Utility of frozen section in pediatric and adolescent malignant ovarian nonseminomatous germ cell tumors: A report from the children's oncology group.

PURPOSE: In adult women, most malignant ovarian tumors are epithelial in origin. The use of intra-operative frozen section to distinguish between benign and malignant histology is reliable in guiding operative decision-making to determine the extent of surgical staging required. Pediatric and adolescent patients with ovarian masses have a much different spectrum of pathology with most tumors arising from germ cell precursors. This review was undertaken to assess the concordance between the intra-operative frozen section and the final diagnosis as an aid to guide extent of surgical staging in a group of pediatric and adolescent patients with malignant ovarian germ cell tumors. METHODS: Records of patients aged 0 to 20 years with malignant ovarian germ cell tumors enrolled on Children's Oncology Group study AGCT0132 were reviewed. Pathology reports from patients who had both intra-operative frozen section diagnosis and final paraffin section diagnosis were compared using descriptive statistics. By inclusion criteria for the study, all patients had a final diagnosis of malignancy with required yolk sac tumor, choriocarcinoma or embryonal carcinoma histology. Available central review of pathology final paraffin section slides were compared with final institution pathology reports. RESULTS: Of 131 eligible patients with ovarian germ cell tumors, 60 (45.8%) had both intra-operative frozen section and final paraffin section diagnoses available. Intra-operative frozen section diagnoses were classified as: incorrect diagnosis of benign tumor (13.3%), confirmation of malignancy (61.7%), immature teratoma (16.7%), germ cell tumor not otherwise specified (5%) and no diagnosis provided (3.3%). Intra-operative frozen section was incorrect in 23 of 60 (38.3%) patients evaluated. Central pathology review was concordant with the final institution pathology diagnosis in 76.3% of patients. Central pathology review identified additional germ cell tumor components in 23.7% of patients. CONCLUSIONS: In pediatric and adolescent patients with a confirmed final diagnosis of ovarian germ cell malignancy, intra-operative frozen section diagnosis is not reliable to inform the extent of surgical staging required. Central review by an expert germ cell tumor pathologist provides important additional information to guide therapy.

Monotherapy with cyclosporine for chronic immunosuppression in pediatric liver transplant recipients.

Children who survive liver transplantation (LT) suffer the adverse effects of life-long immunosuppression. In an attempt to minimize these effects, we have instituted a program of tapering immunosuppression, resulting in chronic monotherapy for children after LT. Seventy-three children ages 4 months to 19 years received LT between January 1987 and December 1992. Patient survival was 85% (62/73), with graft survival of 73%, at one year. Triple therapy with prednisone, cyclosporine, and azathioprine begun at transplant was tapered as follows: 1-2 mg/kg prednisone at discharge was reduced by .2 mg/kg every 2 months until a .2 mg/kg total was reached. Alternate-day steroids (.2 mg/kg) were begun at 1 year and discontinued at 1.5 years. AZA (1 mg/kg) was begun posttransplant and discontinued after any serious viral illness or by 1 year. Currently 37 survivors are > 18 months post-LT and were considered candidates for monotherapy. Monotherapy was attempted in 28 (76%), and 25 of these remain on monotherapy an average of 2 years later. All have normal liver function. After monotherapy and alternate-day steroids were achieved, 66% of children < 5th percentile for height at the time of transplant improved to greater than the 5th percentile. There were 3 (11%) patients who rejected while on monotherapy an average of 1.15 years after it was started. These patients had the following predisposing factors that decreased cyclosporine levels and led to rejection: common bile duct stricture, chronic and intermittent antibiotic administration for urinary tract infection, and noncompliance. In the 9 potential candidates not tapered to monotherapy, 6 have had recurrent acute or chronic rejection; 2 of these now receive FK506. We conclude that the majority of stable pediatric LT recipients may be safely tapered to chronic cyclosporine monotherapy. Increased growth is a major benefit of decreased steroid dosing in these children. Cyclosporine absorption and adequate levels are crucial for success of this approach.

Hyperdiploidy and trisomy 12 in the cystic partially differentiated nephroblastoma.

The karyotype of a cystic partially differentiated nephroblastoma (CPDN) was found to be 51, XY, +7, +8, +12, +13, +17. A review of the literature disclosed three other cytogenetically analyzed CPDNs. As in this case, they were all hyperdiploid. The only chromosomal anomaly common to all four cases was trisomy 12, suggesting this chromosome might have a pathogenetic role. Earlier reports had tentatively attributed this role to chromosome 8.

