Cadaveric analysis of surgical techniques and working space for retroperitoneal tumors as model for improving resection of neuroblastoma.

PURPOSE: Neuroblastoma, the most common extracranial solid tumor in children under 5 years, often surrounds visceral arteries. This study aimed to analyze the working space provided by standardized surgical techniques at key arterial landmarks in adult cadavers. METHODS: We assessed in eight adult cadavers the mobilization of the left colon, spleen and pancreas, right colon, duodenum and mesenteric root, access to the bursa omentalis. The average working space score (AWSS) was evaluated at the left and right renal artery, left and right side of the coeliac trunk, superior mesenteric and common hepatic artery. The score was defined as: (0) vessel not visible, (1) working space at the vessel ≤ 1x diameter of the aorta, (2) < 3x the diameter of the aorta, (3) ≥ 3x diameter of the aorta. RESULTS: The maximum AWSS of 3 was achieved at key vascular landmarks through specific mobilization techniques. CONCLUSION: Additional mobilization of spleen, pancreas and mesenteric root and access to the bursa omentalis increase surgical working space at major visceral arteries. The results of our investigation provide surgeons with a useful guide to prepare for abdominal neuroblastoma resection.

[Autologous kidney transplantation in a high-risk patient with locally advanced retroperitoneal neuroblastoma]. / Autologicheskaya transplantatsiya pochki u patsienta s mestnorasprostranennoi neiroblastomoi zabryushinnogo prostranstva gruppy vysokogo riska. Klinicheskoe nablyudenie.

Surgery of locally advanced neuroblastoma with risk factors is one of the most difficult in pediatric surgery. Incidence of nephrectomy during subtotal or complete tumor resection is higher due to common involvement of renal vessels. We present a patient with locally advanced retroperitoneal neuroblastoma who underwent heterotopic kidney autotransplantation.

Image-defined risk factors in localized thoracic neuroblastoma and ganglioneuroma.

BACKGROUND: The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection. METHODS: Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included. Imaging at diagnosis and operative reports were reviewed retrospectively. IDRFs were assessed centrally and correlated to International Neuroblastoma Staging System (INSS) stage and extent of tumor resection. Additionally, we analyzed data on surgery-related complications. RESULTS: Imaging series of 88 patients were available for central review. In 18 children, no IDRF was present, 28 exhibited one IDRF, 42 two or more IDRFs, resulting in 70 patients with L2 disease. The most frequently observed IDRF was encasement of any vessel (n = 38). Initial surgical resection was aimed for in 45 patients (L1: n = 11; L2: n = 34). Complete and gross total resection rates were higher children with L2 NB (n = 8/25 L1, n = 17/25 L2 vs. n = 2/15 L1, n = 13/15 L2, respectively). The proportion of surgical complications was very similar between INRGSS L1 and L2 (n = 4/11 vs. n = 17/34). All complications were manageable, and no surgery-related deaths were observed. CONCLUSION: In this retrospective cohort, the extent of resection and the rate of surgical complications did not differ substantially between patients classified as L1/L2, indicating that INRGSS L2 does not equate unresectability. It appeared that individual IDRFs differ in value. Larger studies are needed to assess the significance and therapeutic/prognostic impact of such findings.

Safety and feasibility of laparoscopic resection of abdominal neuroblastoma without image-defined risk factors: a single-center experience.

OBJECTIVE: To explore the criteria, safety and efficacy of laparoscopic surgery in pediatric neuroblastoma (NB). METHODS: A retrospective study of 87 patients with NB without image-defined risk factors (IDRFs) between December 2016 and January 2021 at Beijing Children's Hospital was conducted. Patients were divided into two groups according to the surgical procedure. RESULTS: Between the 87 patients, there were 54 (62.07%) cases in the open surgery group and 33 (37.93%) cases in the laparoscopic surgery group. There were no significant differences between the two groups regarding demographic characteristics, genomic and biological features, operating time or postoperative complications. However, in terms of intraoperative bleeding (p = 0.013) and the time to start postoperative feeding after surgery (p = 0.002), the laparoscopic group was obviously better than the open group. Furthermore, there was no significant difference in the prognosis between the two groups, and no recurrence or death was observed. CONCLUSION: For children with localized NB who have no IDRFs, laparoscopic surgery could be performed safely and effectively. Surgeons who are skilled in this can help children reduce surgical injuries, speed up postoperative recovery, and obtain the same prognosis as open surgery.

