Complications and clinical outcome of hepatic artery embolisation in patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Hepatic artery embolisation (HAE) in patients with hereditary haemorrhagic telangiectasia (HHT) is controversial because of the associated complications and unproven long-term benefit. We present our results in 20 such patients over a time span of 17 years. METHODS: Staged HAE was performed using polyvinyl alcohol (PVA) particles and coils. Complications, clinical symptoms and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 92 months, range 26-208 months). RESULTS: Two patients died within 30 days following HAE (10 %). Four further deaths resulted from causes unrelated to HAE. Ischaemic cholangitis, cholecystitis and focal hepatic necrosis with biliary sepsis necessitated re-intervention in four patients. In all but one patient, clinical symptoms resolved with mean cardiac output falling from 11.84 ± 3.22 l/min pre-treatment to 8.13 ± 2.67 l/min at the end of follow-up (P < 0.001). One patient required liver transplantation for de novo symptoms of portal hypertension 4 years after primary symptoms had been cured by HAE. CONCLUSION: The 30-day mortality of HAE in patients with HHT is 10 %. The rate of complications requiring re-intervention is 20 %. Clinical response at long-term follow-up is satisfactory.

Cost-effectiveness of TNF-α inhibition in active ankylosing spondylitis: a systematic appraisal of the literature.

Ankylosing spondylitis (AS) is the most frequent prototype of spondyloarthritides. Substantial direct costs and productivity losses often arise in young patients. Currently, tumor necrosis factor (TNF) inhibitors are the only approved therapy escalation when usual care (physiotherapy and NSAIDs) proves to be insufficient. Owing to their high medication costs, TNF inhibitors are a target of cost-effectiveness analyses. There is consistent evidence regarding the use of TNF inhibitors according to recommendations in patients with active AS finding TNF inhibitors to be cost effective from a societal perspective. However, there are relevant uncertainties (discontinuation rate and progression rate) in the long-term estimates of the cost-effectiveness analyses analyzed. Whether TNF inhibitors are cost effective from an insurance perspective in the long run will have to be addressed by models based on observational data.

Cost of illness in rheumatoid arthritis in Germany in 1997-98 and 2002: cost drivers and cost savings.

OBJECTIVE: Comparison of overall RA-related costs and of relative contribution of single-cost domains before and after the introduction of TNF-blocking agents in Germany. METHODS: Two cohorts of RA outpatients (ACR '87 criteria) with long-standing disease are assessed in terms of disease-related costs and cost composition (n = 106 patients in 1997-98 and n = 180 patients in 2002 with similar patient characteristics). Full-cost analyses are performed including direct disease-related costs (medical and non-medical) and productivity costs as collected by patient questionnaires. Absolute costs (€/patient/year) are compared and the impact of single-cost domains on overall costing in RA is estimated (relative proportions of cost components within samples). RESULTS: Overall costs are comparable (1997-98: €4280; 2002: €3830; not significant). Differences can be observed in medication (1997-98: €550; 2002: €1580; P < 0.001) and hospitalization costs (1997-98: €1240; 2002: €500; P < 0.001). Productivity costs are significantly lower (€1480 vs €850; P < 0.05) in 2002. The impact of medication costs is outstanding in the 2002 sample (42 vs 12%), the proportion of hospitalization costs is substantially lower (29 vs 13%). Costs for DMARDs in 2002 are mostly driven by TNF blockers (37%). The number of DMARDs per patient is higher in 2002 as are costs for osteoporosis medication and gastroprotective treatment. CONCLUSION: Although overall costs before and after the introduction of TNF blockers are comparable, the decrease in hospitalization and productivity costs is promising in terms of future long-term cost savings. The development of these aspects and of the increasing medication costs will have to be evaluated with longer time frames.

Cost-effectiveness analysis of rituximab treatment in patients in Germany with rheumatoid arthritis after etanercept-failure.

