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.

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.

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.

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.

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.

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.

[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.

[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.

Long-term outcome of elastic stable intramedullary fixation (ESIF) of femoral fractures in children.

In 1993 a prospective data collection of all femoral fracture in children below 16 years of age was initiated in 4 hospitals in the Netherlands. Follow-up was at least two years, with the aim to evaluate leg length discrepancies (LLD). Over a period of 10 years, we included 136 patients < 16 years of age with femoral fractures. Seventy-one patients who were treated with an ESIF-(Elastic Stable Intramedullary Fixation) nail were studied: 44 boys and 27 girls, between the ages of 3-16 years, 23 of which had multiple injuries. Five patients had a Ist or IInd degree open fracture. The average length of stay (LOS) of children with an isolated fracture, was 10 days, and in case of multiple injuries: 12 days. Intra-operative complications were: a broken drill in 2 and an open reduction in 6 cases. Two patients with superficial wound infection were successfully treated with antibiotics. Seven patients had knee complaints of the nails, of which 3 had actually been displaced. Three other patients showed displacement of the nails at X-ray, but had no complaints. At six months follow-up, at the time of removal of the nails, 10 patients had a leg length discrepancy (LLD) exceeding 10 mm. Three children had a clinically significant rotational deformity at this time. Two and a half years after injury 6 patients showed a persistent LLD of more than 10 mm. In all 6 the fractured limb was longer. At ten years of follow-up the LLD persisted in 5 patients. One patient had a persistent clinically significant rotational deformity of more than 10 degrees . The advantages of ESIF-nails are: reduction of hospital stay and rapid mobilisation. The disadvantages: two operations (for insertion and removal) with a risk of complication. Long-term follow-up, preferably till growth stops, is necessary to conclude whether persistent lengthening of the fractured limb remains a problem.

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.

Disseminated medullary thyroid carcinoma despite early thyroid surgery in the multiple endocrine neoplasia-2A syndrome.

A 51/2-year-old boy, with a family history of multiple endocrine neoplasia (MEN)-2A syndrome, was evaluated for presence of MEN-2A and medullary thyroid carcinoma (MTC). DNA diagnostics confirmed MEN-2A. Basal (360 ng/L) and pentagastrin stimulated (430 ng/L) calcitonin (CT) levels were slightly elevated, plasma carcinoembryonic antigen (CEA) was normal. Within a year both tumor markers increased and total thyroidectomy was performed. Histologic examination did not show MTC. In the following years, both tumor markers increased progressively but despite the use of multiple imaging techniques no metastases were localized. After 6 years, biopsy of a palpable lymph node showed MTC. The boy was treated with total cervical, suprahyoidal, and mediastinal lymph node dissection, showing MTC in almost all nodes. Again, the tumor markers remained high. At this point in time, the disadvantages of further medical interventions were outweighed against the chance for cure and it was decided to shift the goal of treatment toward palliation rather than cure. At the last visit the boy was clinically well with persistent extremely high levels of plasma CEA and CT. In conclusion, when prophylactic thyroidectomy in the MEN-2A syndrome has failed, it may be best to withdraw from further interventions to prevent more damage.

Pre-operative diagnostic biopsy and surgery in paediatric liver tumours--the Amsterdam experience.

AIM: To report 24 years of pre-treatment biopsy and surgical experience in primary liver tumours in children. METHODS: Between 1979 and 2003, 53 children presented with a primary liver tumour of whom 48 who underwent surgical resection were evaluated (two died, two were unresectable, and one was transplanted). Biopsy data, per- and post-operative complications, mortality, and survival were retrospectively reviewed. RESULTS: Benign tumours were diagnosed in eight patients. Surgical resection for a malignant tumour was performed in 40 patients (26 hepatoblastomas (HB), eight hepatocellular carcinomas (HCC) (four had fibrolamellar HCC), three rhabdomyosarcomas (RMS), one neuroblastoma, one non-hodgkin lymphoma (NHL), and one teratoma). Primary resection was performed in one HB, and four HCCs. The cumulative survival without evidence of disease was 73% for HB (median 7 years) and 88% for HCC (median 3.5 years). CONCLUSION: The treatment results are comparable with those of larger international series except for HCC. The existing diagnostic pitfalls in differentiating between the various liver malignancies justify the use of a diagnostic biopsy.

