Fecal lactoferrin, a marker of intestinal inflammation in children with inflammatory bowel disease.

The aim of this study was to analyze the usefulness of fecal lactoferrin in the diagnosis and monitoring of inflammatory bowel disease (IBD) in children. The study included 52 children with IBD (24 with Crohn's disease and 28 with ulcerative colitis) aged between 0.92 and 18 years, and 41 IBD-free controls of similar age. Fecal concentration of lactoferrin was determined with a quantitative immunoenzymatic test. Fecal concentration of lactoferrin in children with IBD was significantly higher than in the controls. The cut-off value of fecal lactoferrin concentration optimally distinguishing between the children with IBD and the controls was identified as 13 µg/g. The sensitivity and specificity of this cut-off value equaled 80.7% and 92.7%, respectively, and its positive and negative prognostic values were 96.8% and 63.3%, respectively. Patients diagnosed with moderate Crohn's disease had significantly higher fecal concentrations of lactoferrin than children with the mild or inactive disease. Similarly, children with moderate ulcerative colitis showed significantly higher fecal concentrations of lactoferrin than individuals with the mild condition. No significant relationship was found between the fecal concentration of lactoferrin and the severity of endoscopic lesions. Patients with IBD and a positive result of fecal occult blood test were characterized by significantly higher concentrations of lactoferrin than the individuals with IBD and a negative result of this test. In conclusion, fecal concentration of lactoferrin seems to be a useful parameter for diagnosis and monitoring of IBD in children.

Helicobacter pylori increases expression of proapoptotic markers Fas and FasL on CD4 lymphocytes in children.

The pathomechanism of Helicobacter pylori action upon gastric mucosa and its role in the pathogenesis of gastritis have not been fully elucidated. The aim of this study was to evaluate the most prevalent lymphocyte subpopulations of the gastric mucosa in gastritis in children, as well as to evaluate the expression of Fas and Fas ligand receptors (FasL), periapoptotic markers of gastric mucosa lymphocytes before and after H. pylori eradication. Forty nine patients aged 6 to 17 years, investigated due to chronic abdominal pain, were studied. The obtained tissue samples were analysed by immunohistochemistry. Different lymphocyte subsets were quantified on the basis of surface antigen expression (CD3, CD4, CD8, CD20), secreted cytokines (IL-4, IL-6, IFNgamma) and Fas and FasL proteins in the gastric mucosa. B and T helper lymphocytes were found to play a major role in the inflammatory infiltration in the gastric mucosa in children during H. pylori infection. Their expression was found to decrease after eradication. The enhanced expression of Fas receptor on lymphocytes before treatment and a decrease of this expression after eradication of H. pylori were shown. It was demonstrated that there is a correlation between CD4 and Fas receptor expression that may induce apoptosis of the helper lymphocytes in infected children.

Acute acalculous cholecystitis of viral etiology--a rare condition in children?

Acute acalculous cholecystitis (AAC) comprises 5% to 10% of all cases of acute cholecystitis in adults and appears to be even less frequently diagnosed in children. The diagnosis of AAC is established upon some clinical, laboratory, and ultrasonographic findings, which may sometimes be ambiguous and confusing especially in children. Diagnostic difficulties may result in either delayed diagnosis or unnecessary surgical intervention. Acute cholecystitis owing to viral infectious factors is reported to be extremely rare. The aim of the article is to demonstrate 2 cases of AAC as a clinical presentation of both Epstein-Barr virus and cytomegalovirus infection in children.

[Reactive oxygen species and antioxidative barrier in asthma]. / Reaktywne formy tlenu i bariera antyoksydacyjna w astmie.

Reactive oxygen species (ROS) participate in chronic inflammation, e.g. asthma. Augmented ROS production and deteriorated antioxidative barrier on the other hand leads to oxidative stress and increased oxidative damage as a result. Therefore antioxidants may be used in therapy of asthma.

[Analysis of enteral nervous system in children with drug resistant ulcerative colitis]. / Ocena jelitowego ukladu nerwowego u dzieci w przebiegu lekoopornego wrzodziejacego zapalenia jelita grubego.