OBJECTIVE: The present health economic analysis investigated the cost-effectiveness-ratios of either (1) rituximab or (2) an alternative TNF-alpha-inhibiting agent as second line biological treatment in patients with active rheumatoid arthritis (RA) and an inadequate response to etanercept therapy. METHODS: Incremental cost per quality-adjusted life-year (QALY) gained by rituximab treatment of RA is compared to TNF-inhibitor change (standard sequence) in a Markov-model (perspective: health care payer, full life-time approach). Direct cost components taken into account were treatment costs (medication-, administration- and monitoring costs) and resource utilisation (outpatient costs, inpatient costs). Indirect costs were estimated separately by the assessment of impaired work capacity due to RA (2008 Euro currency, discount rate 3.5%). Utility measures for the different treatment options were obtained from the ACR-response rates of published pivotal clinical trials. RESULTS: Direct costs amount to euro 178,373 (standard sequence) and euro 192,295 (rituximab sequence), respectively, rendering incremental direct costs of euro 13,922. Incremental utilities yield 0.57 QALYs and the incremental cost-effectiveness-ratio (ICER) of rituximab compared to the standard sequence amounts to euro 24,517. Inclusion of indirect costs leads to less incremental costs and a lower ICER of euro 15,565/QALY. Thus, ICERs stay beneath the accepted threshold of euro 50,000/QALY. CONCLUSION: Rituximab appears to be a cost-effective treatment alternative compared to the switch between TNF-inhibitors as second line biological treatment in patients with active RA having failed etanercept.

Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: an interventional study.

INTRODUCTION: The acronym SAPHO was introduced in 1987 to unify the various descriptions of a seronegative arthritis associated with skin manifestations and to show synovitis, acne, pustulosis, hyperostosis, and osteitis with and without sterile multifocal osteomyelitis. The etiology of SAPHO syndrome is unknown, but an association with infection by semipathogenic bacteria like Propionibacterium acnes has been suggested. We conducted an interventional study of SAPHO patients receiving antibiotics. METHODS: Thirty-seven patients met the clinical criteria of SAPHO syndrome, 21 of them underwent a needle biopsy of the osteitis lesion, and 14 of them showed positive bacteriological cultures for P. acnes. Thirty patients (14 bacteriological positive and 16 without biopsy) were treated with antibiotics for 16 weeks. The activity of skin disease and osteitis were assessed by a physician using a scoring model (from 0 to 6). In addition, patients completed a Health Assessment Score (HAS, from 0 to 6). The erythrocyte sedimentation rate was determined and a MRI (of the osteitis lesion, radiologic activity score from 0 to 2) was performed in week 1 (W1), week 16 (W16), and week 28 (W28, 12 weeks after antibiotics). RESULTS: Twenty-seven patients continued the medication (azithromycin, n = 25, 500 mg twice a week; clindamycin, n = 1, 300 mg daily; or doxycycline, n = 1, 100 mg daily) for 16 weeks. After W16 the scores for MRI (1.5 to 1.1, P = 0.01), skin activity (3.2 to 1.2, P = 0.01), osteitis activity (4.0 to 2.1, P = 0.02), and HAS (3.3 to 2.1, P = 0.01) decreased significantly. However, this was followed by increasing values for MRI scores (1.2 to 1.4, P = 0.08), skin activity (1.2 to 1.7, P = 0.11), osteitis activity (1.9 to 2.7, P = 0.01), and HAS (2.2 to 3.3, P = 0.02) from W16 to W28. The comparison of the scores in W1 and W28 in these 12 patients showed no significant differences. CONCLUSIONS: For the period of application, the antibiotic therapy seems to have controlled the disease. After antibiotic discontinuation, however, disease relapse was observed. SAPHO syndrome thus groups with other chronic inflammatory arthropathies with a need for permanent therapy.

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival.

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m(2)), doxorubicin (50 mg/m(2)), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics, toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4+/-1.5 courses per patient). Mean maximum tumor size was 75 (+/-43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size 30 months, R(2)=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma.

AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, alpha-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses. RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically. CONCLUSION: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.

Preoperative volume calculation of the hepatic venous draining areas with multi-detector row CT in adult living donor liver transplantation: Impact on surgical procedure.