[The treatment of oesophageal atresia in The Netherlands]. / De behandeling van oesofagusatresie in Nederland.

The first description of oesophageal atresia dates back to 1670. Oesophageal atresia used to be regarded as a lethal disease, but since the successes of Leven and Ladd in 1939 and Haight in 1941 surgical correction is possible. The Dutch history ofoesophageal atresia begins in 1946. After the successes in America became known, several Dutch surgeons started to treat patients with oesophageal atresia, notably J.ten Kate, L.D.Eerland, M. Schoorl and P.J.Kooreman. In those days, paediatric surgery did not yet exist as a separate specialty. Today, paediatric surgery is concentrated in 6 paediatric surgical centres in the Netherlands. Thanks to the pioneers mentioned and the concentration of knowledge and expertise in the centres, the mortality ofoesophageal atresia patients in the Netherlands has decreased to approximately 9%, despite the fact that currently the gestational age and birth weight of patients is lower and the number of patients with comorbidity is higher.

[Children with blunt trauma to the liver]. / Kinderen met stomp traumatisch leverletsel.

In 3 children, 2 boys aged 13 years and an 8-year-old girl, blunt trauma to the liver was diagnosed after a fall. The first patient underwent drainage of abdominal fluid collection on multiple occasions and a stent was introduced in the biliary duct to ensure normal bile flow; the second patient was treated by arterial catheter embolisation of a segmental branch of the right hepatic artery; in the third patient, acute laparotomy was performed in view ofhaemodynamic instability and a large hepatic rupture was treated by packing. All patients recovered successfully. In the paediatric population, blunt trauma to the liver requires a multidisciplinary approach. For haemodynamically stable children, a conservative course can be taken. Arterial embolisation is the treatment of choice if there is a persistent need for volume resuscitation or blood transfusion. In case of massive haemorrhagic shock, the child should undergo laparotomy, and if the bleeding cannot be stopped, the liver should be packed according to damage-control principles.

[Kidney transplant survival rates and surgical complications in kidney transplants in children; experiences in the Emma Children's Hospital AMC]. / Niertransplantaatoverleving en chirurgische complicaties bij kinderniertransplantaties; ervaringen in het Emma Kinderziekenhuis AMC.

OBJECTIVE: To describe surgical complications, and patient and kidney transplant survival rates in children who have had a kidney transplant. DESIGN: Retrospective. METHOD: Data were analysed concerning the children who had been treated with a renal transplantation in the period 1985-2001 because of terminal renal insufficiency in the Emma Children's Hospital of the Academic Medical Centre in Amsterdam, The Netherlands, with arbitrary end date October 7, 2002. RESULTS: In the study period, 55 primary kidney transplantations were performed on 24 girls and 31 boys. 13 living related and 42 post mortem transplantations were performed. The extra-peritoneal approach was performed in all recipients. Up to October 7, 2002, 14 surgical complications (25%) developed: 4 cases of renovascular thrombosis, 4 urinary leakages, 6 urethral strictures, 1 urethral necrosis, 5 haematomas and 3 lymphoceles. 6 patients lost their grafts due to surgical complications (11%); 4 due to thrombosis, 1 due to urethral necrosis and 1 due to haemorrhage or haematoma. Due to hypertension secondary to the underlying kidney disease 2 patients died within one year after transplantation from hypertensive encephalopathy and cerebral bleeding respectively. The one- and five-year graft survival was 83% and 74% for living related transplantations respectively, and for post mortem transplantations 78% and 68% respectively. The main causes of graft loss were chronic rejection (9/21; 43%), acute rejection (4/21; 19%), thrombosis (4/21; 19%) and surgical complications (2/21; 10%). Primary nonfunction was the only factor with a negative prognostic value for graft survival.