Unresectable thoracic neuroblastic tumors: Changes in image-defined risk factors after chemotherapy and impact on surgical management.

PURPOSE: Neuroblastoma management in children is multimodal and depends on multiple factors, including the possibility of complete surgical resection. Image-defined risk factors (IDRFs) are used to assess the feasibility of primary surgery. We studied the changes in IDRFs after neoadjuvant chemotherapy for thoracic neurogenic tumors. METHODS: We performed a multicenter review of 27 patients presenting with unresectable thoracic neurogenic tumors. Patients received neoadjuvant chemotherapy, according to their risk group. IDRF at diagnosis and before surgery were retrospectively analyzed by a radiologist and a surgeon, blind to the initial assessment. Surgical and oncologic outcomes were reviewed. RESULTS: None of the patients presented MYCN amplification, and 78 IDRFs were identified at diagnosis. Vascular IDRFs were the most frequent, with 28 vascular IDRFs detected in 18 patients, 22 of which disappeared after chemotherapy. Reductions of tumor volume were associated with a regression of IDRFs. Patients undergoing minimally invasive surgery had smaller tumor volumes than those undergoing open surgery, and no vascular IDRF. Two patients received two additional courses of chemotherapy to reduce tumor volume sufficiently for surgery. One patient with ganglioneuroblastoma underwent early surgery due to a lack of response to initial chemotherapy. CONCLUSION: Tumor volume reduction with neoadjuvant chemotherapy eliminates most IDRF in thoracic neurogenic tumors. Vascular IDRF are rapidly resolved at this site, making surgical resection and minimally invasive surgery possible.

A phase II JN-I-10 efficacy study of IDRF-based surgical decisions and stepwise treatment intensification for patients with intermediate-risk neuroblastoma: a study protocol.

BACKGROUND: Few clinical trials have been reported for patients with intermediate-risk neuroblastoma because of the scarcity of the disease and the variety of clinical and biological characteristics. A multidisciplinary treatment that consists of multidrug chemotherapy and surgery is expected to lead to a good prognosis with few complications. Therefore, a clinical trial for patients with intermediate-risk tumors was designed to establish a standard treatment that reduces complications and achieves good outcomes. METHODS: We planned a prospective phase 2, single-arm study of the efficacy of image-defined risk factors (IDRF)-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. For the localized tumor group, IDRF evaluations will be performed after each three-course chemotherapy, and surgery will be performed when appropriate. For patients with metastatic tumors, a total of five chemotherapy courses will be performed, and primary lesions will be removed when the IDRF becomes negative. The primary endpoint is 3-year progression-free survival rate, and the secondary endpoints include 3-year progression-free survival rates and overall survival rates of the localized group and the metastasis group and the incidence of adverse events. From international results, 75% is considered an appropriate 3-year progression-free survival rate. If this trial's expected 3-year progression-free survival rate of 85% is statistically greater than 75% in the lower limit of the 95.3% confidence interval, with an accuracy 10% (85 ± 10%), both groups require more than 65 patients. DISCUSSION: This study is the first clinical trial on the efficacy of IDRF-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. We expect that this study will contribute to the establishment of a standard treatment for patients with intermediate-risk neuroblastoma. TRIAL REGISTRATION: UMIN000004700, jRCTs051180203; Registered on December 9, 2010.

How well do image-defined risk factors (IDRFs) predict surgical outcomes and survival in patients with neuroblastoma? A systematic review and meta-analysis.

