The safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy: a new avenue for the treatment of cystic renal tumors

Abstract Purpose Clinically, the management of cystic renal masses is tricky. The study aims to evaluate the safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy (LMAPN) for cystic renal tumors. Methods and materials Between November 2017 and January 2022, LMAPN was performed on 43 patients (29 men and 14 women; age range: 22–80 years; median age 54 years) with Bosniak category III (n = 15) or IV (n = 28) cystic renal tumors (size range: 1.2–5.0 cm; mean size 2.8 cm). The median follow-up period was 26 months (range: 7–56 months). Baseline and perioperative data, pathological features, renal function, postoperative complications and oncologic outcomes were collected and evaluated. Results Forty-three cystic renal tumors were successfully managed by LMAPN. The mean operating time was 79 min (range: 40–130 min). The mean time of renal pedicle clamping was 19 min (range: 12–25 min). Mean intraoperative blood loss was 28.4 mL (range: 10–80 mL). The mean postoperative hospitalization duration was 4 days (range: 2–6 days). Negative surgical margins were diagnosed in all cases. During the follow-up, no patient appeared with distant metastasis, wound or peritoneal cavity implantation. No major but minor complications of Clavien–Dindo grade I were encountered after the operation. The 1-, 3- and 4-year overall survival rate was 100%, 96.6% and 88.5%, respectively. Conclusion This is the first study focusing on LMAPN for cystic renal tumors, demonstrating its favorable feasibility, safety and disease control. Long-term follow-up is necessary to draw conclusions on the preference and advantages of the new therapeutic approach.


Introduction
The spread of imaging technologies and increased awareness of physical examinations have led to an increase in the number of renal masses incidentally diagnosed.The presence of one or more renal tumors is found in approximately 50% of people over the age of 50 years [1].Of these incidental renal tumors, cystic tumors are the most common.In 1986, the Bosniak classification was published to stratify the risk of malignancy in cystic renal tumors [2].It is widely used in the clinical practice of radiology and urology.The Bosniak classification stratifies cystic renal tumors into five grades (I, II, IIF, III or IV) based on the imaging characteristics, with each grade representing an increased probability of malignancy [3,4].Warren et al. [5] summarized the data reported in several studies and showed that the risk of malignancy for Bosniak grade III and IV lesions ranged from 16% to 100% and 90% to 100%, respectively.
According to current guidelines, partial nephrectomy remains the standard treatment for localized small renal tumors, intending to preserve kidney function and provide longer term tumor control [6].Some theoretical questions regarding treating cystic renal tumors remain unanswered, especially concerns about cyst rupture and tumor implantation during surgery.Firstly, patients with renal cysts on preoperative imaging, receiving renal cyst unroofing, may be diagnosed as cystic renal cell carcinoma by postoperative pathology.Second, for patients with a high suspicion of cystic renal cell carcinoma, cyst rupture may occur during nephron-sparing surgery, and this carries the risk of tumor implantation and metastasis.The rate of cyst rupture during partial nephrectomy has been reported to be 20% [7,8].
Thermal ablation techniques have been shown to be safe and effective in treating small renal masses as a new management strategy [9][10][11][12].Therefore, we tried to combine these two surgical methods.Laparoscopic-assisted microwave ablation was performed for cystic renal tumors, followed by partial nephrectomy.The high-temperature environment generated by thermal ablation can coagulate and destroy the tumor cells that may be present in the cyst fluid, thus preventing the risk of tumor implantation due to cyst rupture during partial nephrectomy.
The present study describes our experience of laparoscopic microwave ablation-assisted partial nephrectomy (LMAPN) for cystic renal tumors, emphasizing its feasibility, safety and oncological outcomes.