OBJECTIVE: The purpose was to assess the volumes of the different hepatic territories and especially the drainage of the right paramedian sector in adult living donor liver transplantation (ALDLT). METHODS: CT was performed in 40 potential donors of whom 28 underwent partial living donation. Data sets of all potential donors were postprocessed using dedicated software for segmentation, volumetric analysis and visualization of liver territories. During an initial period, volumes and shapes of liver parts were calculated based on the individual portal venous perfusion areas. After partial hepatic congestion occurring in three grafts, drainage territories with special regard to MHV tributaries from the right paramedian sector, and the IRHV were calculated additionally. Results were visualized three-dimensionally and compared to the intraoperative findings. RESULTS: Calculated graft volumes based on hepatic venous drainage and graft weights correlated significantly (r = 0.86, P < 0.001). Mean virtual graft volume was 930 ml and drained as follows: RHV: 680 ml, IRHV: 170 ml (n = 11); segment 5 MHV tributaries: 100 ml (n = 16); segment 8 MHV tributaries: 110 ml (n = 20). When present, the mean aberrant venous drainage fraction of the right liver lobe was 28%. CONCLUSION: The evaluated protocol allowed a reliable calculation of the hepatic venous draining areas and led to a change in the hepatic venous reconstruction strategy at our institution.

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver.

AIM: In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m(2)) and additional transarterial chemoembolization procedures (50 mg/m(2) cisplatin, 50 mg/m(2) doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.

Hepatic artery embolization for treatment of patients with hereditary hemorrhagic telangiectasia and symptomatic hepatic vascular malformations.

At present there is no established therapy for treating patients with hereditary hemorrhagic telangiectasia (HHT) and symptomatic hepatic involvement. We present the results of a prospective study with 15 consecutive patients who were treated with staged hepatic artery embolization (HAE). Branches of the hepatic artery were selectively catheterized and embolized in stages using polyvinyl alcohol particles (PVA) and platinum microcoils or steel macrocoils. Prophylactic antibiotics, analgesics and anti-emetics were administered after every embolization. Clinical symptomatology and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 28 months; range 10-136 months). Five patients had abdominal pain and four patients had symptoms of portal hypertension. The cardiac output was raised in all patients, with cardiac failure being present in 11 patients. After treatment, pain resolved in all five patients, and portal hypertension improved in two of the four patients. The mean cardiac output decreased significantly ( P<0.001) from 12.57+/-3.27 l/min pre-treatment to 8.36+/-2.60 l/min at the end of follow-up. Symptoms arising from cardiac failure resolved or improved markedly in all but one patient. Cholangitis and/or cholecystitis occurred in three patients of whom two required a cholecystectomy. One patient with pre-existent hepatic cirrhosis died as a complication of the procedure. Staged HAE yields long-term relief of clinical symptoms in patients with HHT and hepatic involvement. Patients with pre-existing hepatic cirrhosis may be poor candidates for HAE.

Transcutaneous perianal sonography: a sensitive method for the detection of perianal inflammatory lesions in Crohn's disease.

AIM: Pelvic magnetic resonance imaging (MRI) and endoanal ultrasound which are established imaging methods for perianal inflammatory lesions in patients with Crohn's disease require expensive specialized equipments and expertise. We investigated the feasibility and sensitivity of transcutaneous perianal ultrasound (PAUS) using regular ultrasound probes in the imaging of perianal inflammatory lesions. The sonographic findings were correlated to pelvic MRI-scans. METHODS: We performed PAUS in 25 patients with Crohn's disease and clinical signs of perianal inflammatory disease. Within a median of 10 d (range 0-75) these patients underwent MRI of the pelvis. Regular convex and linear high resolution probes were used for PAUS. The sonographic findings were correlated to the MRI findings by blinded investigators. RESULTS: The sonographic investigations were well tolerated by all patients. Fistulae typically presented as hypoechoic tracks. Twenty-nine fistulae were detected in 22 patients. Abscesses were detected in 7 patients and presented as hypo- or anechoic formations. Twenty-six of 29 fistulae and 6 of 7 abscesses could be confirmed by MRI. Kappa statistics showed an excellent agreement (kappa>0.83) between the two imaging methods. CONCLUSION: PAUS is a simple, painless, feasible, real-time method that can be performed without specific patient preparation which is comparable in its sensitivity to pelvic MRI in the detection of perianal fistulae and/or abscesses. PAUS can especially be recommended as a screening tool in acute perianal disorders such as perianal abscess and for follow-up studies of perianal inflammatory disease.

