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The International Society of Paediatric Surgical Oncology (IPSO)
Session Type
The International Society of Paediatric Surgical Oncology (IPSO)
Room
Hall 3
Date
14.10.2020, Wednesday
Session Time
11:45 AM - 12:30 PM

A NEW VALID ANIMAL MODEL FOR THE EVALUATION OF HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC) IN PEDIATRIC RHABDOMYOSARCOMA

Session Type
The International Society of Paediatric Surgical Oncology (IPSO)
Date
14.10.2020, Wednesday
Session Time
11:45 AM - 12:30 PM
Room
Hall 3
Lecture Time
11:45 AM - 11:50 AM

Abstract

Background and Aims

Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as novel treatment approach for peritoneal sarcomatosis (PS). Despite of promising clinical reports, there is still a lack of knowledge regarding optimal drug combinations, treatment duration and local effects. To answer these questions, we intended to establish a murine animal model for further evaluation.

Methods

Human alveolar rhabdomyosarcoma cells were xenotransplanted into NOD/LtSz-scid IL2Rγnull-mice (n=96). In the control group, a continuously intraperitoneal lavage with isotonic saline solution (37° or 42°C, n=16) was used. In the treatment group, animals were treated with intraperitoneal cisplatin (30 or 60mg/m2) for 60 minutes at 37° or 42°C (n=16). Tumor dissemination was documented by the peritoneal cancer index (PCI) adapted for the animal model. Tumor samples were harvested at the end of the perfusion. Histopathological and immunohistochemical studies using H&E-, KI-67-, and Cleaved Caspase 3-staining were carried out. Apoptotic effects were evaluated by using TUNEL-assay method. Additionally, abdominal tumor spread was documented by 7-T-small animal MRI.

Results

We found an extensive peritoneal dissemination in over 91% of the cases (Median PCI: 8). HIPEC was feasible without acute side effects. Immunohistochemistry using KI-67 revealed no early concentration- or temperature-dependent effects of cisplatin-based HIPEC on the tumors as there were no observed effects regarding the cell viability. Immunohistochemical investigation with Cleaved Caspase-3 and immunofluorescence microscopy using TUNEL-assay detected scattered apoptotic effects at the outer tumor surface. MRI scans confirmed the observed tumor dissemination.

Conclusions

This is the first successful animal model for evaluation of HIPEC in pediatric rhabdomyosarcoma in mice. Cisplatin-based HIPEC had no early effects on the proliferation whereas circumscribed apoptotic effects could be detected at the tumor surface. This model allows further insights on the possible efficiency of HIPEC in RMS. Further studies using other drug combinations and treatment will follow.

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ALTERNATIVE APPROACHES TO RETROPERITONEAL LYMPH NODE DISSECTION FOR PARATESTICULAR RHABDOMYOSARCOMA

Abstract

Background and Aims

Purpose

The aim of this study was to evaluate outcomes based on surgical approach for retroperitoneal lymph node dissection (RPLND) in patients with paratesticular rhabdomyosarcoma (PT-RMS).

Methods

Patients undergoing RPLND for PT-RMS over 10 years at a single institution were retrospectively reviewed. Length of stay (LOS), complications, oral morphine equivalents per kilogram (OME/Kg), lymph node yield, and time to chemotherapy were assessed. The surgical approaches compared were: open transabdominal, open extraperitoneal, laparoscopic, and retroperitoneoscopic. For cases with lymphatic mapping, indocyanine green (ICG) was injected into the spermatic cord.

Results

Twenty patients were included: five open transabdominal, six open extraperitoneal, three laparoscopic, and six retroperitoneoscopic operations. LOS was shorter in the retroperitoneoscopic group than laparoscopic (p = 0.029) and both open groups (p < 0.001). Mean OME/kg used was lowest in the retroperitoneoscopic (0.13 ± 0.15) group compared to laparoscopic (0.68 ± 0.53, p = 0.043), open transabdominal (14.90 ± 8.87, p = 0.003), and extraperitoneal (10.11 ± 2.44, p < 0.001). Time to chemotherapy was shorter for retroperitoneoscopic patients (0.13 days ± 0.15) compared to open transabdominal (15.6 days ± 6.5, p = 0.005). There was no difference in lymph node yield between groups. Spermatic cord ICG demonstrated iliac lymph node avidity on near-infrared spectroscopy.

