Current surgical approach: Extracranial malignant germ cell tumors.

Germ cell tumors (GCT) are a complex, heterogeneous collection of tumors that may present in either gonadal or extragonadal sites. They consist of a variety of benign and malignant histologies that can occur at several locations throughout the body. An important component of treatment is surgical resection, and while the key components of resection are site specific, the universal goals of GCT resection include the complete resection of tumor without violating the tumor capsule, while preserving function of surrounding organs, minimizing morbidity, and assessing for regional spread.

Critical elements of pediatrics sacrococcygeal germ cell tumor surgery.

Sacrococcygeal teratoma is the most common extragonadal germ cell tumor in the pediatric population, and accounts for approximately 70% of all teratomas in childhood.1,2 They present in two distinct phases, with most cases seen in neonates with large predominately exophytic tumors, often detected in utero on prenatal sonography or at birth. A smaller cohort presents in older infants and children with primarily hidden tumors in the pelvis which have a much higher rate of malignancy. The primary surgical objective is complete tumor resection without compromise to critical structures or function. Herein we outline the critical elements of tumor resection and management of sacrococcygeal germ cell tumors with a focus on the technical aspects of this tumor across a range of presentations.

Critical elements in the operative management of pediatric malignant ovarian germ cell tumors.

Performance of the appropriate operation is highly important to ensure that any patient with a suspected ovarian germ cell tumor receives optimal therapy that prioritizes cure while simultaneoulsy minimizing risk of short and long-term toxicities of treatment. The following critical elements of any operative procedure performed for a suspected pediatric or adolescent ovarian germ cell tumor are reviewed: 1. Complete resection of the tumor via ipsilateral oophorectomy while avoiding tumor rupture and spillage, and 2. Performance of complete intraperitoneal staging at the time of initial tumor resection.

Characterizing Lymphovascular Invasion in Pediatric and Adolescent Malignant Ovarian Nongerminomatous Germ Cell Tumors: A Report from the Children's Oncology Group.

BACKGROUND: Lymphovascular invasion (LVI) has been identified as a poor prognostic factor for a variety of tumors; however, its significance in malignant ovarian germ cell tumors (MOGCT) in pediatric and adolescent patients is not well described. We aim to clarify the significance of LVI in the subset of patients with nongerminomatous MOGCT. METHODS: Records of patients 0-20 years of age with MOGCT enrolled on Children's Oncology Group study AGCT0132 were reviewed. Patients with documented presence or absence of LVI in either institutional or central review pathology reports were included. RESULTS: Of 130 patients with MOGCTs, 83 patients had of the presence or absence of LVI documented in their pathology report. 42/83 patients (50.6%) were found to have LVI present. The estimated odds of having LVI was higher in patients with stage II and III disease, 11 years and older and with the presence of choriocarcinoma. Event-free survival (EFS) and overall survival (OS) remained high in patients with LVI. Approximately 50% of patients with a documented LVI status in either institutional pathology report or central review were found to have LVI. CONCLUSIONS: The presence of LVI was higher in tumors with adverse risk factors including higher stage and age greater than 11 years. While LVI was not associated with EFS or OS in the intermediate risk group, further work is necessary to determine the effect of LVI on long-term disease-free survival. We, therefore, recommend routinely incorporating LVI status into institutional pathology reports for pediatric and adolescent patients with MOGCT. LEVEL OF EVIDENCE: III.

Children's Oncology Group's 2023 blueprint for research: Germ cell tumors.

Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment-related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard-risk disease, and intensify therapy for patients with poor-risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker-negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology-driven, biomarker-defined, histology-specific, risk-stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.

Pediatric patient-specific three-dimensional virtual models for surgical decision making in resection of hepatic and retroperitoneal tumors.

PURPOSE: Typically, preoperative imaging is viewed in two dimensions (2D) only, but three-dimensional (3D) virtual models may improve viewers' anatomical perspective by permitting them to interact with the imaging through manipulating it in space. Research into the utility of these models in most surgical specialties is growing rapidly. This study investigates the utility of 3D virtual models of complex pediatric abdominal tumors for clinical decision making, particularly the decision to proceed with surgical resection or not. METHODS: 3D virtual models of tumors and adjacent anatomy were created from CT images of pediatric patients scanned for Wilms tumor, neuroblastoma or hepatoblastoma. Pediatric surgeons individually assessed the resectability of the tumors. First, they assessed resectability using the standard protocol of viewing imaging on conventional screens and then reassessed resectability after being presented with the 3D virtual models. Inter-physician agreement on resectability for each patient was analyzed using Krippendorff's alpha. Inter-physician agreement was used as a surrogate for correct interpretation. Participants were also surveyed afterward on the utility and practicality of the 3D virtual models for clinical decision making. RESULTS: Inter-physician agreement when using CT imaging alone was "fair" (Krippendorff's alpha α = 0.399), while inter-physician agreement when using 3D virtual models increased to "moderate" (Krippendorff's alpha α = 0.532). When surveyed about model utility, all 5 participants considered them helpful. Two participants felt the models would be practical for clinical use in most cases, while 3 felt they would be practical for select cases only. CONCLUSION: This study demonstrates the subjective utility of 3D virtual models of pediatric abdominal tumors for clinical decision making. The models are an adjunct that can be particularly useful in complicated tumors that efface or displace critical structures that may impact resectability. Statistical analysis demonstrates the improved inter-rater agreement with the 3D stereoscopic display over the 2D display. The use of 3D displays of medical images will increase over time, and evaluation of their potential usefulness in various clinical settings is necessary.