Bednar tumor pattern in recurring giant cell fibroblastoma.

Giant cell fibroblastoma (GCF) and Bednar tumor (BT) have been perceived as two rare, not directly related, soft tissue neoplasms. Recent studies, separately conducted on each process, have presented evidence indicating that, in each instance, the tumor seemed to be related to the dermatofibrosarcoma protuberans. The case being reported provides additional evidence supporting those previous results and, for the first time, documents a direct link between GCF and BT, as seen in this girl who had a vulvar GCF resected at 1-year of age, with recurrence, 1.5 years later, as a mixed BT-GCF.

Germ cell, mesenchymal, and thymic tumors of the mediastinum.

Germ cell, mesenchymal, and thymic tumors of the mediastinum are an uncommon and heterogeneous group of neoplasms. Together they account for less than 25% of mediastinal tumors in childhood. The majority of these tumors are found in the anterior and superior mediastinum, but germ cell tumors and mesenchymal tumors may be located in all compartments. They share a broad range of histological subtypes and clinical behavior, tendency to be large in size, and a requirement for complete surgical excision as the major requirement for successful therapy.

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.

Duplication of the cervical esophagus in children.

True duplication of the cervical esophagus is rare. An 18-month-old girl presented with a large asymptomatic neck mass, which was found to be an intramural duplication of the esophagus. The evaluation and treatment of this patient is presented as well as a review of the six previously reported cases.

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.

Is age less than 1 year a high-risk category for orthotopic liver transplantation?

The aim of this study was to determine if age less than 1 year is a high risk group for orthotopic liver transplantation (OLT). Retrospective analysis was done of patients with liver failure who received OLT. Comparison was made between patients aged < 1 year and > 1 year with regard to survival, allograft survival, hepatic artery thrombosis, and medical status at OLT. Between January 1, 1987 and September 30, 1991, 46 children received OLT. Fifteen (35%) were < 1 year (average age, 7.93 months). Survival in children < 1 year was 80% and children > 1 year was 91%. Allograft survival in children < 1 year was 57% (21 allografts required for 12 survivors) and 78% in children > 1 year (37 allografts required for 29 survivors). Retransplantation was required in 5 of 15 children < 1 year (33%) and in 5 of 29 children (17%) > 1 year. Medical status in children < 1 year was similar to medical status in children > 1 year at the time of transplant. Children with chronic stable liver disease represented 60% of children < 1 year and 60.1% of children > 1 year. Children requiring hospitalization represented 26% of children < 1 year and 29% of children > 1 year. Children in intensive care represented 13% of children < 1 year and 11% of children > 1 year. Survival for all status groups was similar. Hepatic artery thrombosis occurred in one child < 1 year and in 2 children > 1 year. No statistical difference (chi 2 analysis) was found by age between the categories evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of iohexol in the radiographic diagnosis of ischemic bowel.

This study evaluates the use of iohexol as a radiographic diagnostic contrast agent in normal animals and those with experimental bowel ischemia and obstruction. Eighteen rats and 12 rabbits were gavaged with iohexol in a dose of 7.5 mL/kg using concentrations of 140 mg I/mL (isotonic with blood) or 300 mg I/mL. In addition, four rabbits had intraperitoneal iohexol injection and three were given gastrografin gavage. Experimental groups included normal bowel controls, bowel injury induced by ischemia and alcohol contact, bowel obstruction by ligature, and intraperitoneal injection. Serial abdominal radiographs and plasma concentrations of iohexol were obtained. Iohexol remained stable throughout the gastrointestinal tract, retained its intensity, and was well visualized up to four days after administration. Bowel images were fair at concentrations of 140 mg I/mL and excellent at 300 mg I/mL. Gastrografin caused bowel distention and poor visualization related to dilution. It also precipitated in the stomach. Iohexol was rapidly absorbed from the peritoneal cavity and excreted by the kidneys, without causing peritonitis. Rat plasma iohexol levels were three times controls in obstructed bowel and 80 times controls if there was mucosal injury without perforation. Rabbit peak plasma levels were 30 times greater following intraperitoneal injection than with gastric gavage. These observations suggest that iohexol may be useful as a gastrointestinal contrast agent. Measuring plasma iohexol levels may be helpful in the evaluation of suspected bowel ischemia or perforation in the clinical setting.