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.

Morphologic features of bone in human osteopetrosis.

Trabecular bone biopsies obtained from six patients with malignant osteopetrosis, one patient with benign osteopetrosis, and two controls were examined by light and electron microscopy. Osteopetrotic osteoclasts showed little to no signs of active involvement in bone resorption. Ruffled borders and clear zones were absent in most cells. In all patients there were large numbers of osteoclasts. Numbers of osteoblasts, bone lining cells, and bone marrow stromal cells were extremely low in all patients with malignant osteopetrosis. In six of the patients a mineralized layer of amorphous organic material lacking collagen fibrils was seen covering large areas of the bone or cartilage matrix. We suggest that this layer represents a pathological calcification on which subsequently organic material has accumulated. The abnormalities in osteopetrotic bone are discussed in the light of the pathogenesis of this disease.

Frequent adverse events after treatment for childhood-onset differentiated thyroid carcinoma: a single institute experience.

Since the mortality rate for childhood differentiated thyroid carcinoma is nearly zero, the focus must be to minimise morbidity following treatment. Our aim was to analyse early and late adverse events. Twenty-five of 26 children treated between 1962 and 2002 were evaluated. Median follow-up was 14.2 years (range 0.9-39.4 years). All underwent total thyroidectomy, 15 (60%) with lymph node dissection and 15 (60%) with adjuvant radio-iodide therapy. Mortality was zero. Seven developed recurrent disease, two developed a third recurrence. Twenty-one (84%) had > or =1 adverse event. Eight had permanent hypoparathyroidism (PH), six permanent recurrent nerve paralysis (PRNP) and two Horner's syndrome. Risk factors for PH and PRNP were total thyroidectomy with lymph node dissection (RR: 6.45, P = 0.015) and recurrent nerve tumour encasement (RR: 8.00, P = 0.001), respectively. Other adverse events were fatigue (n = 5), scar problems (n = 4) and chronic myeloid leukaemia (n = 1). These results emphasise the need to improve treatment strategies.

Hereditary protein S deficiency in young adults with arterial occlusive disease.

Protein S is the vitamin K dependent cofactor of activated protein C. It has an important role in the regulation of blood coagulation and fibrinolysis. Hereditary protein S deficiency is associated with familial venous thrombophilia. Since a few patients with arterial occlusions have been reported to be protein S deficient, it is speculated that hereditary protein S deficiency may be also a risk factor for the development of arterial thrombosis. In a group of 37 consecutive patients with arterial occlusive disease presenting before the age of 45, three patients were found heterozygous for hereditary protein S deficiency. None of the patients had a protein C deficiency or an antithrombin III deficiency. Family investigations showed a clear association between the hereditary deficiency and venous thrombosis, but a relation between the deficiency and arterial thrombosis was less obvious. A review of previous literature on patients with arterial thrombosis and protein S deficiency revealed that more extensive studies are needed to demonstrate whether or not hereditary protein S deficiency is a risk factor for the development of arterial thrombosis.

SIOP treatment guidelines for renal tumours in small infants: fact or fantasy?

AIMS: Since as far back as 1980, SIOP (Société Internationale d>>Oncologie Pédiatrique) have advocated primary nephrectomy (PN) only for unilateral renal tumours in patients > tumour (WT). Fourteen of the 25 patients (56%) were treated with PN, including four patients with CMN. In group B there was one patient (2%) with CMN and 40 patients with WT. Thirteen of the patients (31%) were treated with PN. A total of 15 patients were treated before 1980 and 26 after 1980. Eight of 15 (53%) patients were treated with PN before 1980 and 21/26 (81%) were pre-treated after 1980, according to the protocol. CONCLUSION: Despite the SIOP recommendations, only 56% of patients