In the present study, we analyzed the incidence of all perioperative complications and risk factors for perioperative complications in patients who underwent tumor resection for NB. IDRFs, high stage of INRGSS, retroperitoneal lymph node metastasis, and vascular encasement were significant risk factors for perioperative complications, yet MYCN amplification and tumor size were not significant risk factors. Furthermore, despite the high incidence of perioperative complications, the associated mortality rate was quite low.

Surgery plays an important role in the treatment of NB and is associated with improved survival [3, 12]. Compared with tumor PR, patients who underwent GTR had significantly decreased mortality at 3 years and 5 years [13]. However, there are conflicting viewpoints. Gehad reported that the extent of tumor resection had no impact on EFS and OS, and the concept of accepting incomplete resection to avoid serious complications was successful [14].

Theoretically, the incidence of complications increased with the extent of tumor resection. However, this was not the case in the present study. In fact, the surgeon was forced to terminate the procedure due to severe complications during the operation, such as vascular injury and bleeding. As a result, GTR is not achievable, which increases the incidence of complications in patients with PR. The reported incidence of complications of NB ranged from 20% to 50%, depending on sample size, surgeon’s experience, and the definition criteria for complications. In this study, the overall complication rate was 44.7%. LL, diarrhea, and injury were the most frequent complications in the cohort.

As of yet, there is no official definition of LL, and each study differs in its definition. The occurrence of LL was closely related to the scope of lymph node dissection, and skeletonization resection around the superior mesenteric artery was identified as a significant risk factor. Prophylactic mesenteric lymphatic ligation contributed to its effectiveness in the prevention of chylous fistulae [15]. In our experience, another way to prevent LL was to suture the side peritoneum in a meticulous manner so that the retroperitoneal area was completely isolated from the abdominal cavity. The side peritoneum was often removed along with the tumor. In that case, the mesocolon could be sutured to the liver and lateral abdominal wall on the right side, while the stomach and descending colon could be sutured to the diaphragm and lateral abdominal wall on the left side to close the posterior peritoneum. When LL occurred, encapsulated effusion formed in the enclosed space behind the peritoneum and no longer increased once the tension reached a certain level.

Diarrhea, one of the paraneoplastic syndromes, is due to hypersecretion of vasoactive intestinal peptide by the tumor and will disappear after tumor resection [16]. In contrast, postoperative diarrhea has rarely been reported. In fact, diarrhea was fairly routine after retroperitoneal NB resection, occurring in up to 13.5% of our cohort, and was significantly related to tumor dissection around the aorta and inferior mesenteric artery. It was inferred that the accompanying excision of sympathetic nerve fibers leading to autonomous nerve dysfunction might be the culprit. This type of diarrhea was characterized by being refractory to medication and having a long duration. The symptoms become favorable when the autonomous nervous system gradually achieves equilibrium. However, it was the detail of the operational method with retaining as many nerve fibers as possible that counts.

Vascular injury is always a concern in retroperitoneal NB surgery due to the tumor's proclivity for encasing visceral vessels. Massive hemorrhage, transfusion requirements, renal hypertension and unscheduled nephrectomy were all not uncommon following high-risk NB resection. A critical step for avoiding and minimizing injury to these vessels is their identification before they pass through the tumor, most often at their take-off from the aorta or vena cava [17]. Additionally, 3D-printed models could be of great assistance to pediatric surgeons in understanding the spatial relationships of tumors with adjacent anatomic structures, especially vessels [18]. Do not panic if vascular injury occurred during the operation. Perfusion can be sustained in most cases with primary suture and vascular anastomosis or prosthetic vascular graft repair.

Catecholamines released by the NB were a significant cause of preoperative hypertension, while postoperative hypertension was most likely renovascular. If postoperative hypertension is not actively treated, it might lead to cardiovascular or cerebrovascular problems and interfere with the effectiveness of chemotherapy. The majority of individuals could return to normal with hypotensors. Percutaneous transluminal angioplasty was considered for refractory hypertension that failed antihypertensive medications [19], and nephrectomy was often employed as a last resort.

Unscheduled organ excision primarily involved the kidney. Tumor invasion of the kidney and wrapping around the kidney or renal pedicle did not mean the need for nephrectomy, and when these occurred in our cohort, the kidney could be saved while the tumor was removed. The most frequent cause for organ removal was accidental blood vessel damage, which should be removed when there was postoperative organ atrophy or refractory symptoms such as resistant hypertension.

In 2009, the INRG created a new staging system that relies on preoperative imaging for staging [20, 21]. Central to the INRGSS are IDRFs combined with clinical data to provide upfront risk stratification. IDRFs are a consensus of radiologic findings across multiple organ systems that can be applied consistently to diagnostic imaging to describe organ, nerve, and vessel involvement [22]. Evidently, there was a direct correlation between IDRFs and complications, and complications were more likely to occur when more IDRFs were involved [10]. The presence of IDRFs as a risk factor for perioperative complications requires surgeons to pay more attention to patients with IDRFs during surgery, and this should not discourage the determination to pursue total resection of NB.

MYCN amplification is one of the strongest independent adverse prognostic factors, accounting for 20% to 25% of NB and is strongly associated with advanced-stage disease [23,24,25]. MYCN-amplified NB was sensitive to chemotherapy and could considerably lower IDRFs after chemotherapy. In patients with localized NB harboring MYCN amplification, extended surgery of the primary tumor site improved the local control rate and survival [12].

We observed that MYCN-amplified NB was extremely invasive to the vascular adventitia and adjacent tissues, fusing tumors, vessels, and surrounding tissue into a sticky mass, making the surgery more challenging and potentially increasing the occurrence of complications. Unexpectedly, MYCN amplification was not a significant risk factor for perioperative complications in the study, which should be due to the high incidence of LL and diarrhea. It was recommended that GTR should be carried out on MYCN-amplified NB, and suspicious adjacent tissue should be excised as much as possible, which may prevent local recurrence and improve prognosis to some extent.

Reports showed that operative complications had no significant adverse effect on EFS or OS [3], but this was not the case in this study. It is important to consider that the complication rate was associated with a high stage of INRGSS and risk group of INRG. In addition, any perioperative complication would result in delays in the timely delivery of systemic therapy and/or the ability to deliver full-dose therapies.

In conclusion, despite the high incidence of perioperative complications, the associated mortality rate was quite low. The presence of IDRFs, high-stage INRGSS, retroperitoneal lymph node metastasis, superior mesenteric artery encasement, and inferior mesenteric artery encasement were significant risk factors for perioperative complications of retroperitoneal NB. Surgery for retroperitoneal NB has always been a challenge for pediatric oncologists. To improve clinical outcomes for these patients, surgeons take on the challenge of eliminating these tumors. Future large-sample and multicenter studies are expected to explore additional information, develop a more intuitive understanding of the complications and risk factors for NB surgery, and assist surgeons in providing better management for NB patients.