Background and Aims

Incomplete tumor resection increases the risk of local recurrence. However, the standard of care approach to distinguishing tumor tissue is less than optimal, as it depends on a conglomeration of preoperative imaging and visual and tactile indicators in real time. This approach is associated with a significant risk of inadequate resection; therefore, a novel approach that delineates the accurate intraoperative definition of pediatric tumors is urgently needed.

ICG is a fluorescent dye that when administered intravenously accumulates passively in the tumor because of enhanced permeability and retention (EPR) effect, thereby providing tumor contrast for intraoperative real-time tumor recognition.

This retrospective study examines the feasibility of ICG-guided tumor resection in common childhood solid tumors such as neuroblastoma, sarcomas, hepatic tumors, pulmonary metastases, and other rare tumors. Pediatric dosing and challenges related to the optimization of tumor-to-background ratio are also examined.

Methods

This study was approved by the St. Jude institutional review board and waiver of informed consent was approved. We retrospectively reviewed the charts of all patients who underwent fluorescence-guided tumor resection at our institution from 2019 through 2020. Data on preoperative diagnosis and imaging findings, ICG dose, timing of ICG administration, operative notes, Iridium system video recording, intraoperative fluorescence, background noise, histopathology report, and complications were collected.

Results

Fifty-five patients (28 males and 27 females; median age 10 years [range <1–21 years]) underwent fluorescence-guided tumor resection. Of them, eight underwent two procedures and one patient underwent three procedures. The total number of procedures done was 65, including 37 thoracic, 19 abdominal (other than nephron-sparing resections) and 9 trunk and extremity operations. The sensitivity of NIR to identify tumor was 88% and specificity was 77%.

Conclusions

ICG-guided tumor localization is a feasible adjunct for most pediatric solid tumors and is highly sensitive for tumor tissue but its specificity is low

Background and Aims

Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. Therefore, an enhancement of HIPEC using photodynamic therapy might be beneficial. For this approach, we tested a combination of the photosensitizer Hypericin with HIPEC in an animal model.

Methods

Alveolar rhabdomyosarcoma cells were xenotransplanted into NOD/LtSzscid IL2Rγnullmice (n=80) inducing intraperitoneal sarcomatosis. All groups received Hypericin (100 µg/200 µl) intraperitoneally with and without cisplatin-based (30 or 60mg/m2 ) HIPEC (37 or 42°C, for 60 min) (five groups, each n=16). Hypericin-based photodynamic therapy (PDT) of a representative tumor bulk was performed in all groups for ten minutes. Tumor dissemination was documented visually and by using Hypericin-based fluorescence guidance. Tumor and tissue samples, harvested at the end of the perfusion, were evaluated regarding morphology (H&E staining), proliferation (Ki-67 staining) and apoptosis (TUNEL-assay).

Results

A time dependent Hypericin uptake even in smallest tumor nodes (< 1 mm) was found. Hypericin-based fluorescence guidance detected a higher tumor dissemination compared to the visible tumor spread. Immunohistochemistry revealed a Hypericin penetration across the tumor surface. Hypericin-based PDT without HIPEC induced marginal apoptotic effects only at the tumor surface. Combining Hypericin with HIPEC revealed cisplatin-concentration dependent decrease in proliferation capacity and induction of apoptosis across determined cell layers of the tumor surfaces.

Conclusions

Hypericin as fluorescending photosensitizer offers an intraoperative diagnostic advantage detecting the exact intraperitoneal tumor dissemination. The combination of Hypericin and cisplatin-based HIPEC was feasible in vivo. Effects on tumor proliferation and apoptosis induction across the tumor surface were observed. Further studies combining Hypericin and HIPEC as new therapy approach will follow to establish a clinical application.

Background and Aims

Surgery for posteromediastinal paediatric tumors carries the risk of injury to the Artery of Adamkiewicz (AKA). Cases of severe neurological complications in children following tumor resection in this area have been reported. Spinal diagnostic subtraction angiography (DSA) is the method of choice for visualization of AKA. Data on the preoperative use of spinal DSA in children for this purpose are rare.

Methods

Between 2002 und 2021 36 children with posterior mediastinal tumors were evaluated for surgery at our department. DSA was used to asses AKA during the preoperative workup in 10/36 children with left sided or bilateral tumor localized at the vertebral level T8 to L1. We analyzed patient’s data, tumor characteristics as well as diagnostic and therapeutical procedures.

Results

Tumor entities were neuroblastoma (n = 3), ganglioneuroblastoma (n = 2), ganglioneuroma (n = 2), local relapse of a hepatocellular carcinoma (n = 1), and neurofibroma (n = 2). Median age of the children at examination was 79 months (16 – 217), 3 of them were younger than two years. The AKA could be visualized in all children. In 5 children, the tumor and AKA were on the same side and at the same level; consequently, 2 of these children underwent irradiation instead of tumor resection. In 1 child with thoracoabdominal neuroblastoma resection of the abdominal and irradiation of the thoracic tumor part was performed. Two children with neurofibroma underwent surgery in the form of intracapsular resection. Spinal DSA and subsequent operations were carried out without complications.