INTRODUCTION: Since their introduction to the International Neuroblastoma Risk Group (INRG) staging system in 2009, the role of Image-Defined Risk Factors (IDRFs) in predicting outcomes has been studied in heterogeneous populations with varying results. We conducted a systematic review and meta-analysis in order to determine quantitative measures of precisely how well pre-treatment IDRFs predict surgical outcomes and survival. METHODS: A systematic review was performed for studies between January 1990 and July 2019 that compared surgical outcomes and/or survival in pediatric neuroblastoma patients with one or more IDRFs to patients without IDRFs. Summary risk ratios (RR) and hazard ratios (HR) were calculated using a random-effects model. RESULTS: 19 retrospective cohort studies were included, representing data from 1132 patients. The risk ratio (RR) of incomplete surgical resection in IDRF-positive patients compared to IDRF-negative patients was 2.45 (95% CI 1.51-3.97). The RR of surgical complications was 2.30 (95% CI 1.46-3.61). The hazard ratio (HR) for 5-year EFS was 2.08 (95% CI 2.93-4.13) while the 5-year HR for OS was 2.44 (95% CI 1.46-4.08). CONCLUSION: IDRF-positive neuroblastoma patients have a higher risk of incomplete surgical resection, surgical complications, and 5-year mortality and/or relapse. Our results affirm that IDRFs remain a useful prognostic tool for neuroblastoma patients both for short and long-term outcomes. LEVEL OF EVIDENCE: II.

Image-defined risk factors in unresectable neuroblastoma: SIOPEN study on incidence, chemotherapy-induced variation, and impact on surgical outcomes.

PURPOSE: To evaluate the impact of image-defined risk factor (IDRF) modification after chemotherapy on surgical outcomes, event-free survival (EFS), and overall survival (OS) among patients enrolled in the European Unresectable Neuroblastoma (EUNB) study. METHODS: IDRFs were assigned according to the corresponding surgical risk factors list reported in the database. Surgical outcomes, EFS, and OS were related to IDRF modification with chemotherapy. The predictive value of preoperative IDRF for surgical outcomes was analyzed. Cox proportional hazards models for EFS and OS, including preoperative IDRF, surgical outcomes, and other known clinical risk factors, were created. RESULTS: Of the 160 patients enrolled in the EUNB study, 143 patients met the inclusion criteria. A total of 228 IDRF were thus collected. Following chemotherapy, 76 (33%) IDRF disappeared in 32.2% of patients, 33 (14%) new IDRF appeared in 18.8% of patients, and 49% of patients did not show any IDRF change. Complete resection/minimal residual disease (71.2%) was more frequent among children who had disappearance/numerical reduction of IDRF (P = 0.005). Infiltration of the branches of the mesenteric artery was predictive of an unfavorable surgical outcome. Prolonged preoperative chemotherapy over five courses and encasement of the celiac axis and/or mesenteric artery origin impacted EFS and OS. CONCLUSIONS: The unchanged IDRF pattern in 50% of patients and the appearance of new IDRF during chemotherapy in approximately 20% of patients strengthens the idea that prolonged chemotherapy is useless for improving surgical resection in this population of patients. In addition, midline perivascular abdominal preoperative IDRF appeared to be predictive not only of surgical outcomes but also of EFS and OS.

Bilateral adrenal neuroblastoma in the infant: Is it an image-defined risk factor?

The treatment of neuroblastoma is based on the International Neuroblastoma Risk Group stratification considering life-threatening symptoms, image-defined risk factors (IDRFs), presence and site of metastases, biology, and histopathology. The authors present an infant with bilateral nonmetastatic adrenal neuroblastoma with favorable biology. Both tumors were resectable and without IDRFs, but bilateral resection was considered mutilating, so it was decided to operate one side only. The authors suggest considering bilaterality among IDRFs.

Contraindications and image-defined risk factors in laparoscopic resection of abdominal neuroblastoma.

