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.

Diurnal cortisol and coping responses in close relatives of persons with acquired brain injury: a longitudinal mixed methods study.

OBJECTIVE: To examine the impact of having a close relative experience a severe brain injury. DESIGN: Six-month longitudinal mixed methods concurrent embedded study. Quantitative data provided the primary database and qualitative data provided the secondary source. METHODS: Assessment included psychosocial factors of perceived stress, traumatic stress symptoms, coping and social support in addition to salivary cortisol as a biological marker of stress. Written accounts of the experience were provided in response to an open-ended question. Participants composed 15 close relatives of adults with severe brain injury admitted to a specialist rehabilitation facility (mean age 49.4 years; SD 11.79). Assessments were conducted on admission, at 6 weeks, 3 months and 6 months post-admission. RESULTS: Quantitative data revealed high traumatic stress at admission, with a non-significant decline at follow-up. Diurnal cortisol output declined significantly from baseline to all follow-up assessments. Coping sub-scales of acceptance and religion were repeated associated with cortisol indices at baseline, 6 weeks, 3 months and 6 months follow-up. Qualitative data revealed two themes; 'relational impact' and 'passage of time'. CONCLUSIONS: Findings offer the potential for effective and timely intervention in family members of persons with severe brain injury.

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.

Dietary assessment can be based on pattern recognition rather than recall.

Diet is the leading predictor of health status, including all-cause mortality, in the modern world, yet is rarely measured; whereas virtually every adult in a developed country knows their approximate blood pressure, hardly any knows their objective diet quality. Leading authorities have called for the inclusion of nutrition in every electronic health record as one of the many remedial steps required to give dietary quality the routine attention it warrants. Existing tools to capture dietary intake are based on either real-time journaling or recall. Journaling, or logging, is time and labor intensive. Recall is notoriously unreliable, as humans are notably bad at remembering detail. Even allowing for the challenge of recall, these dietary intake methods are labor and time intensive, and require analysis at the n-of-1 level. We hypothesize that dietary intake assessment can be "reverse engineered"-predicating assessment on the recognition of fully formed dietary patterns-rather than endeavoring to assemble such a representation one food, meal, dish, or day at a time. This pattern recognition-based method offers potential advantages over existing methods, including speed, efficiency, cost, and applicability. We have developed and provisionally tested such a system, and the results thus far support our hypothesis. We are convinced that leveraging pattern recognition to make dietary assessment quick, user-friendly, economical, and scalable can allow for the conversion of dietary quality into a universally measured and routinely managed vital sign. In this paper, we present the supporting case.

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.

Exercise stimulates the mitogen-activated protein kinase pathway in human skeletal muscle.

Physical exercise can cause marked alterations in the structure and function of human skeletal muscle. However, little is known about the specific signaling molecules and pathways that enable exercise to modulate cellular processes in skeletal muscle. The mitogen-activated protein kinase (MAPK) cascade is a major signaling system by which cells transduce extracellular signals into intracellular responses. We tested the hypothesis that a single bout of exercise activates the MAPK signaling pathway. Needle biopsies of vastus lateralis muscle were taken from nine subjects at rest and after 60 min of cycle ergometer exercise. In all subjects, exercise increased MAPK phosphorylation, and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2. Furthermore, exercise increased the activities of the upstream regulators of MAPK, MAP kinase kinase, and Raf-1. When two additional subjects were studied using a one-legged exercise protocol, MAPK phosphorylation and p90 ribosomal S6 kinase 2, MAP kinase kinase 1, and Raf-1 activities were increased only in the exercising leg. These studies demonstrate that exercise activates the MAPK cascade in human skeletal muscle and that this stimulation is primarily a local, tissue-specific phenomenon, rather than a systemic response to exercise. These findings suggest that the MAPK pathway may modulate cellular processes that occur in skeletal muscle in response to exercise.

Generation of the combined prothrombin activation peptide (F1-2) during the clotting of blood and plasma.

