Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn's disease.

BACKGROUND: In patients with active Crohn's disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD. METHODS: A multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1-14 days, 15-30 days and more than 30 days) for comparison of outcomes. RESULTS: The cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24-44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6-15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042). CONCLUSION: Smoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence.

Increased abundance of proteobacteria in aggressive Crohn's disease seven years after diagnosis.

Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn's disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed a significant increase (p = 0.03) in CD patients. We found a change in the microbial abundance in UC patients with active disease and in CD patients with aggressive disease. These results suggest that dysbiosis of the gut in IBD patients is not only related to current activity but also to the course of the disease.

Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota.

OBJECTIVE: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk). METHODS: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region. RESULTS: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication). CONCLUSION: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder.

Meningioma as second malignant neoplasm after oncological treatment during childhood.

A total of 38 patients (18 female/20 male) with childhood meningioma were recruited from the German registry HIT-Endo (1989-2009). In 5 cases meningioma occurred as second malignant neoplasm (SMN). Histologies were confirmed by reference assessment in all cases (SMN: 2 WHO I, 1 WHO II, 2 WHO III). The SMNs were diagnosed at a median age of 12.4 years with a median latency of 10.2 years after primary malignancy (PMN; 4 brain tumors, 1 lymphoblastic leukemia; median age at diagnosis 2.7 years). Meningioma occurred as SMN in the irradiated field of PMN (range 12-54 Gy). The outcome after treatment of SMN meningioma (surgery/irradiation) was favorable in terms of psychosocial status and functional capacity in 4 of 5 patients (1 death). We conclude that survivors of childhood cancer who were exposed to radiation therapy at young age harbor the risk of developing meningioma as a SMN at a particularly short latency period in case of high dose exposure.

Survival of Salmonella on cuts of beef carcasses subjected to dry aging.

AIMS: The aim of this study was to determine the survival of 15 different strains of Salmonella of selected serotypes during prolonged cold storage of beef. METHODS AND RESULTS: Fifteen strains of eight different serotypes of Salmonella were spiked onto fresh cuts beef portions, and the survival was followed during storage in a laboratory cooling system. Over a 14-day period, all strains were reduced significantly in numbers; however, strains of Salmonella Typhimurium DT104 and Salmonella Enteritidis PT4 and PT8 survived significantly longer than strains of the serovars Dublin, Derby, Infantis and Newport. For five selected strains, the observations were verified in a pilot plant cooling facility mimicking industrial cooling. No significant differences in reduction were found between the two cooling methods. CONCLUSIONS: A significant reduction in Salmonella can be obtained by dry aging of beef during cold storage but the survival is strain dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: From a hygienic point of view, cold storage of unpacked beef, which is still performed in small slaughterhouses, is a good alternative to vacuum packaging.

Strict follow-up programme including CT and ¹8F-FDG-PET after curative surgery for colorectal cancer.

AIM: The risk of local recurrence following curative surgery for colorectal cancer (CRC) is up to 50%. A rigorous follow-up program may increase survival. Guidelines on suitable methods for scheduled follow up examinations are needed. This study evaluates a strict follow-up program including carcinogenic embryonic antigen (CEA), chest X-ray, abdominal ultrasound (US), computed tomography (CT) and (18)F-FDG positron emission tomography (FDG-PET). METHOD: A cohort of 132 patients, treated by surgery with curative intent for CRC, was included. Patients were followed prospectively with scheduled controls at 3, 6, 12 and 24 months after curative surgery. CEA, chest X-ray, US, CT and FDG-PET supplemented by clinical examination. The end-point was recurrence. Sensitivity and specificity was estimated 2 years after surgery. RESULTS: Of the 132 patients included in the study, 25 experienced recurrence, detected at scheduled controls (n = 18) and at intervals between them (n = 7). The results of CT and FDG-PET were correlated with recurrence. CT combined with FDG-PET had the highest specificity and sensitivity. CONCLUSION: A total of 72% of recurrences were detected at scheduled controls. The findings supported a strict follow-up program following curative surgery for colorectal cancer. FDG-PET combined with CT should be included in control programs.

