Characteristics of non-melanoma skin cancers of the cutaneous perioral and vermilion lip treated by Mohs micrographic surgery.

BACKGROUND: The lip and surrounding perioral region are susceptible to non-melanoma skin cancer, but the distribution of basal cell and squamous cell carcinoma on the cutaneous and vermilion lips has not been fully elucidated. OBJECTIVE: To investigate the distribution of cutaneous and vermilion lip non-melanoma skin cancer and to better describe risk factors, anatomic location, treatment characteristics and oncologic outcomes. METHODS: A retrospective comparative case series of patients undergoing Mohs micrographic surgery (MMS) at a single academic centre for lip and perioral basal cell and squamous cell carcinoma was performed over a 5-year period. Demographics, medical comorbidities, surgical characteristics and recurrence status were extracted. RESULTS: Forty-five vermilion and 116 cutaneous lip cancers were identified. Basal cell carcinoma (BCC) was more common in the cutaneous perioral region, while squamous cell carcinoma (SCC) was more common on the vermilion lip (P < 0.001). BCCs were more common on the upper vermilion lip and SCCs were more common on the lower vermilion lip (P < 0.001). Within the cutaneous perioral region, both BCCs and SCCs were more common on the upper perioral surface (P = 0.002). Male gender was associated with lower lip SCC (P = 0.015). Smoking, immunosuppression, anticoagulant use and hydrochlorothiazide use were not associated with cancer type or location. Recurrences were rare, but more common in vermilion lip cancers (6.6%) compared to perioral cutaneous cancers (0.8%). Outcomes for all groups were similar; BCCs of the vermilion lip had significantly greater mean MMS stages (P < 0.001) as did SCCs (P = 0.05). CONCLUSION: Basal cell carcinoma is more commonly encountered on the cutaneous lip, whereas SCC is more common on the vermilion lip. Within the vermilion lip, BCC favours the upper lip, while SCC favours the lower lip. Within the cutaneous perioral region, both BCC and SCC favour the upper cutaneous tissue. Early stage lip cancers are curable by Mohs micrographic surgery with rare recurrences.

A review of non-invasive imaging in extramammary Paget's disease.

Extramammary Paget's Disease (EMPD) is a rare intraepithelial adenocarcinoma that classically manifests with pruritic, erythematous and scaling plaques. The clinical picture frequently mimics inflammatory or infectious conditions and is thus commonly misdiagnosed. The assessment of tumour margins is equally challenging as tumours have a propensity to spread beyond clinically visible boundaries. Appropriate non-invasive diagnostic tools can assist in the early detection, diagnosis and management of EMPD. This paper will review the literature on non-invasive imaging modalities used in EMPD. Articles from the PubMed database were selected based on relevance to the topic of this review. Articles that were not specific to EMPD and non-invasive imaging were excluded. Search strategy is further described in the methods section below. Eighteen articles were selected for this review: six PET/CT, five reflectance confocal microscopy (RCM), two photodynamic diagnosis (PDD), two dermoscopy, two MRI and one optical coherence tomography (OCT) paper(s). Dermoscopy, PDD, RCM and OCT can help to distinguish malignant conditions, including EMPD, from benign conditions. RCM and OCT can identify atypical cells in real-time, and have the potential to improve the accuracy of surgical margins intraoperatively and overall management. Distinctive confocal characteristics of EMPD have been described using RCM. The sensitivity and specificity of these findings require additional validation. Radiographic techniques also play a central role in the diagnosis of EMPD and assessment of disease spread. PET/CT and MRI can detect primary disease, nodal and distant metastases, with superior delineation of disease spread on MRI. Limitations of PET/CT are mainly related to primary tumour thickness, and size and FDG-avidity of nodal and distant metastases. Limitations of MRI include the fact that few studies have examined its use in EMPD; additional research is warranted. Randomized controlled trials and large prospective studies evaluating the use of non-invasive imaging in EMPD are needed.

Rectification of the background potassium current: a determinant of rotor dynamics in ventricular fibrillation.

