Basal cell carcinomas in a tertiary referral centre: a systematic analysis.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer with increasing incidence and generally high cure rates. BCC can be quite aggressive and is difficult to treat. OBJECTIVES: To investigate BCCs with a focus on histological subtypes, treatment procedures and correlation to clinical progress to collect further information on complex BCC cases. METHODS: In this retrospective single-centre analysis the dermatopathology database, a network of cooperating dermatological surgeons, was queried for BCC cases between January 2007 and December 2011. Of 14,423 samples from a total of 9652 patients initially identified, 2938 patients were treated at the University Hospital Zurich and had corresponding local electronic patient records. RESULTS: Patients (n = 2938) (with 4769 diagnoses, 2006 re-excisions with 1180 microscopically controlled surgeries) were classified based on severity estimations into 2240 simple, 640 moderate, and 58 severe cases, including one BCC-treatment-associated death and 11 patients with subsequent participation in a clinical trial. In moderate and severe cases (n = 698), there were significantly higher rates of unique histological diagnoses (n = 2·5; P < 0·0001), higher association with basosquamous carcinoma [odds ratio (OR) 3·6; P < 0·0001] and sclerosing BCC (OR 2·48; P < 0·0001). Of the patients with basosquamous carcinoma 82·6% had a previous history of BCC. CONCLUSIONS: This is the first study that analyses the frequency of complicated BCCs in a tertiary referral centre. There were 6·6% moderate (640 of 9652) and 0·6% (58 of 9652) severe cases. We found significantly more varying histological diagnoses and significant association with aggressive subtypes in moderate and severe cases. These patients might especially benefit from new therapeutic options.

Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay.

Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression it is important to know the natural variation of dystrophin expression between different muscles and over time. Dystrophin was quantified using capillary Western immunoassay (Wes) in the anterior tibial (TA) muscle of 37 BMD patients. Variability was studied using two samples from the same TA biopsy site in nine patients, assessing nine longitudinal TA biopsies, and eight simultaneously obtained vastus lateralis (VL) muscle biopsies. Measurements were performed in duplicate with two primary antibodies. Baseline dystrophin levels were correlated to longitudinal muscle strength and functional outcomes. Results showed low technical variability and high precision for both antibodies. Dystrophin TA levels ranged from 4.8 to 97.7%, remained stable over a 3-5 year period, and did not correlate with changes in longitudinal muscle function. Dystrophin levels were comparable between TA and VL muscles. Intra-muscle biopsy variability was low (5.2% and 11.4% of the total variability of the two antibodies). These observations are relevant for the design of clinical trials targeting dystrophin production, and may urge the need for other biomarkers or surrogate endpoints.

Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.

Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.