First experiences with laparoscopic adjustable gastric banding (LAGB) in the treatment of patients with childhood craniopharyngioma and morbid obesity.

Craniopharyngiomas are embryogenic malformations which lead to eating disorders and morbid obesity due to hypothalamic involvement in about 50% of all patients with pediatric craniopharyngioma. The experience with laparoscopic adjustable gastric banding (LAGB) in obese craniopharyngioma patients is limited. We are reporting on four patients with childhood craniopharyngioma diagnosed at age 2, 11, 12, and 21 years. BMI-SDS at diagnosis was +0.9, +4.5, +4.7 and -0.1 SD. During follow-up, all patients developed morbid obesity (BMI-SDS: +13.9, +10.3, +11.4, +7.3) so that 11, 6, 9 and 3 years after diagnosis LAGB were performed. After a follow-up of 4.5, 1.5, 3.0 and 2.5 years BMI decreased or stabilized continuously in all patients (BMI-SDS at latest visit: +9.9, +9.7, +9.5, +5.9 SD). The eating behavior changed in all patients profoundly. The addiction to food and especially sweets significantly improved based on self-assessment. In two patients a dislocation of the LAGB occurred and resulted in weight gain. We conclude that LAGB could be effective in weight reduction of obese craniopharyngioma patients with hypothalamic syndrome. Close follow-up is necessary in order to analyze long-term effects and complications of LAGB in patients with childhood craniopharyngioma and morbid obesity.

Investigation of tissue inhibitor of metalloproteinases 1 in plasma from colorectal cancer patients and blood donors by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

Early detection of colorectal cancer (CRC) improves patient survival. Plasma tissue inhibitor of metalloproteinases 1 (TIMP-1) measurements by enzyme-linked immunosorbent assay (ELISA) have been suggested as a new method for the early detection of CRC. To further investigate the nature of TIMP-1 in plasma, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS) was used. TIMP-1 measurements of plasma from 16 healthy donors and 14 CRC patients were performed using TIMP-1 monoclonal antibody in SELDI TOF MS and ELISA. SELDI TOF MS applying an antibody to TIMP-1 revealed that human plasma TIMP-1 has a mass of 25.1 kDa and exhibits several isoforms. Both methods showed increased plasma TIMP-1 values for cancer patients as compared to healthy individuals. The p values for the separation of the groups were 0.0019 for ELISA and <0.0001 for SELDI TOF MS. CRC did not fundamentally affect the appearance of TIMP-1 as evaluated by SELDI TOF MS.

SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas.

In a genome-wide screen using differential methylation hybridization (DMH), we have identified a CpG island within the 5' region and untranslated first exon of the secretory granule neuroendocrine protein 1 gene (SGNE1/7B2) that showed hypermethylation in medulloblastomas compared to fetal cerebellum. Bisulfite sequencing and combined bisulfite restriction assay were performed to confirm the methylation status of this CpG island in primary medulloblastomas and medulloblastoma cell lines. Hypermethylation was detected in 16/23 (70%) biopsies and 7/8 (87%) medulloblastoma cell lines, but not in non-neoplastic fetal (n=8) cerebellum. Expression of SGNE1 was investigated by semi-quantitative competitive reverse transcription-polymerase chain reaction and found to be significantly downregulated or absent in all, but one primary medulloblastomas and all cell lines compared to fetal cerebellum. After treatment of medulloblastoma cell lines with 5-aza-2'-deoxycytidine, transcription of SGNE1 was restored. No mutation was found in the coding region of SGNE1 by single-strand conformation polymorphism analysis. Reintroduction of SGNE1 into the medulloblastoma cell line D283Med led to a significant growth suppression and reduced colony formation. In summary, we have identified SGNE1 as a novel epigenetically silenced gene in medulloblastomas. Its frequent inactivation, as well as its inhibitory effect on tumor cell proliferation and focus formation strongly argues for a significant role in medulloblastoma development.

Relapse pattern after complete resection and early progression after incomplete resection of childhood craniopharyngioma.