Conclusions

Minimally invasive RPLND appears to offer a faster recovery without compromising lymph node yield for patients with PT-RMS.

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99MTC-TILMANOCEPT FOR PEDIATRIC SENTINEL LYMPH NODE BIOPSY (SLNB)? RESULTS OF A PROSPECTIVE, OPEN-LABEL MULTICENTER TRIAL EVALUATING SLNB IN PEDIATRIC PATIENTS WITH SOLID TUMORS

Session Type
The International Society of Paediatric Surgical Oncology (IPSO)
Date
14.10.2020, Wednesday
Session Time
11:45 AM - 12:30 PM
Room
Hall 3
Lecture Time
11:55 AM - 12:00 PM

Abstract

Background and Aims

Reliable evaluation of lymphatic metastases is essential in many pediatric solid tumors, allowing for accurate diagnostic staging and determination of appropriate therapeutic regimens. Few studies examining the safety and utility of sentinel lymph node biopsy (SLNB) in pediatric patients have been performed, particularly with newer targeted lymphatic agents. The purpose of this study was to prospectively evaluate the safety and tolerability of the SLN radiotracer 99mTc‑tilmanocept (LYMPHOSEEK®, Cardinal Health), a technetium-based agent uniquely targeted to CD206 receptors in lymph nodes, for pediatric patients with solid tumors.

Methods

A prospective, open-label, within-subject trial was approved by the Food and Drug Administration (FDA) and the Institutional Review Boards at all participating institutions. Enrolled patients received 50-mcg tilmanocept radiolabeled with 0.5-mCi 99mTc, 15 minutes to 8 hours before SLNB procedure. Safety measurements included collection of adverse events, vital signs, clinical labs, and ECGs. Preoperative lymphoscintigraphy was obtained and/or vital blue dye administered at the discretion of the surgeon. Patients underwent SLNB identification and removal of identified nodes utilizing a handheld gamma probe. Excised nodes underwent histopathology evaluation per institutional SLN protocols and cooperative group central review.

Results

Twenty-four eligible patients (5-melanomas, 5-rhabdomyosarcomas, 12-nonrhabdomyosarcoma soft tissue sarcomas, 2-others; 15-females; mean age 11.6±4.9 years) were enrolled over 3.5 years, with early closure requested by FDA due to meeting primary objective. No patient experienced adverse events attributed to 99mTc‑tilmanocept. 99mTc‑tilmanocept identified SLNs in 96% of patients, with a mean of 3.3±3.1 SLNs/patient. Two patients (1-melanoma, 1-rhabdomyosarcoma) had pathology-positive SLNs, both successfully identified by 99mTc‑tilmanocept.

Conclusions

In this feasibility and safety study, 99mTc‑tilmanocept demonstrated high SLN localization with excellent safety profile in pediatric patients. Although the sample size was small, these results suggest that 99mTc‑tilmanocept appears to be safe and effective in identifying SLNs, with fast transit and minimal pain, in pediatric solid tumors.

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RESULTS OF TESTICULAR TRANSPOSITION TO DECREASE THE DELIVERED DOSE OF BRACHYTHERAPY TO THE TESTES IN BLADDER PROSTATE RHABDOMYOSARCOMA.

Session Type
The International Society of Paediatric Surgical Oncology (IPSO)
Date
14.10.2020, Wednesday
Session Time
11:45 AM - 12:30 PM
Room
Hall 3
Lecture Time
12:00 PM - 12:05 PM

Abstract

Background and Aims

Local control of bladder-prostate rhabdomyosarcoma (BPRMS) is achieved by a combination of a conservative surgery and brachytherapy (CSBT), however, if the dose to the testis in the vicinity of the brachytherapy wires is above 2Gy it may impair the fertility. We previously described a technique of unilateral testicular transposition (TT) in 8 patients to decrease the delivered dose to the testis. We wanted to assess the surgical outcome of this technique on a larger set of patients with a longer follow-up.