Isolated liver transplantation for liver failure in patients with short bowel syndrome.

The ultimate prognosis for patients with short bowel syndrome (SBS) has become progressively more favorable over the past decade. Advances in long-term total parenteral nutrition (TPN) have allowed this group of patients to meet nutritional needs while the process of intestinal adaptation occurs. Unfortunately, a subgroup of patients with SBS have hepatic failure (HF), most often secondary to TPN-induced cholestasis. Combined small bowel and liver transplantation (LT) offers a sound anatomic solution for cases of HF with SGS, but it remains experimental at this time. We propose that an isolated LT is a viable alternative mode of therapy for the patient with HF and SBS. The following characteristics were reviewed for five patients with SBS and HF who underwent LT: age at transplantation, weight, liver function, survival, intestinal length, volume of feeding before surgery, and current feeding tolerance and liver function. Four boys and one girl, aged 5.5 to 15 months (average, 11.9), had LT. The total bilirubin level at the time of transplantation was 14.4 to 37 mg/dL (average, 24.7). The patients weighed between 3.8 and 12 kg (average, 8.0), and feeding tolerance ranged from no enteric to complete enteric feeding (average, < 33% of calories by enteric feeding). Bowel loss was attributed to necrotizing enterocolitis in two cases, volvulus in two, and birth hypoxia in one. Bowel length ranged from 60 to 120 cm (average, 88.6). Four children (80%) survived LT, and the average follow-up period was 9.3 months. Three (75%) are home; one is on combined hyperalimentation and enteral feeding, and two are on full enteric feeding. One remains in a chronic care facility, on combined enteral and intravenous feeding. The average daily enteral feeding now comprises more than 70% of caloric requirements. The total bilirubin level is .6 to .8 mg/dL (average, .71). Isolated LT for HF in the patient with SBS effectively restores liver function, allowing time for further intestinal adaptation.

Rejection after pediatric liver transplantation is not the limiting factor to survival.

Liver transplantation became a very successful therapy when cyclosporin A was introduced as an immunosuppressive agent. In an effort to evaluate the contribution of difficult or uncontrolled allograft rejection to mortality, the authors determined the most important factors that limited survival after liver transplantation. Eighty-two children received a total of 94 liver transplants from January 1987 to the present. Patients' records were reviewed for complications that contributed to morbidity and mortality and to assess which complications were preventable. Twelve patients died (15%), nine within 6 weeks of liver transplantation. The chief contributing cause of death was hepatic artery thrombosis (one patient), brain death after liver transplantation for fulminant hepatic failure (two patients), primary allograft nonfunction or dysfunction (two patients), allograft rejection (three patients), or other problems (four patients). Overall, hepatic artery thrombosis occurred in 3.1%, allograft rejection in 57%, fulminant hepatic failure in 7%, and donor organ dysfunction in 7%. Allograft rejection contributed directly to the cause of death in three children (4%). The authors conclude that few deaths after pediatric liver transplantation are caused by failure of immunosuppression. A high survival rate can be achieved after transplantation by eliminating the correctable complications that most frequently occur in the early postoperative period.

Milk of calcium cholelithiasis in children.

Milk of calcium bile is uncommon and occurs mainly in the adult population. The authors report on 2 children, each having a distinct clinical history and presentation, and each with milk of calcium bile/calculi possessing differing chemical composition and highly notable gross morphology. J Pediatr Surg 36:644-647.

Fibrosing colonopathy in children with cystic fibrosis.