In HIT Endo data on therapy and prognosis of 306 patients with childhood craniopharyngioma (CP) were analyzed. The 5 years-overall survival rate was 94 +/- 4 % in irradiated patients and 93 +/- 5 % in non-irradiated patients. Aims of the prospective study KRANIOPHARYNGEOM 2000 were to collect data on the incidence and time course of relapses after complete surgery and tumour progressions after incomplete resection. Furthermore, the impact of irradiation therapy (XRT) on tumour relapse and recurrence rates was analyzed. Since 2001 ninety-eight patients with CP were recruited at a median age at diagnosis of 9.9 years ranging from 1.8 to 18.0 years. Complete resection was achieved in 44 %, incomplete resection in 54 %. XRT was performed in 24 of 98 CP patients; in 10 early after incomplete resection, in 14 of 24 after progression of residual tumour or relapse, in 3 of 14 after second surgery of relapse. XRT was performed at a median age of 12.0 years ranging from 5.0 to 18.9 years and in median after an interval of 9 months after first diagnosis. The analysis of event-free survival rates (EFS) in patients with CP showed a high rate of early events in terms of tumour progression after incomplete resection (3y-EFS: 0.22 +/- 0.09) and relapses after complete resection (3y-EFS: 0.60 +/- 0.10) during the first three years of follow-up. A high rate of early events (1y-EFS: 0.78 +/- 0.10; 2y-EFS: 0.57 +/- 0.15) was also found for patients after XRT (3 cystic progressions, 3 progressions of solid tumour; in 24 patients after XRT). We conclude that tumour progression and relapse are frequent and early events even in irradiated patients. Monitoring of cerebral imaging and clinical status is recommended in follow-up of patients with childhood CP. In order to analyze the appropriate time point of XRT after incomplete resection, QoL, EFS and overall survival in patients (age > or = 5 years) will be analyzed in KRANIOPHARYNGEOM 2007 after stratified randomization of the time point of irradiation after incomplete resection (early irradiation versus irradiation at progression of residual tumour).

Improving the yield of Mozzarella cheese by phospholipase treatment of milk.

Part-skim Mozzarella cheese was manufactured from milk hydrolyzed with fungal phospholipase A1 prior to renneting. The phospholipase treatment reduced fat losses in whey and cooking water and increased cheese yield as a result of improved fat and moisture retention in the cheese curd. The amount of phospholipids in the whey was reduced because of improved retention of lysophospholipids in the cheese curd. Water binding in the fresh curds and young cheeses up to 3 wk of storage was investigated by a 1H nuclear magnetic resonance spin-spin relaxation technique. In the fresh curds, 2 dominant water fractions were present, characterized by average spin-spin relaxation times (T2) of 14 and 86 to 89 ms, respectively. These 2 fractions of low- and high-molecular-mobility water were similar in all cheeses and presumed to represent water associated with the casein matrix and water present in the pores. A few hours after manufacture, cheeses made with phospholipase showed decreased T2 of the high-mobility fraction, indicating improved water-holding capacity. It is suggested that lysophospholipids released from the fat globule membranes act as surface-active agents in the cheese curd, helping emulsification of water and fat during processing and reducing syneresis. During 3 wk of storage after manufacture, the mobility of both water fractions increased in all cheeses, but was highest in the cheeses made with phospholipase. The increase in mobility during the first weeks of storage has earlier been ascribed to structural changes in the protein matrix, which in principle could be accelerated because of the higher moisture content. However, the microstructure of phospholipase-treated cheese was investigated by confocal laser scanning microscopy and found to be very similar to the control cheese during processing and up to 28 d of storage. In addition, flowability, stretchability, and browning were acceptable and similar in all the manufactured cheeses. Thus, phospholipase hydrolysis of cheese milk improved the cheese yield without changing the cheese microstructure, and resulted in cheese with functional properties that were identical to traditional Mozzarella cheese.

TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of four inhibitors of the matrix metalloproteinases, which are capable of degrading most components of the extracellular matrix. However, in recent years, TIMP-1 has been recognised as a multifunctional protein, playing a complex role in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells and their genetically identical wild-type controls. For future studies, this cell system can be used to uncover the mechanisms and signalling pathways involved in the TIMP-1-mediated inhibition of apoptosis as well as to investigate the possibility of using TIMP-1 inhibitors to optimise the effect of conventional chemotherapy.

The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis.

The pig acute phase protein (APP) response to experimental Streptococcus suis (S. suis) infection was mapped by the measurement of the positive APPs C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp) and major acute phase protein (pig-MAP) and the negative APPs albumin and apolipoprotein (Apo) A-I. The aim was to elucidate the differences in the acute phase behaviour of the individual APPs during a typical bacterial septicaemic infection. Pigs were inoculated subcutaneously with live S. suis serotype 2 and blood was sampled before and on various days post inoculation (p.i.), until the pigs were killed and autopsied on day 14 p.i. Clinical signs (fever and lameness) were observed in four of the five inoculated pigs from day 2 p.i., and these pigs also had arthritic lesions at autopsy. CRP and SAA showed fast increases in serum concentrations, CRP being elevated from days 1 to 12 p.i. and peaking at 10 times the day 0-levels on day 1 p.i. SAA rose quickly to peak levels of 30-40 times the day 0-level on days 1-2 and returned to pre-inoculation level on day 5 p.i. Hp and pig-MAP showed slightly slower responses, both peaking around 5 days p.i. Hp was increased throughout the experiment with maximum levels around 10 times the day 0-levels, and pig-MAP was elevated on days 1-12 p.i. with peak levels of around seven times the day 0-levels. Apo A-I was decreased from days 1 to 8 and showed minimum levels of about 40% of day 0-levels around 1-2 days p.i. No clear pattern of changes in albumin levels could be identified. One pig, showing clinical signs on day 2 only, also showed an APP response, although of a relatively short duration, whereas three pigs presenting clinical signs for several days had a more protracted acute phase response. Remarkably, the one pig showing no clinical signs and no arthritic lesions showed an APP response comparable to that of the other, clinically affected pigs. Thus, both acute clinical and subclinical S. suis infection could be revealed by the measurement of one or more of the APPs CRP, SAA, Hp, pig-MAP and Apo A-I. The combined measurement of two or three APPs, including proteins with slow and fast kinetics, should be used to achieve the highest sensitivity for the detection of ongoing S. suis infection during a prolonged time period. A diagnostic tool based on such APP-measurements could considerably improve strategic control procedures for this important infection.

Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with bladder cancer.

AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma (n=3) or adenocarcinoma (n=7). RESULTS: Free and total TIMP-1 in plasma were weakly but significantly correlated with age; urinary TIMP-1 was not. A strong correlation between free and total TIMP-1 in plasma was observed, with an average ratio of 0.85. No correlation between total TIMP-1 in urine and plasma was found (p=0.55). No significant differences in free or total TIMP-1 in plasma were found between healthy individuals, patients with cystitis or bladder cancer (p=0.4). Urinary TIMP-1 levels were significantly increased in patients with cystitis (p=0.001). No apparent differences in TIMP-1 levels were found in patients with bladder cancer at different stages. CONCLUSION: Our previous observation of a weak but significant correlation between plasma TIMP-1 and age was confirmed. Likewise, an association between free and total TIMP-1 in plasma with a ratio of 0.85 was established. No correlation between plasma and urine TIMP-1 was found. Measurement of TIMP-1 in plasma and/or urine is apparently not useful for the identification of bladder cancer.

Early periinsular hemispherotomy in children with Sturge-Weber syndrome and intractable epilepsy--outcome in eight patients.