INTRODUCTION: pathogenesis of inflammatory bowel diseases has been intensively investigated for many years. The role of enteric nervous system (ENS) and neuroprotective transmitters such as galanine (GAL), vasoactive intestinal peptide (VIP) and pituitary adenosine cyclase activating peptide (PACAP) has been underlined recently. Neuroprotective transmitters play a role in the regulation of intestinal contractions, ion transport in the intestinal epithelium and modulation of the proinflammatory cytokine production, which may result in diminuation of inflammation. AIM OF THE STUDY: was to investigate activity of ENS in children with drug resistant ulcerative colitis measured by the density of GAL, VIP and/or PACAP containing nervous fibres in mucosal membrane in course of pharmacological treatment and 12 months after colectomy. MATERIAL AND METHODS: 16 children were included in the study. Group I consisted of 7 children with drug resistant ulcerative colitis. Mucosal biopsy specimen was taken twice: colonoscopy before colectomy during (12 months earlier on average) and from resected colon. Group II (reference group) consisted of 9 children with excluded inflammatory bowel diseases based on colonoscopy and biopsy mucosal specimen assessment. Histology and immunochemistry of mucosal samples were analysed. RESULTS: decreased density of GAL, VIP and/or PACAP containing nervous fibres in colon mucosal membrane of children with ulcerative colitis was found: GAL-IR (3.5 +/- 3.15), VIP-IR (19.7 +/- 2.7), PACAP-IR (6.3+/-2.52) as compared to the reference group: GAL-IR (11.2+/-5.58), VIP-IR (36.1 +/- 16.0) and PACAP-IR (15.7 +/- 9.95). Significant diminuation of the density of GAL, VIP and/or PACAP containing nervous fibres was found in the study. CONCLUSION: 1. The density of VIP, PACAP and GAL containing nerve fibres diminishes in the course of ulcerative colitis, which may be a result of progressive degradation of colon mucosal membrane. 2. The hypothesis that absence of chemotaxis inhibition by low levels of neuroprotective transmitters might be a reason for drug resistance in ulcerative colitis.

[Analysis of risk factor treatment failures in therapeutic programme for malignant germ cell tumours in children. Multicentre prospective study of Polish Pediatric Group for Solid Tumours 1998--2006]. / Analiza czynników ryzyka niepowodzenia terapii w programie leczenia dzieci ze zlosliwymi guzami terminalnymi. Wieloosrodkowe badania prospektywne Polskiej Pediatrycznej Grupy Guzów Litych (PPGGL) w Latach 1998--2006.

AIMS: The aim of the study was the analysis of risk factors of therapeutic failures in children with malignant germ cell tumours treated within the multicentre programme of PPGGL from 1999--2006. MATERIALS AND METHODS: The investigated group included 18 (14.3%) patients, of 123 who have finished the treatment of malignant germ cell tumour, in whom no remission was obtained or relapse occurred. All the patients were treated according to the TGM 95 programme. Both clinical and morphological data of the group have been analysed. RESULTS: Among 18 patients with therapeutic failures 12 died. Two patients from the high risk group died of complications of the treatment--sepsis during neutropenia after chemotherapy and one after haemorrhage to the central nervous system. The other 9 died from progression of malignancy, 6 of them belonged to the high risk group. 10 (82%) of 12 patients who died had extragonadal location and in 11 (92%) the tumour was in stage III or IV of the disease. The most frequent histology in this group was mixed germ cell tumour with component of yolk sac tumour or carcinoma embrionale. 92% patients had elevated AFP, in 4 it was above 15000 ng/ml. In 11 (92%) patients primary chemoresistance was observed, and radical surgery was not possible for the reason of advanced stage of the disease. In 6 patients relapse occurred. In 3 patients testis was the primary location (I and II stage), in 3 patients the tumour was localized in the sacrococcygeal region (III and IV stage). All the patients are alive in remission after second line therapy, with 78 months (median) of follow-up. CONCLUSIONS: 1. The main risk factor for therapeutic failures in malignant germ cell tumours was primary chemoresistance in inoperable tumours of the sacrococcygeal region. 2. The mortality of treatment complications was low. 3. The relapse of cancer was not a risk factor for therapeutic failure due to the high probability of second remission 4. Therapeutic failures are mainly observed in patients with mixed germ cell tumour with components of yolk sac tumour or carcinoma embrionale. 5. Tumour chemoresistance should be considered an essential factor in identifying high risk patients.

