The overall goal of a meta-analysis is to combine the results of previous studies to draw a summary conclusion about a subject of research. In this study, we analyzed the outcomes of laparoscopic enucleation with preoperative SAE and non-SAE for RAML using a meta-analysis to obtain a powerful conclusion. The findings of our meta-analysis demonstrated that preoperative SAE can shorten operation time (SMD − 2.15, 95% CI: -2.85 to -1.46, P < 0.001) and warm ischemia time (SMD − 2.57, 95% CI: -3.04 to -2.10, P < 0.001), and reduce blood loss (SMD − 1.77, 95% CI: -2.06 to -1.47, P < 0.001) and postoperative complication (RR 0.29, 95% CI: 0.08 to 0.98, P = 0.047) in laparoscopic enucleation for RAML, compared with Non-SAE group. However, SAE didn’t shorten postoperative hospitalization (SMD − 0.82, 95% CI: -3.26 to 1.63, P = 0.512), and improve renal function, including serum creatinine (SMD − 0.59, 95% CI: -1.35 to 0.18, P = 0.133) and GFR (SMD 0.59, 95% CI: -0.15 to 1.32, P = 0.116). As far as we know, this is the first meta-analysis providing comprehensive insights into the effects of the preoperative SAE on perioperative outcomes of laparoscopic nephron-sparing surgery for renal angiomyolipoma.
As a first-line management option for RAMLs, SAE was recommended in cases of acute hemorrhage and refractory hemodynamic instability. In 2015, Murray et al performed a systematic review of trans-arterial embolization for RAMLs and reported a high technical success of 93.3% and a mean reduction in tumor size of 3.4 cm [15]. Lin et al reported SAE of RAMLs affected renal function preservation, and had a low complication rate, with a mean reduction in the size of 2.09 cm after meta-analyzing 30 studies [16]. Sun et al conducted a real-world study to compare embolization and nephrectomy for renal RAMLs associated with TSC, and embolization was effective, with a reduction in gross hematuria (− 27.7%), retroperitoneal hemorrhage (− 8.4%), and abdominal mass (− 6.9%) [17]. Anis et al assessed long-term outcomes after SAE as first-line treatment for large or symptomatic AML and found SAE was a safe procedure that was associated with freedom from surgery and CKD of 94% and 92.4%, respectively at 10 years post-procedure [3]. However, as reported by most studies, SAE's role in reducing tumor volume is limited. Most RAMLs have shrunk by only 20%-30% after successful embolization[18–20], and showed a high re-embolization rate (41.1%) [3]. Embolization is effective in controlling severe spontaneous hemorrhage in the acute phase, but be of limited value in treating large RAMLs in the long run [21].
Therefore, surgical treatment is an essential option for RAML. And NSS is advocated as preferred management in patients with symptomatic or large tumors due to a high risk of hemorrhage [5, 22, 23]. However, partial nephrectomy may be dangerous when the tumor is too large. Therefore, some people began to explore the feasibility of SAE used before partial nephrectomy to improve perioperative outcomes. Yeniyol reported a patient with life-threatening hamartoma [24]. They successfully performed nephrectomy five days after selective arterial embolization and no complications were observed. Although the author finally removed the entire kidney, preoperative embolization played a role in reducing the difficulty of the operation. Hoshii reported a 38-year-old female without TSC was diagnosed with a right RAML of 10 cm in diameter [25]. She experienced laparoscopic retroperitoneal NSS without renal artery clamping with preoperative SAE to avoid a significant risk of hemorrhage and the damage of the renal function during NSS. The time taken to accomplish the procedure was 4 hours 11 minutes, with 780mL blood loss. Taiwanese scholars conducted a comparative study of large RAML with or without SAE before partial nephrectomy and found TAE before partial nephrectomy had shorter WIT, decreased intra-operation blood loss, shorter length of stay, and fewer residual tumor than those did not performed TAE [26]. However, it was not included in our meta-analysis, because it was a meeting abstract. Combined with the results of our meta-analysis, it was not difficult to admit that preoperative SAE can shorten the operation time and reduce the amount of intraoperative blood loss, thereby making the operation easier to succeed for large RAMLs. However, Coskuner reported on a patient with a 24 cm AML of the right kidney who successfully underwent nephrectomy without arterial embolization [27]. Warm ischemia time was 35 min and intraoperative bleeding volume was 200cc. Most studies on this topic are case reports, which affect the level of evidence. Multi-center research can expand the sample size and obtain more reliable results, which is worthy of recommendation.
Warm ischemia time was recognized as a crucial factor governing early renal function after partial nephrectomy. Thompson et al reported > 20 min of warm ischemia was an important predictor of adverse renal outcomes, and each additional minute was associated with a 5% and 6% increased odds of developing acute renal failure (ARF) or a GFR < 15 ml/min per 1.73 m2 in the postoperative period, respectively, and was associated with a 6% increased risk of new-onset stage IV chronic kidney disease during follow-up [28]. With the help of SAE, the clear operative vision enables the surgeon to finish the operation in a shorter time. Surgery could be completed without clamping the renal artery if the tumor’s blood supply was blocked by SAE. Thus, our study found the preoperative SAE reduced the warm ischemia time of the operation, but no difference was observed in the postoperative renal function. A review of the literature suggests there is little or no significant deterioration in the mean GFR after selective embolization is performed [29]. Another point to consider is that the studies included in this meta-analysis all observed the renal function of patients in the relatively early postoperative period (6 months after surgery). Numerous factors can influence renal function after surgery, and long-term observation is needed to get more reliable conclusions.
In terms of surgical complications, this analysis demonstrated that preoperative SAE combined with laparoscopic partial nephrectomy reduced the surgical complication rate. While, some of the specific complications such as pleural injury, retroperitoneal hematoma, hematuria, urine leakage, incision infection, and re-embolization to stop bleeding were not significantly different between the two groups. The lack of statistical significance might be explained by the low sample size. For example, only two patients developed hematuria, urine leakage, and incision infection in the Non-SAE group, but none in the SAE group. Urine leakage is a serious complication after partial nephrectomy, which can be caused by unclear boundaries and excessive resection of the renal parenchyma. Preoperative SAE can reduce blood loss and make the surgical field clear, which enables the surgeon to separate the tumor from normal renal parenchyma and avoid damaging the renal parenchyma. Due to the limitation in sample size, larger sample cohorts are still needed to observe surgical safety.
However, some limitations in the present meta-analysis should be mentioned. The major limitation is the small number of eligible studies and sample size. We only enrolled in four observational studies. In addition, heterogeneities existed in some outcomes of our study, and the reasons for heterogeneities were complicated. Heterogeneity may be attributed to different patient characteristics, study designs, and sample sizes. Furthermore, all four studies were from Asia, which might bring a certain selection bias to our meta-analysis.