Is hepatocellular carcinoma the same disease in children and adults? Comparison of histology, molecular background, and treatment in pediatric and adult patients.

Pediatric hepatocellular carcinoma (HCC) is rare, resulting in scattered knowledge of tumor biology and molecular background. Thus far, the variant in children has been treated as a different entity from adult HCC. We weigh the hypothesis that HCC in the pediatric and adult groups may be the same entity and may benefit from the same treatment. Although certain differences between adult and pediatric HCC are obvious and certain types of HCC may ask for a customized approach, in conventional HCC, similarities predominate, warranting treatment aiming at common molecular targets in adult and pediatric HCC patients.

Cushing syndrome as presenting symptom of calcifying nested stromal-epithelial tumor of the liver in an adolescent boy: a case report.

BACKGROUND: Ectopic adrenocorticotropic hormone-producing primary liver tumors are rare, especially in children. We report the case of an adolescent boy of mixed Dutch and Moroccan descent with an adrenocorticotropic hormone-producing calcifying nested stromal-epithelial tumor with long-term follow-up. Thus far, only two such cases have been reported. CASE PRESENTATION: A 16-year-old boy of mixed Dutch and Moroccan descent presented with Cushing syndrome and a palpable abdominal mass. A calcifying nested stromal-epithelial tumor was diagnosed. Postoperatively, his plasma adrenocorticotropic hormone concentration normalized. He remains in complete remission 13 years after tumor resection. CONCLUSIONS: Calcifying nested stromal-epithelial tumor should be in the differential diagnosis of liver tumors, especially if associated with Cushing syndrome as significant morbidity and mortality may be associated. Literature on the topics involved is comprehensively reviewed.

Transverse colon volvulus in children: A case series and a review of the literature.

Volvulus of the transverse colon is very rare in children. Three cases that occurred in a short time span are described and the scarce literature is reviewed. All patients presented with colonic obstruction and in all three the condition was diagnosed at laparotomy, as CT-scanning is not an available option in either of the two institutions. The transverse colon had not become gangrenous but was resected after detorsion for redundancy. The postoperative course was complicated and relaparotomy had to be performed for reobstruction in all cases. Only if the 'reverse' bean sign is recognized on the preoperative plain abdominal radiograph this rare diagnosis can be suspected.

Age is not a prognostic factor in children with Wilms tumor beyond stage I in Africa.

BACKGROUND: Patients under age 4 with stage I favorable histology (FH) Wilms tumor have a reported survival advantage. Among children above 10 years, a poorer prognosis has been associated with a higher prevalence of diffuse anaplasia. PURPOSE: To determine if, in our practice, patients with Wilms tumors >8 years of age (stage II-V) have a poorer prognosis than those aged <8 years or <4 years. PROCEDURE: Case-control study of 19 patients >8 years with Wilms tumor stages II-V who were identified from a cohort of 192 new patients (2002-2012). For each patient two controls were chosen matched for stage and histology, one 0-3 years and one 4-7 years. Neo-adjuvant chemotherapy was offered to all, combined with intensive supportive care. Postoperative treatment was determined by local stage and histology. OS and EFS at 5 years for the different age groups were compared. RESULTS: Each age group contained 19 patients, of whom 6 had stage II tumors, 3 stage III, 8 stage IV, and 2 stage V. Histology was intermediate risk (IR) in 17 and high risk (HR) in 2. OS at 5 years was 80.8% and EFS was 79.2% for the whole group. No significant difference in outcome could be shown between age groups. Loss to follow up was 6/57 (11%). CONCLUSIONS: The survival advantage of young age (<4 years) associated with stage I FH could not be demonstrated in higher stages. Age had no significant impact on prognosis although a trend to better outcome was seen in children <4 years.

Fibrolamellar variant of hepatocellular carcinoma does not have a better survival than conventional hepatocellular carcinoma--results and treatment recommendations from the Childhood Liver Tumour Strategy Group (SIOPEL) experience.

