Deborah F. Billmire

Teratomas in childhood: analysis of 142 cases

This report concerns 142 infants and children with teratomas treated from 1960 to 1984. The primary site of tumor was sacrococcygeal in 84, ovarian in 15, testicular in 15, mediastinal in 14, retroperitoneal in 7, cervical in 3, and other in 4. Malignancy occurred in 40 of 142 (28%) patients. Serum for alphafetoprotein (AFP) was obtained preoperatively in 29 patients. Elevated AFP was seen in all patients with malignancy, 3 of 6 with immature lesions and 1 of 19 with a benign lesion. Postoperative rise in AFP levels was a good indicator of malignant recurrence. Beta human chronic gonadotropin (BHCG) levels were only helpful in following teenage boys with testicular lesions. Benign tumors were treated by complete excision alone with a 97% survival. Testicular malignancies had a good prognosis with 13 of 15 surviving (87%) despite distant metastasis in four. In contrast, survival was only 32% with nontesticular malignancies. Survival was 17% for resectable malignant cases treated with surgery alone compared with 100% when operation was followed by multiagent chemotherapy. Unresectable malignant lesions were usually fatal despite multiagent chemotherapy and/or second-look procedures.

Treatment of Children and Adolescents With Stage II Testicular and Stages I and II Ovarian Malignant Germ Cell Tumors: A Pediatric Intergroup Study—Pediatric Oncology Group 9048 and Children's Cancer Group 8891

PURPOSE To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity. PATIENTS AND METHODS Between May 1990 and July 1995, eligible pediatric patients with stage II or recurrent from stage I (as a stage II) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Childrens Cancer Group study. PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1, cisplatin 20 mg/m2/d on days 1 to 5, and etoposide 100 mg/m2/d on days 1 to 5. Patients received four cycles of therapy at 21-day intervals. RESULTS Seventy-four patients with a median age of 10.5 years (range, 8.7 months to 16.7 years) were enrolled. Primary sites included: stage II testicular (n = 17), stage I ovarian (n = 41), and stage II ovarian MGCT (n = 16). Treatment with standard PEB resulted in 6-year EFS of 95% and overall survival (OS) of 95.7%. EFS and OS by primary site were as follows: stage II testicular, 100% and 100%; stage I ovarian, 95.1% and 95.1%; and stage II ovarian, 87.5% and 93.8%, respectively. Two patients died from recurrent disease, and one patient died of secondary acute myelocytic leukemia. Infrequent grade 3 to 4 hematologic toxicity was reported. No grade 3 to 4 renal, pulmonary, or ototoxicity was observed. CONCLUSION Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT.

American College of Surgeons National Surgical Quality Improvement Program Pediatric: A beta phase report

PURPOSE The American College of Surgeons (ACS) National Surgical Quality Improvement Program Pediatric (NSQIP-P) expanded to beta phase testing with the enrollment of 29 institutions. Data collection and analysis were aimed at program refinement and development of risk-adjusted models for inter-institutional comparisons. METHODS Data from the first full year of beta-phase NSQIP-P were analyzed. Patient accrual used ACS-NSQIP methodology tailored to pediatric specialties. Preliminary risk adjusted modeling for all pediatric and neonatal operations and pediatric (excluding neonatal) abdominal operations was performed for all cause morbidity (other than death) and surgical site infections (SSI) using hierarchical logistic regression methodology and eight predictor variables. Results were expressed as odds ratios with 95% confidence intervals. RESULTS During calendar year 2010, 29 institutions enrolled 37,141 patients. 1644 total CPT codes were entered, of which 456 accounted for 90% of the cases. 450 codes were entered only once (1.2% of cases). For all cases, overall mortality was 0.25%, overall morbidity 7.9%, and the SSI rate 1.8%. For neonatal cases, mortality was 2.39%, morbidity 18.7%, and the SSI rate 3%. For the all operations model, risk-adjusted morbidity institutional odds ratios ranged 0.48-2.63, with 9/29 hospitals categorized as low outliers and 9/29 high outliers, while risk-adjusted SSI institutional odds ratios ranged 0.36-2.04, with 2/29 hospitals low outliers and 7/29 high outliers. CONCLUSION This report represents the first risk-adjusted hospital-level comparison of surgical outcomes in infants and children using NSQIP-P data. Programmatic and analytic modifications will improve the impact of this program as it moves into full implementation. These results indicate that NSQIP-P has the potential to serve as a model for determining risk-adjusted outcomes in the neonatal and pediatric population with the goal of developing quality improvement initiatives for the surgical care of children.