[Therapy of chronic viral hepatitis type B in children after previous ineffective interferon-alpha treatment]. / Terapia przewleklego wirusowego zapalenia watroby typu B u dzieci po uprzednim, nieskutecznym leczeniu interferonem alfa.

UNLABELLED: THE AIM of this study was to estimate the efficacy of nucleoside analogue (lamivudine) in the therapy of chronic viral hepatitis type B in children, after previous, ineffective treatment with interferon-alpha. PATIENTS AND METHODS: we analyzed 53 children with chronic viral hepatitis type B, who had not responded to Interferon-alpha treatment conducted 1-7,5 years before this study (mean 4,0 +/- 7,5; median 4 years). Inclusive criteria to re-therapy with lamivudine were as follows: increased serum alanine aminotransferase activity, detected at least three times during 6 months before treatment, HBsAg and HBeAg present in the blood, viral HBV DNA detected for at least 6 months before the beginning of lamivudine therapy (above 200 genome copies per mL) and inflammation activity observed in liver biopsy specimen (biopsy performed within previous 24 months). Evaluation of side-effects of lamivudine therapy was based on anamnesis (subjective data) and laboratory tests performed regularly in the time of clinical visits during and after the end of the treatment. RESULTS: all the children concluded the treatment. Before lamivudine therapy, serum alanine aminotransferase activity ranged between 20-590 IU/L. In 28,4% of children it was less than 100 IU/L. In almost all the children moderate staging and grading were observed in liver biopsy specimens. HBV DNA in serum ranged between 200-200000 copies/mL: in 31 children (58,4%) HBV DNA exceeded 200000 copies/mL, in 5 (28,3%) was between 10000 and 200000 copies/mL, and in 7 (13,2% ) was below 10000 copies/mL. Applied treatment resulted in alanine aminotransferase activity normalization in 79,2% of children, mostly after 2-11 months (mean 3,9 +/- 2,7; median 3,8 months). HBeAg/HBeAb seroconversion was achieved in 28,3% of children, usually at the end of lamivudine therapy (approximately after 12 months). Sustained viral response was observed in 24,5% of treated children. There were no undesirable effects of therapy noted. Serum alanine aminotransferase activity increased slightly and temporarily in 4 children between 3rd and 12th month of therapy. In 2 of these children YMDD mutation was detected. CONCLUSIONS: lamivudine is effective, safe and well tolerated in treatment of chronic viral hepatitis type B, following unsuccessful interferon-alpha therapy. Serum alanine aminotransferase activity normalized in most of the patients. HBeAg/HBeAb seroconversion as well as positive viral response is mostly connected with low level of HBV DNA before therapy.

[HBV gene variants and polymerse gene mutations in children with chronic hepatitis B in the course of the antiviral therapy]. / Genotypy HBV oraz mutacje genu polimerazy HBV u dzieci z przewleklym zapaleniem watroby typu B w przebiegu leczenia lamiwudyna.

UNLABELLED: THE AIM OF THE STUDY was to evaluate the occurrence of HBV genotypes and the emergence of polymerase gene mutations in children with chronic hepatitis B in the course of the lamivudine therapy. MATERIAL AND METHODS: eighteen children (aged from 6 to 15 years, mean age 11,8 years, 10 boys and 8 girls) with chronic hepatitis B were included in the study. All patients were treated with 100 mg lamivudine tablets given daily orally for 12-16 months. All amino acid substitutions within HBV polymerase were detected by PCR amplification and direct sequencing HBV genotypes and polymerase gene mutations were determined by comparing the sequences in the overlapping PollS genes with published sequences, available in GenBank. RESULTS: HBVgenotyping showed the presence of genotype A in 17 children and genotype H in one. No change of HBV genotype was noted in any of the studied patients as the sequencing of HBV DNA was repeated during the lamivudine therapy. The presence of lamivudine-resistance mutations involving the YMDD motif was detected in 5 patients. Four children had YVDD mutation, while in one child YIDD mutation was detected. YIDD mutation appeared to be the single one in the viral polymerase gene, while YVDD mutations in four patients were accompanied by other changes at amino acid sequence of the HBV polymerase: rtL180M, rtN124D and rtL164M. CONCLUSIONS: 1) Genotype A was predominant in the studied population of patients. 2) The risk of the emergence of drug-resistant HBV polymerase mutations is high and increases in the course of the lamivudine therapy. 3)Drug-resistant mutations in the YMDD motif are accompanied by other amino acid substitutions in the viral polymerase of unclear clinical significance.