Ventricular fibrillation (VF) is the leading cause of sudden cardiac death. Yet, the mechanisms of VF remain elusive. Pixel-by-pixel spectral analysis of optical signals was carried out in video imaging experiments using a potentiometric dye in the Langendorff-perfused guinea pig heart. Dominant frequencies (peak with maximal power) were distributed throughout the ventricles in clearly demarcated domains. The fastest domain (25 to 32 Hz) was always on the anterior left ventricular (LV) wall and was shown to result from persistent rotor activity. Intermittent block and breakage of wavefronts at specific locations in the periphery of such rotors were responsible for the domain organization. Patch-clamping of ventricular myocytes from the LV and the right ventricle (RV) demonstrated an LV-to-RV drop in the amplitude of the outward component of the background rectifier current (I(B)). Computer simulations suggested that rotor stability in LV resulted from relatively small rectification of I(B) (presumably I(K1)), whereas instability, termination, and wavebreaks in RV were a consequence of strong rectification. This study provides new evidence in the isolated guinea pig heart that a persistent high-frequency rotor in the LV maintains VF, and that spatially distributed gradients in I(K1) density represent a robust ionic mechanism for rotor stabilization and wavefront fragmentation.

Mechanisms underlying ventricular tachycardia and its transition to ventricular fibrillation in the structurally normal heart.

Reentrant ventricular tachycardia (VT) is the most common sustained arrhythmia leading to ventricular fibrillation (VF). However, despite more than a century of research, the mechanism(s) of the conversion from reentrant VT to VF have not been elucidated. Based on their different electrocardiographic appearance, reentrant VT and VF have traditionally been thought of as resulting from two widely different mechanisms. Whereas VT is seen as a rapid but well organized process whereby the excitation wave rotates about a single well-defined circuit, fibrillation has been described as turbulent cardiac electrical activity, resulting from the random and aperiodic propagation of multiple independent wavelets throughout the cardiac muscle. Recently, the application of concepts derived from the theory of non-linear dynamics to the problem of wave propagation in the heart and the advent of modern high-resolution mapping techniques, have led some investigators to view VT and VF in terms of a single mechanism, whereby the self-organization of electrical waves forms 'rotors' that give rise to rapidly rotating spiral waves and results in either VT or VF, depending on the frequency of rotation and on the interaction of wave fronts with the cardiac muscle. As such, monomorphic VT is thought to result from a stationary rotor, whose frequency of rotation is within a range that allows 1:1 excitation of both ventricles. On the other hand, VF is thought to result from either a single rapidly drifting rotor, or a stationary rotor whose frequency of excitation is exceedingly high, thus resulting in multiple areas of intermittent block and giving rise to complex patterns of propagation with both deterministic and stochastic components. This article reviews the prevailing theories for the maintenance of VF, and discusses recently proposed mechanisms underlying transitions between VT and VF.

Left-to-right gradient of atrial frequencies during acute atrial fibrillation in the isolated sheep heart.

BACKGROUND: Recent studies demonstrated spatiotemporal organization in atrial fibrillation (AF). We hypothesized that waves emanating from sources in the left atrium (LA) undergo fragmentation, resulting in left-to-right frequency gradient. Our objective was to characterize impulse propagation across Bachmann's bundle (BB) and the inferoposterior pathway (IPP) during AF. METHODS AND RESULTS: In 13 Langendorff-perfused sheep hearts, AF was induced in the presence of acetylcholine (ACh). Fast Fourier transform of optical and bipolar electrode recordings was performed. Frequency-dependent changes in the left-to-right dominant frequency (DF) gradient were studied by perfusing D600 (2 micromol/L) and by increasing ACh concentration from 0.2 to 0.5 micromol/L. BB and IPP were subsequently ablated. At baseline, a left-to-right decrease in DFs occurred along BB and IPP, resulting in an LA-right atrium (RA) frequency gradient of 5.7+/-1.4 HZ: Left-to-right impulse propagation was present in 81+/-5% and 80+/-10% of cases along BB and IPP, respectively. D600 decreased the highest LA frequency from 19.7+/-4.4 to 16.2+/-3.9 Hz (P<0.01) and raised RA DF from 8.6+/-2.0 to 10.7+/-1.8 Hz (P<0.05). An increase in ACh concentration increased the LA-RA frequency gradient from 4.9+/-1.8 to 8.9+/-1.8 Hz (P<0.05). Ablation of BB and IPP decreased RA DF from 10.9+/-1.2 to 9.0+/-1.5 Hz (P<0.01) without affecting LA DF (16.8+/-1.5 versus 16.9+/-1.8 Hz, P=NS). CONCLUSIONS: Left-to-right impulse propagation and frequency-dependent changes in the LA-RA frequency gradient during AF strongly support the hypothesis that this arrhythmia is the result of high-frequency periodic sources in the LA, with fibrillatory conduction away from such sources.

