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1.
Pediatr Blood Cancer ; 71(7): e31026, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38679864

RESUMO

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Sarcoma de Ewing/patologia , Feminino , Masculino , Criança , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/secundário , Estudos Retrospectivos , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/patologia , Pré-Escolar , Taxa de Sobrevida , Prognóstico , Seguimentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto Jovem , Indução de Remissão , Lactente , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Quimioterapia de Indução
4.
J Pediatr Surg ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38548494

RESUMO

BACKGROUND: Limb-sparing surgery is the standard of care for primary bone tumors. However, such procedures are associated with high rates of wound complications, specifically in lower-extremity surgeries. Therefore, identifying and implementing interventions to minimize the likelihood of wound complications after limb-sparing resection of the lower extremity is crucial. METHODS: Patients who underwent limb-sparing osteosarcoma or Ewing sarcoma resection during a 7-year period at a single institution were retrospectively reviewed. Data were collected on 39 patients who underwent limb-sparing resection of the femur. Patient demographics, tumor characteristics, and perioperative and postoperative data were extracted and analyzed. Patients who underwent resection before April 2017 received conventional postoperative incision dressings. Starting in April 2017, patients received vacuum-assisted closure (VAC) with the 3 M™ Prevena VAC system after surgical closure. Eighteen patients received conventional postoperative incision dressing, and 21 received incisional wound VAC. A wound complication was defined as any Clavien-Dindo classification greater than 0 within a 28-day postoperative period. RESULTS: Patients who received postoperative incisional wound VAC had lower rates of wound complications than those who received conventional incision dressings (14% vs. 50%; p = 0.035). Additionally, patients in whom wound complications developed had a longer average hospital stay than those without wound complications (5 days vs. 4 days; p = 0.029). CONCLUSIONS: Wound complications prolong the hospital stay and can delay adjuvant chemotherapy for bone tumors. The use of postoperative incisional wound VAC is associated with less likelihood of wound complications and should be considered in any high-risk surgical closure. LEVEL OF EVIDENCE: Level III Treatment Study.

5.
Ann Surg ; 279(3): 536-541, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37487006

RESUMO

OBJECTIVE: To determine the impact of nodal basin ultrasound (US) surveillance versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma. BACKGROUND: Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma. METHODS: Patients ≤18 years diagnosed with cutaneous melanoma between 2010 and 2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information. RESULTS: Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. A total of 67 patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 y) than CLND (median age 11.3 y; P =0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P =0.28) or death from disease (2.2% vs 9.7%; P =0.36) for those who underwent US versus CLND, respectively. CONCLUSIONS: Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.


Assuntos
Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Adulto , Humanos , Adolescente , Criança , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Melanoma/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Linfonodo Sentinela/patologia , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Estudos Retrospectivos
6.
J Pediatr Surg ; 58(11): 2119-2127, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37550134

RESUMO

Although survival for many pediatric cancers has improved with advances in conventional chemotherapeutic regimens and surgical techniques in the last several decades, it remains a leading cause of disease-related death in children. Outcomes in patients with recurrent, refractory, or metastatic disease are especially poor. Recently, the advent of alternative classes of therapies, including immunotherapies, have revolutionized systemic treatment for pediatric malignancies. Several classes of immunotherapies, including chimeric antigen receptor (CAR) T cell therapy, transgenic T-cell receptor (TCR)-T cell therapy, bispecific T-cell engagers, and monoclonal antibody checkpoint inhibitors have been FDA-approved or entered early-phase clinical trials in children and young adults. The pediatric surgeon is likely to encounter these therapies during the care of children with malignancies and should be familiar with the classes of therapy, indications, adverse events, and potential need for surgical intervention in these cases. This review from the APSA Cancer Committee offers a brief discussion of the three most encountered classes of immunotherapy in children and young adults and discusses surgical relevance. LEVEL OF EVIDENCE: IV.

7.
J Pediatr Surg ; 58(11): 2135-2140, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37385908

RESUMO

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.