[Evaluation of selected immunocompetent cells expression in gastric mucosa in children with Helicobacter pylori infection before and after eradication treatment--a preliminary study]. / Ocena ekspresji wybranych komórek immunokompetentnych w blonie sluzowej zoladka u dzieci zakazonych Helicobacter pylori przed i po eradykacji zakazenia--doniesienie wstepne.

INTRODUCTION: Helicobacter pylori infection activates local immunological response and causes mononuclear cells infiltration in the gastric mucosa. On this account the studies on lymphocyte subpopulations in the gastric mucosa in children during Helicobacter pylori infections are inconsistent. It has been shown that the morphological status of gastric mucosa in children with Helicobacter pylori infection is different than in adult patients. THE AIM OF THE STUDY was the evaluation of chosen immunocompetent cells expression in gastric mucosa in children before and after eradication treatment. MATERIAL AND METHODS: Forty-nine children with chronic abdominal pain was enrolled in the study. They were divided into the following groups: 22 children without infection (negative urease test and absence of Helicobacter pylori antigen assessed by immunoenzymatic and immunofluorescent methods) and 27 with Helicobacter pylori infection. Part of the children (11) from the second group had a follow-up endoscopy after eradication therapy. The tissue samples from the gastric antrum and fundus were obtained for morphological and immunohistochemistry assays by direct immunofluorescent and immunoenzymatic methods. RESULTS: There were negative Helicobacter pylori tests in group I. In the group of infected children superficial colonisation of pathogen dominated In analysed groups percentage of patients with superficial antigens and cytokines (CD3, CD4, CD8, CD20, IL-4, IL-6, INF-gamma) characteristic for each lymphocytes subpopulations were established. In infammatory infiltrations T lymphocytes CD4 and B lymphocytes CD20 dominated localised mainly in the lamina propria of the gastric mucosa. Expression of above lymphocytes subpopulations diminished after eradication treatment. After treatment the total eradication of Helicobacter pylori was observed in 5 children and in 6 patients the pathogen persisted. CONCLUSIONS: The dominant role in local response during Helicobacter pylori infection in children is played by T CD4 and B CD20 lymphocytes localised mainly in lamina propria of gastric mucosa. Degree of T cells CD4 and CD20 expression decreases after eradication treatment.

[Congenital extrahepatic biliary atresia as a cause of cholestasis in newborns and infants]. / Wrodzona atrezja dróg zólciowych zewnatrzwatrobowych jako pryczyna cholestazy u noworodków i niemowlat.