We have investigated the pathway of prothrombin activation in blood and plasma. By means of a rapid purification procedure involving chromatography on DEAE-cellulose and hydroxyapatite, we demonstrated that the major prothrombin fragment in serum is that representing the amino-terminal half of prothrombin (i.e. F1-2). The F1-2 isolated was characterized by its size, amino acid and antigenic compositions, amino-terminal residue, and the peptides (designated F1 and F2, respectively) it yielded upon hydrolysis by thrombin. Measurements by the isotope dilution technique showed that F1-2 could account for the fate of at least 90% of the prothrombin originally present in plasma. By contrast, the serum concentration of the fragment representing the amino-terminal third of prothrombin (viz. F1) was less than 10% that of F1-2. These results demonstrated that the major route of prothrombin conversion in blood or plasma involves the removal of the combined activation fragment (F1-2) as a single peptide.

[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.

Cardiac troponin-I as a predictor of mortality in patients with first episode acute atrial fibrillation.

BACKGROUND: Recent-onset atrial fibrillation (AF) is a frequent cause for presentation to the emergency department. Recent studies proposed that the addition of biomarker information might improve the prediction of clinical outcomes by enabling identification of patients at high risk. AIM: We aimed to examine the role of cardiac troponin I as a predictor of clinical outcome in patients with first episode acute AF. DESIGN: Patients, 18 years or older, presenting to our hospital with a primary diagnosis of first episode acute AF were included in this retrospective study. METHODS: The association between elevated cTnI with mortality or the composite endpoint (mortality, stroke or heart failure) was examined in a univariate Cox regression model. RESULTS: Of the 274 study patients, 111 had elevated cTnI levels (41%). Increased cTnI was associated with older age, history of myocardial infarction, higher creatinine levels and higher heart rate (All P < 0.01). Elevated cTn was associated with an adjusted hazard ratio of 1.86 [95% confidence interval (CI) 1.17-2.96; P = 0.009] for mortality and 1.89 (95% CI 1.27-2.84; P = 0.002) for the combined endpoint. CONCLUSIONS: Elevated cardiac Troponin I is a significant predictor of mortality and a composite endpoint of mortality, stroke or heart failure in patients presenting with first episode acute AF.

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.

Alteration of fibronectin receptors (integrins) in phorbol ester-treated human promonocytic leukemia cells.

We describe the isolation of human fibronectin receptors (integrins) from two nonadherent promonocytic cell lines and from peripheral blood monocytes. Integrins purified from U-937 and THP-1 cells exhibited identical electrophoretic migrations on sodium dodecyl sulfate gels run under reducing (approximately Mr 150,000) and nonreducing (alpha, Mr 160,000; beta, Mr 130,000) conditions. Treatment of U-937 or THP-1 cells with phorbol esters induced these cells to express different integrins with electrophoretic mobilities (alpha, Mr 140,000; beta, Mr 115,000, nonreduced) identical to those from normal human peripheral blood monocytes. Receptors isolated from uninduced, nonadherent promonocytic leukemia cells (U-937 and THP-1) were distinct from glycoproteins IIb and IIIa and from leukocyte adhesion molecules (p150/95). However, receptors isolated here did react with an antibody known to block cell adhesion to fibronectin. The differences observed in apparent molecular masses of fibronectin receptors from uninduced and induced U-937 or THP-1 cells are removed by treatment of purified integrins with endoglycosidase F or N-glycanase. In summary, the data presented here demonstrate the purification of integrins by fibronectin affinity chromatography from human leukemia cells and normal peripheral blood monocytes. Our results suggest that these receptors differ in immature and mature monocytic cells, and are altered by glycosylation in the course of cellular maturation.

Tumor cell generation of thrombin via functional prothrombinase assembly.