PURPOSE: Fibrosing colonopathy is a newly described entity seen in children with cystic fibrosis. The radiological hallmarks are foreshortening of the right colon with varying degrees of stricture formation. High-dose enzyme therapy has been implicated as the cause of this process. The purpose of this study is to review the author's experience with evaluation and treatment of these patients. METHODS: There are currently 380 patients being treated at our CF center. Fifty-five of these patients have been treated with high-dose enzyme therapy (> 5,000 units of lipase/kg). The medical records of these patients, who are at risk for developing fibrosing colonopathy, were reviewed for the presence of recurrent abdominal complaints, and the work-up and treatment of these symptoms. RESULTS: Chronic complaints of abdominal pain, distension, change in bowel habits, or failure to thrive were present in 24 of the 55 patients treated with high-dose enzymes. So far, 18 of these 24 patients have been evaluated by contrast enema. Thirteen of eighteen have been found to have fibrosing colonopathy characterized by foreshortening and strictures of the colon. Additional findings included focal strictures of the right colon (7 of 13), long segment strictures (5 of 13), and total colonic involvement (1 of 13). Nine patients with the most severe symptoms have undergone colon resection, including five segmental right colectomies, three extended colectomies (ileo-sigmoid anastomosis), and one subtotal colectomy with end-ileostomy. Pathological evaluation has shown submucosal fibrosis, destruction of the muscularis mucosa, and eosinophilia. No postoperative complications or deaths occurred. All nine postoperative patients have noted marked symptomatic improvement. Contrast enema follow-up results are available for six patients, and have documented no recurrent strictures to date. Three of four nonoperative patients have less severe symptoms and are currently being treated conservatively. The other family has refused surgery and the patient is being treated symptomatically. CONCLUSION: High-dose lipase replacement has been implicated as the etiology for FC and was present in all of our patients. Our cystic fibrosis center now routinely limits lipase to 2,500 U/kg per dose. We recommend the use of the contrast enemas to evaluate at-risk patients who have chronic abdominal complaints or who present with recurrent bowel obstruction. Colon resection should be performed in those with clinically and radiographically significant strictures with the expectation of a good outcome.

Split liver transplantation benefits the recipient of the 'leftover liver'.

The division of a single hepatic allograft to create two reduced-size grafts has been reported with decreased graft survival (50%) resulting in decreased enthusiasm for this approach. The authors reviewed their experience with 12 recipients of this procedure to evaluate the outcome of the children electively undergoing transplant with the "leftover liver." A retrospective review of six pairs of children receiving part of one hepatic allograft included donor anatomy, recipient operation, and allograft and patient outcomes. Recipient pairs were selected according to blood type compatibility, medical priority, and size restrictions of the larger right lobe and the smaller left lateral segment. Patient and graft survival were compared with elective and urgent patients undergoing whole or reduced-size transplants. Six donors weighed 71.8 +/- 17.4 kg and were 22.6 +/- 11.0 years of age. Recipients of the right lobe were 11.8 +/- 4.2 years of age and weighed 41.9 +/- 14 kg. Recipients of the left lateral segment were 1.81 +/- 1.1 years of age and weighed 9.85 +/- 1.82 kg. Six patients were initially offered the donor allograft because of their hospitalization, critical illness or waiting time. Six additional patients electively underwent transplantation with the leftover liver. Donor organs were screened for normal arterial anatomy. Division of the allograft was performed on the back table in the falciform groove. Generally the left lateral segment graft received the major portion of the hepatic artery and the right lobe the major portion of the portal vein. Five of six (83%) elective patients, two receiving the right lobe and three receiving the left lateral segment had prompt recovery and left the hospital without surgical complication. One recipient of a right lobe transplant died from primary allograft nonfunction. These results are not different from the outcomes of all elective patients who underwent transplantation with whole or reduced-sized transplants in the same program. The authors conclude that split liver transplantation benefits the stable patient who electively receives the liver leftover after reducing the size of a large donor liver for a critically ill child.

Pediatric recipients of three or more hepatic allografts: results and technical challenges.

BACKGROUND/PURPOSE: Children who require a liver transplant at an early age risk chronic allograft rejection (CAR) and other causes of allograft loss. Multiple retransplants may be required for long-term patient survival. The authors evaluate this approach based on our results and technical difficulties. METHODS: Charts of 7 children who received 3 or more liver transplants from 1989 to the present were reviewed retrospectively. RESULTS: A total of 151 children required liver transplantation at our institution since 1989. Of these, 4 boys and 3 girls (mean age, 6.2 years; range, 3 to 14 years) have received 3 or more allografts. The etiology of liver failure for the penultimate allograft was CAR (n = 6) and hepatic artery thrombosis (HAT; n = 1). Five cases required modification of portal vein or hepatic artery anastomoses. Two patients with vena caval strictures required supradiaphragmatic vena caval reconstruction. The original Roux-en-Y limb was adequate for biliary reconstruction in all cases. Five children currently are alive (survival rate, 71%) with good graft function having had a mean follow-up of 23 months (range, 2 to 48 mos.). CONCLUSIONS: The operative procedure for the multiple hepatic transplant child is challenging. The transplant team must be prepared for intraoperative issues such as extended organ ischemia time during hepatectomy, extensive blood loss, and potential need for creative organ revascularization techniques. Overall, multiple retransplant results are good and justify the use of multiple allografts.

