Osteosarcoma of the mobile spine.

BACKGROUND: The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine. PATIENTS AND METHODS: Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome. RESULTS: The median age was 29 years (range 5-58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1-22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05). CONCLUSIONS: Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcomas.

Successful treatment of steroid refractory active ulcerative colitis with natural interferon-beta--an open long-term trial.

INTRODUCTION: In some steroid refractory patients with active ulcerative colitis (UC), treatment with immunosuppressive agents, such as cyclosporin, azathioprine or 6-mercaptopurin is effective. However, there are patients who fail to respond to these treatment options or who cannot tolerate them. Application of natural interferon-beta (nIFN-beta) may offer an alternative. Following our positive results with nIFN-beta in a previously published open-labeled study, the present study was designed as an extension with the hypothesis that administration of higher dosage of nIFN-beta (1.0 vs. 0.5 MIU) could result in fewer relapse events. PATIENTS AND METHODS: 46 steroid refractory patients with active UC and a mean clinical activity index (CAI) of 13.2 +/- 3.7 (range 9-23) were treated with nIFN-beta in addition to existing basic medication (5-ASA/SASP plus corticosteroids). During an induction period of eight weeks, 18 patients (group A) received 0.5 MIU nIFN-beta daily and 28 patients (group B), 1.0 MIU nIFN-beta daily intravenously as a bolus injection. Patients who achieved complete remission (decrease of CAI to < or = 4) during the induction period received maintenance therapy with nIFN-beta at the same dose level three times a week and corticosteroids were withdrawn. Remissions and maintenance of remissions were evaluated. RESULTS: In both groups, a comparable number of complete remissions occurred during the induction period: in 16 / 18 patients (89 %) in group A and in 24 / 28 patients (86 %) in group B. Duration of maintenance treatment was 60.0 +/- 90.0 weeks in group A and 52.7 +/- 9.6 weeks in group B. Under this treatment, relapses (increase of CAI to > or = 6) occurred in 5 / 16 patients (31 %) vs. 1 / 24 patients (4 %) (p < or = 0.05). Hence, regarding maintaining remissions, the 1.0 MIU group outscored the 0.5 MIU group. Apart from known flu-like side effects, the therapy was well tolerated by all patients in both groups. CONCLUSION: nIFN-beta may be a safe and effective alternative to induce and maintain remissions in patients with steroid refractory active UC. To validate the presented results, its effect has to be investigated in a randomized, placebo-controlled dose-finding trial.

Lack of correlation between the vitamin D receptor Fokl start codon polymorphism and bone mineral density in patients with Crohn's disease.

INTRODUCTION: We have examined the association of bone mineral density of patients with inflammatory bowel disease with a polymorphism in the gene encoding the vitamin D receptor. The thymine/cytosine (T/C) polymorphism in the first of two start codons can be defined by a restriction fragment length polymorphism using the restriction endonuclease FokI. Vitamin D receptor alleles containing the polymorphism have been denoted by f and alleles lacking the site by F. METHODS: We report on an association analysis of a basic population of 244 caucasian patients with Crohn's disease. We have genotyped the FokI polymorphism of the VDR in these patients and associated the genotype with the bone mineral density of the lumbar spine and the femoral neck. RESULTS: In the cohort 42% of the patients were scored FF homozygous, 43.7% Ff heterozygous, and 14.3% ff homozygous. 14.4% of the FF patients, 18.8% of the Ff patients, and 9.7% of the ff patients had osteoporosis of the lumbar spine and 21.25% of the FF patients, 25.3% of the Ff patients, and 18.5% of the ff patients had osteoporosis of the femoral neck. In this cohort no association between the genotype and the bone mineral density in the group as a whole nor when separated according to sex or age was found. CONCLUSIONS: In summary in our cohort no association of the FokI polymorphism and the BMD of the lumbar spine and femoral neck in patients with inflammatory bowel disease was found.

[Obesity surgery: the refusal rate of health care cost reimbursement despite expert opinion]. / Adipositaschirurgie: Ablehnung der Kostenübernahme trotz ärztlicher Gutachten.