Validation of a Wound Tool for Assessment of Surgical Wounds in Infants.

BACKGROUND: Wound assessment is a critical part of the care of hospitalized infants in neonatal intensive care. Early recognition and initiation of appropriate treatment of wounds are imperative to facilitate wound healing and avoid complications such as secondary infection and wound dehiscence. There are, however, no validated tools for assessing surgical wounds in infants. PURPOSE: The aim of this study was to develop and interrogate a tool for the assessment of surgical wounds. Specific aims for the tool included interrater reliability (give a consistent and dependable result independent of user) and test criterion validity (give an accurate assessment of the wound compared with an expert). METHODS: This was an exploratory cohort study involving a structured wound tool applied by nursing staff to 40 surgical wounds. The wounds were also assessed by wound experts (a pediatric wound care nurse and a pediatric surgeon). Comparisons were made to elucidate estimates of reliability and validity. RESULTS: The wound tool demonstrated interrater reliability with intraclass correlation coefficient of 0.775 (95% CI, 0.665-0.862) as well as criterion validity with rank correlation coefficient of 0.55 (95% CI, 0.34-0.76) to 0.71 (95% CI, 0.53-0.88). To obtain 100% sensitivity to distinguish mild from moderate-severe wounds, a low cutoff score was needed. IMPLICATIONS FOR PRACTICE AND RESEARCH: Wound assessment continues to be a subjective exercise, even with the utilization of a tool. Additional research is needed for strategies to support the assessment of surgical wounds in infants. Such tools are needed for future research, particularly when multiple institutions are involved.

Clinicopathologic predictors of outcomes in children with stage I testicular germ cell tumors: A pooled post hoc analysis of trials from the Children's Oncology Group.

BACKGROUND: Patients with clinical stage I (CS I: cN0M0) testicular germ cell tumors (TGCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I TGCT, we lack reliable means to predict relapse among pediatric and adolescent patients. OBJECTIVE: We sought to identify predictors of relapse in children with CS I TGCT. STUDY DESIGN: We performed a pooled post hoc analysis on pediatric and adolescent AJCC CS I TGCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of events, defined as relapse, secondary malignant neoplasm, or death. RESULTS: 106 patients were identified with outcomes data available. Most patients were pT1-2 stage. Among patients with evaluable histopathology, yolk sac tumor elements were present in all patients and lymphovascular invasion in 51% of patients. Over a median follow-up of 56 months, no patients died, and 25 patients (24%) experienced an event (median event-free survival not reached). Independent predictors of events on multivariable analysis included age ≥12 years at diagnosis (HR 8.87, p < 0.001) and higher pT stage (pT2 HR 7.31, p = 0.0017; pT3 HR 13.5, p = 0.0043). DISCUSSION: Although our study population reflects the largest pooled prospective cohort of CS I pediatric and adolescent TGCT to our knowledge, the relatively low event rate limits our multivariable analysis, and longer follow-up duration would help further characterize the natural history of these patients. Centralized pathologic review was also unable to be performed for several patients. CONCLUSION: Pediatric and adolescent CS I TGCT patients exhibit remarkable 5-year survival. Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and inform personalized treatment for these patients by potentially guiding surveillance versus adjuvant treatment strategies.

'Teratoid' Hepatoblastoma: An Intriguing Variant of Mixed Epithelial-Mesenchymal Hepatoblastoma.

Liver neoplasms are quite rare in childhood. They often involve 6.7 cases per 10 million children aged 18 years or younger. Hepatoblastoma (HB) is the most frequent tumor, but this neoplasm's rarity points essentially to the difficulty of performing biologic studies and large-scale therapeutic trials. On the pathological ground, HB is separated into an entirely epithelial neoplasm or a mixed neoplasm with epithelial and mesenchymal components. This last category has been further subdivided into harboring teratoid features or not. The 'teratoid' HB includes a mixture of components with heterologous origin. The heterologous components include neuroectoderm, endoderm, or melanin-holding cells with or without mesenchymal components. The most important criterium for the teratoid component is neuroepithelium, melanin, and, more recently, a yolk-sac-like component and neuroendocrine components. The mesenchymal components include muscle, osteoid, and cartilage, which are most often observed mainly in 'teratoid' neoplasms. The teratoid component or mesenchymal components are diagnosed with biopsies. They appear more prominent after chemotherapy due to the response and shrinkage of epithelial elements and non- or low-responsive components of mixed HB. This review focuses on the clinical, radiological, and pathological findings of HB with teratoid features.

