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.     

Binocular contrast detection with unequal monocular illuminance

Binocular summation was measured in eight normal subjects by means of psychometric functions for contrast detection. An average 47% increase in binocular over monocular performance was obtained. Our data agreed with the simple summation model of Signal Detection Theory (Legge, 1984). Binocular psychometric functions were also measured when the sensitivity of one eye was decreased by means of a 1.0 neutral density (ND) filter. We found that binocular detectability in this case was reduced to below that of the better eye. This binocular inhibition was seen in all subjects. The slope of a contrast detection function gives a measure of the rate of change in detectability with contrast. If the slopes of two functions are equal, then the difference in detectability between these functions remains constant for all the contrast values used. When the slopes of the measured functions were analysed, no significant differences were found under any of the testing conditions. This indicates that the magnitude of summation (with equal monocular sensitivities), and of inhibition (with unequal monocular sensitivities), remains constant across the range of stimulus contrasts. The clinical implications of binocular inhibition are discussed.     

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.     

Respiratory syncytial virus

RSV is now understood to be the most significant viral respiratory pathogen of infants and is capable of causing both bronchiolitis and pneumonia. It is a particular risk to hospitalized infants as the virus is easily spread through close contact. The most vulnerable infants are those who suffer with either congenital heart disease or bronchopulmonary dysplasia who easily fall prey to pulmonary complications of infection. Strict environmental control and the use of protective clothing and eyewear should be implemented to decrease the nosocomial spread of RSV. Available diagnostic studies include viral isolation, fluorescent antibody stains, and enzyme immunoassays. Treatment of the disease is usually supportive but hospitalized patients frequently benefit from aerosolized ribavirin therapy. Hopefully, current vaccine trials will be successful and this pathogen will not only be treatable but will also be preventable.     

Instrumentation and patient characteristics that influence postoperative haemorrhage rates following tonsil and adenoid surgery

Objectives: To investigate the effect of the type instrumentation used and the age and gender characteristics of patients on postoperative haemorrhage rates following tonsil and adenoid surgery. Design: A retrospective analysis of 13 593 procedures was performed from The Patient Episode Database for Wales between 1 January 1999 and 31 March 2004. Setting: National health policy changes created four periods of different instrument usage (reusable, single‐use with diathermy, single‐use alone, specified single‐use with diathermy). These and the age and gender distribution of the patients were examined against four categories of postoperative haemorrhage. Main outcome measures: Postoperative haemorrhage rates were expressed as the number of complications per operations performed. Primary postoperative haemorrhage that occurred during the initial admission either required a return to theatre [R1] or was managed conservatively [N1]; secondary postoperative haemorrhage that required a return to hospital either returned to theatre [R2] or was managed conservatively [N2], were compared. Results: Primary haemorrhage with return to theatre doubled, from the baseline rate with reusable instruments, from 0.6% (CI 0.5–0.8) to 1.2% (CI 0.7–1.9) when single‐use instruments were introduced and remained high at 1.4% (CI 0.9–2.1) after the withdrawal of single‐use diathermy. This haemorrhage rate returned to the baseline rate (0.6% CI 0.3–1.0) when specified single‐use instruments were introduced. None of the other haemorrhage rates changed significantly throughout the four observation periods. Adenotonsillectomy and tonsillectomy patients have different age and gender patterns. In a univariate analysis, males over the age of 12 years were twice as likely to have haemorrhage with return to theatre than girls of the same age, 3.8% (CI 3.0–4.7) versus 1.7% (CI 1.4–2.1). Conclusions: A significant rise in serious postoperative primary haemorrhage but not secondary haemorrhage was seen following the initial introduction of single‐use instruments that reverted to baseline with the introduction of specified single‐use instruments. Diathermy does not appear to have affected the haemorrhage rates. There is a distinct age and gender pattern for tonsil and adenoid surgery and risk of postoperative haemorrhage. The use of arbitrary divisions of age may be misleading in studies that examine post‐tonsillectomy haemorrhage.     

The hereditary spectrum of pancreatic cancer: the Edmonton experience.

OBJECTIVE: Pancreatic cancer is known to aggregate in some families and has been associated with a wide variety of cancer syndromes. The authors describe their experience with pancreatic cancer and the range of associated cancer syndromes. METHODS: The charts of all patients seen for concern of a hereditary cancer syndrome in the Cancer Genetics Clinic at the University of Alberta between 1995 and 2002 were reviewed. RESULTS: Forty families reported a personal or family history of pancreatic cancer in the context of a possible hereditary cancer syndrome. Three additional families reported a history of pancreatitis. Twenty-four (56%) of those families were suspected of having a hereditary breast and ovarian cancer syndrome. A further seven (16%) were suspected of having hereditary nonpolyposis colon cancer. Only three (7%) were believed to be at risk for a site-specific pancreatic cancer syndrome. Another three (7%) were suspicious for hereditary pancreatitis. The remaining family histories were suggestive of Li-Fraumeni syndrome, von Hippel-Lindau syndrome or a nonspecific cancer predisposition. CONCLUSIONS: With such a wide variety of hereditary cancer syndromes associated with pancreatic cancer, an accurate assessment of the family history is essential to determine the most appropriate cancer screening for at-risk family members and to guide any molecular testing that may be offered.     

