Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study.

OBJECTIVES: To investigate the safety of transarterial chemoembolisation (TACE) in combination with sorafenib in patients with hepatocellular carcinoma (HCC). METHODS: Patients with Child-Pugh A/B liver function, ECOG performance status 0-2 and HCC treatable with TACE received continuous sorafenib 800 mg/day, and TACE with doxorubicin (75, 50 and 25 mg/m(2) according to serum bilirubin: <1.5, 1.5-3, and >3 mg/dL) and lipiodol 2 weeks after sorafenib initiation and repeated every 4 weeks. RESULTS: Fifteen patients were included (Child-Pugh A/B, n = 12/3; Barcelona Clinic Liver Cancer-A/B/C, n = 1/9/5; ECOG 0/2, n = 14/1). Median time on sorafenib was 5.2 months (2.6-7.4 months); median number of TACE sessions was 3. Common adverse events were abdominal pain (n = 14), weight loss (n = 13), alopecia (n = 12), fatigue (n = 12) and hyperbilirubinaemia (n = 11). There were 32 serious adverse events (grade ≥ 3); 9/10-unscheduled hospital admissions and 4/5 deaths were considered TACE-related. The study was stopped prematurely because of safety concerns. At 6 months, 2 and 5 patients had complete or partial responses; 1 had stable disease. Median overall survival was 10.6 months (95% CI: 5.2-16 months). CONCLUSION: These findings do not support use of an intensive, high-dose doxorubicin-based TACE regimen in combination with sorafenib in this study population. KEY POINTS: • Transarterial chemoembolisation (TACE) is widely used in patients with hepatocellular carcinoma (HCC) • Various antiangiogenic and other agents have been used to augment this treatment • We tested lipiodol-TACE with bilirubin-adjusted doxorubicin dosing in combination with sorafenib • This trial was stopped prematurely because of safety reasons • Our safety results do not support the combination of sorafenib with this TACE regimen.

Quantification of the subcutaneous fat layer with MRI in fetuses of healthy mothers with no underlying metabolic disease vs. fetuses of diabetic and obese mothers.

OBJECTIVE: To assess the age-dependent fetal subcutaneous fat layer (SCFL) of non-diabetic, normal-weight mothers and fetuses of mothers with gestational diabetes (GDM) and normal body weight or obesity. METHODS: In a prospective study, we evaluated 115 MRI examinations of fetuses with no history of (maternal) metabolic disease [gestational week (GW) 29 to 39/40] and 50 examinations of mothers with GDM and normal body weight or obesity. The SCFL was measured at predetermined anatomical landmarks. Measurements were correlated with the maternal body mass index (BMI) and glycated hemoglobin A1c (HbA1c)-values in diabetic mothers. RESULTS: In fetuses of non-diabetic, normal-weight mothers, measurements showed high consistency within the respective GW and ranged from 2 mm at GW 29 at all measured points, up to 4.5 mm at the trunk and 6.0 mm at the extremities at GW 39/40. In 47/50 fetuses of mothers with GDM, the SCFL was within the range of fetuses of mothers with no metabolic disease. In three patients with GDM and BMI<30, the SCFL-thickness was decreased. No fetuses showed an increased SCFL-thickness. CONCLUSION: The SCFL of normally developed fetuses is easily detectable from GW 29 on T1-weighted images (T1-W), and increases with gestational age. The presented data provide physiological benchmarks to evaluate developmental status and may help in the prenatal diagnosis of abnormal growth and macrosomia. In pregnant women with well-controlled GDM, an increase of the SCFL is not expected.

Sorafenib in unresectable intrahepatic cholangiocellular carcinoma: a case report.

BACKGROUND: The oral multikinase inhibitor sorafenib is the new reference standard for the treatment of advanced hepatocellular carcinoma. Only few data are available on the use of sorafenib in cholangiocellular carcinoma (CCC). METHODS: A 70-year-old male patient with histologically confirmed unresectable intrahepatic cholangiocellular carcinoma not amenable to any other systemic chemotherapy was treated with sorafenib 400 mg bid. RESULTS: Sorafenib treatment led to a significant improvement of tumor symptoms, liver function parameters, and a decrease in tumor marker levels. The best radiologic tumor response according to RECIST and mRECIST was stable disease (SD) with a time to progression (TTP) of 5.7 months. Side effects of sorafenib (diarrhea, fatigue, and skin toxicity) were low-grade and manageable. Twenty-four months after sorafenib initiation the patient is still alive and presents in a well-preserved physical constitution, performance status 0. Gene analyses revealed that neither B-raf nor K-ras was mutated in our patient. CONCLUSIONS: Sorafenib was effective and well-tolerated in a patient with advanced cholangiocellular carcinoma. Prospective trials are warranted to evaluate the benefit of sorafenib in unresectable CCC.

CT-guided ozone/steroid therapy for the treatment of degenerative spinal disease--effect of age, gender, disc pathology and multi-segmental changes.

INTRODUCTION: Oxygen-ozone nucleolysis (ONL) is a new, minimally invasive procedure for the treatment of discogenic low back pain with or without radicular symptoms. The aim of the present study was to determine associations between the morphology of the basic disease, patient-specific factors and the outcome of the treatment. MATERIALS AND METHODS: Six hundred and twelve patients not responding to conservative therapy were divided into five groups (disc bulging, disc herniation, postoperative patients, osteochondrosis, others) and subjected to nucleolysis with ozone and to periradicular infiltration with steroids and local anaesthesia. The success of treatment was assessed by means of a visual analog pain scale (VAS) and the Oswestry Disability Index (ODI). RESULT: A significant reduction in the VAS was registered after 2 and 6 months (from 8.6 to 5.4 and 6.0; p < 0.001) in all patient groups; an excellent therapy response (VAS below 3.0) was achieved by about a third of the patients. A significant improvement in ODI was registered in all patients (46 to 31; p < 0.001), most pronounced in the herniation group (25.5, p = 0.015). Patients below 50 years had significantly better values in the VAS and ODI score 6 months after treatment. Final VAS and ODI scores for patients with a single diseased segment were 4.2 and 28.0, in two affected segments 6.5 and 32 and in three segments 6.7 and 38.5 (p < 0.001 and p = 0.051). CONCLUSION: ONL with periradicular steroid therapy might exert a functional and sustained analgesic effect in patients with degenerative changes in the lumbar spine not responding to conservative therapy and was most effective below 50 years with disc herniation in one segment.

An automatic model-based system for joint space measurements on hand radiographs: initial experience.

This ethics committee-approved pilot study was performed with informed consent. A Web-based service that was developed for automated measurement of joint space and automatic analysis of radiographs was tested prospectively. A total of 160 metacarpophalangeal joint spaces were measured in 20 patients (average age, 48 years; age range, 18-89 years; 16 women) suspected of having rheumatoid arthritis or osteoarthritis. The technical success rate was 93%. The smallest detectable difference in repeated automatic joint space width measurements varied from 0.08 to 0.31 mm, and the coefficient of variation was 2%-7%. Compared with the reference standard (interactive segmentation of the joint space widths) measurements, results were within a mean error of 0.19-0.40 mm. The proposed Web-based service enables reproducible joint space measurements to be obtained in metacarpophalangeal joints with moderate erosive and osteophytic disease.