UNLABELLED: Congenital extrahepatic biliary atresia (CEBA) is one of the most common causes of cholestasis in newborns and infants. THE AIM OF THE STUDY: was the analysis of clinical presentation, results of laboratory and imaging investigations as well as clinical outcome of children with extrahepatic cholestasis caused by CEBA. MATERIALS AND METHODS: the analyzed group included 15 children aged from 2 weeks to 4 months. Data concerning: pregnancy and delivery, newborn's health condition, faeces color; jaundice onset, manifestation of coagulation disorders coexisting malformations and disorders of other systems were obtained. The following investigations were performed: biochemical tests evaluating the function of the liver and cholestasis (serum bilirubin concentration and fractions, bile acids in serum, AlAT, AspAT, GGTP, FALK activities, serum electrophoresis, prothrombin index). We also performed tests focusing on hepatotropic infections, - metabolic disorders tests and in all children - ultrasound of the abdomen, scintigraphy of the bile ducts - HEPIDA. 14 children had undergone hepatoportoenterostomy, modo Kasai. RESULTS: jaundice, acholic stools and hepatomegaly were present in all children. The serum concentration of bilirubin and its conjugated fraction and bile acids in all children were increased. GGTP and FALK activities were markedly elevated in all children. Aminotransferases activities elevations were observed, more distinctively for AST. Active cytomagalovirus infection was detected in 3 children. Abdominal ultrasound revealed gallbladder in 7 children, whereas intrahepatic bile ducts were described as normal in 12 cases. In all cases the HEPIDA scintigraphy showed no passage of the tracer to the GI tract even after 24 hours delay. Hepatoportoenterostomy was performed in 14 children, 5 of them had liver transplantation. CONCLUSIONS: 1. There is still not one effective and specific diagnostic method in differentiating between the causes of cholestasis in the newborns and infants. Thus many investigation methods should be run simultaneously. 2. Congenital atresia must be definitely excluded before cholestasis with other background is finally diagnosed. 3. The hepatoportoenterostomy should be considered as the first line treatment in children with CEBA. Most cases will need liver transplantation in the future.

[Tryptase activity in colon mucosal samples of children with inflammatory bowel disease]. / Aktywnosc tryptazy w bioptatach blony sluzowej jelita grubego u dzieci z przewleklym nieswoistym zapaleniem jelit.

INTRODUCTION: mast cells are dispersed in many tissues, especially in the digestive and respiratory system mucosal membranes. Tryptase is the most important proteinase released from mast cells after degranulation. It influences strongly the cells and tissues by activating the inflammatory process. THE AIM OF THE STUDY: was to assess the activity of tryptase in colon mucosa samples in children with inflammatory bowel diseases (IBD) and in children with bleedings from lower part of gastrointestinal tract (GTB), without inflammation. MATERIAL AND METHODS: a group of 30 children with IBD was analyzed in the study. IBD is formed by three disease entities: ulcerative colitis (UC) - 14 patients, Crohn's disease (CD) - 9 patients and non-specific colitis (NSC) - 7 patients. Moreover, a group of 18 children with bleeding from lower part of gastrointestinal tract was studied. The activity of tryptase in homogenates of colon mucosal samples was estimated fluoroimmunoenzymatically. RESULTS: the results of our analysis showed no statistically important difference between the mean activity of tryptase in groups of children with IBD and GTB (31442 +/- 1304 vs 31868 +/- 775 ug/l). The study of tryptase activities in different disease entities of IBD group showed, that its value in ulcerative colitis group was 31382 +/- 1170 ug/l, in Crohn's disease group it was 31536 +/- 1120 ug/l; in non-specific colitis group the tryptase activity was 32277 +/- 498 ug/l. The analysis with Kruskal-Wallis Anova test revealed that the differences are statistically significant (p = 0.034). In post hoc test the outstanding value is the tryptase activity in children with NSC. Activity of tryptase in colon in much higher than its activity in plasma (normal range 1-19 ug/l). CONCLUSIONS: the activity of tryptase in mucosal membrane samples is much higher than in blood. The extent of mast cells degranulation may be dependent on the form of IBD.

[Giardiasis in children - clinical diversity and diagnostic problems based on own experience]. / Zakazenia giardia lamblia u dzieci- zmiennosc obrazu klinicznego i trudnosci diagnostyczne w swietle doswiadczen wlasnych.