8.
Pediatr Blood Cancer ; 70(10): e30437, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37194488

RESUMO

BACKGROUND: Clearing all pulmonary metastases is essential for curing pediatric solid tumors. However, intraoperative localization of such pulmonary nodules can be challenging. Therefore, an intraoperative tool that localizes pulmonary metastases is needed to improve diagnostic and therapeutic resections. Indocyanine green (ICG) real-time fluorescence imaging is used for this purpose in adult solid tumors, but its utility in pediatric solid tumors has not been determined. METHODS: A single-center, open-label, nonrandomized, prospective clinical trial (NCT04084067) was conducted to assess the ability of ICG to localize pulmonary metastases of pediatric solid tumors. Patients with pulmonary lesions who required resection, either for therapeutic or diagnostic intent, were included. Patients received a 15-minute intravenous infusion of ICG (1.5 mg/kg), and pulmonary metastasectomy was performed the following day. A near-infrared spectroscopy iridium system was optimized to detect ICG, and all procedures were photo-documented and recorded. RESULTS: ICG-guided pulmonary metastasectomies were performed in 12 patients (median age: 10.5 years). A total of 79 nodules were visualized, 13 of which were not detected by preoperative imaging. Histologic examination confirmed the following histologies: hepatoblastoma (n = 3), osteosarcoma (n = 2), and one each of rhabdomyosarcoma, Ewing sarcoma, inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, and papillary thyroid carcinoma. ICG guidance failed to localize pulmonary metastases in five (42%) patients who had inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, or papillary thyroid carcinoma. CONCLUSIONS: ICG-guided identification of pulmonary nodules is not feasible for all pediatric solid tumors. However, it may localize most metastatic hepatic tumors and high-grade sarcomas in children.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Neuroblastoma , Neoplasias da Glândula Tireoide , Adulto , Humanos , Criança , Verde de Indocianina , Estudos Prospectivos , Câncer Papilífero da Tireoide , Estudos de Viabilidade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Nódulos Pulmonares Múltiplos/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Espectroscopia de Luz Próxima ao Infravermelho
9.
Artigo em Inglês | MEDLINE | ID: mdl-36997313

RESUMO

Infantile fibrosarcoma is the most common soft-tissue sarcoma in children under the age of 1 yr and is defined molecularly by NTRK fusion proteins. This tumor is known to be locally invasive; however, although rare, metastases can occur. The NTRK fusion acts as a driver for tumor formation, which can be targeted by first- and second-generation TRK inhibitors. Although NTRK gatekeeper mutations have been well-described as mechanisms of resistance to these agents, alternative pathway mutations are rare. Here, we report the case of a patient with infantile fibrosarcoma treated with chemotherapy and TRK inhibition that developed metastatic, progressive disease with multiple acquired mutations, including TP53, SUFU, and an NTRK F617L gatekeeper mutation. Alterations in pathways of SUFU and TP53 have been widely described in the literature in other tumors; however, not yet in infantile fibrosarcoma. Although most patients have a sustained response to TRK inhibitors, a subset will go on to develop mechanisms of resistance that have implications for clinical management, such as in our patient. We hypothesize this constellation of mutations contributed to the patient's aggressive clinical course. Taken together, we report the first case of infantile fibrosarcoma with ETV6::NTRK3 and acquired SUFU, TP53, and NTRK F617L gatekeeper mutation along with detailed clinical course and management. Our report highlights the importance of genomic profiling in recurrent infantile fibrosarcoma to reveal actionable mutations, such as gatekeeper mutations, that can improve patient outcomes.


Assuntos
Fibrossarcoma , Segunda Neoplasia Primária , Sarcoma , Criança , Humanos , Fibrossarcoma/genética , Mutação , Inibidores de Proteínas Quinases , Progressão da Doença
10.
Pediatr Surg Int ; 39(1): 118, 2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36773111

RESUMO

PURPOSE: There is still debate over the safest route for the placement of long-term central venous access devices. The aim of this study was to review a large, single-institution experience to determine the impact of access location on peri-operative complications. METHODS: The records of patients undergoing subcutaneous port (SQP) and tunneled catheter insertion over a seven-year period were reviewed. Vein cannulated (subclavian (SCV) versus internal jugular (IJ) vein), and 30-day complications were assessed. Surgical complications included pneumothorax, hemothorax, infections, arrhythmia or malpositioning requiring intervention. RESULTS: A total of 1,309 patients were included (618 SQP, 691 tunneled catheters). The location for insertion was SCV (909, 69.4%) and IJ (400, 30.6%). There were 69 complications (5.2%) (41, 4.5% SCV, 28, 7.0% IJV) including: malpositioning/malfunctioning (SCV 13, 1.4% and IJV 14, 3.0%), pneumothorax (SCV 4, 0.4% and IJV 1, 0.3%), hemothorax (SCV 0 and IJV 1, 0.3%), arrhythmia (SCV 1, 0.1%, and IJV 0), and infection within 30 days of placement (SCV 20, 2.2% and IJ 11, 2.8%). The complication rates were not significantly different based on site (p = 0.080). CONCLUSION: There was no significant difference in complication rates when using the subclavian versus the internal jugular vein as the site for long-term central venous access. LEVEL OF EVIDENCE: III, retrospective comparative study.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Pneumotórax , Humanos , Veia Subclávia , Cateterismo Venoso Central/efeitos adversos , Estudos Retrospectivos , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Hemotórax , Veias Jugulares , Cateteres Venosos Centrais/efeitos adversos
11.
Nat Biotechnol ; 41(10): 1434-1445, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36732477