PURPOSE: Fibrolamellar hepatocellular carcinoma (FL-HCC) and conventional hepatocellular carcinoma (HCC) cases in two consecutive paediatric HCC trials were analysed to compare outcome and derive treatment implications. PATIENTS AND METHODS: Data of 24 FL-HCC (24% PRETEXT IV) and 38 HCC (42% PRETEXT IV) cases from SIOPEL-2 and -3 (1995-1998, 1998-2006) were analysed. Patients were treated according to SIOPEL-2 and -3 high-risk protocol (carboplatin+doxorubicin alternating with cisplatin; seven preoperative, three postoperative cycles) or with primary surgery followed by chemotherapy as indicated. RESULTS: Thirteen of 24 FL-HCC (54%) and 32/38 HCC (84%) were initially treated with chemotherapy. Eight FL-HCC (33%) and five HCC patients (13%) had primary surgery. Partial response was observed in 31% of FL-HCC versus 53% of HCC patients (p=0.17). Complete resection was achieved in ten FL-HCC and seven HCC patients (p=0.08). Three-year event free survival (EFS) was 22% for FL-HCC versus 28% for HCC. Overall survival (OS) was not significantly different at 3 years follow up (42% for FL-HCC versus 33% for HCC, p=0.24). EFS/OS Kaplan-Meier curves did not differ significantly, with median follow up of 43 (FL-HCC) and 60 (HCC) months. No significant correlation was found between potential prognostic factors and OS. In the entire cohort nine out of 23 (39%) patients with complete resection or orthotopic liver transplantation versus 34/39 (87%) without successful surgical treatment, died. CONCLUSIONS: Long-term OS in FL-HCC and HCC is similar. With low response rates, complete resection remains the treatment of choice.

Relapses in hepatoblastoma patients: clinical characteristics and outcome--experience of the International Childhood Liver Tumour Strategy Group (SIOPEL).

PURPOSE: To analyse the clinical characteristics and outcome of hepatoblastoma (HB) patients who relapsed after enrolment on SIOPEL studies 1-3. PATIENTS AND METHODS: Analysis of clinical data of all 59 patients (pts) registered in SIOPEL 1-3 studies, who relapsed after achieving complete remission (CR). RESULTS: The median time from the initial diagnosis to relapse was 12 months (4-115 m). The site of relapse was lung N=27, liver N=21, both liver and lung N=5 and other N=5 (missing data-MD: 1 patient). All but 9 pts had an alpha-fetoprotein level >10 ng/mL at the time of relapse. Treatment of the relapse included chemotherapy and surgery N=25, chemotherapy alone N=21, surgery alone N=7 and only palliative treatment N=5 (MD: 1 pt). Overall, 31 pts (52%) achieved a second CR. With a median follow-up of 83 months, 23 pts are alive, (18 in 2nd CR, 5 after a second relapse) and 36 pts have died (35 from disease and 1 from complications). Three-year event-free survival and overall survival are 34% and 43% respectively (95% confidence interval [CI] 0.28-0.69). The main factors associated with a good outcome were PRETEXT group I-III at diagnosis, a high AFP level at relapse and relapse treatment including both chemotherapy and surgery. CONCLUSION: Relapses in HB are rare events occurring in less than 12% of pts after CR. Combined treatment with chemotherapy and surgical removal of the tumour is essential for long-term survival.

Course of life into adulthood of patients with biliary atresia: the achievement of developmental milestones in a nationwide cohort.

PURPOSE: To investigate the course of life of young adults diagnosed with biliary atresia (BA) in infancy by comparing patients who did and did not underwent transplantation with an age-matched Dutch reference group. METHODS: All patients from the Dutch BA registry, aged >18 years, were invited to complete the course of life questionnaire. RESULTS: Forty patients participated (response = 74%). Twenty-five had not undergone transplantation; 15 had undergone orthotopic liver transplantation. One significant between-group difference was found, namely in substance use and gambling. BA patients who underwent transplantation reported less use than the reference group (p = .01, moderate effect size). Additional moderate effect sizes were found for differences in psychosexual and social development and antisocial behavior. Patients who underwent transplantation had lower scores than one or both other groups. CONCLUSIONS: Development of BA survivors who did not undergo transplantation seems not delayed, whereas that of transplanted patients does seem somewhat delayed. However, patients who underwent transplantation display less risk behavior. Larger samples are necessary to confirm these findings.

Quality of life and disease-specific functioning of patients with anorectal malformations or Hirschsprung's disease: a review.

The objective of this review was to examine disease-specific functioning (ie, faecal functioning and disease-related psychosocial problems) and quality of life (QoL)in patients with anorectal malformations (ARMs) or Hirschsprung's disease across different developmental stages. A search on PubMed yielded 22 eligible studies which were analysed. Patients with ARM or Hirschsprung's disease report slightly more QoL problems than comparison groups. As compared with adolescents, children reported better QoL but worse disease-specific functioning. Relationships between disease-specific functioning and QoL remain unclear. Therefore, to disentangle the complex relationship between the faecal functioning of these patients and their QoL through childhood, adolescence and adulthood, longitudinal studies should examine disease-specific functioning with validated QoL questionnaires that include age-specific versions.

Management of trichobezoar: case report and literature review.