UNLABELLED: Parasitosis still remains a significant pediatric health problem, despite improving hygienic conditions and social awareness. THE AIM OF THIS STUDY: was to analyze clinical manifestations of Giardia lamblia infection in children hospitalized in the Department of Pediatrics, Pediatric Gastroenterology and Oncology of Medical University of Gdansk. MATERIAL AND METHODS: studied children included 49 patients aged 2.2 - 17.3 years: group I children below and group II above 5 years of age. The patients were admitted for further diagnosis of unexplained clinical manifestations in outpatient care. Parasitosis was confirmed by immuno-enzymatic technique detecting protein GSA 65; only in one child parasites cysts were found by microscopic technique in faecal samples obtained from infected children. RESULTS: chronic abdominal pain was noted in 16 (72.7%) children in group I and in 22 (81.5%) patients in group II. Chronic diarrhea was observed in 20 (90.9%) children in group I and in 4 (14.8%) in group II. Ultrasound scans revealed mesenteric lymphadenopathy in 42 children (16 in group I and 26 in group II). CONCLUSIONS: chronic and recurrent abdominal pain was the main clinical complain and chronic diarrhea in children under 5 years of age. In few cases hepatobiliary involvement was observed, which might suggest a changing clinical course of giardiasis. Most of the children presented with mesenteric lymphadenopathy, which was confirmed by abdominal ultrasound scan. Thus, this method should be included in the diagnostic algorithm, if parasitosis is considered.

[Changes in the number of neuroprotective transmitter containing mucosal nerve fibres in children with ulcerative colitis]. / Zmiany w liczebnosci wlókien nerwowych zawierajacych transsmitery o charakterze neuroprotekcyjnym w blonie sluzowej jelit w przebiegu wrzodziejacego zapalenia jelita grubego u dzieci.

INTRODUCTION: Ulcerative colitis and Crohn's disease are two main disease entities that belong to the group of inflammatory bowel diseases (IBD). Chronic inflammatory process concerning intestinal mucosal membrane causes structural and functional changes of intestinal nervous system. This phenomenon is called the plasticity of the nervous system and is due to the ability of nerve cells to adapt to changing environmental conditions. The resulting alterations of intestinal neurons' chemical code are augmentation, inhibition or initiation of the neurotransmitters' synthesis (synthesis "de novo"). The role of neuroprotective transmitters - galanine (GAL), vasoactive intestinal peptide (VIP) and pituitary adenosine cyclase activating peptide (PACAP) seems to be important in the pathogenesis of inflammatory bowel diseases. They are responsible for the regulation of intestinal contraction and modification of ions' transport in the intestinal epithelium. They also diminuate the inflammation by modulation of the proinflammatory chemokines and cytokines production. THE AIM: of the study was to analyse the changes in the nerve fibres' containing GAL, VIP and/or PACAP, density in the mucosal membrane of children with ulcerative colitis (UC) with different Clinical activity index. MATERIAL AND METHODS: the study included 33 children hospitalised due to UC with different activity and 9 children in the control group, after exclusion of IBD. All the studied patients underwent colonoscopic examination with colon mucosa biopsies. Histology and immunochemistry of mucosal samples were analysed. Those studies helped to assess the changes in the number of nerve fibres containing analysed transmitter substances in the mucosal membrane of the colon. RESULTS: the results showed a statistically significant diminuation of nerve fibres containing analysed neurotransmitters number in colon mucosa samples of children with UC. There were no statistically significant changes in number of nerve fibres dependent on the clinical activity index of UC. CONCLUSIONS: the process of degradation present in UC is accompanied by the important diminuation on neurotransmitter containing fibres number. However, their density is not dependent of the clinical activity of the disease.

[Milk in the diet of children between 7 and 24 months of age]. / Mleko w diecie dzieci miedzy 7 a 24 miesiacem zycia.

THE AIM OF THIS STUDY: was to estimate what kind of milk is administrated to children between 7-23 months of age in Poland. MATERIAL AND METHODS: the study included 1390 children 13-36 months of age, from 4 different regions in Poland. Data were obtained on the basis of questionnaires filled in by mothers visiting the outpatient clinic. RESULTS: 16.7% of studied population were fed with human milk (9.l% only with human milk, 7.6% received both human milk and formula); 0.03% were fed with cow milk. Regional differences were observed. In the second year of life, 11.44% children were still given human milk, 60.3% -formula and 28.6% - cow milk. CONCLUSIONS: in Poland, only small percentage of children, older than 6 months, are still breastfed. Considering WHO recommendations, that children should be given human milk till 2nd year of age, breastfeeding recommendations are still to be promoted in our country.

The "sugar" clear cell tumor of the lung-clinical presentation and diagnostic difficulties of an unusual lung tumor in youth.