Steroids and poor nutrition are associated with infectious wound complications in children undergoing first stage procedures for ulcerative colitis

BACKGROUND Risk factors for postoperative infections have not been evaluated in pediatric patients with ulcerative colitis (UC). This review was undertaken to evaluate the effects of immunosuppressive therapy and other preoperative factors on infectious wound complications in children undergoing first stage surgical therapy for UC. METHODS A 10-year retrospective review of children under 18 years of age receiving first stage surgical therapy for UC at a major childrens hospital was performed. Preoperative clinical and treatment variables were identified and correlated with postoperative wound complications. RESULTS A total of 51 children were identified: 19 underwent colectomy with ileo-anal-pouch anastomosis and 32 underwent total abdominal colectomy with Hartmanns pouch. A total of 20 infectious complications were identified in 18 patients. Preoperative steroid use was associated with a greater postoperative wound infection rate. Preoperative hemoglobin less than 10 g/dL (P < .05) and albumin less than 3 g/dL (P = 0.1) were associated with greater rates of postoperative infection. Preoperative body mass index and other immunosuppressive agents did not influence postoperative infectious morbidity. CONCLUSIONS The majority of pediatric patients who require operative intervention for UC are debilitated from their disease and medication use. Children with normal serum albumin and hemoglobin who are not on steroid therapy have a low risk of postoperative infectious complications.

Surveillance After Initial Surgery for Pediatric and Adolescent Girls With Stage I Ovarian Germ Cell Tumors: Report From the Children's Oncology Group

PURPOSE To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. PATIENTS AND METHODS Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Childrens Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. RESULTS Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). CONCLUSION Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults.

Gastroesophageal dysfunction in cornelia de lange syndrome

Children with Cornelia de Lange (CDL) syndrome present with feeding problems related to swallowing incoordination, poor esophageal motility, and gastroesophageal reflux (GER). These abnormalities of esophageal function result in failure to thrive and life-threatening aspiration pneumonia. Severe GER was documented in four patients with CDL syndrome. Three were managed successfully with an antireflux procedure (Nissen fundoplication) and a concomitant feeding gastrostomy. These observations confirm the high incidence of abnormal esophageal function in patients with CDL syndrome, and suggest that an antireflux procedure and feeding gastrostomy are important considerations in their clinical management.

Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data From the United Kingdom and United States

PURPOSE To risk stratify malignant extracranial pediatric germ cell tumors (GCTs). PATIENTS AND METHODS Data from seven GCT trials conducted by the Childrens Oncology Group (United States) or the Childrens Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method. RESULTS In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications. CONCLUSION Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy.

Predictors of ovarian malignancy in children: Overcoming clinical barriers of ovarian preservation

BACKGROUND/PURPOSE Ovarian preservation is desirable in girls with benign ovarian masses. We aimed to 1) identify clinical predictors of malignant ovarian masses, 2) investigate how often ovarian tissue is present to preserve in benign masses, and 3) identify factors associated with successful ovarian preservation. METHODS Retrospective analysis (1997-2012) of girls age 1-18years with an ovarian mass managed operatively. Data on presenting symptoms, imaging, biochemical markers, treatment, outcome, and pathology were extracted. RESULTS We identified 150 patients. Large mass size, solid components, and elevated tumor markers (AFP, βHCG, and/or LDH) were significantly predictive of malignancy. All masses <10cm, predominantly cystic, and with negative tumor markers were benign. Masses with all three of these characteristics would decrease a 20% malignancy pretest probability to a posttest probability of 0.25%. Benign masses managed by oophorectomy contained normal ovarian tissue in 76% of the specimens. For benign masses, successful ovarian preservation was significantly associated with size <10cm, predominantly cystic, laparoscopy, and absence of torsion or calcifications. CONCLUSION Ovarian masses that are <10cm, primarily cystic, and have negative tumor markers are most likely benign. Viable ovarian tissue is frequently present in benign masses, so significant efforts should be made for ovarian preservation.

The effect of neoadjuvant chemotherapy and surgery in children with malignant germ cell tumors of the genital region: a pediatric intergroup trial

PURPOSE This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors (MGCT) of the genital region. METHODS Fourteen of 317 children enrolled in to the Pediatric Oncology Group/Childrens Cancer Group intergroup study of MGCT from 1990 through 1996 had genital tumors. Thirteen were eligible for inclusion (12 vaginal, one penile). The initial procedure was biopsy in 11 and subtotal resection in 2. Patients were assigned randomly to receive 4 cycles of etoposide, bleomycin, and either standard or high-dose cisplatin. RESULTS Nine children underwent postchemotherapy excision of the residual site, and 2 had subsequent biopsies to confirm a complete response. Two with relapse were saved with additional therapy, and one with progressive disease died. The 4-year event-free survival rate in these patients is 76.2% +/- 13.1%, and 4-year survival rate is 91.7% +/- 8.4%. CONCLUSIONS The author conclude that: (1) the current survival rate for genital MGCT is excellent, (2) delayed surgical resection with organ preservation is not associated with an adverse outcome, and (3) the treatment comparison of the effect of cisplatin dose was inconclusive in this small study population.

Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration

During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.