma in 1 patient. The initial contrast-enhanced CT scan revealed a lack of iodofilia of the cryolesions.
Discussions
Cryotherapy for small renal tumors is safe and effective with good oncologic results on intermediate term follow-up (1, 3, 4, 9).
Among the energy based ablative techniques, cryotherapy provides the best results with excellent control of the energy delivery (4, 10).
The freezing produce cell death due to several mechanisms. The immediate mechanisms consists in formation of ice crystals both intra and extracellular, creating a hyperosmolar environment leading to cell shrinkage and dehydration, enzyme denaturation and dysfunction of the cytoskeleton and cell membrane. Rapid freezing followed by gradual thawing maximize this effects. The delayed mechanisms consist in thrombosis with secondary necrotic lesions (11, 12).
Freezing is produced using liquid nitrogen or liquid argon and the thawing process using helium gas. Experiments in a porcine model indicate that a temperature of -20º C provide complete tissue necrosis. The temperature at the edge of the ice ball is 0º C and therefore, the visible ice ball should extend 1 cm beyond the tumor margins.
Cryoablation can be done percutaneously under ultrasound or CT scan control, retroperitoneoscopic or laparos-copic assisted or by open access. Direct visual control during laparoscopy and real-time intraoperative ultrasound monito-ring provides most reliable tumor destruction comparing with percutaneous techniques (13).
Recent studies on a murine model indicated that cryoablation allow releasing tumor antigens responsible for generating a specific immune response. Tumors are rejected significantly more frequent after criotherapy comparing with surgical excision. This method could provide further research in this field.
Using multiple ultrathin cryoprobes allows control of tumors with asymmetric shape. Also, multiple cryoprobes allows reaching lowest temperatures along the entire volume (14).
Due to small diameter, tumor bleeding is reduced. Also removal of the cryoprobes should be done carefully, without force to avoid renal fracture. Bleeding controll could be achieved using refreezing, fibrin glue, Surgicell, Avitene, or argon beam coagulation. Renal fracture is associated with using of solitary cryoprobes of 3.2 mm. Usually such events are not encountered when using multiple ultrathin cryoprobes.
Tumor dimension considered for cryoablation is less than 4 cm, similar with indication for enucleation. The rational for this indication is the requirement for extension of the ice ball more than 1 cm beyond the tumor margin and the main concern is the proximity of the tumor to the renal pelvis. Even so, partial nephrectomy could be performed for tumors larger than 4 cm rising the question if cryotherapy could be feasible for larger tumors. The risk of recurrence, urinary or vascular complications could be higher. If considering multiple synergic effects: immediate lethal cell lesions, delayed ischemic lesions and potential immune response to released tumor antigens, cryoablation of the renal tumors larger than 4 cm could be feasible (11, 12, 13).
Potential tumor cell spilling is still under debate. Published data shows that laparoscopic procedures are not associated with increased tumor cell circulation or port side metastasis. Intraoperative biopsy is taken to provide histological diagnosis (15).
MRI guided cryoablation of renal tumors seems less invasive but with increased recurrence rate when compared with retroperitoneoscopic assisted procedure, and require repeated treatment. Retroperitoneoscopic assited cryoablation gives excellent visual identification of the tumor margins. Also real time endoscopic ultrasound allows control of the cryoneedles placement and ice ball formation. On the other hand, bleeding after cryoprobes removal is easily controlled by retroperitoneoscopy (4, 9, 16).

Conclusion
Cryosurgical ablation of small renal tumors using multiple ultrathin 17 Gauge cryoprobes is a feasible treatment option. Retroperitoneoscopic approach allows optimal access to the kidney and endoscopic real-time ultrasound control of the freezing process.

References
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