Peripheral nerve repair by means of a flexible biodegradable glass fibre wrap: a comparison with microsurgical epineurial repair.

In this study, a new technique for the repair of divided peripheral nerves using a flexible controlled-release glass wrap is described and its successful use is reported. Corglaes is a biodegradable and biocompatible glass which, when used as a solid glass tube form as a nerve conduit, allows nerve regeneration. It is now produced as a flexible, porous wrap (CRG-wrap). In this study, the CRG-wrap was used to repair divided median nerves in the upper forelimb of sheep. The wrap was secured in place around the divided nerve ends using fibrin glue or 6/0 polyglactin sutures. Microsurgical epineurial suturing was used to repair the same injury in another group. Twelve sheep were used in each group. A control group of sheep, on which no operations had been carried out, was also examined. The outcome of each repair was assessed at 7 months by measuring transcutaneous stimulated jitter (TSJ), maximum conduction velocity (CVmax), wet muscle mass and morphometric measurements. Testing was carried out on the limb that had been operated upon and the normal contralateral forelimb. The ratio of the measurements taken in the operated and the normal limb (the right and left forelimbs in the control group) was used when carrying out statistical analyses on the results. The mean and variance of the ratios of each of the measured variables in the three repair groups were similar suggesting that nerve regeneration had occurred to a similar degree in all the repair groups (analyses were carried out using one-way ANOVA and Scheffé's test, with statistical significance assumed at p<0.05). The repair of peripheral nerves using the CRG-wrap is easy to learn, quicker and cheaper than microsurgical epineurial suturing, and can be carried out by any surgeon with basic surgical skills. It was concluded that CRG-wrap is a useful alternative to microsurgical epineurial suturing for the repair of peripheral nerves.     

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.     

The effect of parathyroidectomy on bone mineral density in primary hyperparathyroidism.

Bone mineral density was studied before, and at one year after successful parathyroidectomy in six postmenopausal, three premenopausal females and one male with primary hyperparathyroidism. Dual photon absorptiometry was used to measure bone mineral density at the lumbar spine in all subjects, and at three areas of the hip in eight of the subjects. There was no significant change in bone mineral density at the lumbar spine after one year. Bone mineral density increased 7.4% at the femoral neck from 0.822 (SEM 0.053) g/cm2 to 0.895 (0.04) g/cm2; p less than 0.01, 8.7% at Wards triangle from 0.681 (0.065) g/cm2 to 0.745 (0.07) g/cm2; p less than 0.02. A 5.6% increase at the trochanteric region from 0.785 (0.053) g/cm2 to 0.803 (0.053) g/cm2 was not significant. These results indicate that significant increases occur in bone mineral density at the hip, but not at the lumbar spine at one year after parathyroidectomy in patients with primary hyperparathyroidism.     

Is there a role for laparoscopic appendectomy in pediatric surgery?

Although laparoscopic procedures are currently in vogue in general surgery, the role of this approach in children has not been prospectively evaluated in the United States using the new instrumentation now available to us. To assess the value of laparoscopic appendectomy (LA) in childhood, we prospectively compared 14 LAs with 50 open appendectomies (OA) over 6 months in a single children's hospital. Antibiotic usage was at the discretion of the surgeon regardless of the procedure performed and was not different between groups. LA was performed under the direction of a single laparoscopy-trained surgeon and patient selection was based on parental consent. A three-puncture LA technique was used; children from this group were allowed to return to full activities as soon as they were comfortable. There were no significant differences between groups for severity of disease, age, weight, hospital cost, or complications. The types of complications that developed were comparable in both groups. The percent of complicated appendicitis (gangrene or perforation) was 32% in the OA group and 36% in the LA group. Patients in the LA group spent significantly fewer days in the hospital and returned to unrestricted activities (school, athletics, etc) faster than patients in the OA group. LA is approximately $1,000 more expensive than OA, the differences being easily explainable by the cost of the disposable supplies necessary for the procedure (laser fibers, trocars, etc), but because of the shorter hospital stay in the LA group the mean total cost for each group was comparable. These data suggest that although there appears to be no cost advantage, LA shortens the hospital stay and allows children to return to unrestricted activity sooner than OA.(ABSTRACT TRUNCATED AT 250 WORDS)