BACKGROUND AND OBJECTIVE: Surgery is an effective method to treat patients with morbid obesity. However health insurance companies frequently refuse to cover the costs for the procedure despite an existing DRG-code for this operation. Individual medical expertise are necessary to receive reimbursement. In the present study the acceptance of medical expertise to receive cost coverage was analysed in our patients of the years 2000-2003 eligible for obesity surgery. PATIENTS AND METHODS: 617 medical expertise of patients eligible for obesity surgery in our hospital were reviewed and the acceptance rate was evaluated. Parameters such as body mass index, personal medical history, diets, comorbidity and prognosis were included. Expertise were submitted to the health care insurance companies and in case of acceptance the operation was performed. RESULTS: The average age of our patients was 39.1 +/- 11.2 years, 72.1% were female, 27.9% male. The average BMI was 47.5 +/- 7.4 kg/m2. There was a high incidence of comorbidity in these patients (58.7% arterial hypertension, 38.6% diabetes mellitus, 95.8% dyspnoea, 96.1% arthropathy, 89.0% psychosocial disorders). The difference between accepted and non-accepted regarding these secondary complications was not significant. 209 patients (33.8%) were operated. 14 patients of these paid the costs themselves. Only in 195 cases (31.6%) the health care insurance company covered the costs for the operation. CONCLUSION: The high number of refusals of medical expertise is not justified in view of the strict criteria for indication, the high frequency of comorbidity and the good results after the operation.

Severe acute cholestatic hepatitis by infiltration of monoclonal plasma cells in multiple myeloma.

BACKGROUND: Plasma cell infiltration of the liver can be detected in 25 to 40% of patients with multiple myeloma. However, there are only rare cases of multiple myeloma clinically presenting as acute liver disease. CASE REPORT: We report an 88-year-old woman with painless jaundice and abnormal liver function tests, resembling acute cholestatic hepatitis. Viral hepatitis as well as autoimmune hepatitis could be excluded. Liver biopsy revealed a diffuse portal and sinusoidal infiltration of plasma cells with lambda light chain restriction. Serological immune fixation disclosed monoclonal gammopathy of IgG lambda with bone marrow infiltration of 25% plasma cells. After administration of 60 mg prednisolone per day, the elevated liver enzymes declined considerably. CONCLUSION: Hepatic plasma cell infiltration of multiple myeloma can, in rare cases, manifest as acute cholestatic hepatitis, which may respond to treatment with corticosteroids.

Patient education in inflammatory bowel disease does not influence patients knowledge and long-term psychosocial well-being.

BACKGROUND AND AIMS: Patient education is accepted in many disciplines as a valid component of disease management in chronic diseases. The aim of this prospective study was to analyze the effects of an education program in patients with inflammatory bowel disease. METHODS: 145 patients with inflammatory bowel disease were prospectively included: 73 were educated in four sessions, 72 were educated after the one year evaluation period (control group). The following topics were presented: pathogenesis, diagnostic procedures, course of disease, medical and surgical treatment, nutrition, social problems and support, stress management, and coping with the disease. RESULTS: The repeated measurement two-way analysis of variances showed no effects of the patient education program on disease-related knowledge, depression and quality of life. CONCLUSION: This patient education program was not able to increase disease-related knowledge or psychosocial variables in patients with IBD. However, most of the patients were very satisfied with the education program, since as judged by their own assessment it helped them to act responsibly for themselves and their disease.

Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis.

BACKGROUND: In acute or chronic inflammatory bowel disease (IBD) interferon gamma (IFNgamma) is still considered to be an important pro-inflammatory mediator. In the present study we investigated the impact of IFNgamma on interleukin-8 (IL-8) production as a read-out for cell activation in intestinal epithelial cell (IEC) lines and primary human colonic epithelial cells (CEC). METHODS: Primary cultures of human CEC were established from the mucosa of patients without inflammatory disease. CEC, HT-29 or Caco-2 cells were incubated with either IFNgamma, tumor necrosis factor (TNF)alpha or IL-10. IL-8 and IL-1Ra secretion was determined by ELISA. Competicon PCR was used for quantification of IL-8mRNA. Apoptosis was quantified by propidium iodine incorporation and fluorescence activated cell sorting (FACS) analysis. RESULTS: In contrast to HT-29 cells in primary human CEC 100 U/ml IFNgamma inhibited IL-8 secretion significantly to 70+/-15% of unstimulated primary CEC (p<0.005) more effectively than IL-10 (87+/-21% versus unstimulated cells, n.s.). In HT-29 cells, IL-8 secretion was induced to 405+/-101% of unstimulated cells. In Caco-2 cells, IFNgamma had no significant effect on IL-8 secretion. The effect in HT-29 and CEC was concentration dependent. In primary CEC, 200 U/ml IFNgamma further reduced IL-8 secretion to 48+/-18% of unstimulated CEC (p<0.05). Whereas IL-8 mRNA was strongly upregulated in HT-29 cells, no upregulation or even a downregulation was found in CEC. Pre-incubation with 100 U/ml IFNgamma did not increase the susceptibility to apoptosis mediated by anti-Fas antibody (CH-11) in primary CEC, whereas HT-29 cells showed increased rates of apoptosis after priming with IFNgamma. CONCLUSION: In contrast to HT-29, IFNgamma downregulated IL-8 secretion and did not induce IL-8 mRNA expression in primary human CEC. This effect was not due to induction of apoptosis.