Methods

We reviewed the minimal physical radiation dose to the most exposed 98% of the testis (D98), clinical (location) and ultrasound (asymmetry >30% in volume and Doppler signal) data of transposed and non-transposed testes from male patients treated for a BPRMS with a CSBT, at last follow-up, from Sept 2016 to February 2019.

Results

Out of 26 patients: 23 had a right, 2 left, 1 bilateral TT. The D98 was 1.30 Gy [0-4.10] to the transposed compared to 5.16 Gy [1.24-12.31] to the non-transposed testis, with a significant decrease of 75% [7-100] (P<0.001) of the dose. Two patients (7.7%) experienced post-operative events (one wound infection and one scrotal exploration for pain). After 11 months [2-34] of follow-up, 15 (57%) patients had a clinical examination: 2patients (14%) had symmetric but oscillating or inguinal testis. Fourteen patients (53%) had a Doppler ultrasound: 5 (35%) had a decrease of their testis volume by 47% [36-60%], compared to the non-transposed testis. The Doppler was impaired in 2 patients and was symmetric for the others. There was no testicular atrophy or necrosis.

Conclusions

Unilateral TT for CSBT in BPRMS avoids a significant amount of irradiation, although a significant decrease in size and vascular impairment in 35% and 14% of patient’s transposed testes prevents us from performing a bilateral transposition.

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MICROCOIL LOCALIZATION AS AN EFFECTIVE ADJUNCT TO THORACOSCOPIC RESECTION OF PULMONARY NODULES IN CHILDREN

Session Type
The International Society of Paediatric Surgical Oncology (IPSO)
Date
14.10.2020, Wednesday
Session Time
11:45 AM - 12:30 PM
Room
Hall 3
Lecture Time
12:05 PM - 12:10 PM

Abstract

Background and Aims

Pulmonary nodules in children have variable etiologies, and surgery is often required for diagnostic or therapeutic purposes. Thoracoscopic excision is a widely accepted technique, however, subpleural and sub-centimeter nodules can be difficult to visualize. Various CT-guided localization techniques have been described, though there is minimal published pediatric data regarding the use of microcoils. We hypothesize that microcoil localization facilitates thoracoscopic resection of pulmonary nodules in children.

Methods

A multi-institutional retrospective review of children who underwent preoperative CT-guided localization of lung nodules was conducted from 2012-2019. A combination of methylene blue dye, wires, and microcoils were utilized for CT-guided localization. When microcoils were utilized, they were identified under fluoroscopic guidance, and then resected, with fluoroscopy confirming coil removal.

Results

Eighteen patients (mean age 13 years, range 2-21 years) underwent thoracoscopic resection of 24 preoperatively localized pulmonary nodules. Mean size and depth of the lesions were 5.5 mm and 10 mm, respectively. Twenty-three of twenty-four nodules were localized preoperatively; eighteen (75%) by microcoil placement alone, four (17%) by a combination of microcoil and wire placement, and two (8%) with wire placement alone. Methylene blue dye was also utilized for fourteen nodules (58%), twelve of which were localized with microcoils. Wire localization was not a durable technique, as 3 of 5 wires became dislodged upon lung isolation. Microcoil placement was successful 95% of the time and assisted in lesion localization in 88% of cases. Median postoperative hospitalization was three days, and there were no major complications during any of the procedures.

Conclusions

Preoperative CT-guided localization with microcoils is an effective technique to facilitate fluoroscopic-guided wedge resection of pulmonary nodules in children. This technique avoids the pitfall of wire dislodgement and can provide a consistent approach to localizing and resecting sub-centimeter, subpleural nodules.

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