PURPOSE: Minimally invasive surgery (MIS) has become widely accepted as a technique for abdominal neuroblastoma resection. However, the indications for MIS are still controversial. The aim of this study was to evaluate image-defined risk factors (IDRFs), complications, and oncologic outcomes in patients with abdominal neuroblastomas treated with MIS. METHODS: Between August 1998 and February 2016, MIS was planned for 20 children with abdominal neuroblastomas. Clinical data were retrospectively reviewed and compared between the IDRF-negative and IDRF-positive patients. RESULTS: On the basis of the latest IDRF guidelines, five patients were classified as IDRF-positive and four of them had operative complications; namely, partial infarction of the ipsilateral kidney or open conversion. Concerning the two patients who needed open conversion, the primary reason for open conversion was difficulty in dissection of the tumor from the vena cava. Preoperative images of these cases showed either deformation or subtotal encasement of the vena cava. Relapse occurred in three high-risk patients and in none of the low/intermediate-risk patients. No complication occurred in the IDRF-negative cases. CONCLUSIONS: IDRF-negative might be a good indication for MIS for abdominal neuroblastoma. However, deformation or subtotal encasement of the vena cava should be considered as IDRF-positive for MIS.

Image-defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra-operative risk factors and the completeness of resection.

BACKGROUND: Patients with neuroblastoma are now stratified at diagnosis according to the presence and number of image-defined risk factors (IDRFs). We examined the added value of IDRF assessment after neoadjuvant chemotherapy for predicting surgical resection. MATERIAL AND METHODS: From 2009-2012, 39 out of 91 patients operated on in our institution for neuroblastic tumors received neoadjuvant chemotherapy based on ongoing SIOPEN protocols or treatment guidelines. IDRFs were assessed both at diagnosis and preoperatively on CT and/or MRI. RESULTS: Median age at diagnosis was 30 months [range 2-191]. The tumor locations were adrenal (n = 20), paravertebral (n = 13) and perivascular (n = 6). INRGSS stages were L2 (n = 13), M (n = 25) and Ms (n = 1). Eleven tumors (28%) were MYCN-amplified. Chemotherapy reduced the number of IDRFs in 54% of patients overall (21/39): 61.5% (16/26) of M and Ms patients, and 38.5% (5/13) of non metastatic patients (P < 0.001). The number of IDRFs lost after chemotherapy was proportional to the degree of tumor shrinkage (P = 0.002), independent of the primary tumor location (P = 0.73), although the number was higher in patients with left versus right adrenal locations (P = 0.004). Patients with neuroblastoma on post-surgical histology lost more IDRFs (median: 1[0-9]) than patients with ganglioneuroblastoma (median: 0[0-4]) (P < 0.001). The completeness of resection was related only to the number of preoperative IDRFs (P = 0.028). CONCLUSION: IDRF assessment after neoadjuvant chemotherapy is useful for predicting completeness of resection of neurogenic tumors. A larger international study is needed to confirm these results and to explore a possible correlation between preoperative IDRF status and survival.

Minimally invasive surgery of neuroblastic tumors in children: Indications depend on anatomical location and image-defined risk factors.