Analysis of the therapeutic efficacy of different doses of budesonide in patients with active Crohn's ileocolitis depending on disease activity and localization.

BACKGROUND AND AIMS: The nonsystemic steroid budesonide has been used to treat active ileocecal and ileocolonic Crohn's disease (CD). This study investigated the optimal budesonide dose using a pH-dependent release formulation. The goal of treatment was the remission of CD (CDAI <150) within 6 weeks of treatment. PATIENTS AND METHODS: The study was of randomized, double-blind, dose-finding design. Patients with active CD ileocolitis without steroid pretreatment were treated with 3x2 mg ( n=39), 3x3 mg ( n=33), or 3x6 mg ( n=32) oral pH-modified released budesonide daily. RESULTS: The remission rates after 6 weeks were 36% with 3x2 mg, 55% with 3x3 mg, and 66% with 3x6 mg. Significantly more patients were in remission while treated with 3x6 mg than with 3x2 mg budesonide/day. Subgroup analyses revealed that patients with high disease activity (CDAI >/= 300) or ileocolonic disease with disease manifestation distal to the transverse colon responded better to the highest budesonide dose. CONCLUSION: Oral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9 mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response

Treatment of pouchitis with dehydroepiandrosterone (DHEA) - a case report.

BACKGROUND: Dehydroepiandrosterone (DHEA) inhibits activation of nuclear factor kappa B (NF-kappaB), which is known to be activated in inflammatory lesions of ulcerative colitis, via PPARalpha. In a pilot trial DHEA was effective for the treatment of active ulcerative colitis. Pouchitis is a common complication after proctocolectomy for ulcerative colitis and still a therapeutical challenge. CASE: DHEA 200 mg/d was tested in chronic active pouchitis in a 35-year-old female patient. DHEA was given for eight weeks, and follow up for further eight weeks was performed. The number of stools dropped from 15-18/d to 8/d, the addition of mucus, which was observed initially, was absent during treatment. The consistence of stools improved from liquid/soft to soft/solid. Abdominal pain resolved and endoscopical signs of inflammation improved. Eight weeks after termination of treatment with DHEA, the patient again suffered from 12 to 18 soft to liquid stools per day and mild abdominal pain. CONCLUSION: Therapeutic effects of DHEA in pouchitis should be evaluated systematically.

[Value of abdominal ultrasound screening in patients with benign diseases of the skin]. / Diagnostische Wertigkeit der Abdominalsonografie im Primärscreening benigner Hauterkrankungen.

OBJECTIVE: We investigated the value of abdominal ultrasound screening of abdominal foci in patients with benign diseases of the skin. PATIENTS AND METHODS: The data of 151 patients (age (mean) 56,6 years; male n = 79, female n = 72) from the department of dermatology were retrospectively analysed. The patients were sent for ultrasound evaluation of abdominal foci as cause of benign diseases of the skin. RESULTS: In these 151 patients 3 potential foci were found (2 yen suspicion of a liver tumor, 1 yen thickened bowel wall). The liver tumors could not be confirmed by computed tomography, in the patient with a thickened bowel wall, a Crohns disease was newly diagnosed. Abdominal ultrasound led to clinically relevant findings in fewer than 1 % of cases. We diagnosed 142 abnormal findings, mostly without clinical relevance. These abnormal findings caused follow-up examinations in 30 of the cases (19 computed tomographies; 2 magnetic resonance tomographies). CONCLUSION: Abdominal ultrasound does not seem useful in the primary screening of patients with benign diseases of the skin. Perhaps a more restrictive and selective use of ultrasound could be valuable.

Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn's disease: results of an open, prospective, multicenter trial.

Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5-30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 x 3 mg budesonide. Thereafter, patients received 3 x 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study.

