Mary M. Davis

Extraskeletal Ewing's sarcoma

Ewings sarcoma usually is identified as a primary malignancy of bone affecting children and young adults. Extraskeletal Ewings sarcoma is rare, and very few data are available addressing optimal surgical and oncologic treatment modalities.

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.

Congenital disseminated malignant rhabdoid tumor: a distinct clinicopathologic entity demonstrating abnormalities of chromosome 22q11.

The clinical, pathologic, and immunohistochemical features of a widely disseminated tumor with rhabdoid phenotype are described in nine infants < or = 3 months of age. Five neonates had tumor evident at birth, two of which had placental metastases. The average survival following diagnosis was < 6 weeks. None of the infants had an apparent primary tumor in either the kidney or brain. In four cases, the dominant mass involved the head and neck region, and in two cases, the primary mass was paraspinal. The histologic features were those of a high-grade, round cell neoplasm with abundant cytoplasm and containing cells with cytoplasmic filamentous inclusions. Immunohistochemical studies revealed polyphenotypic antigen expression. Genetic information was available from eight of nine cases. Karyotype analysis revealed abnormalities of chromosome band 22q11-12 in three of six tumors. Fluorescence in situ hybridization studies or molecular studies demonstrated 22q11.2 deletions in all five cases with available frozen tissue, two of which had translocations involving 22q by karyotype analysis. The similar clinical and pathologic findings in these rapidly fatal tumors in infants and the demonstration of abnormalities of chromosome 22q11 in a majority of the cases supports their histogenetic and nosologic relationship to the family of malignant rhabdoid tumors that typically occur in young children in several anatomic sites, including kidney, soft tissues, liver, and brain. Like neuroblastoma and rhabdomyosarcoma, malignant rhabdoid tumor can appear as disseminated disease at birth or shortly thereafter.

Evaluation of small intestine submucosa and acellular dermis as diaphragmatic prostheses

BACKGROUND/PURPOSE The repair of large congenital diaphragmatic defects in the neonate continues to be a challenge. Polytetrafluoroethylene (PTFE) is the synthetic material most widely used for reconstruction in instances of partial and complete diaphragmatic agenesis. Recurrent hernia is a frequent complication, because this material does not grow with the infant. This study evaluates two novel materials; small intestine submucosa (SIS; Cook Biotech, Lafayette, IN), and acellular dermis (AlloDerm; Lifecell Corp, The Woodland, TX) for diaphragm reconstruction in growing animals. METHODS Sprague-Dawley rats (100 g, n = 87) were anesthetized and underwent laparotomy. The control group (n = 18) underwent a sham laparotomy with a left subcostal incision and closure. The other two groups underwent central excision of the left hemidiaphragm (50% loss) and reconstruction with either a SIS (n = 35) or AlloDerm (n = 19) patch sutured circumferentially with 6-0 prolene. Seventy-two animals survived the operation, and were killed at five separate time intervals (2 weeks, 1, 2, 3, and 4 months). Chest radiographs were performed monthly and before death. Radiographs were reviewed in a blinded fashion by two observers as were the necropsies, and rib deformity was noted if present. Histological examination of the diaphragm patch was performed in each animal. RESULTS There was no evidence of rib deformity noted on gross examination at necropsy or on chest radiograph in either experimental group. At necropsy, all patches were intact without hernia, eventration, or contraction. Histology findings initially showed acute and chronic inflammatory changes in both patch materials that lessened at the 2-month time interval. Both prosthetic patches began to thin at 3 months and was most prominent in the SIS rats. At 4 months, both SIS and AlloDerm remained viable without evidence of necrosis. Each patch showed evidence of fibroblastic incorporation and small capillary ingrowth. These changes were more prominent in the AlloDerm group. There was no evidence of skeletal muscle ingrowth. CONCLUSIONS These data indicate SIS and AlloDerm may be useful materials for prosthetic repair in instances of partial or total agenesis of the diaphragm. Further investigation in a large animal model over a longer duration is indicated.

White specks in the esophageal mucosa: an endoscopic manifestation of non-reflux eosinophilic esophagitis in children☆

BACKGROUND White specks in the esophageal mucosa have been observed in children with eosinophilic esophagitis. The aim of this study was to determine the relationship between white specks in the esophageal mucosa and allergic (non-reflux) eosinophilic esophagitis. METHODS Endoscopic data, pH probe results, and histopathology reports for children with esophageal endoscopic abnormalities seen during a 17-month period were reviewed. Eosinophilic esophagitis was grouped according to the number of eosinophils per high power field (non-allergic, <15 eosinophils/high power field; allergic, > or =15 eosinophils/high power field). RESULTS Of 1041 endoscopies performed during the study period, 153 revealed evidence of eosinophilic esophagitis. Of these 153, 61 had fewer than 15 eosinophils/high power field and 92 had 15 or more eosinophils/high power field. At 31 of the 153 procedures, white specks were noted in the esophageal mucosa. The sensitivity of white specks in the esophageal mucosa for allergic eosinophilic esophagitis was only 30%, but the specificity was 95%. pH probe testing was performed in 21 patients with white specks and was normal in all. CONCLUSIONS This report describes a new endoscopic finding associated with allergic eosinophilic esophagitis in children. Eosinophilic esophagitis tends to be severe when white specks are present (> or =15 eosinophils/high power field) and is not associated with pathologic gastroesophageal reflux, as demonstrated by pH probe testing.