RESUMO

Chimeric antigen receptor (CAR) technologies have been clinically implemented for the treatment of hematological malignancies; however, solid tumors remain resilient to CAR therapeutics. Natural killer (NK) cells may provide an optimal class of immune cells for CAR-based approaches due to their inherent anti-tumor functionality. In this study, we sought to tune CAR immune synapses by adding an intracellular scaffolding protein binding site to the CAR. We employ a PDZ binding motif (PDZbm) that enables additional scaffolding crosslinks that enhance synapse formation and NK CAR cell polarization. Combined effects of this CAR design result in increased effector cell functionality in vitro and in vivo. Additionally, we used T cells and observed similar global enhancements in effector function. Synapse-tuned CAR immune cells exhibit amplified synaptic strength, number and abundance of secreted cytokines, enhanced killing of tumor cells and prolonged survival in numerous different tumor models, including solid tumors.

12.
Pediatr Surg Int ; 38(9): 1335-1340, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35849175

RESUMO

PURPOSE: Placement of a central venous catheter (CVC) is the most commonly performed pediatric procedure. This study aims to develop simple formulas to calculate intravascular length of CVCs prior to insertion to minimize reliance on fluoroscopic and radiographic imaging, which may not be uniformly available. METHODS: We performed a single-institution, retrospective review of 115 pediatric patients who received both CVC placement and computed tomography (CT) imaging of the chest within 3 months of the procedure. Using measurements from the CT imaging, formulas calculating the length of the intravascular component of the CVC based on height and insertion laterality were developed and compared to previously published formulas. These formulas were then trialed prospectively to validate reliability and application. RESULTS: Formulas were developed for right-sided and left subclavian insertion. The right-side formula accurately predicted CVC length in 52.6% of patients, compared to 47.4% by the Andropoulos formula. The left subclavian formula accurately estimated 62.5%, compared to 34.5% by the Stroud formula. CONCLUSIONS: The optimal intravascular length of central venous catheters may be determined by simple formulas based on patient height and insertion site. LEVEL OF EVIDENCE: III.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Cateterismo Venoso Central/métodos , Criança , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Int J Cancer ; 151(10): 1696-1702, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-35748343

RESUMO

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.


Assuntos
Neoplasias Renais , Derrame Pleural Maligno , Derrame Pleural , Oncologia Cirúrgica , Tumor de Wilms , Criança , Humanos , Incidência , Neoplasias Renais/epidemiologia , Neoplasias Renais/cirurgia , Derrame Pleural/epidemiologia , Derrame Pleural/etiologia , Derrame Pleural Maligno/epidemiologia , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/cirurgia , Estudos Retrospectivos , Tumor de Wilms/epidemiologia , Tumor de Wilms/cirurgia
14.
iScience ; 25(4): 104100, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35402877

RESUMO

Pediatric osteosarcomas (OS) exhibit extensive genomic instability that has complicated the identification of new targeted therapies. We found the vast majority of 108 patient tumor samples and patient-derived xenografts (PDXs), which display an unusually dilated endoplasmic reticulum (ER), have reduced expression of four COPII vesicle components that trigger aberrant accumulation of procollagen-I protein within the ER. CRISPR activation technology was used to increase the expression of two of these, SAR1A and SEC24D, to physiological levels. This was sufficient to resolve the dilated ER morphology, restore collagen-I secretion, and enhance secretion of some extracellular matrix (ECM) proteins. However, orthotopic xenograft growth was not adversely affected by restoration of only SAR1A and SEC24D. Our studies reveal the mechanism responsible for the dilated ER that is a hallmark characteristic of OS and identify a highly conserved molecular signature for this genetically unstable tumor. Possible relationships of this phenotype to tumorigenesis are discussed.