Patients
The study was approved by the institutional review board (No. 2020KT21) and conducted following Good Clinical Practice and the Declaration of Helsinki.Informed consent was obtained from the patients.Between November 2017 and January 2022, LMAPN was performed on 43 patients (29 men and 14 women; age range: 22-80 years; median age 54 years) with Bosniak category III (n ¼ 15) or IV (n ¼ 28) cystic renal tumors (size range: 1.2-5.0cm; mean size 2.8 cm) (Table 1).These cystic renal tumors were categorized according to the Bosniak classification.Twenty tumors were located in the left kidney, and the remaining 23 cases were in the right kidney.The Eastern Cooperative Oncology Group (ECOG) score was 0 for 37 patients and 1 for the other 6 patients.The mean body mass index (BMI) was 26.3 kg/m 2 (range: 19.5-33.9kg/m 2 ).The R.E.N.A.L. composite score was assessed according to preoperative imaging, which was categorized as low (4)(5)(6), moderate (7)(8)(9) or high complexity (10)(11)(12) [13].Of these cystic renal tumors, 15 (34.9%) were categorized as low, 24 (55.8%) as moderate and 4 (9.3%) as high complexity.The decision to perform LMAPN was based on the risk of cyst rupture that was evaluated by urological discussions.

Procedure
As we previously reported, a microwave ablation system (KY-2000, Nanjing Kangyou, China) with 2450 MHz emission frequency was used in this study [14].The microwave needle has an effective length of 18 cm, with an outer diameter of 18 G and an 11 mm active tip.The operation was performed under general anesthesia and tracheal intubation.The perirenal fascia was incised laparoscopically to separate the renal hilar vessels and expose the renal tumor.The microwave ablation needle was preheated and then percutaneously inserted into the cystic renal tumor for ablation under direct laparoscopic vision.However, for endogenic tumors, laparoscopic ultrasound was used to precisely target the tumor, and then percutaneously inserted the microwave needle into the tumor for ablation.Single-site ablation was applied when the cystic tumor diameter was less than 2.0 cm.Multiple-site ablation was performed for tumors larger than 2.0 cm in diameter.The ablation power was adjusted to 50-80 W, and the ablation duration was set at 3-6 min.During the ablation, it showed that the internal liquid of the cystic mass evaporated at high temperature.The tumor gradually shrank and hardened in texture, similar to the denaturation and solidification of egg whites upon heating.When the treatment was completed, the microwave antenna was withdrawn, and the puncture needle tract was ablated simultaneously to avoid tumor cell seeding along the needle tract and to prevent bleeding from small vessels.The tumor was excised along the unsupplied plane around the ablated tumor with hilar clamping.The cut surface was sutured with 3-0 and 2-0 barbed stitches, and then the renal artery was opened.Depending on bleeding control, the decision was made whether to suture and reinforce the wound to ensure that there was no active bleeding.A schematic diagram of LMAPN process is shown in Figure 1.

Follow-up
Post-operation-related complications, such as hemorrhage, hematuria, fever, pain and skin burn, were closely observed.If necessary, computed tomography (CT) or magnetic resonance imaging (MRI) scan was performed to evaluate the immediate or late complications after the operation.The Clavien-Dindo classification was used to report and grade possible immediate or late complications [15].Clinical followup and enhanced CT or MRI imaging were performed at 1, 3 and 6 months and every 1 year thereafter to determine local tumor control and metastatic disease.The routine blood test, serum biochemical levels and urinalysis were evaluated at the following time points: before surgery, 1 day, 1 month and 3 months after surgery, and every 6 months thereafter.

Statistical analysis
Continuous variables were expressed as mean ± SD.Followup duration was expressed as the median.Kaplan-Meier curve was used to describe overall survival.The statistical analyses were performed with SPSS26.0 software (SPSS, Chicago, IL, USA), and p < 0.05 was considered to be statistically significant.

Results
Forty-three cystic renal tumors were managed successfully by laparoscopic-assisted microwave ablation treatment.The mean operating time was 79 min (40-130 min) (Table 1).The mean time of renal pedicle clamping was 19 min (12-25 min).
Mean intraoperative blood loss was 28.4 mL (10-80 mL).The median visual analog score of postoperative pain was 1 (0-2).The mean post-operative hospitalization duration was 4 days (2-6 days).Pathological results indicated renal cell carcinoma in 37 (86%) patients, cystic renal neoplasm of low malignant potential in one patient, mixed epithelial and stromal renal tumor in one patient and benign renal tumor in four patients (Table 2).Negative surgical margins were diagnosed in all cases.The pathological features after ablation are shown in Figure 2. The median follow-up period was 26 months (7-56 months).During the follow-up, one patient genetically diagnosed with Von Hippel-Lindau (VHL) syndrome showed local recurrence at 45 months post-surgery.No patient appeared with distant metastasis, wound or peritoneal cavity implantation metastasis of renal cell carcinoma (Figure 3).One patient died of heart failure at 22 months after surgery, and one patient died of metastatic colon cancer at 37 months post-operation.The 1-, 3-and 4-year overall survival rate was 100%, 96.6% and 88.5%, respectively (Figure 4).
In this study, no major complications were encountered.However, minor complications of Clavien-Dindo grade I were observed after the operation, including flank pain, nausea, vomiting, fever and constipation, without any clinical consequences (Table 1).No hemorrhage, hematuria or skin burn was reported.Renal function indicators were routinely evaluated before and after the surgery.Among the three solitary kidney patients, serum creatinine levels and the estimated glomerular filtration rate were maintained within the normal range before the operation, 1 day, 1 month and 3 months after the operation.Besides, no renal insufficiency was observed after the operation in the other patients.