The Ontogeny of Canine Small Intestinal Submucosa Regenerated Bladder

AbstractPurpose: Small intestinal submucosa has previously been shown to promote regeneration of transitional epithelium, smooth muscle and peripheral nerves in rat and dog bladders. The origin of these regenerated components is presently unknown. This study attempts to define the origin of vascular, smooth muscle and peripheral nerve regeneration.Materials and Methods: A total of 22 adult male dogs weighing 25 to 30 kg. underwent partial cystectomy and immediate augmentation with a small intestinal submucosa patch graft. The small intestinal submucosa graft-native bladder interface was marked with permanent marking sutures for future reference. Small intestinal submucosa regenerated bladders were harvested at 2, 3, 4, 6, 8 and 10 weeks after augmentation. The tissue was then studied with routine histology and immunohistochemistry using factor VIII, smooth muscle specific actin (1A4) and neurofilament staining.Results: Results demonstrated that epithelialization of the graft surface was complete by 3 to 4...

Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors: a Children's Oncology Group study.

High‐dose cisplatin combined with etoposide and bleomycin (HDPEB) improves event‐free survival (EFS) in advanced pediatric germ‐cell tumors (PGCT), but has significant ototoxicity. Amifostine appears to protect against toxicity. The authors combined amifostine with HDPEB and evaluated the efficacy and toxicity, specifically whether ototoxicity deccreased.

A protocol for the handling of tissue obtained by operative lung biopsy: recommendations of the chILD pathology co-operative group.

This is the first of a series on pediatric pulmonary disease that will appear as Perspectives in Pediatric Pathology over the coming months. The series will include practical issues, such as this protocol for handling lung biopsies and another on bronchoalveolar lavage in childhood, as well as reviews of advances in various areas in pediatric pulmonary pathology. It has been 11 years since the last Perspectives on pulmonary disease. Much has happened since then in this area, and this collection will highlight some emerging and rapidly advancing areas in pediatric lung disease. These will include a review of molecular mechanisms of lung development, and another of mechanisms of pulmonary vascular development. The surfactant system and its disorders, as well as recent advances in the biology of the pulmonary neuroendocrine system and mechanisms of respiratory viral disease, will be addressed. Articles on pulmonary hypertension, pulmonary neoplasia, and pediatric lung transplantation, with their implications for the pediatric pathologist, are also planned. The contributors to this series are a diverse group with special interests and expertise in these areas. As Dr. William Thurlbeck noted in his foreword to the previous volume, Pulmonary Disease, volume 18 of Perspectives in Pediatric Pathology, pediatric pathology had been largely concerned with phenomenology, rather than with mechanisms, model systems, and experimental investigation. I think he would have been pleased to see the changes that have occurred over the past 10 years in pediatric lung biology and pathology in particular, because these were particularly favored interests of his later years.

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.

Experience with juvenile polyps in North American children: the need for pancolonoscopy

We report a recent experience with juvenile polyps (JP) in a large cohort of North American children to determine if a pancolonoscopy (PC) is needed in all children with suspected polyps. We reviewed hospital charts of all patients with JP seen over a 9-yr period (January, 1990–October, 1998). A total of 331 JP were encountered during 195 procedures in 184 patients (64% males, 88% white, mean age 5.93 yr [range 0.42–15.5 yr], median age 4.84 yr). Painless rectal bleeding was the commonest symptom. PC was performed in 42% (82/195) of procedures, and 177 JP were encountered: 54% (97/177) were in the rectosigmoid colon, 14% (24/177) were in the descending colon, and 32% (56/177) were proximal to the splenic flexure (i.e., proximal polyps). Overall, proximal polyps were seen in 37% (31/82) of PC. Only proximal polyps were noted in 12% (10/82) of PC. Five patients were re-endoscoped after an initial limited examination because of continuing symptoms from proximal polyps. All but one of the polyps had typical features of a JP on histological examination. Though most JP are located in the left colon, a PC should be the initial procedure because: 1) 37% of PC revealed proximal polyps, 2) 32% of polyps were located proximal to splenic flexure, 3) persistence of symptoms from missed proximal polyp(s) necessitates a repeat study with attendant risks, and 4) there is a possibility of malignant transformation in an unidentified JP.