15.
J Pediatr Surg ; 57(6): 1013-1017, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35307194

RESUMO

BACKGROUND: Pulmonary nodules that are deep within lung parenchyma and/or small in size can be challenging to localize for biopsy. This study describes current trends in performance of image-guided localization techniques for pulmonary nodules in pediatric patients. METHODS: A retrospective review was performed on patients < 21 years of age undergoing localization of pulmonary nodules at 15 institutions. Localization and resection success, time in interventional radiology (IR), operating room (OR) and total anesthesia time, complications, and technical problems were compared between techniques. RESULTS: 225 patients were included with an average of 1.3 lesions (range 1-5). Median nodule size and depth were 4 mm (range 0-30) and 5.4 mm (0-61), respectively. The most common localization techniques were: wire + methylene blue dye (MBD) (28%), MBD only (25%), wire only (14%), technetium-99 only (11%), coil + MBD (7%) and coil only (5%). Localization technique was associated with institution (p < 0.01); technique and institution were significantly associated with mean IR, OR, and anesthesia time (all p < 0.05). Comparing techniques, there was no difference in successful IR localization (range 92-100%, p = 0.75), successful resection (94-100%, p = 0.98), IR technical problems (p = 0.22), or operative complications (p = 0.16). CONCLUSIONS: Many IR localization techniques for small pulmonary nodules in children can be successful, but there is wide variability in application by institution and in procedure time. LEVEL OF EVIDENCE: Retrospective review, Level 3.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Oncologia Cirúrgica , Criança , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Azul de Metileno , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos
16.
J Pediatr Surg ; 57(9): 229-233, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34456040

RESUMO

PURPOSE: We sought to identify clinical features associated with difficult subcutaneous port removals in children. METHODS: Ports placed between April 2014 and September 2017 at our institution were prospectively tracked for difficult removals. A case-control analysis was performed. Patients with ports that were difficult to remove (stuck; cases) were compared to biological sex and age-matched controls in a ratio of 1:3. Logistic regression determined the association between case/control status and clinical features adjusting for biological sex and age as covariates. A multivariable analysis was performed to identify independent associations. RESULTS: 57 stuck ports (28 extreme [10 endovascular intervention] and 29 moderate) and 171 controls were analyzed. Stuck ports were associated with a diagnosis of acute lymphoblastic leukemia (86% cases versus 22.2% controls; p < 0.001) and a longer placement duration (median 2.6 years [interquartile range (IQR) 2.5-2.6] versus 0.8 years [IQR 0.5-1.4]; p < 0.001). On univariate analysis, procedural and device features associated with stuck ports included subclavian access (71.9% cases versus 48.5% controls; p = 0.0126), a polyurethane versus silicone catheter (96.5% cases versus 79.9% controls; p = 0.001), and a rough catheter appearance at removal (92.6% cases versus 9.4% controls; p < 0.0001). A diagnosis of ALL and duration of line placement were associated with having a stuck port on multivariate analysis. CONCLUSION: Polyurethane central venous catheters placed for the two-year treatment of acute lymphoblastic leukemia may become difficult to remove. This constellation of factors warrants more extensive preoperative discussion of risk, endovascular backup availability, and scheduling for longer operating room time.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Leucemia-Linfoma Linfoblástico de Células Precursoras , Estudos de Casos e Controles , Cateteres de Demora , Criança , Humanos , Poliuretanos , Estudos Retrospectivos
17.
Front Pediatr ; 9: 689612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616696

RESUMO

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. To date, there is no reliable method for the intraoperative assessment of tumor extent and real-time differentiation between tumor- involved tissues and tumor-free tissues. Use of intraoperative frozen sections is challenging, time consuming, and covers a small surface area. Increased vascular permeability and impaired lymphatic drainage in the tumor microenvironment leads to an enhanced permeability and retention effect of small molecules. ICG is a fluorescent dye that when administered intravenously accumulates passively in the tumor because of EPR, thereby providing some tumor contrast for intraoperative real-time tumor recognition. Preclinical and clinical studies suggest that the tumor-to-background fluorescence ratio is optimized when imaging is obtained 24 h after dye injection, and many studies suggest using a high dose of ICG to optimize dye retention in the tumor tissue. However, in childhood cancers, little is known about the ideal dosing, applications, and challenges of ICG-guided tumor resection. 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.