The Genetics of Postoperative Recurrence in Crohn Disease: A Systematic Review, Meta-analysis, and Framework for Future Work.

Background: Recurrence following abdominal surgery in Crohn disease is over 50%. The impact of genetics on postoperative recurrence is not well defined. Methods: A literature search was conducted where inclusion required an assessment, by genotype, of postoperative recurrence. The primary endpoint was odds of surgical recurrence. Results: Twenty-eight studies identified a total of 6715 patients. Thirteen loci were identified as modifying the risk of recurrence. NOD2 was identified as a risk factor for recurrence by multiple works (cumulative odds ratio: 1.64, P = 0.003). Conclusions: A NOD2 risk allele is associated with recurrence following surgery in Crohn disease. Progress in this area will require standardized reporting in future works.

Imaging Appearance of Nongerminoma Pediatric Ovarian Germ Cell Tumors Does Not Discriminate Benign from Malignant Histology.

STUDY OBJECTIVE: Pediatric ovarian neoplasms with imaging appearance suggestive of teratoma are often presumed to have low risk of malignancy. We assessed the pre-operative imaging appearance of pediatric malignant ovarian germ cell tumors (MOGCT) and the presence of associated teratoma in a series of MOGCT. DESIGN: Retrospective review of clinical and pathology data. SETTING: Multicenter trial for extracranial malignant germ cell tumors in young female individuals by the Children's Oncology Group (COG study AGCT0132) that included yolk sac tumor, embryonal carcinoma and choriocarcinoma. PARTICIPANTS: Female individuals 0-20 years of age at enrollment with ovarian primary nonseminomatous malignant germ cell tumors. INTERVENTIONS: Review of data forms, including prospectively collected surgical checklist documenting imaging characteristics of the tumor, and review of pathology reports. MAIN OUTCOME MEASURES: Description of imaging appearance and frequency of mixed histology with benign teratoma elements. RESULTS: A total of 138 female individuals (11 months to 20 years of age) had primary ovarian tumors. Imaging appearance and pathology information were available for 133 patients. Among the 133 patients, tumor appearance was solid (10.5%), solid with calcification (3.0%), mixed cystic and solid (58.7%), mixed cystic and solid with calcification (24.8%), and unknown (3.0%). In all, 54% had elements of teratoma in addition to malignant histology. CONCLUSION: Mixed cystic and solid appearance with or without calcification was seen in 83.5% of pediatric ovarian malignant germ cell tumors. Associated benign teratoma was common. The presence of a mixed cystic and solid appearance on preoperative imaging should not dissuade the surgeon from obtaining preoperative serum markers and undertaking complete surgical staging.

Pneumonectomy in a Child with Multilobar Pneumatocele Secondary to Necrotizing Pneumonia: Case Report and Review of the Literature.

BACKGROUND: Community-acquired pneumonia (CAP) is common within pediatrics and contributes disproportionately to morbidity and mortality. Necrotizing pneumonia is a well-documented complication of CAP. It is thought to be caused by necrosis and liquefaction of consolidated lung and can result in damage to lung parenchyma, including pneumatocele development. Management of necrotizing pneumonia with pneumatocele may include hospitalization, intensive care unit admission, and lengthy antibiotic courses. Severe cases may need invasive procedures. CASE PRESENTATION: We present a case of severe necrotizing pneumonia requiring prolonged venovenous extracorporeal membrane oxygenation (V-V ECMO) with development of persistent pneumatoceles, requiring pneumonectomy while on ECMO support to allow for decannulation and extubation. CONCLUSIONS: In critically ill patients with extensive unilateral necrotizing pneumonia with pneumatocele development, surgical intervention can be considered when attempts to wean ventilation have been unsuccessful. This case provides evidence that V-V ECMO and pneumonectomy is a viable salvage therapy in the most critically unwell children.

Heterotaxy Syndrome and Intestinal Rotation Abnormalities.