A case of the "sugar" clear cell tumor of the lung in a 16-year-old boy is presented. The course of the disease with general symptoms, never reported before, highlights diagnostic difficulties of an extremely rare lung tumor in youth. The boy presented with daily spikes of unexplained high fever of 6 weeks' duration with features of hypochromic microcytic anemia, elevated erythrocyte sedimentation rate, C-reactive protein, alpha(2)- and beta-globulins, and elevated platelet count. The lung tumor was a yellow, circumscribed mass confined to the sixth segment of the left lung. Histological examination revealed the tumor composed of cells with clear cytoplasm with large content of glycogen, with no signs of necrosis, and immunoreactive for HMB-45, but not for cytokeratin, LCA, CD34, and CD68. The performed thoracotomy and segmentectomy were both diagnostic and curative.

Lamivudine therapy for children with chronic hepatitis B.

AIM: To assess the effectiveness and side-effects of lamivudine therapy for children with chronic hepatitis B (CHB) who fail to respond to or have contraindications to interferon-alpha (IFN-alpha) therapy. METHODS: Fifty-nine children with CHB were treated with 100 mg lamivudine tablets given orally once daily for 12 mo. Alanine aminotransferase (ALT) activity was evaluated monthly during the therapy and every 3 mo after its discontinuation. HBe antigen, anti-HBe antibodies, HBV DNA level in serum were evaluated at baseline and every six months during and after the lamivudine therapy. Sustained viral response (SVR) to lamivudine therapy was defined as permanent (not shorter than 6 mo after the end of the therapy), namely ALT activity normalization, seroconversion of HBeAg to anti-HBe antibodies, and undetectable viral HBV-DNA in serum (lower than 200 copies per mL). The analysis of the side-effects of the lamivudine treatment was based upon interviews with the patients and their parents using a questionnaire concerning subjective and objective symptoms, clinical examinations, and laboratory tests performed during clinical visits monthly during the therapy, and every 3 mo after the therapy. RESULTS: ALT normalisation occurred in 47 (79.7%) patients between the first and 11(th) mo of treatment (mean 4.4+/-2.95 mo, median 4.0 mo), and in 18 (30.5%) of them after 2 mo of the therapy. There was no correlation between the time of ALT normalization and the children's age, the age of HBV infection, the duration of HBV infection, inflammation activity score (grading), staging, ALT activity before treatment, serum HBV DNA level, and lamivudine dose per kg of body weight. HBeAg/anti HBe seroconversion was achieved in 27.1% of cases. The higher rate of seroconversion was connected with lower serum HBV DNA level and longer duration of HBV infection. There was no connection between HBeAg/anti HBeAb seroconversion and the children's age, age of HBV infection, grading, staging, ALT activity before treatment, and lamivudnie dose per kg of body weight. No complaints or clinical symptoms were observed during lamivudine therapy. Impairment of renal function or myelotoxic effect was noted in none of the patients. CONCLUSION: One year lamivudine therapy for children with chronic hepatitis B is effective and well tolerated. Seroconversion of HBeAg/HBeAb and SVR are connected with lower pre-treatment serum HBV DNA level.

Preliminary experience with arterial chemoembolization for hepatoblastoma and hepatocellular carcinoma in children.

The objective of this work was to test feasibility and efficacy of hepatic artery chemoembolization (HACE) in unresectable malignant liver tumors. Five patients aged from 1-12 years were treated in the Medical University of Gdansk from 1999 to 2002. All had locally advanced tumors, which did not respond to systemic chemotherapy: four, hepatoblastoma (HB) and one, hepatocellular carcinoma (HCC). Arteriography was performed and chemoembolization suspension (cisplatin + doxorubicin + mitomycin mixed with lipiodol) was injected, followed by gelatin foam particles. The procedure was performed one to three times in each patient. In four patients (three, HB, one, fibrolamellar HCC), tumor response was observed, with decrease in the diameter of the mass of 25-33% and fall in the AFP level of 83-99%. One child with HB was non-evaluable due to early death caused by systemic myelotoxicity. Two patients (2 HB) underwent macroscopically complete tumor resection, 1 is alive and well, and 1 died at the end of surgery for an unknown reason (possibly related to cardiotoxicity of earlier systemic chemotherapy). One HB patient was successfully transplanted after two HACE courses. The only HCC patient died because of pulmonary oil embolism immediately after the third HACE course. HACE can lead to tumor regression in most cases and may be considered an alternative for patients with unresectable liver tumors who do not respond to primary systemic chemotherapy and are not candidates for liver transplantation for various reasons.