BACKGROUND: Periinsular hemispherotomy is used to treat catastrophic epilepsy in hemispheric lesions. It avoids complications of tissue resection performed in other hemispherectomy procedures. We report on the effectiveness, complications, and neurological sequelae in patients with Sturge-Weber syndrome (SWS). METHODS: Eight patients (mean age at operation 15 months, mean surveillance time 7.1 years, 5 girls) were operated between 1994 and 2000, one with additional subpial resections of the insular cortex. Preoperatively hemiparesis was evident in all patients, mental retardation in six. Charts were reviewed for pre- and perioperative data. Outcome data were collected by structured telephone interview and questionnaires. RESULTS: No severe complications occurred. Five patients with unilateral angiomatosis were seizure-free without medication, rare non-disabling seizures occurred in one. Two patients with bilateral angiomatosis had seizure reduction of > 90%. Hemiparesis deteriorated in all patients with a marked deficit of hand function and less severe deficit in the lower extremity and trunk. Seven became ambulatory and achieved community language. Mental development improved with seizure control. Six patients have learning disability, two are mentally handicapped. CONCLUSION: Periinsular hemispherotomy is a valuable treatment modality in this patient group. The sequelae of hemiparesis, hemianopsia, and developmental delay must be seen in relation to the natural course in severe SWS.

Cerebral mass in a 13-year-old girl following long-term sojourn in the Tropics.

Cysticercosis of the central nervous system is the main cause of late-onset epilepsy in tropical countries. The case of a 13-year-old German girl with a generalized seizure following long-term sojourns in the Tropics is reported. Cranial imaging showed two cerebral lesions with central calcifications. Serological, molecular and cultural examination of cerebrospinal fluid and blood was negative for various parasites, fungi and bacteria including mycobacteria. Histopathological examination after neurosurgical resection revealed calcareous bodies pathognomonic for platyhelminths, in particular tapeworms. Taken together, the radiological and histopathological findings indicate infection with cysticerci, the larvae of Taenia solium.

Cutaneous lesions in occult spinal dysraphism--correlation with intraspinal findings.

OBJECTS: This study was conducted to investigate the frequency and type of cutaneous stigmata in different forms of occult spinal dysraphism (OSD) and their correlation to the underlying malformation. METHODS: Fourteen different forms of spinal malformations were identified in 358 operated patients with OSD. Most frequent findings (isolated or in combinations) were spinal lipoma, split cord malformation, pathologic filum terminale, dermal sinus, meningocele manqué, myelocystocele and caudal regression. Stigmata were present in 86.3% of patients, often in various combinations. Using a binary logistic regression analysis, significant correlations with distinct malformations were found for subcutaneous lipomas, skin tags, vascular nevi, pori, hairy patches, hypertrichosis, meningoceles and "cigarette burn" marks. CONCLUSIONS: Cutaneous markers in a high percentage accompany spinal malformations. Due to the correlations of different stigmata to distinct malformations, they can aid the clinician in further diagnostic and therapeutic work.

Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood.

Supratentorial primitive neuroectodermal tumors (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of the CNS represent a biological and clinical enigma, despite advances in both molecular techniques and clinical management for these two rare embryonal brain tumors of childhood. Epigenetic changes hold great potential as possible disease mechanisms and may be manipulated therapeutically. We thus studied aberrant methylation of the genes RASSF1A and CASP8 and its consequence on expression in cell lines and primary tumors using a combination of semiquantitative methylation specific PCR (MSP), bisulfite sequencing and RT-PCR. In all, 17 samples of autopsy-derived normal appearing brain served as controls. Opposed to control tissues 19/24 sPNET and 4/6 AT/RT demonstrated aberrant methylation for the RASSF1A promoter region. Treatment of cell lines using 5-Aza-2'-deoxycytidine (5AZA) alone or in combination with trichostatin A (TSA) succeeded in re-establishing expression of RASSF1A in cell lines derived from a renal rhabdoid, an AT/RT and a medulloblastoma. A 5' CpG-rich region of CASP8 was methylated in normal tissues and in tumors. However, CASP8 showed inconsistent expression patterns in normal and tumor tissues. Our results indicate that aberrant methylation of the RASSF1A promoter region may be of importance in the origin and progression of sPNET and AT/RT while the analysed 5'-CpG rich region of the CASP8 gene does not seem to play an important role in these tumors. Further studies of epigenetic changes in these rare tumors are warranted as their biology remains obscure and treatment efforts have been rather unsuccessfull.