Discussion
To our knowledge, this is the first study concentrating on LMAPN for cystic renal tumors, emphasizing its feasibility, safety and prognosis.We showed that the combination of these two surgical procedures was effective and safe for the treatment of cystic renal tumors.Nephron sparing surgery still represents the standard treatment for patients with small incidental renal tumors ( 4 cm).However, it also remains a challenge for the surgeon to manage cystic renal tumors because of the concern regarding intraoperative cyst rupture and spillage of cyst contents leading to tumor seeding in the retroperitoneum.It reported that tract seeding was observed during percutaneous biopsy of renal masses [16,17].Our  previous study indicated that renal cell carcinoma cell clusters were scattered in renal cyst cavities of VHL patient [18].Therefore, renal cysts should be carefully managed to prevent tumor cell implantation.
Several studies demonstrated that image-guided percutaneous radiofrequency ablation was an effective treatment for Bosniak category III or IV cystic renal tumors with a satisfactory prognosis [19][20][21].Furthermore, Carrafiello et al. [22] defined a potential role for image-guided percutaneous microwave ablation in treating Bosniak category III or IV cystic renal lesions.These studies suggested that thermal ablation is a selective procedure for treating cystic renal tumors.Accordingly, in this study, partial nephrectomy was performed after microwave ablation.It not only prevents the possible risk of spreading viable tumor cells to adjacent tissues caused by cyst rupture, but also avoids tumor recurrence caused by incomplete ablation.On this bias, the new avenue combines the advantages of both microwave ablation and partial nephrectomy.
The characteristic of microwave ablation is not susceptible to tissue perfusion, especially in highly perfused tissues, such as the kidney.Interestingly, microwave ablation minimizes heat diffusion and reduces the 'heat sink effect', producing practical ablative effects in larger cystic lesions.However, relatively few studies have investigated the efficacy of microwave ablation in cystic renal tumors [22,23].This study represents one of the largest cohorts of cystic renal tumors   treated with microwave ablation.All the 43 cystic lesions achieved technical success and effectiveness.When the proteins in the cyst fluid were heated, they got denatured and solidified, similar to gelatinous.There was no extravasation of cyst fluid into adjacent tissues during the operation.In addition, microwave ablation technology has been applied to assist partial nephrectomy by reducing intraoperative bleeding [24,25].It works by coagulating the paracancerous tissue, forming a chestnut-shaped ablated area, and is suitable for performing partial nephrectomy.As we summarized, the mean time of renal pedicle clamping was 19 min and the mean intraoperative blood loss was 28.4 mL.Considering the successful completion of the procedure, microwave ablation played a vital auxiliary role.
Of the 43 patients who received LMAPN for cystic renal tumors, the median follow-up period was 26 months, and the 1-, 3-and 4-year overall survival rate was 100%, 96.6% and 88.5%, respectively.However, two patients' deaths were attributed to heart failure and metastatic colon cancer, respectively.Among the 43 samples, no instances of metastatic renal cell carcinoma were observed.Though one patient with VHL syndrome has a local recurrence, the tumor has not yet reached the size threshold for surgery, and active surveillance has been adopted [26].Hence, the preliminary oncologic outcomes of this study were satisfactory.Carrafiello et al. [22] assessed the efficacy and safety of percutaneous image-guided microwave ablation in six patients with seven Bosniak category III or IV cystic renal lesions after 24 months of follow-up duration.The results showed that the technical success rate was 100%, the local tumor progression rate was 0%, and the overall survival rate was 100%.Zhou et al. [23] reported that five patients with cystic renal cell carcinoma treated with computed tomography-guided microwave ablation, during the mean follow-up period of 18 months, no local recurrence was identified.Thus, microwave ablation could open new prospects as a viable alternative for treatment of cystic renal tumors.