BACKGROUND: Infants with heterotaxy syndrome (HS) have abnormal lateralization of organs along the right-left body axis. Intestinal rotation abnormalities (IRAs) are a potential source of morbidity and mortality. For this study, our objective was to prospectively observe a cohort of infants with HS and determine the incidence and natural history of IRA. METHODS: Infants ≤6 months of age with HS were enrolled in this prospective observational study. Exclusion criteria were other congenital abnormalities that necessitated abdominal surgery. HS was defined as any arrangement of organs that was not situs solitus or situs inversus along with associated congenital heart disease. The investigation for IRA was at the discretion of each participating center. RESULTS: Infants were recruited from January 2012 to December 2016. Thirty-eight infants from 7 institutions were included; 22 infants had right isomerism and 16 infants had left isomerism. Twenty-nine infants (76%) were evaluated for IRAs; 21 of 29 evaluations (72%) were abnormal. Eight infants were investigated because of symptoms, and 21 infants were evaluated routinely. The median age at symptom presentation was 46 days (range: 5-171 days). Seven infants had a Ladd procedure; 4 were prophylactic, with 3 as part of a combined procedure, and 3 were emergent. No child suffered acute midgut volvulus over a median follow-up of 1.6 years (range: 0.06-4.93 years). CONCLUSIONS: IRAs are common in infants with HS. Infants with symptoms presented by 6 months of age. There was no failure of expectant management resulting in midgut volvulus during a median follow-up of 1.6 years.

Endospore forming bacteria may be associated with maintenance of surgically-induced remission in Crohn's disease.

Crohn's disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.

A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease.

BACKGROUND: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in more than half of patients after their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence. STUDY DESIGN: A cohort of patients with Crohn's disease who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at 8 loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariable survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively. RESULTS: One hundred and ninety-one patients with Crohn's disease and 11.2 years mean postoperative follow-up were included. Forty-six percent experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male sex (p = 0.05) and shortened time to first intestinal operation (5.0 vs 7.3 years; p = 0.03); inflammatory disease behavior was associated with a lower chance of repeat operation (p < 0.01). Of the loci assessed on multivariable analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence (hazard ratio 1.54; 95% CI 1.00 to 2.36; p < 0.05). CONCLUSIONS: We identify BACH2 as a susceptibility locus for postoperative recurrence of Crohn's disease in our cohort. BACH2 is critical in the differentiation and function of T cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in postoperative Crohn's disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process.

Gonadal dysgenesis is associated with worse outcomes in patients with ovarian nondysgerminomatous tumors: A report of the Children's Oncology Group AGCT 0132 study.

PURPOSE: In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with normal gonadal development. PATIENTS AND METHODS: Patients from the Children's Oncology Group AGCT0132 with malignant ovarian GCTs were included. Within this population, we sought to identify patients with gonadoblastoma, streak ovaries, or other evidence of gonadal dysgenesis (GD). Patients with malignant GCTs containing one or more of the following histologies-yolk sac tumor, embryonal carcinoma, or choriocarcinoma-were included. Patients were compared with respect to event-free survival (EFS) and overall survival (OS). RESULTS: Nine patients with GD, including seven with gonadoblastoma (mean age, 9.3 years), were compared to 100 non-GD patients (mean age, 12.1 years). The estimated 3-year EFS for patients with GD was 66.7% (95% CI 28.2-87.8%) and for non-GD patients was 88.8% (95% CI 80.2-93.8%). The estimated 3-year OS for patients with GD was 87.5% (95% CI 38.7-98.1%) and for non-GD patients was 97.6% (95% CI of 90.6-99.4%). CONCLUSION: Patients presenting with nongerminomatous malignant ovarian GCTs in the context of GD have a higher rate of events and death than counterparts with normal gonads. These findings emphasize the importance of noting a contralateral streak ovary or gonadoblastoma at histology for any ovarian GCT and support the recommendation for early bilateral gonadectomy in patients known to have GD with Y chromosome material. In contrast to those with pure dysgerminoma, these patients may represent a high-risk group that requires a more aggressive chemotherapy regimen.

The Spectrum of General Surgery Interventions in Pediatric Patients with Ventricular Assist Devices.

Ventricular assist devices (VADs) have positively impacted the management of heart failure. However, they come with a range of complications. Although general surgical complications have been assessed in adults with VADs, there is no study to date that has assessed general surgery intervention in the pediatric population. Fifty-two patients who received VADs from 2005 to 2015 at the Stollery Children's Hospital were assessed for general surgery intervention and anticoagulation status at the time of intervention. Eighteen patients (35%) had general surgery intervention; there were 21 nonemergency procedures and six emergency procedures performed. For nonemergency procedures, 89% of patients had anticoagulation held within 24 hours of surgery and 84% had anticoagulation resumed within 4 hours postoperatively. Antiplatelet therapy was not held perioperatively. In both emergency and nonemergency procedures, anticoagulation status was not a factor in the success of the procedure. This study shows that it is safe to have general surgery intervention on the same admission as a VAD implant provided an appropriate interdisciplinary healthcare team is involved with the perioperative management of the patient.