18.
Front Immunol ; 12: 691741, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211478

RESUMO

The outcome for metastatic pediatric osteosarcoma (OS) remains poor. Thus, there is an urgent need to develop novel therapies, and immunotherapy with CAR T cells has the potential to meet this challenge. However, there is a lack of preclinical models that mimic salient features of human disease including reliable development of metastatic disease post orthotopic OS cell injection. To overcome this roadblock, and also enable real-time imaging of metastatic disease, we took advantage of LM7 OS cells expressing firefly luciferase (LM7.ffLuc). LM7.ffLuc were implanted in a collagen mesh into the tibia of mice, and mice reliably developed orthotopic tumors and lung metastases as judged by bioluminescence imaging and histopathological analysis. Intratibial implantation also enabled surgical removal by lower leg amputation and monitoring for metastases development post-surgery. We then used this model to evaluate the antitumor activity of CAR T cells targeting B7-H3, an antigen that is expressed in a broad range of solid tumors including OS. B7-H3-CAR T cells had potent antitumor activity in a dose-dependent manner and inhibited the development of pulmonary metastases resulting in a significant survival advantage. In contrast T cells expressing an inactive B7-H3-CAR had no antitumor activity. Using unmodified LM7 cells also enabled us to demonstrate that B7-H3-CAR T cells traffic to orthotopic tumor sites. Hence, we have developed an orthotopic, spontaneously metastasizing OS model. This model may improve our ability not only to predict the safety and efficacy of current and next generation CAR T cell therapies but also other treatment modalities for metastatic OS.


Assuntos
Antígenos B7/imunologia , Neoplasias Ósseas/terapia , Imunoterapia Adotiva , Osteossarcoma/terapia , Receptores de Antígenos Quiméricos/imunologia , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Camundongos , Osteossarcoma/patologia , Tíbia/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Laparoendosc Adv Surg Tech A ; 31(5): 589-593, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33599543

RESUMO

Background: Posterolateral thoracotomy provides limited access to the thoracic apex that can result in poor visualization of subclavian vessels, their branches, and the brachial plexus. A thoracoscopic approach may overcome these limitations. Purpose: We report a thoracoscopic approach and associated technical challenges in resecting apical thoracic neuroblastoma encasing the subclavian artery. Methods: A single-institution retrospective chart review was performed (2018-2020) for patients undergoing thoracoscopic resection of apical neuroblastoma encasing the subclavian artery. Patient demographics, imaging, and hospital course were reviewed. Operative video recordings were assessed for exposure quality, technical challenges, and percentage of tumor resection. Patients were placed laterally, with three 5-mm ports triangulated to the apex. Dissection started at the tumor edge and followed along the vessel and branches. Results: Four patients (median age 2.7 years) underwent thoracoscopic apical neuroblastoma resection. Median length of stay was 2.5 days. One low-risk patient underwent resection for tumor growth during observation. One intermediate and 2 high-risk patients received neoadjuvant chemotherapy. Two patients continued having persistent vascular encasement, whereas in 1 patient the mass decreased in size and only abutted the subclavian and vertebral arteries. In 1 patient, tumor involved the brachial plexus, which was freed and preserved thoracoscopically. All cases had substantial tumor-feeding vessels branching from the subclavian artery. There was one conversion to open thoracotomy due to dense tumor adherence to the subclavian artery and vein. More than 95% resection was achieved in all cases. All patients had baseline Horner syndrome. No complications were reported. Conclusion: The thoracoscopic approach for resecting apical neuroblastoma provides optimal exposure and safe access in selected patients.


Assuntos
Neuroblastoma/cirurgia , Artéria Subclávia/cirurgia , Neoplasias Torácicas/cirurgia , Toracoscopia/métodos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Invasividade Neoplásica , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/patologia , Estudos Retrospectivos , Artéria Subclávia/diagnóstico por imagem , Neoplasias Torácicas/diagnóstico por imagem , Neoplasias Torácicas/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Pediatrics ; 147(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33504609

RESUMO

BACKGROUND: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration. METHODS: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period. RESULTS: Sixty-six children, with a median age of 11 years (range 1-17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; P = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% (n = 11) and count recovery in 35% (n = 6). Cancer therapy was delayed in 35% (n = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, P = .05) and longer LOS (29 vs 12 days; P = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications (P < .01). CONCLUSIONS: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.


Assuntos
Apendicectomia/tendências , Apendicite/terapia , Neutropenia Febril Induzida por Quimioterapia/terapia , Neoplasias/terapia , Conduta Expectante/tendências , Adolescente , Apendicite/diagnóstico , Apendicite/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/diagnóstico , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Estudos Retrospectivos , Conduta Expectante/métodos
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