Trichobezoars (hair ball) are usually located in the stomach, but may extend through the pylorus into the duodenum and small bowel (Rapunzel syndrome). They are almost always associated with trichotillomania and trichophagia or other psychiatric disorders. In the literature several treatment options are proposed, including removal by conventional laparotomy, laparoscopy and endoscopy. We present our experience with four patients and provide a review of the recent literature. According to our experience and in line with the published results, conventional laparotomy is still the treatment of choice. In addition, psychiatric consultation is necessary to prevent relapses.

Outcome of total parathyroidectomy and autotransplantation as treatment of secondary and tertiary hyperparathyroidism in children and adults.

BACKGROUND: Treatment safety and effectiveness of total parathyroidectomy and autotransplantation for secondary and tertiary hyperparathyroidism have been extensively proven in adults; the evidence for children, however, is scarce. Children and adolescents cannot simply be seen as young adults in the case of chronic kidney disease and hyperparathyroidism. The aim of this retrospective study was therefore, to evaluate whether parathyroidectomy with forearm autograft is as effective and safe in children and adolescents as in adults. METHODS: A group of 64 adults and 8 children and adolescents treated for secondary or tertiary hyperparathyroidism were retrieved from our database. The outcomes were compared on patient demographics, operation results, and blood parameters consisting of parathyroid hormone (PTH) and calcium levels. Our results were compared with all currently available articles on parathyroidectomy in children with secondary or tertiary hyperparathyroidism (n = 11). RESULTS: For adults, preoperative mean serum calcium was 2.67 +/- 0.29 mmol/l and mean parathyroid hormone (PTH) level was 120 +/- 86 pmol/l. For children, preoperative mean serum calcium was 2.62 +/- 0.20 mmol/l and mean parathyroid hormone (PTH) level was 80 +/- 38 pmol/l. Postoperative calcium and parathyroid hormone levels for adults dropped to 2.39 +/- 0.23 mmol/l and 30 +/- 53 pmol/l, respectively. Postoperative calcium and parathyroid hormone levels for children dropped to 2.41 +/- 0.16 mmol/l and 26 +/- 33 pmol/l, respectively. The effectiveness of parathyroidectomy with autotransplantation was 75% in children and 72% in adults. Thus, effectiveness did not differ significantly between children and adults. CONCLUSIONS: Combining the results of our own study with a literature review on pediatric parathyroidectomy, we conclude that parathyroidectomy and forearm autograft is as effective a treatment for secondary and tertiary hyperparathyroidism in children and adolescents as it is in adults.

Is endoscopic retrograde cholangiopancreatography valuable and safe in children of all ages?

OBJECTIVE: To evaluate indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children of the Emma Children's Hospital Academic Medical Centre in Amsterdam, the Netherlands. DESIGN: Descriptive. Retrospective analysis by medical records. PATIENTS AND METHODS: Information was obtained by chart review of patients between 0 and 18 years who underwent ERCP from 1995 to 2005 in our center. The following data were analyzed: indications, findings, therapies, safety, and technical success. Success was defined as obtaining accurate diagnostic information or succeeding in endoscopic therapy. RESULTS: Sixty-one children (age 3 days to 16.9 years, mean age 7.0 years) underwent a total of 99 ERCPs. Of those patients, 51% (31/61) were younger than 1 year, 84% had biliary indications, and 16% had pancreatic indications for the performance of ERCP. The complication rate was 4% (4/99) and included substantial pancreatitis and mild irritated pancreas. No complications occurred in children younger than 1 year. CONCLUSIONS: ERCP is a safe and valuable procedure for children of all ages with suspicion of pancreaticobiliary diseases. Indications for ERCP are different for children and adults. A laparotomy could be prevented in 12% of children with suspicion of biliary atresia. Further research is required to determine the role of MRCP versus ERCP.

[An unusual presentation of a periappendicular infiltrate]. / Een ongebruikelijke manifestatie van een periappendiculair infiltraat.

A 17-year-old boy presented with an atypical manifestation of acute appendicitis. The clinical aspect, radiological investigations and peroperative aspect of the appendix were not conclusive but nevertheless a neuroendocrine tumour (carcinoid tumour) of the appendix was suspected. After ileocaecal resection and resection of pathological lymph nodes, histopathological evaluation revealed the diagnosis: a periappendicular mass without any sign of malignancy. In retrospect, ileocaecal resection was performed for a benign disease. This case illustrates that an unusual presentation of a common disease occurs more frequently than a typical presentation of a rare disease.

Paraplegia after thoracotomy under combined general and epidural anesthesia in a child.