3D CT modeling of hepatic vessel architecture and volume calculation in living donated liver transplantation.

The aim of this study was to evaluate a software tool for non-invasive preoperative volumetric assessment of potential donors in living donated liver transplantation (LDLT). Biphasic helical CT was performed in 56 potential donors. Data sets were post-processed using a non-commercial software tool for segmentation, volumetric analysis and visualisation of liver segments. Semi-automatic definition of liver margins allowed the segmentation of parenchyma. Hepatic vessels were delineated using a region-growing algorithm with automatically determined thresholds. Volumes and shapes of liver segments were calculated automatically based on individual portal-venous branches. Results were visualised three-dimensionally and statistically compared with conventional volumetry and the intraoperative findings in 27 transplanted cases. Image processing was easy to perform within 23 min. Of the 56 potential donors, 27 were excluded from LDLT because of inappropriate liver parenchyma or vascular architecture. Two recipients were not transplanted due to poor clinical conditions. In the 27 transplanted cases, preoperatively visualised vessels were confirmed, and only one undetected accessory hepatic vein was revealed. Calculated graft volumes were 1110 +/- 180 ml for right lobes, 820 ml for the left lobe and 270 +/- 30 ml for segments II+III. The calculated volumes and intraoperatively measured graft volumes correlated significantly. No significant differences between the presented automatic volumetry and the conventional volumetry were observed. A novel image processing technique was evaluated which allows a semi-automatic volume calculation and 3D visualisation of the different liver segments.

Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up.

Propionibacterium acnes (P. acnes) is suspected to be involved in the pathophysiology of SAPHO syndrome, since it has been isolated repeatedly through open surgical bone biopsy. This study demonstrates the role of MRI in identifying inflamed bone areas in patients with SAPHO syndrome and the role of CT-guided bone biopsies in obtaining samples from these areas for microbiological and histopathological investigations, thus obviating open surgery. Fourteen consecutive patients with SAPHO syndrome were investigated by MRI to identify acute inflammatory changes in hyperostotic periarticular bone. The CT-guided biopsies for microbiological investigations were taken from the areas identified. Patients positive for P. acnes were started on long-term antibiotic therapy according to antibiotic susceptibility. On MRI the inflammatory changes appeared as hyperintense areas on fat-saturated T2 fast-spin-echo (FSE) images and showed signal increase on fat-saturated T1 SE images after Gd-DTPA. With MR localization CT-guided bone biopsies yielded P. acnes in 8 patients. No bacteria could be isolated from the remaining 6 patients. Acute inflammatory bone changes in SAPHO syndrome are well localized by MRI. With MR localization, CT-guided bone biopsies offer a minimally invasive alternative to open surgery in the detection of. P. acnes leading to the institution of a specific antibiotic therapy.

Computer assisted pelvic surgery: registration based on a modified external fixator.

A fundamental step in Computer Assisted Surgery (CAS) is the registration, when the preoperative virtual data and the corresponding operative anatomy of the region of interest are merged. To provide exact landmarks for anatomical registration, a tubular external fixator was modified. Two intact pelvic bones (one artificial foam pelvis and one cadaver specimen) were used for the experimental setup. Registration was carried out using a standardized protocol for anatomy-based registration in the control group; anatomical registration was achieved using a modified external fixator in the study group. This external fixator had titanium fiducials wedged into the fixator carbon tubes serving as landmarks for paired-point registration. The tubes were used for surface registration. The standard anterior pelvis fixator assembly was augmented with additional bilateral tubes oriented towards the posterior, enabling registration of the sacroiliac areas. The accuracy of registration was checked by "reversed verification", where the examiner used only the screen display to control the virtual position of the pointer tip in relation to selected landmarks. By virtual matching, the real distance was measured with a digital caliper. We defined the verification as "accurate" when the residual distance was less than 1 mm; "acceptable" when it was between 1 mm and 2 mm; and "insufficient" when it exceeded 2 mm. The paired T-test with significance levels of p < 0.05 was used for statistical analysis. The anatomical registration based on the external fixator landmarks was statistically as accurate as that obtained using anatomical landmarks on the pelvic bone. This study concludes that the external fixator, a conventional tool in the management of acute traumatic pelvic instability, can also be useful for landmark registration in CAS.