Prothrombinase affects the proteolytic conversion of prothrombin to thrombin and is the penultimate enzyme in the common coagulation pathway. Prothrombinase is a complex in which the proteinase, Factor Xa, a cofactor, Factor Va, and calcium are bound to a membrane surface to generate the active enzyme. Guinea pig line 1 and line 10 tumor cells, grown as primary cultures from ascites tumors or as cell lines in culture, provide a surface that interacts with coagulation Factor Va and Xa and with calcium ions to form this enzyme complex. Cultured human colorectal carcinoma cells (Colo 205) also participate in prothrombinase complex assembly and function. Prothrombinase generation was measured by following the kinetics of prothrombin conversion to thrombin. Thrombin generation was monitored continuously using the reversible thrombin inhibitor, dansylarginine N-(3-ethyl-1,5-pentanediyl)amide, which displays enhanced fluorescence upon binding to thrombin. Analyses of kinetic data indicate that the apparent dissociation constants (1-4 X 10(-10) mol/liter) and the number of Factor Va-Xa binding sites per tumor cell are comparable to values reported for human and bovine platelets, human lymphocytes, and monocytes. Guinea pig lymphocytes were also active, while erythrocytes were inactive, in the prothrombinase assay. Membrane vesicles, shed by guinea pig and human tumor cells into conditioned medium, also supported functional prothrombinase activity. Although earlier studies indicated that tumor cells may initiate coagulation, this is the first demonstration that tumor cells are competent to bring clotting to fruition by generating thrombin, a step essential to fibrin generation. These data suggest that tumor cells, in the presence of clotting initiators and appropriate coagulation factors, are sufficient to generate the fibrin deposited in solid tumors.

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.

Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group.

PURPOSE: To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncology's first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty patients (51%) never became operable. Overall survival at 5 years was 28%, and event-free survival was 17%. Most deaths resulted from tumor progression (26 of 28). Presence of metastases and pretreatment extent of disease system grouping at diagnosis had an adverse influence on overall survival in multivariate analysis. CONCLUSION: Survival for pediatric HCC patients is significantly inferior to that for children with hepatoblastoma. Complete tumor excision remains the only realistic chance of cure, although it is often prevented by advanced disease. The presence of metastases is the most potent predictor of poor prognosis. A prospective worldwide cooperation in the field of pediatric HCC should be encouraged to look for novel therapeutic concepts.

Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes.

Total GLUT4 content in skeletal muscle from individuals with type 2 diabetes is normal; however, recent studies have demonstrated that translocation of GLUT4 to the plasma membrane is decreased in response to insulin stimulation. It is not known whether physical exercise stimulates GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes. Five subjects (two men, three women) with type 2 diabetes and five normal control subjects (5 men), as determined by a standard 75-g oral glucose tolerance test, were recruited to determine whether an acute bout of cycle exercise activates the translocation of GLUT4 to the plasma membrane in skeletal muscle. Each subject had two open biopsies of vastus lateralis muscle; one at rest and one 3-6 weeks later from the opposite leg after 45-60 min of cycle exercise at 60-70% of VO2max. Skeletal muscle plasma membranes were prepared by subcellular fractionation, and GLUT4 content was determined by Western blotting. Plasma membrane GLUT4 increased in each subject in response to exercise. The mean increase in plasma membrane GLUT4 for the subjects with type 2 diabetes was 74 +/-20% above resting values, and for the normal subjects the increase was 71+/-18% above resting values. Although plasma membrane GLUT4 content was approximately 32% lower at rest and after exercise in the muscle of the subjects with type 2 diabetes, the differences were not statistically significant. We conclude that in contrast to the previously reported defect in insulin-stimulated GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes, a single bout of exercise results in the translocation of GLUT4 to the plasma membrane in skeletal muscle of individuals with type 2 diabetes. These data provide the first direct evidence that GLUT4 translocation is an important cellular mechanism through which exercise enhances skeletal muscle glucose uptake in individuals with type 2 diabetes.

Potential mechanisms promoting restenosis in diabetic patients.

Diabetes is associated with greater restenosis rates after successful balloon angioplasty. The metabolic alterations that occur as a result of hyperglycemia or hyperinsulinemia can accelerate many of the pathophysiologic processes that lead to restenosis. Diabetes results in endothelial dysfunction and accelerated platelet deposition, which increase the propensity to thrombosis. Several growth factors known to promote the restenosis process are overexpressed in the presence of hyperglycemia. Advanced glycosylation promotes inflammatory cell recruitment and smooth muscle cell proliferation. Many of the potential mechanisms promoting restenosis in diabetic patients can be ameliorated by improved metabolic control.