BACKGROUND: Minimally invasive surgery (MIS) is still not a well-accepted surgical approach to remove neuroblastic tumors. We aimed to assess the indications and limits of MIS in this childhood tumor according to tumor location and image-defined risk factors (IDRFs). PROCEDURE: Between 2006 and 2012, 39 patients underwent MIS for neuroblastic tumors, using thoracoscopic (n = 20), retroperitoneoscopic (n = 1) or laparoscopic approaches (n = 18). The tumor locations were paravertebral (n = 18; thoracic n = 15, lumbar n = 3), perivascular (n = 5; abdominal n = 2; thoracic n = 3), adrenal (n = 13), pleural (n = 2) and pelvic (n = 1). Two patients were treated for relapses. According to the INRG staging system, IDRFs were absent in 20 patients and present in 19 patients. Ten patients received chemotherapy preoperatively. Mean largest diameter was 35 mm for thoracic tumors (range: 7-85 mm) and 34 mm for abdominal tumors (range: 10-75 mm). Mean follow-up was 25 months (range: 5-116 months). RESULTS: Resection was macroscopically incomplete (R2) for six thoracic tumors and one adrenal tumor. Conversion was necessary for three thoracic L2 tumors. Postoperative complications consisted of chylothorax in three patients with L2 paravertebral thoracic tumors, Horner's syndrome in a patient with a cervicothoracic tumor, and renal atrophy in a patient with a L2 abdominal tumor. No perioperative or postoperative complications occurred in patients with adrenal and abdominal paravertebral tumors. The overall survival rate was 98%. CONCLUSION: In carefully selected cases, MIS permits safe and efficient resection of neuroblastic tumors in children. Open surgical approach should be considered if organ or vascular control or quality of resection is jeopardized. Pediatr Blood Cancer 2015;62:257-261. © 2014 Wiley Periodicals, Inc.

Retroperitoneoscopic or Transperitoneal Approach for Neurogenic and Adrenal Tumors in Children? A Comparison on the Way to Enhanced Recovery in Pediatric Surgical Oncology.

BACKGROUND: Minimally invasive surgery is increasingly utilized for resection of neurogenic tumors in children. The minimally invasive retroperitoneoscopic approach was recently reported in children, but transperitoneal laparoscopy still remains the most common technique. The aim of this study is to compare a novel single-port retroperitoneoscopy (SPR) approach for pediatric neurogenic tumor resection with transperitoneal laparoscopic (TPL). METHODS: Patients undergoing minimally invasive resection of abdominal neurogenic tumors over 5 years at a single institution (from 2018 to 2022) were retrospectively reviewed. Tumor volume, stage, presence of image-defined risk factors (IDRFs), neoadjuvant chemotherapy, operative time, estimated blood loss (EBL), length of stay (LOS), complications, oral morphine equivalents per kilogram (OME/Kg), and time to chemotherapy were assessed and compared with SPR and TPL approaches. RESULTS: Eighteen and fifteen patients underwent TPL and SPR, respectively. No significant differences were found between the TPL and SPR approaches in terms of tumor characteristics and IDRFs. Patients who underwent SPR had a significantly faster recovery (p = 0.008) and less postoperative opioid use compared to those in TPL (p = 0.02), thus allowing an enhanced recovery after surgery (ERAS) protocol application. TPL and SPR approaches were performed in presence of IDRFs, respectively in 2 (11%) and 4 patients (27%), with a IDRFs-related conversion in one TPL procedure. Both approaches had one < Grade 3 Clavien Dindo complication, but not requiring further surgery. DISCUSSION: SPR approach can be considered as a safe and feasible minimally invasive approach for the resection of pediatric primary adrenal and neurogenic tumors. The retroperitoneoscopic approach performed using a single port technique represents a promising new frontier of ERAS application in pediatric surgical oncology. CONCLUSION: SPR is a viable surgical alternative in selected neurogenic abdominal tumors with limited IDRFs, thus allowing for the application of ERAS protocols in these patients. LEVEL OF EVIDENCE: Level III.

Minimally invasive surgery for neuroblastic tumours: A SIOPEN multicentre study: Proposal for guidelines.

INTRODUCTION: Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. MATERIALS & METHODS: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. RESULTS: A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. CONCLUSIONS: MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours.

Safety and Feasibility of Laparoscopic Resection of Neuroblastoma Without Image-Defined Risk Factors Performed by Pediatric Surgical Trainees: A Multicenter Comparison Study.