A mechanism of transition from ventricular fibrillation to tachycardia : effect of calcium channel blockade on the dynamics of rotating waves.

Abbreviation of the action potential duration and/or effective refractory period (ERP) is thought to decrease the cycle length of reentrant arrhythmias. Verapamil, however, paradoxically converts ventricular fibrillation (VF) to ventricular tachycardia (VT), despite reducing the ERP. This mechanism remains unclear. We hypothesize that the size and the dynamics of the core of rotating waves, in addition to the ERP, influence the arrhythmia manifestation (ie, VF or VT). The objectives of this study were (1) to demonstrate functional reentry as a mechanism of VF and VT in the isolated Langendorff-perfused rabbit heart in the absence of an electromechanical uncoupler and (2) to elucidate the mechanism of verapamil-induced conversion of VF to VT. We used high-resolution video imaging with a fluorescent dye, ECG, frequency and 2-dimensional phase analysis, and computer simulations. Activation patterns in 10 hearts were studied during control, verapamil perfusion (2x10(-6) mol/L), and washout. The dominant frequency of VF decreased from 16.2+/-0.7 to 13.5+/-0.6 Hz at 20 minutes of verapamil perfusion (P<0.007). Concomitantly, phase analysis revealed that wavefront fragmentation was reduced, as demonstrated by a 3-fold reduction in the density of phase singularities (PSs) on the ventricular epicardial surface (PS density: control, 1.04+/-0.12 PSs/cm(2); verapamil, 0.32+/-0.06 PSs/cm(2) [P=0.0008]). On washout, the dominant frequency and the PS density increased, and the arrhythmia reverted to VF. The core area of transiently appearing rotors significantly increased during verapamil perfusion (control, 4.5+/-0.6 mm(2); verapamil, 9.2+/-0.5 mm(2) [P=0.0002]). In computer simulations, blockade of slow inward current also caused an increase in the core size. Rotating waves underlie VF and VT in the isolated rabbit heart. Verapamil-induced VF-to-VT conversion is most likely due to a reduction in the frequency of rotors and a decrease in wavefront fragmentation that lessens fibrillatory propagation away from the rotor.

Characterization of conduction in the ventricles of normal and heterozygous Cx43 knockout mice using optical mapping.

INTRODUCTION: Gap junction channels are important determinants of conduction in the heart and may play a central role in the development of lethal cardiac arrhythmias. The recent development of a Cx43-deficient mouse has raised fundamental questions about the role of specific connexin isoforms in intercellular communication in the heart. Although a homozygous null mutation of the Cx43 gene (Cx43-/-) is lethal, the heterozygous (Cx43+/-) animals survive to adulthood. Reports on the cardiac electrophysiologic phenotype of the Cx43+/- mice are contradictory. Thus, the effects of a null mutation of a single Cx43 allele require reevaluation. METHODS AND RESULTS: High-resolution video mapping techniques were used to study propagation in hearts from Cx43+/- and littermate control (Cx43+/+) mice. Local conduction velocities (CVs) and conduction patterns were quantitatively measured by determining conduction vectors. We undertook the characterization of ECG parameters and epicardial CVs of normal and Cx43+/- mouse hearts. ECG measurements obtained from 12 Cx43+/+ and 6 Cx43+/- age matched mice did not show differences in any parameter, including QRS duration (14.5 +/- 0.9 and 15.7 +/- 2.3 msec for Cx43+/+ and Cx43+/-, respectively). In addition, using a sensitive method of detecting changes in local CV, video images of epicardial wave propagation revealed similar activation patterns and velocities in both groups of mice. CONCLUSION: A sensitive method that accurately measures local CVs throughout the ventricles revealed no changes in Cx43+/- mice, which is consistent with the demonstration that ECG parameter values in the heterozygous mice are the same as those in wild-type mice.