Conclusions

Spinal DSA is a safe and reliable method for preoperative identification of AKA for surgery in posteromediastinal paediatric tumors. With its possible impact on the decision regarding local treatment it can help to avoid critical situations during or after surgery and to determine the most appropriate local therapy.

Background and Aims

Sacrococcygeal teratoma (SCT) is a rare paediatric germ cell tumour (1:40 000). Long-term data regarding urinary tract and bowel function after SCT resection is limited. This surgeon-led UK multicentre study aimed to critically analyse long-term functional sequalae in patients following resection of SCT.

Methods

A multicentre study registry amongst UK paediatric surgical oncology centres was established. All index cases of newborns/ infants and children <16 years with SCT diagnosis during 2005-2015 were included.

Results

110 patients treated at 10 surgical oncology centres were included. Mean age at surgery was 1 day [IQR 0-7 days]. Seventy (64%) patients were female, 40 male. Diagnosis was established antenatally in 52% (57) cases. 61% of patients were Altman Stage I or II, 39% were Altman Stage III or IV. Follow-up data was available on 105 out of 110 (95%) patients. Median length of follow-up was 60 months [IQR 43-87 months]. Eight (7%) patients had recurrent disease at a median time of 9.5 months [IQR 7-50.5 months] following operation. Thirty-seven out of 110 patients (34%) developed bladder and/or bowel dysfunction. Fifteen patients required urinary clean intermittent catheterisation (CIC). Bowel dysfunction was managed purely medically in 19 patients; 7 patients required surgery for management of bowel dysfunction (ACE [n=2], colostomy [n=4], anorectal reconstruction [n=1]).

Conclusions

In this UK nationwide study, 34% of patients developed bladder or bowel dysfunction after primary SCT resection. Full assessment of bladder and bowel function is mandatory during follow-up of all patients having SCT resection(s). A multi-disciplinary surgical care pathway is crucial to facilitate best practice, monitor long term health and improve patient quality of life (QoL).

Background and Aims

WAGR syndrome (Wilms Tumor Aniridia Genitourinary Malformations and range of development delays) is a rare disease. Children with WAGR have a predisposition to Wilms Tumor (WT). We present an epidemiological analysis of tumor characteristics, treatment, and associated congenital risk factors in WAGR patients with WT.

Methods

The IWSA conducted a survey between 2015-2021. Demographic, surgical, chemotherapeutic, radiotherapy and congenital anomalies that predisposed to WT were analyzed. Categorical comparisons were made with chi-squared test and continuous comparisons were made using t-test and ANOVA.

Results

Parents of 145 children with WAGR completed the questionnaire, of whom 64(44.1%) had WT and 12(8.2%) had nephrogenic rests. Median length of follow-up from the diagnosis of WT was 6.7 years (IQR 2.5-13.4 years), median age at diagnosis was 26 months (IQR 18-26 months). One child was diagnosed after 5 years of age. Fifty-four(84.3%) had unilateral stage 1-2 disease and 59(92.1%) had favorable histology WT(FHWT). One child developed bilateral WT (BWT); only 2 had stage IV disease. Treatment included preoperative chemotherapy for 47 children and primary nephrectomy for 15. At least one kidney was removed in 38. Nephron sparing surgery (NSS) was associated with preoperative chemotherapy 19/24(79.1%) compared to upfront surgery 5/24(20.8%). The duration of chemotherapy was between 1-12 months in 50 children and was more prolonged in 8 (duration was unknown for 6 children). Chemotherapy included a two-drug regimen for 21 and a three-drug or more intensive therapy in 34. Relapse occurred in 3(4.6%) children. There was one death. No congenital genitourinary anomalies in children with WAGR (e.g. hypospadias, cryptorchidism) were associated with the development of WT.

Conclusions

In this analysis of children with WAGR syndrome and WT their disease was primarily unilateral and FHWT with infrequent relapse. Regrettably, NSS was performed in only 1/3 of children.

Background and Aims

No widely agreed protocols exist for the management of benign ovarian tumors (BOT) in children. Patients present in a multitude of settings, and to various specialties including paediatric oncology surgeons, paediatric general surgeons and gynaecologists. Recent studies demonstrate significant risk of metachronous disease. The lack of unified guidance and heterogeneity of approaches present a substantial risk for suboptimal management.

This study aimed to generate a multi-specialty consensus statement to clarify current perioperative controversies and establish clear follow-up guidance for children with BOTs.

Methods

A prospective consensus study with a two-round confidential e-Delphi consensus survey was distributed amongst a multi-specialty expert panel; concluded by two semi-structured videoconferences.