A 9-year-old boy underwent a thoracotomy for excision of his right third rib under combined general and epidural anesthesia for a Ewings sarcoma. Postoperatively, he was found to have a complete T2-3 paraplegia. Permanent paraplegia was described as a rare complication of thoracotomy in adults, and very rarely after epidural analgesia in adults and babies. This was the first report in a child.

Adults with corrected oesophageal atresia: is oesophageal function associated with complaints and/or quality of life?

The aim of this study was to evaluate oesophageal function after correction of oesophageal atresia in adults, and to investigate the association between complaints, oesophageal function and quality of life (QoL). Twenty-five adults were included who participated in previous follow-up studies, during which complaints of dysphagia and gastro-oesophageal reflux (GOR), results of upper gastrointestinal endoscopy, oesophageal biopsies and QoL had been collected. Manometry was performed in 20 patients, 24 h pH-measurements were performed in 21 patients. pH-values (sample time 5 s) were calculated using criteria of Johnson and DeMeester. Associations were tested with ANOVA and chi (2)-tests. Ten patients (48%) reported complaints of dysphagia, seven (33%) of GOR. The amplitude of oesophageal contractions was low (<15 mmHg) in four patients (20%). pH-measurements showed pathological reflux in three patients (14%). Patients reporting dysphagia more often had disturbed motility (P = 0.011), and lower scores on the domains "general health perceptions" (SF-36) (P = 0.026), "standardised physical component" (SF-36) (P = 0.013), and "physical well-being" (GIQLI) (0.047). No other associations were found. This study shows a high percentage of oesophageal motility disturbances and a moderate percentage of GOR after correction of oesophageal atresia. Patients reporting dysphagia, whom more often had disturbed motility, seemed to be affected by these symptoms in their QoL.

Bryant traction in paediatric femoral shaft fractures, home traction versus hospitalisation.

AIM: To evaluate Bryant traction at home in terms of feasibility, morbidity, effect on length of hospital stay, outcome and costs. PATIENTS AND METHODS: Retrospective analysis of 54 children treated for femoral shaft fracture (1991-2004). Results of 'home traction' (A, n=38) and 'hospital traction' (B, n=16) were compared. Data were collected regarding demographics, length of hospital stay, traction period, various aspects of the fractures, co-morbidity, morbidity, and follow-up. The parents' experience was evaluated by telephone questionnaire. RESULTS: Two early treatment failures occurred. One patient stopped home traction at 8 days due to skin problems and had a spica cast applied at another hospital, with subsequent development of a compartment syndrome. The other patient was placed in a hip spica after 2 weeks of hospital traction because of difficulty in getting satisfactory X-rays. At follow-up, one unacceptable shortening of 3 cm had occurred in the home traction group. There was only a significant difference in hospital stay (A 7.0 days versus B 22.5 days), total traction period (A 28.0 days versus B 22.5 days) and costs (group B 3x versus group A). The parents were overall pleased with traction at home. Complications occurred as much in the home traction group as in the control group and fracture position at union was equal in both groups. CONCLUSIONS: Treatment with home traction is feasible, simple and effective; it reduces hospital stay to 1 week, and costs to one-third. Good patient selection and instructions of the parents are mandatory.

[A colo-colic invagination on the basis of MutYH-associated polyposis in a boy aged 14]. / Een colocolische invaginatie op basis van MutYH-geassocieerde polyposis coli bij een jongen van 14 jaar.

A 14-year-old boy presented with acute abdominal pain, vomiting and diarrhoea. Colo-colic intussusception was diagnosed by means of a colonic contrast X-ray. The intussusception was successfully reduced during this procedure. Hundreds of polyps were seen throughout the entire colon. Genetic research showed a mutation of the MutYH gene. Proctocolectomy with ileoanal pouch anastomosis was carried out. The pathology specimen showed an intramucosal carcinoma and multiple adenomas. MutYH-associated polyposis coli is an autosomal recessive disease that occurs as a result of a mutation in the MutYH gene. This will lead to polyposis coli. An intussusception is a rarely seen symptom. Patients need preventive surgical treatment because of the high risk developing a colorectal carcinoma.

Management of solid-pseudopapillary neoplasms of the pancreas: a comparison with standard pancreatic neoplasms.

