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.

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.

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.

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.

Gastrostomy Tube Feeding after Neonatal Complex Cardiac Surgery Identifies the Need for Early Developmental Intervention.

OBJECTIVE: To compare the proportion of developmental delay in early complex cardiac surgery (CCS) survivors with and without gastrostomy tube feeding (GTF). To explore acute care predictors of GTF that might help improve care in CCS survivors. STUDY GROUP: This comparison study of 2 groups within an inception cohort included 334 CCS survivors after cardiopulmonary bypass at ≤6 weeks of age (2005-2012) who did not require extracorporeal membrane oxygenation or heart transplantation. Children were assessed at 21 ± 3 months with the Bayley Scales of Infant and Toddler Development-Third Edition and the Adaptive Behavior Assessment System-Second Edition: general adaptive composite score. Delay was determined by scores >2 SD below mean. The χ(2) test compared groups. Predictors of GTF were analyzed using multiple logistic regression analysis, results expressed as OR with 95% CI. RESULTS: Of the survivors, 67/334 (20%) had GTF any time before the 21-month assessment. Developmental delays in children with GTF were cognitive in 16 (24%), motor in 18 (27%), language in 24 (36%) vs without GTF in 7 (3%), 8 (3%), and 32 (12%), respectively (P < .001). Gastrostomy group had almost 8 times the number of children delayed on the general adaptive composite score. Independent OR for GTF are presence of a chromosomal abnormality, OR 4.6 (95% CI 1.8, 12.0) (P = .002), single ventricle anatomy, OR 3.4 (95% CI 1.7, 6.8) (P < .001), total postoperative days of open sternum, OR 1.15 (95% CI 1.1, 1.3) (P = .031), and total number of hospital days at CCS, OR 1.03 (95% CI 1.1, 1.04) (P = .002). CONCLUSIONS: GTF identifies CCS survivors at risk for delay, who would benefit from early developmental intervention. The described mostly nonmodifiable predictors may guide counseling of these children's families.

Bedside to bench: The risk of bleeding with parenteral omega-3 lipid emulsion therapy.

Our clinical experience led us to reassess the effect of sole omega-3 lipid therapy on hemostasis. We compared thromboelastography platelet mapping in neonatal piglets given sole omega-3 lipid. We identified abnormalities in reaction time (P = .025) and the arachidonic acid pathway (P = .025). The potential for bleeding complications from parenteral omega-3 lipid emulsion therapy in high-risk infants with liver disease has been dismissed but, on the basis of this data, should be reconsidered.

Cardiac effects of vasopressin.

Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits.

Heterotaxy syndrome: is a prophylactic Ladd procedure necessary in asymptomatic patients?

Heterotaxy syndrome (HS) is a complex disorder involving thoracic and abdominal asymmetries. Congenital heart disease is often accompanied by an intestinal rotation abnormality (IRA) that may predispose to bowel ischemia and infarction. There is controversy in the literature whether asymptomatic infants with HS must be screened for IRA and, if present, whether a prophylactic Ladd procedure should be performed. We performed a retrospective chart review of all patients who underwent a Ladd procedure from January 2007 to December 2010 at Stollery Children's Hospital, Edmonton, Canada. Twenty-nine patients underwent a Ladd procedure, 22 without HS but with symptomatic malrotation and 7 with HS and asymptomatic malrotation. Asymptomatic HS patients had a complication rate of 57 % after a prophylactic Ladd procedure compared with a complication rate of 9 % in the symptomatic non-HS population. The management of asymptomatic IRA in patients with HS remains controversial. We suggest that HS patients be screened for IRA and that asymptomatic patients be managed conservatively.

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.

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.

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.

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.

'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.

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.

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.

Predicting node positivity in gastric cancer from gene expression profiles.

Lymphovascular invasion (LVI) in gastric cancer is readily demonstrated pre-operatively by mucosal biopsy during endoscopy, which can also provide samples for gene expression profiling. We have examined gene expression associated with lymphovascular invasion in a cohort of gastric cancer patients and have developed a 28-gene predictor of tumor aggressiveness for forecasting risk of node positivity (N+), which could potentially be useful pre-operatively. The resulting model's ranking of increasing tumor aggressiveness correlated positively with N+ status, reaching statistical significance, and was three times the correlation of LVI with N+ status.

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.