Gastrointestinal perforation after pediatric orthotopic liver transplantation.

PURPOSE: The aim of this review was to determine the incidence of gastrointestinal perforation after pediatric liver transplantation and to identify risk factors and clinical indicators that may lead to an earlier diagnosis. METHODS: A retrospective chart review of all children who presented with gastrointestinal perforation after liver transplantation at our institution between January 1, 1987 and August 1, 1996 was performed. RESULTS: One hundred fifty-seven orthotopic liver transplants were performed in 128 children. Fifty-eight reexplorations, excluding those for retransplantation, were performed in 38 children. Ten perforations occurred in six children (incidence, 6.4%). Two children required multiple reexplorations because of several episodes of perforation. The sites of perforation were duodenum (n=1), jejunum (n=8), and ileum (n=1). A single-layer closure was used to repair five perforations, two-layer closures in four, and resection with primary anastomosis in another. The type of repair did not affect the occurrence of subsequent perforations. All the children were less than 18 months old. Four children had undergone prior laparotomy. All children had choledochoenteric anastomoses, but only one had a perforation associated with it. One child sustained bowel injury during the dissection for the liver transplant, but none of the perforations occurred at this site. Bowel function had returned before perforation in five children. Five children were receiving systemic antibiotics at the time of their perforation, and none had been dosed with pulse steroids for rejection. All of the children had significant changes in their temperature. Acute leukopenia developed in one child. A leukocytosis developed in the rest of the children. Abdominal radiographs demonstrated pneumoperitoneum in only one child. All children had positive culture findings from their abdominal drains. Cytomegalovirus developed in one child. Although the diagnosis of gastrointestinal perforation after pediatric liver transplant remains difficult, positive drain culture findings and significant alterations in temperature and leukocyte counts suggest its presence. Pneumoperitoneum is rarely present. CONCLUSION: A high index of suspicion and timely laparotomy, especially in children less than 2 years of age, may be the only way to rapidly diagnose and treat this potentially devastating complication of liver transplant.

Simple technique for determination of the correct length of percutaneous tunnelled catheters in neonates and children.

A simple technique for determining the correct catheter length in percutaneous tunnelled catheters in infants and young children has been devised that virtually guarantees accurate catheter tip placement. Sixty-six patients, aged newborn to 5 years (mean, 1.6 years) have successfully undergone this technique. It is safe, simple, precise, quick, and cost effective. It requires only a hemostat, a suture, and the supplies provided in the prepackaged catheter kit. This technique should be used whenever a percutaneous technique for accessing the vein is used and fluoroscopy is available.

Hypothyroidism impairs colonic motility and function. An experimental study in the rat.

Hypothyroidism (HT) may be associated with either megacolon or severe constipation that mimics Hirschsprung's disease. The exact nature of this relationship is unclear. This report evaluates colonic motility in experimental HT. HT was produced by a total thyroidectomy in 20 male Sprague-Dawley rats (200-300 g). Ten of the HT rats were given thyroxin (30 micrograms/kg/day i.p. for 4 weeks) for a replacement study (RS). Ten sham operated rats (SH) and 50 unoperated rats (UN) were studied as controls. HT was documented at 4 weeks following total thyroidectomy by measuring serum T3, T4 uptake, and TSH. At four to 6 weeks the animals were evaluated for several studies concerning colonic motility. Normal weight gain was significantly impaired under HT. In addition, daily stool volume as well as the number of fecal pellets were significantly reduced in HT. A barium enema showed a dilated colon in HT with an increase of recto-colonic ratio. Anal canal pressure was relatively low in HT. HT rats had a decreased frequency of rhythmic colonic activity (cycle/min) (HT: 10.22 +/- 2.16 vs. UN: 18.09 +/- 4.79, SH: 15.88 +/- 3.92, p less than 0.001). RS rats showed a recovery of rhythmic frequency (15.56 +/- 4.46, p less than 0.001). A positive recto-anal reflex was seen in all UN and SH rats, but only 40% in HT and 80% in RS. The effect of isoproterenol on anal canal pressure was significantly less in HT. Colonic transit at 4 hours was considerably slower in HT (HT: 29.0 +/- 21.0% vs. US: 60.4 +/- 18.3%, SH: 58.7 +/- 14.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)