Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study

ObjectivesTo develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases.Materials and methodsA review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer.ResultsLimited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic.ConclusionsThe international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.     

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Background  The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Methods and Results  Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity. Conclusions  We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR. Supported in part by grants from the National Institutes of Health (R01-HL66034 and K-08-HL074290-01). Bethesda. Md. The radio-labeled microspheres were provided by DuPont Pharmaceuticals, North Billerica. Mass, and the ultrasound equipment was supplied by Philips. Andover, Mass. Dr Leong-Poi was the recipient of a Fellowship Training Grant from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada.     

Correlates of lung/heart ratio of thallium-201 in coronary artery disease

We studied 306 patients with chest pain (262 with coronary artery disease and 44 with no coronary artery disease) to determine which of 23 clinical, exercise, thallium, and angiographic variables best discriminate between patients with increased lung/heart ratios of thallium versus those with normal ratios. Normal lung/heart ratio values were defined using an additional 45 subjects with less than 1% probability of coronary artery disease. The number of diseased vessels was the best discriminator between patients with increased ratios versus those with normal ratios. Double product at peak exercise, number of segments with abnormal wall motion, patient gender, and duration of exercise were also significant discriminators. Using discriminant function analysis these variables could correctly identify 81% of cases with increased lung/heart ratios and 72% of cases with normal ratios. These results indicate that an increased lung/heart ratio of thallium reflects exercise-induced left ventricular dysfunction and affords a better understanding of why this thallium parameter is a powerful prognostic indicator in patients with chest pain.     

Inhibition and induction of rabbit liver microsomal cytochrome P-450 by pyridine

The effects of acute and chronic administration of pyridine (PY) on rabbit hepatic microsomal cytochrome P-450-catalyzed drug metabolism have been examined. PY inhibited cytochrome P-450-catalyzed drug metabolism in vitro and in vivo. Noncompetitive inhibition of microsomal drug metabolism was observed with inhibitory constant (Ki) values ranging between 2.0 and 6.0 mM. Acute PY administration, 100 mg/kg i.p., prolonged hexobarbital sleep time in rats 2.5-fold. Chronic administration of PY to rabbits resulted in increased hepatic microsomal cytochrome P-450 content, with induction of different form(s) exhibiting elevated catalytic activities toward PY, N-nitrosodimethylamine, alcohols and aniline. PY administration (100 mg/kg i.p. for 5 days) to rabbits increased hepatic microsomal cytochrome P-450 content over 2-fold relative to uninduced animals. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of PY-induced microsomes revealed protein bands of enhanced intensity occurring in the regions of P-450 LM3 and LM4. Both PY- and imidazole-induced microsomes were effective in the production of PY N-oxide, with Vmax values of 1.6 and 1.8 nmol/min/mg of protein, respectively. When rates were normalized for P-450 content, PY- and imidazole-induced microsomes produced 0.9 nmol of PY N-oxide/min/nmol of P-450, comparable to that obtained for PB-induced suspensions. N-nitrosodimethylamine N-demethylase activity was enhanced 2.5- and 6-fold relative to PB- and beta-naphthoflavone-induced microsomes, respectively. A single low KM value of 0.17 mM was obtained for N-nitrosodimethylamine N-demethylase activity in PY-induced microsomes; in contrast PB- and beta-naphthoflavone-induced microsomes yielded biphasic kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of right ventricular function using two-dimensional echocardiography

With the use of two-dimensional echocardiography (2DE), we analyzed apical and subcostal four-chamber views for evaluation of right ventricular (RV) function in 30 individuals as compared to RV ejection fraction (RVEF) obtained by radionuclide angiography. In addition to previously reported parameters of changes in areas and chords, a new simple measurement of tricuspid annular excursion was correlated with RVEF. A close correlation was noted between tricuspid annular plane systolic excursion (TAPSE) and RVEF (r = 0.92). The RV end-diastolic area (RVEDA) and percentage of systolic change in area in the apical four-chamber view also showed close correlation with RVEF (r = -0.76 and 0.81); however, the entire RV endocardium could only be traced in about half of our patients. The end-diastolic transverse chord length and the percentage of systolic change in chord length in the apical view showed a poor correlation with RVEF. The correlation between RVEF and both areas and chords measured in the subcostal view was poor. It is concluded that the measurement of TAPSE offers a simple echocardiographic parameter which reflects RVEF. This measurement is not dependent on either geometric assumptions or traceable endocardial edges. When the endocardial outlines could be traced, the apical four-chamber view was superior to the subcostal view in assessment of RV function.     