Results

Consensus guidance was developed for 4 domains: Pre-operative, intra-operative management, follow-up and referral to adolescent gynaecology. Summary of salient points:

1) Children with BOTs should receive the same management as other children with potentially neoplastic lesions. This includes pre-operative discussion at the oncology multi-disciplinary meeting to risk stratify tumours, and management by specialists with expertise in ovarian-sparing surgery and laparoscopy.

2) Ovarian-sparing surgery for BOTs should be performed wherever possible to maximise fertility preservation.

3) Ovarian masses detected during emergency diagnostic laparoscopy/laparotomy should be left in situ and investigated appropriately (imaging/tumour markers) prior to planned resection.

4) Follow-up: The first appointment should be scheduled with ultrasound within 3 months following resection, then within 2 years after resection, then every 2 years until 16 years. Following resection of an ovarian tumour all patients should be referred to adolescent gynaecology to discuss implications on future fertility/ fertility preservation. The referral should take place once the patient is post-pubertal (16 years).

Conclusions

This first multi-specialty consensus guideline emphasizes the importance of treating children with BOTs according to oncological principles, highlights the need for maximal fertility preservation by ovarian-sparing surgery for BOTs, and outlines a clear follow-up protocol which facilitates detection of metachronous disease early.

Background and Aims

Thyroid gland malignancy is rare in pediatrics (0.7% of tumors); only 1.8% are observed in patients < 20 yrs with a higher prevalence recorded in females and adolescents. Risk factors include genetic syndromes - MEN disorders, autoimmune disease and ionizing radiation exposure. Radiotherapy is also linked with increased risk of secondary thyroid cancers. The present study describes the clinical features and surgical outcomes of primary and secondary thyroid tumors.

Methods

Institutional data was collected on pediatric patients with thyroid cancer during 2000 - 2020 from 8 International Surgical Oncology centers. Statistical analysis was performed using GraphPad Prism.

Results

Of 298 cases of thyroid cancer, only 19 (6.4%) were secondary tumors. Primary thyroid malignancies were more likely to be multifocal in origin (odds ratio [OR] 1.993, 95% confidence interval [CI] 0.7466-5.132, p 0.2323), had bilateral glandular location (OR 2.847, 95% CI 0.6835-12.68, p 0.2648) and proved metastatic at 1^st diagnosis (OR 1.259, 95% CI 0.3267-5.696 p>0.999). Secondary tumors showed a higher incidence of disease relapse (OR 1.556, 95% CI0.4579-5.57, p 0.4525) and surgical morbidity (OR 2.042, 95% CI 0.7917-5.221, p 0.1614) including hypoparathyroidism and recurrent laryngeal nerve injury. Overall survival (OS) was 99% at 1 year and 97% after 10 years. No EFS differences were evident with primary vs. secondary tumors (Chi square 0.7307, p 0.39026).

Conclusions

This multicenter study demonstrates excellent survival for pediatric thyroid malignancy. Secondary tumors exhibit greater disease relapse (15.8% vs 10.5%) and a higher incidence of surgical related complications (36.8% vs 22.2%).

Background and Aims

Introduction: Regional lymph node disease (RLND) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of RLND to prognosis for patients with nonmetastatic embryonal RMS (ERMS).

Methods

Methods: Between 2005 and 2016, of the 1760 children enrolled onto EpSSG RMS 2005 protocol we analyzed 143 patients (pts) diagnosed with ERMS and RLND. Local therapy with radiotherapy (primary tumor and involved nodes) began at week 12.

Results

Results: most pts had tumors with unfavorable characteristics: tumor size >5 cm 70%, T2 invasiveness 70%, IRS III 84%, and parameningeal (PM) (40%). The 5-year event-free survival (EFS) was 65.2%, Overall Survival (OS) 70%. N1 ERMS pts had a significantly better outcome than those with N1 alveolar RMS (EFS 65% vs 49%; OS 70% vs 51.2%; p=0.03). Outcomes were significantly better for pts with favorable vs unfavorable tumor site (EFS 73% vs 50%, OS 77% vs 53% p=0.002) and those with tumor size< 5 cm vs >5 cm (EFS 72.5% vs 49.4%, OS 76% vs 53.9%, p=0.0009). IRS II pts have also a significantly better outcome vs IRS III pts (EFS 84.5% vs 52.2%, OS 89% vs 56.5%, p=0.0006). EFS and OS was not statistically different comparing 94 pts receiving and 32 not receiving nodal irradiation (65.5% vs 75%, 69.6% vs 77.7% p=0.3) but in the first group unfavorable features (PM site, size, age, IRS III and invasiveness) were more frequent. On univariate analysis, larger tumor, unfavorable site, invasiveness, IRS group III, correlated with worse prognosis. On multivariate analysis, IRS Group remained as the only significant prognostic variable but it does not seem to be a consistent estimator.

Conclusions

Conclusion: Regional lymph node disease does not alter prognosis for ERMS. The role of radiotherapy to nodes has to be reconsidered in a larger prospective study.