One of the major concerns with thermal ablation is the lack of clear histopathology of the ablated lesion, which would help to determine the patient's prognosis.In addition, in some cystic renal tumors, cystic structures dominate the morphologic appearance of the tumor, and it is not always possible to obtain sufficient malignant cell samples for conclusive histologic evaluation, making biopsy useless.Some studies report that a biopsy of renal masses is helpful in evaluating Bosniak II or III cystic renal masses.In contrast, others report that biopsy may be unreliable, especially in the pathological diagnosis of cystic masses.Muto et al. [25] reported 10 patients with small renal masses underwent laparoscopic-guided biopsy, microwave tumor ablation and enucleation.In all cases, the histopathological diagnosis was based on the preablation pathology, as complete necrosis after ablation made the treated specimens challenging to interpret.However, in our study, the goal of microwave ablation was not for complete tumor ablation, but was to be assistant in coagulating the cystic fluid that had the risk of neoplastic implants caused by cyst rupture.Of the 43 cases, post-operative pathology was successfully diagnosed.Similar to the previous study, Clark et al. [27] demonstrated that ablation did not affect the postoperative pathological diagnosis.Therefore, LMAPN for cystic renal tumors allowed for precise pathological diagnosis, which may identify positive surgical margins.
With regard to postoperative complications, no major complications but minor complications defined as Clavien-Dindo grade I were found in this study.For these patients, the symptoms were relieved after supportive management.According to published data, refractory complications related to thermal ablation include arteriovenous fistula and urine leakage, owing to intraoperative collateral damage to arteries, veins and collecting system with poor recovery ability after ablation [28,29].Therefore, double suturing was recommended after partial nephrectomy.Besides, the loss of renal function was frequently reported for patients receiving ablative therapy.In this study, the creatinine levels of all patients, including three solitary kidney cases, were basically maintained within the normal range before the operation, 1 day, 1 month and 3 months post-operation.It might be due to the attention for protecting normal renal parenchymal and shortened renal pedicle blocking time intraoperatively.
As far as we know, this is the first study focused on LMAPN for cystic renal lesions.Nevertheless, the limitations should be noted.First, the sample size of this study is still small, and more extensive studies are needed to validate our results.Moreover, the study was retrospectively performed, which had a selection bias.There was no comparison to standard single treatment as partial nephrectomy or ablation.Additionally, long-term follow-up may be necessary to conclude the preference and advantages of the new therapeutic approach.
In conclusion, LMAPN is technically feasible and effective in the management of cystic renal tumors, and is accompanied by promising oncologic and functional outcomes as well as a low rate of perioperative complications.Considering this is our preliminary experience, further investigation is required.

Figure 1 .
Figure 1.A schematic diagram of microwave ablation-assisted partial nephrectomy process.(A) The microwave ablation needle is inserted into the cystic renal tumor for ablation.(B) The tumor shrank and hardened in texture.(C, D) Partial nephrectomy and suturing are performed.

Figure 2 .
Figure 2. Pathological features of cystic renal tumors after ablation.(A) The protein in the cyst fluid was denatured and solidified by heating (marked with a black arrow).(B) The tumor tissue around the cyst cavity showed coagulation necrosis (marked with a blue arrow).

Figure 3 .
Figure 3.A 28-year-old female, with a cystic renal tumor, received laparoscopic microwave ablation-assisted partial nephrectomy.(A-D) Preoperative imaging indicated the renal mass as Bosniak category III.(E-H) No tumor recurrence was observed on postoperative imaging evaluation ((E) Enhanced CT scanning, 3 months after the operation.(F) Enhanced CT scanning, 1 year after the operation.(G) Enhanced CT scanning, 2 years after the operation.(H) Enhanced MRI scanning, 3 years after the operation).

Table 1 .
Patient demographics, tumor and treatment characteristics.