Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Reproducibility of flow cytometric assessment of follicular tumours of the thyroid.

The reproducibility of the DNA index of paraffin wax sections from 44 follicular tumours of the thyroid (18 follicular adenomas and 26 follicular carcinomas), which had been assessed by flow cytometry was analysed in two laboratories, using consecutive sections of the same specimens and two different commercially available flow cytometers. Two slightly different cell preparation and staining techniques were used in the two laboratories. Using strictly defined criteria the histograms were classified blind as diploid, peritetraploid, aneuploid, or inadequate and insufficient by two independent investigators. Both the concordance between the two different flow cytometers and the agreement of duplicate assessments within the same flow cytometers were assessed. The mean coefficient of variation of the G0/G1 peak of the diploid tumours in the PARTEC flow cytometer was 5.5 (range 2.3-9.8) and in the FACS flow cytometer 5.2 (range 3.7-8.3); this difference was not significant. There was concordance of classification between the two laboratories in 35 of 36 cases. In 25 cases (18 diploid, seven aneuploid) the intralaboratory variation showed a 100% concordance in histogram classification. It is concluded that flow cytometer DNA index assessment of follicular tumours of the thyroid is reproducible and can be used to evaluate the discriminating and prognostic value of this feature.     

Prognostic value of thallium-201 exercise scintigraphy in low-risk patients after Q-wave myocardial infarction: comparison with exercise testing and catheterization.

In a prospective study of 100 consecutive patients discharged after a Q-wave myocardial infarction, the value of reversible ischemia on thallium-201 scintigraphy to assess the risk of cardiac events (death or reinfarction) during 4 years was compared with variables from exercise testing and cardiac catheterization. Patients with markedly impaired left ventricular function [ejection fraction (EF) < or = 0.30] were excluded. During follow-up there were 20 cardiac events (10 cardiac deaths and 10 reinfarctions). Thallium-201 scintigraphy was significantly better than all exercise test variables and better than an EF < 0.40, with good sensitivity and specificity (75 and 51%, respectively). Exercise-induced reversible ischemia on scintigraphy yielded the same information as the presence of multivessel disease. Exercise test variables were of limited value to assess prognosis. Thus, thallium-201 scintigraphy can be used as the only tool to predict future cardiac events in low-risk patients after a Q-wave myocardial infarction.     

Early and 8 year results of aortic valve replacement: a clinical study of 232 patients

The study concerns early and late results of aortic valve replacement (AVR) in 232 patients with aortic valve disease, using the Bj?rk-Shiley tilting-disc prosthesis. Of the 232, 27 patients had some evidence of mitral valve disease with valvulotomy having been undertaken in 7 previously, and in 12 at the time of the aortic valve replacement. Patients who underwent simultaneous mitral valve replacement and/or aorta coronary artery bypass grafting are not included in this analysis. To establish predictions of early death and late survival the patients were divided into two groups (A and B), taking 6 pre-operative risk factors into consideration: systolic pressure gradient greater than or equal to 100 mmHg; NYHA class IV; depressed left ventricular function (heart failure); previous valvulotomy of the aortic valve; advanced age (greater than or equal to 70 years) and surgery during the acute stage of bacterial endocarditis. In group A, consisting of 132 patients with no preoperative risk factors, early mortality was 1.5% (2/132). In group B, with 1 or more risk factors, early mortality amounted to 15% (15/100), (P less than 0.01). Subdividing group B into patients with one of the first three risk factors and patients with two or three of these risk factors, mortality was 12% (9/73) and 27% (6/22), respectively. Actuarially determined survival curves showed an 8-year survival rate of 84.2% for patients in group A and 59.6% for patients belonging to group B. Corrected for early mortality, however, the difference in late mortality is not significant. Analysis showed that early mortality was related to myocardial preservation: results for coronary perfusion and cardioplegic arrest were similar, but results were far less good when hypothermic ischaemic arrest was applied. Late results were less favourable in patients who had prior mitral valve disease not requiring mitral valve replacement at the time of AVR, or in those who developed mitral valve disease. The results allow the authors to conclude that AVR is a relatively safe procedure with a low operative mortality and few postoperative complications in patients with no 'risk factors'.