Quantitation of myocardial infarct size from thallium-201 images: validation of a new approach in an experimental model

A new computer-based method has been developed to quantitate myocardial infarct size from the size of the regional thallium-201 deficit. The operator outlines the left ventricular myocardial activity with an ellipse. The program then plots the background-corrected activities of the highest mean value in a 3 pixel myocardial band perpendicular to and within the ellipse. The approach uses a new interpolative background correction. To determine the accuracy of this approach in assessing regional thallium deficit size, acute myocardial infarction was produced in six dogs by 24 hour occlusion of the proximal left anterior descending coronary artery. Infarct size was assessed from planar thallium images of the dog heart in three views, each with the chest opened and closed and with the heart excised and placed in a cradle. Before removal of the heart, triphenyltetrazolium chloride was infused to delineate normal from infarct tissue. Transverse slices of left ventricle were made and thallium images of the slices acquired. Infarct size delineated by triphenyltetrazolium chloride staining was expressed as a percent of the total left ventricular slice surface area (planimetric infarct size). Infarct size from whole heart and left ventricular slice thallium images was expressed as a percent of the total length of the left ventricular perimeter (perimetric infarct size). This was determined from points below a certain percent of normalized peak thallium activity in the computer-generated thallium activity curve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of labetalol on left ventricular mass and function in hypertension--an assessment by serial echocardiography

We determined echocardiographic (M-mode) indices of left ventricular mass and function serially at 1-month intervals in 10 patients with uncomplicated mild or moderate essential hypertension, before and after adequate control of blood pressure with labetalol, a combined alpha- and beta-receptor blocking agent. Seven patients had pretreatment echocardiographic evidence of left ventricular hypertrophy with disproportionate septal thickness in 4. Systolic blood pressure in the untreated state correlated well (r = 0.96) with left ventricular mass but poorly (r = 0.30) with diastolic pressure. Following a satisfactory blood pressure reduction, achieved in all patients, left ventricular mass decreased from 240.5 +/- 71.1 g to 159.5 +/- 40.7 g (P less than 0.01), interventricular septal thickness from 1.33 +/- 0.3 cm to 0.92 +/- 0.25 cm (P less than 0.01) and posterior wall thickness from 1.03 +/- 0.23 cm to 0.93 +/- 0.23 cm (P less than 0.05). While the maximum changes in left ventricular mass were noted by the end of first month (P less than 0.01) with insignificant changes thereafter, the correlation of fall in blood pressure with change in left ventricular mass was significant only after 2 months of treatment (P less than 0.05). Indices of left ventricular function (end-diastolic volume, ejection fraction, fractional diameter shortening, left atrial dimension and posterior aortic wall motion) were normal before treatment and remained unchanged during 3 months of treatment. In this short-term study, labetalol reduced left ventricular hypertrophy (expressed as left ventricular mass and wall thickness) without altering left ventricular function indices in patients with uncomplicated essential hypertension. This has important implications in the treatment of hypertensive patients.     

Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease

There is little information concerning the prevalence and clinical correlates of increased pulmonary thallium-201 uptake during dipyridamole thallium-201 stress imaging. Accordingly, the clinical characteristics and quantitative thallium-201 findings were correlated with quantitative lung/heart thallium-201 ratio in 87 patients undergoing dipyridamole thallium-201 stress testing. Nineteen patients (22%) had an elevated ratio (greater than 0.51). These patients were more likely to have had an infarction, to be taking beta blockers, and have a lower rate-pressure product after dipyridamole administration than those with a normal ratio (p less than 0.03). An elevated ratio was associated with a greater likelihood of initial, redistribution and persistent defects, as well as left ventricular cavity dilatation on thallium-201 imaging (p less than 0.05). In addition, the number of myocardial segments demonstrating initial, redistribution and persistent defects was also greater in patients with increased ratios (p less than 0.03). Multivariate analysis demonstrated that the presence of redistribution and left ventricular cavity dilatation were the most significant correlates of lung/heart thallium-201 ratio. It is concluded that the prevalence of increased lung/heart thallium-201 ratio with dipyridamole thallium-201 stress imaging is similar to that seen with exercise stress imaging. As with exercise thallium-201 imaging, increased pulmonary thallium-201 uptake may be a marker of functionally more significant coronary artery disease.     

Clinical experience with low profile fixed wire balloon catheter system for percutaneous transluminal coronary angioplasty

Clinical records of the first 45 consecutive patients (66 lesions) in whom the Probe TM a balloon on the wire, was used for percutaneous transluminal coronary angioplasty have been reviewed. The aim of this analysis was to establish the efficacy and safety of this device. Majority of the lesions taken up were considered severe and difficult to cross. The probe was the 1st catheter used in 51 lesions (77%) and in 15 lesions (23%) it was used after other balloon catheters. In 88% (58/66) of lesions treated the Probe reduced the stenosis to less than 50% of the luminal diameter. Of the 45 patients treated 39 (87%) had a successful result. Of the 19 patients with multiple lesions 74% (14/19) had complete revascularisation and in 16% (3/29) had the most significant vessel dilated. Two patients (3%) required urgent coronary artery bypass surgery for acute occlusions. There was no hospital death. Of 50 probe devices used 5 (10%) malfunctioned: the balloon ruptured (at 5 Bars pressure) in 2 instances, balloon twisted causing "Volvulous" in 1 and balloon failed to deflate in 2 cases. The probe has significant advantages over other balloon systems for treating severe coronary lesions because of its low profile. It is however a delicate catheter system and prone to malfunction if not handled with care. Our results show that it is an excellent system for opening difficult and tight coronary lesions.