Introduction: Laparoscopic resection has gradually been adopted for neuroblastoma patients; however, some authors reported that, due to its technically demanding procedures, this operation should be performed only by highly experienced surgeons. The aim of this study was to evaluate the safety and feasibility of laparoscopic resection of abdominal neuroblastoma by pediatric surgical trainees. Subjects and Methods: In this multicenter, retrospective study, including 18 children with abdominal neuroblastoma indicated for 19 laparoscopic resections (1 with bilateral neuroblastomas) from 1999 to 2018, the clinical data were retrospectively reviewed and compared between trainee and attending surgeons. Results: None of the cases had image-defined risk factors (IDRFs) at surgery. All patients successfully underwent complete laparoscopic resection without blood transfusion, open conversion, or intraoperative or postoperative complications. Of the 19 cases, 6 were performed by pediatric surgical trainees under the guidance of attending surgeons, and 13 were performed by attending surgeons. With comparable tumor, largest diameter, operative time, and bleeding amount were not significantly different between the two groups. In the trainee surgeon group, one local recurrence occurred at a secondary resection site in the bilateral neuroblastoma patient with Stage L2. Conclusions: Laparoscopic resection of neuroblastoma could be safe and feasible when limited to absent IDRFs at surgery by pediatric surgical trainees under the guidance of experienced attending surgeons, as well as by attending surgeons.

Long term outcomes after concurrent ipsilateral nephrectomy versus kidney-sparing surgery for high-risk, intraabdominal neuroblastoma.

PURPOSE: The impact of the extent of surgical resection including nephrectomy for high-risk neuroblastoma patients is controversial. In this study, we compared the renal late effects and long-term survival for patients who underwent kidney-sparing surgery (KSS) versus concurrent ipsilateral nephrectomy (CIN) for high-risk, intraabdominal neuroblastoma (HRIN). METHODS: A retrospective analysis of patients diagnosed with HRIN between Jan 1998 and Dec 2008 in a tertiary referral center was performed. Demographics, preoperative features, surgical resection extent and outcomes were analyzed. RESULTS: Of 58 patients who underwent surgical management of HRIN, 6 underwent CIN and 52 underwent KSS. Renal image-defined risk factors (IDRFs) were more common in patients who underwent CIN. Operating time was longer and EBL higher in CIN patients. There was no difference in recurrence or overall survival between the groups. Estimated GFR (eGFR) was comparable between the groups preoperatively, but was reduced postoperatively and at long-term follow-up in patients who underwent CIN. CONCLUSION: Compared to KSS, CIN is not associated with an increase in local recurrence or inferior survival but does lead to reduced kidney function (eGFR of 90 ml/min/1.73 m2 for CIN versus 127 ml/min/1.73 m2 for KSS, p = 0.03) but without significant impact on clinical outcome. LEVELS OF EVIDENCE: III (Retrospective comparative study).

Anatomical reduction and precise internal fixation of intra-articular fractures of the distal radius with virtual X-ray and 3D printing.

To evaluate and precisely internal fix intra-articular distal radial fracture (IDRF) using the virtual X-ray and three-dimensional (3D) printing technologies. Twenty-one patients with IDRF were recruited, and the data from digital design group (DDG) and real surgery group (RSG) were collected and analyzed. In DDG, the data from thin-slice computed tomography scan, virtual X-ray measurement parameters, including volar tilt, palmar tilt, radius length (D1), ulnar variation (D2), locking plate position parameter (D3) and distance between key nail and joint surface (D4) were collected. The bone was virtually fixed with the locking plate, and the final model of radius with the screw was obtained by 3D printing. In RSG, the locking plate was precisely pre-bended and used in surgery. During the surgery, the key K-wire was accurately placed and the locking plate was adjusted with the aid of the U-shaped navigation arm. The C-arm was used to observe the positions of key K-wires and the locking plate, and the same above-mentioned parameters were measured intra- and post-operatively. The data from RSG and DDG were compared statistically by t test. This approach proved to be successful in all 21 patients, and none of the screws pierced through the wrist joint surface. All the measured parameters, including the volar tilt, palmar tilt, D1-4, in RSG were not significantly different from preoperative DDG data. Virtual X-ray measurement of anatomical reduction parameters and 3D printing can help the anatomical reduction and precise internal fixation by providing quantitative references, preoperatively, intraoperatively and postoperatively.