BACKGROUND: Dehydroepiandrosterone is a steroid hormone used as an 'over-the-counter' drug in the USA. Treatment with dehydroepiandrosterone was effective in randomized controlled trials in patients with systemic lupus erythematosus. Dehydroepiandrosterone sulphate concentrations are decreased in patients with inflammatory bowel disease. Dehydroepiandrosterone inhibits nuclear factor-kappaB and the secretion of interleukin-6 and interleukin-12 via the peroxisome proliferator-activated receptor alpha. AIM: A phase II pilot trial was started to evaluate the effect of dehydroepiandrosterone in active inflammatory bowel disease. METHODS: Twenty patients with chronic active inflammatory bowel disease [seven Crohn's disease (Crohn's disease activity index, 242 +/- 51; mean +/- s.d.); 13 ulcerative colitis (clinical activity index, 7.8 +/- 2.1)] took 200 mg dehydroepiandrosterone per day orally for 56 days. RESULTS: Six of the seven patients with Crohn's disease and eight of the 13 patients with ulcerative colitis responded to treatment, with a decrease in the Crohn's disease activity index of > 70 points and a decrease in the clinical activity index of > 4 points, respectively. Six Crohn's disease patients and six ulcerative colitis patients went into remission (Crohn's disease activity index < 150; clinical activity index

Induction and maintenance of clinical remission by interferon-beta in patients with steroid-refractory active ulcerative colitis-an open long-term pilot trial.

BACKGROUND: The imbalance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of inflammatory bowel disease. Shifting this disturbed ratio by means of TNF-antibodies or interferon has been shown to be helpful in treating Crohn's disease and multiple sclerosis, respectively. AIM: This pilot study investigated whether interferon-beta can induce clinical remission in corticoid-refractory ulcerative colitis. METHODS: Twenty-five patients with steroid-refractory active ulcerative colitis (Clinical activity index according to Rachmilewitz: 13.5 +/- 5.2) were treated in an open pilot trial with 0.5 MIU human natural interferon-beta (hn-IFN-beta) i.v. (n=18) or 1 MIU recombinant interferon-beta-1a (r-IFN-beta-1-a) s.c. (n=7) daily with the goal of induction of remission. Subsequent maintenance treatment was carried out for 52.0 +/- 78.8 weeks (range 4-336 weeks) with the same dose, three times per week. RESULTS: Twenty-two of 25 patients (88%) went into remission during induction treatment (hn-IFN-beta 16/18, r-IFN-beta-1a 6/7). Mean time to response was 3.0 +/- 1.3 weeks. Mean length of remission was 13.0 +/- 19.7 months. Only eight of 22 patients in remission relapsed during maintenance treatment. Five of these went into remission again after increasing the dose. Adverse events consisted of slight to moderate flu-like symptoms and slight to moderate hair loss in five of 15 female patients. CONCLUSION: Although this open pilot study included only a small number of patients, the high response rate suggests that interferon-beta may be a safe and effective treatment for steroid-refractory active ulcerative colitis.

Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation.

BACKGROUND & AIMS: Bacterial wall products play an important role in the activation of immune and nonimmune cells of the intestinal mucosa. Toll-like receptors (TLRs) TLR2 and TLR4 have been identified as signaling receptors activated by bacterial wall components. METHODS: Expression of TLRs in human intestinal mucosa obtained by endoscopy and surgery was analyzed by immunohistochemistry. Intestinal macrophages were isolated by immunomagnetic beads armed with a CD33 antibody. Reverse-transcription polymerase chain reaction was performed for TLR1-5. Results were confirmed by Northern blot and flow cytometry. Interleukin-1beta messenger RNA (mRNA) was quantified by a polymerase chain reaction-enzyme-linked immunosorbent assay-kit. RESULTS: Immunohistochemistry revealed a significant increase in the TLR2 and TLR4 antigen expression on submucosal cells in inflamed intestinal mucosa compared with non-inflamed mucosa. TLR expression was localized in intestinal macrophages by double-labeling techniques. No TLR-polymerase chain reaction product could be obtained with mRNA from CD33-positive macrophages from normal mucosa. We observed an induction of mRNA for TLR2, TLR4, and TLR5 in inflammation-associated macrophages. TLR1 and TLR3 were only detectable in blood monocytes. Monocytes reacted to lipopolysaccharide stimulation with a 3-fold and in vitro differentiated macrophages with a 16-fold increase of cellular interleukin-1beta mRNA. Macrophages from normal mucosa did not respond to lipopolysaccharide showing the functional relevance of TLR expression. CONCLUSIONS: This study shows the inflammation-dependent induction of TLR2 and TLR4 expression in intestinal macrophages. The absence of TLRs abolishes the reactivity of mucosal macrophages to bacterial wall products. Presence of TLRs may thereby contribute to the inflammatory process.