Reentry and fibrillation in the mouse heart. A challenge to the critical mass hypothesis.

The idea that fibrillation is only possible in hearts exceeding a critical size was introduced by W. Garrey >80 years ago and has since been generally accepted. In ventricular tissue, this critical size was originally estimated to be 400 mm(2). Recent estimates suggest that the critical size required for sustained reentry is approximately 100 to 200 mm(2), whereas 6 times this area is required for ventricular fibrillation. According to these estimates, fibrillation is not possible in the mouse heart, where the ventricular surface area is approximately 100 mm(2). To test whether sustained ventricular fibrillation could be induced in such an area, we used a high-speed video imaging system and a voltage-sensitive dye to quantify electrical activity on the epicardial surface of the Langendorff-perfused adult mouse heart. In 6 hearts, measurements during ventricular pacing at a basic cycle length (BCL) of 120 ms yielded maximum and minimum conduction velocities (CV(max) and CV(min)) of 0.63+/-0.04 and 0.38+/-0.02 mm/ms, respectively. At a BCL of 80 ms, CV(max) and CV(min) changed to 0.55+/-0.03 and 0. 34+/-0.02 mm/ms. Action potential durations (APDs), measured at 70% repolarization at those pacing frequencies were found to be 44.5+/-2. 9 and 40.4+/-2.6 ms, respectively. The wavelengths (CVxAPD) were calculated to be 28.6+/-3.4 mm in the CV(max) direction and 16.8+/-1. 5 mm in the CV(min) direction at BCL 120 ms. Wavelengths were significantly reduced (P<0.05) at BCL 80 ms (CV(max), 22.2+/-1.8 mm; CV(min), 13.7+/-0.9 mm). In 5 hearts, stationary vortex-like reentry organized by single rotors (4 of 5 hearts) or by pairs of rotors (1 of 5 hearts) was induced by burst pacing. In the ECG, the activity manifested as sustained monomorphic tachycardia. Detailed analysis showed that the local CVs were reduced in the vicinity of the rotor center, which allowed the reentry to take place within a smaller area than was calculated from wavelength measurements during pacing. In 4 of 7 hearts, burst pacing resulted in a polymorphic ECG pattern indistinguishable from ventricular fibrillation. These data challenge the critical mass hypothesis by demonstrating that ventricular tissue with an area as small as 100 mm(2) is capable of undergoing sustained fibrillatory activity.

The morphology and physiology of a "mini-ommatidium" in the median optic nerve of Limulus polyphemus.

Examination of the Limulus median optic nerve with low-magnification light microscopy allows clear visualization of an ultraviolet-sensitive mini-ommatidium enshrouded by pigment cells, glial cells, and guanophores. Serial 1-micron sections of median optic nerves containing mini-ommatidia revealed the presence of a single, heavily pigmented photoreceptor (retinular) cell and a single, unpigmented arhabdomeric cell. Computer-assisted serial reconstructions from 1-micron sections confirmed the presence of two cells, each bearing a nucleus, and two axons leaving the mini-ommatidium. The retinular cell is morphologically similar to retinular cells from the median and lateral eyes. Its rhabdomere appears to be a continuous sheet of microvilli with much infolding. The structure of the arhabdomeric cell is nearly identical to those found in the median ocellus. As in other photoreceptors in Limulus, the retinular cell of the mini-ommatidium is innervated by efferent fibers from the brain. Each mini-ommatidium generates a single train of nerve impulses in response to light, presumably from the arhabdomeric cell. Measurement of the spectral sensitivity of the mini-ommatidium based upon a constant-response criterion indicated that the retinular cell is maximally sensitive to near ultraviolet light with lambda max = 380 nm. Comparison of intensity-response functions revealed that those of the mini-ommatidium are significantly steeper than those of the ocellus almost certainly as the result of neural processing in the ocellus which is absent in the mini-ommatidium.