BACKGROUND: Solid-pseudopapillary neoplasms (SPNs) of the pancreas are increasingly diagnosed, but the exact surgical management in terms of extent of the resection is not well defined. MATERIALS AND METHODS: Patients operated on in our hospital between January 1993 and March 2005 formed the study groups. RESULTS: From 659 consecutive resections for pancreatic neoplasms, 12 female patients (1.8%) with a median age of 21 years who underwent resection for (SPN) are compared with the remaining 647 pancreatic resection patients. Jaundice (SPN 0 versus PR 73%, p < 0.001) and weight loss (SPN 0 versus PR 49%, p = 0.001) occurred significantly less often. Neoplasms were distributed equally among the pancreatic head (SPN 5 out of 12 patients versus PR 88%, p < 0.001) and corpus/tail (SPN 6 out of 12 patients versus PR 8%, p < 0.001). The operative time was significantly shorter (SPN 233 min versus PR 280 min, p = 0.012), and there were significantly fewer complications (SPN 1 of 12 patients versus PR 48%, p = 0.007). The mortality was not different (SPN 0 versus PR 1.6%, p = 1.000), and the hospital stay was significantly shorter (SPN 9 days versus PR 15 days, p = 0.012). The median size of the neoplasms was significantly larger (SPN 6.9 cm versus PR 2.5 cm). The median number of lymph nodes harvested was significantly fewer (SPN 1 versus PR 6, p = 0.001), and lymph node metastases occurred significantly less often (SPN 0 versus PR 64%, p < 0.001). The 5-year survival of SPN patients was 100% and is significantly better compared with survival of patients with pancreatic adenocarcinoma (12%, p < 0.001) and ampulla of Vater adenocarcinoma (22%, p = 0.005). CONCLUSIONS: Patients with solid-pseudopapillary neoplasms of the pancreas present differently and the course of the disease is more benign. These patients can be adequately managed by pylorus-preserving pancreatoduodenectomy or spleen-preserving distal pancreatectomy with excellent early and long-term results.

Factors associated with recurrence and metastasis in sacrococcygeal teratoma.

BACKGROUND: Sacrococcygeal teratoma (SCT) is a relatively uncommon tumour, with a high risk of recurrence and metastasis. The factors associated with recurrence and metastatic disease were studied. METHODS: A retrospective review was conducted of 173 children with SCT treated between January 1970 and February 2003 at the paediatric surgical centres in the Netherlands. Risk factors were identified by univariate and multivariate analysis. RESULTS: Eight children died shortly after birth or around the time of operation. Nine children, all over 18 months old, had metastases at presentation. Four teratomas with metastasis showed mature histology of the primary tumour. Nineteen children had recurrence of SCT a median interval of 10 months (range 32 days to 35 months) after primary surgery. Risk factors for recurrence were pathologically confirmed incomplete resection (odds ratio (OR) 6.54 (95 per cent confidence interval (c.i.) 2.11 to 20.31)), immature histology (OR 5.74 (95 per cent c.i. 1.49 to 22.05)) and malignant histology (OR 12.83 (95 per cent c.i. 3.27 to 50.43)). Size, Altman classification, age and decade of diagnosis were not risk factors for recurrence. One-third of the recurrences showed a shift towards histological immaturity or malignancy, compared with the primary tumour. Seven patients died after recurrence, five with malignant disease. CONCLUSION: This national study showed that SCT recurred in 11 per cent of the children within 3 years of operation. Risk factors were immature and malignant histology, or incomplete resection. Mature teratoma has the biological capability to become malignant.

Long-term results of boerema anterior gastropexy in children.

OBJECTIVES: To analyze the long-term results of Boerema anterior gastropexy using the Visick grading system in a university teaching hospital. METHODS: Retrospective review of 247 children with severe or complicated gastroesophageal reflux disease (GERD). Patients who underwent primary gastropexy between 1990 and 2001 were divided in 3 groups: (A) neurologic impaired patients (n = 83); (B) esophageal atresia patients (n = 36); and (C) patients without underlying disease (n = 128). The median length of follow-up after gastropexy was 7 years and 8 months (range, 1.5-13 years). Follow-up was carried out using a standardized questionnaire and was obtained by telephone. Postoperative recurrence of symptoms during follow-up was considered as failure of the operation. RESULTS: Postoperative complications occurred in 20 patients (24%) in group A, in 13 patients (36%) in group B and in 23 patients (18%) in group C. Thirty-three patients died during the follow-up period, 5 of whom during the postoperative period. Six children could not be traced; thus, 208 were available for long-term follow-up. Postoperative failures occurred in 12 patients (23%) in group A, in 11 patients (31%) in group B and in 17 patients in group C (14%). Reoperation for recurrence of symptoms due to GERD was performed in 6 patients in group A, in 7 patients in group B and in 2 patients in group C. The final outcome at the time of interview was successful in 81% of group A, in 88% of group B and in 91% of group C. CONCLUSIONS: In the long term, Boerema anterior gastropexy is an effective operation for complicated GERD in children without underlying disease as well as in neurologically impaired children and patients with esophageal atresia.