[Pulmonary metastases in children with solid tumours--own experiences]. / Przerzuty do pluc w guzach litych u dzieci--obserwacje wlasne.

BACKGROUND: The most frequent reasons of relapses in solid tumours among children are lung metastases. AIM: Analysis of lung metastatic cases among children with solid tumours treated from 1995-2005. MATERIAL AND METHODS: 26 lung metastatic cases (17 males, 9 females) were analysed. At the moment of the diagnosis lung metastases were present in 19.2% of patients while in the rest (80.8%) occurred during and after treatment. The most often lung metastases were recognised in osteosarcoma (15-57.8%) and carcinoma embryonale (3-11.6%). Secondary metastases in lungs occurred within 4-48 months after the diagnosis. In 57.7% were bilateral. 36 thoracotomies (average 1.7/ a child) were performed. The after-surgery chemotherapy for tumour recurrence was introduced in each case. RESULTS: In the analysed group 14 (53.8%) children are alive with the overall survival time 8-120 months. The rest 12 (46.2%) are dead with the survival time 6-24 months. The statistically significant difference was found in comparison of complete surgery versus incomplete (p=0.02), no significance was found in primary or secondary metastases (p=0.27). Time of occurrence was statistically insignificant (p=0.26). CONCLUSIONS: The occurrence of metastases in children solid tumours worsened the prognosis. The active search for lung metastases at the moment of diagnosis, treatment and follow-up combined with complete surgery procedures may prolong survival. There is a need to find new methods of lung metastases treatment.

[Assessment of angiogenesis in children' s osteosarcoma]. / Ocena stopnia angiogenezy w miesaku kosciopochodnym u dzieci.

INTRODUCTION: Tumour angiogenesis is one of the most important hallmarks of cancer, which enables its development, progression and metastasizing. The extent of angiogenesis seems to be an essential prognostic factor in many solid tumours of children and adults. There have also been reports on the significance of angiogenesis in osteosarcoma. The most common methods to estimate angiogenesis is assessment of microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. AIM: The aim of the study was assessment of angiogenesis in osteosarcoma patients treated in our centre on the basis of MVD and VEGF expression. PATIENTS AND METHODS: Histopathological specimens of 16 patients with osteosarcoma aged 9-18 years (median 13.5), treated in Department of Paediatrics, Paediatric Gastroenterology and Paediatric Oncology of Medical University in Gdansk, between 1997-2004, were studied retrospectively. Immunochemistry was performed using anti CD34 monoclonal antibody and chromogen to highlight vessels, which were counted at 200 x magnification on 3 microscopic fields. In the same specimens VEGF expression was evaluated semiquantitatively using immunohistochemical method. Patients were divided into two groups depending on presence of metastases. The two parameters were also compared in patients who died and the survivors. RESULTS: 11 of 16 patients are alive, with time of follow up 19-100 months (median 52). Five children died. Mean vascular density ranged from 25 to 87 (46 +/- 16.5). No significant statistical difference in microvessel density between metastatic and non-metastatic patients was observed. Microvessel density in these groups is 46.8 +/- 22.7 and 45.2 +/-7.0 respectively. In the group of survivors MVD was 44.3 +/- 5.9, inpatients who died it was 47.1 +/- 21.0 showing no significant statistical difference. In all patients positive VEGF expression was seen. Only one patient presented low expression of VEGF, the rest had high or medium degree of VEGF expression. MVD in the group with high expression of VEGF was higher than in the group with low and medium expression of VEGF. It was 51.8 +/- 18.7 and 39.2 +/- 14.2. The difference was not significant. CONCLUSIONS: In the presented group of patients no differences in the extent of angiogenesis were seen in relation to treatment outcome or presence of metastases.