Oncological and functional outcomes after repeat transoral laser microsurgery for the treatment of recurrent early glottic cancer.

BACKGROUND: Transoral laser microsurgery for glottic squamous cell carcinoma is the standard of care at many institutions. Repeat transoral laser microsurgery for recurrence may avoid the need for radiotherapy and total laryngectomy. This study aimed to identify oncological and functional outcomes in a cohort of patients who had undergone repeat transoral laser microsurgery procedures. METHOD: A retrospective review of prospectively collected data of patients treated with transoral laser microsurgery for carcinoma in situ or tumour stages T1 or T2 glottic cancer, from 2003 to 2018. RESULTS: Twenty patients were identified. Additional treatment was not needed in 45 per cent of patients. The five-year overall survival rate was 90 per cent. The disease-specific survival rate was 100 per cent. The laryngeal preservation rate was 85 per cent. There was improvement in mean Voice Handicap Index-10 scores following repeat transoral laser microsurgery treatment, when comparing the pre- and post-operative periods (mean scores = 15.5 vs 11.5, p = 0.373). CONCLUSION: Repeat transoral laser microsurgery can be an oncologically safe alternative to other salvage therapies for glottic squamous cell carcinoma recurrence, without sacrificing functional outcomes.

Squamous cell carcinoma: pain as a clue to increased tumour diameter, increased invasion depth, the grade of differentiation, acantholysis and perineural invasion.

BACKGROUND: Pain may be associated with actinic keratosis (AK), intraepidermal carcinoma (IEC) and invasive squamous cell carcinoma (SCC), which may all display high-risk features. AIM: To examine variation in pain frequency associated with these three conditions, and assess their invasive SCC surface diameter, invasion depth, grade of differentiation, presence of acantholysis and perineural invasion (PNI). METHODS: Pain was prospectively recorded for consecutive cases of AK, IEC and SCC from three institutions in Australia during the period 2016-2018. RESULTS: Pain with palpation was recorded with 15.8% of AK (n = 30/190), 15.1% of IEC (n = 345/299) and 29.0% invasive SCC (n = 247/853). Pain without palpation was respectively 1.1% (2/190), 4.0% (12/299) and 6.7% (57/853). Invasive SCC with increased surface diameters and deeper invasion recorded increased pain frequency. Pain did not vary significantly by the grade of differentiation in males. In females, well-differentiated SCC recorded more pain (45.4%; n = 473) than poorly differentiated SCC (9.1%; n = 11). Acantholytic SCC recorded more pain 48.7% (n = 29) than nonacantholytic SCC 35.2% (n = 824). Three out of five cases of PNI recorded pain. Pain intensity was not recorded, which was a limitation. CONCLUSION: Pain presence increases from AK to invasive SCC. Pain was more frequent in invasive SCC with increased surface diameter, deeper invasion, acantholysis and PNI. Pain frequency did not vary between the grades of differentiation in males. In females, pain was less frequent in poorly differentiated than in well-differentiated SCC.

Invasive squamous cell carcinoma: comparison of differentiation grade and tumour depth by anatomical site in 1666 tumours.

BACKGROUND: Invasive squamous cell carcinomas (SCCs) presents with different grades of differentiation and depths of invasion. AIM: To compare the grade of differentiation, tumour diameter and tumour depth by anatomical site in invasive SCC. METHODS: Retrospective clinical and histopathological data on consecutive cases of SCC came from a clinic in Sydney, Australia were assessed. A multinomial logistic regression model was applied to compare grades of differentiation by age, sex, anatomical sites, and histological tumour maximum diameter and depth. RESULTS: In total, 1666 SCCs were identified, including 82.1% (n = 1367) well-differentiated, 13.3% (n = 222), moderately differentiated and 4.6% (n = 77) poorly differentiated SCCs. Patients with poorly differentiated tumours were more likely to be older and male (both P < 0.001). The most common site for poor differentiation was the scalp in men (n = 12; 15.6%) and the cheek or chin in women (n = 7; 9.1%). In the multivariate model, compared with well-differentiated SCC, older age was significantly associated with poorly and moderately differentiated SCC (P < 0.01 and P = 0.02, respectively). Larger tumour diameters were related to poor differentiation (P = 0.03). Ear, forehead and chest sites had increased tumour depth and poor differentiation. CONCLUSIONS: This study found increased rates of poorly differentiated SCC on the forehead and cheek for both sexes, while men displayed increased rates of poorly differentiated SCC on the bald scalp and the ears. Tumour diameter and depth increased as tumours varied from well-differentiated to moderately differentiated and from moderately differentiated to poorly differentiated. An increase in depth and increased prevalence of poorly differentiated tumours were found on the ears for men and on various facial sites for both sexes.

Acantholytic invasive squamous cell carcinoma: tumor diameter, invasion depth, grade of differentiation, surgical margins, perineural invasion, recurrence and death rate.

BACKGROUND: Squamous cell carcinoma (SCC) may present with or without the feature of acantholysis. METHODS: Investigate invasive acantholytic SCC by microscopic maximum tumor surface diameter, depth of invasion, grade of differentiation, perineural invasion (PNI) and percentage of acantholysis. Assess recurrence following excision. RESULTS: A total of 1658 consecutive invasive SCC cases were examined, comprising 4.9% acantholytic SCC. Median tumor microscopic maximum diameter was 8 mm for acantholytic SCC and 7.3 mm for non-acantholytic SCC. Median tumor invasion depth was 1.0 mm for acantholytic SCC and 1.5 mm for non-acantholytic SCC. Well, moderate and poor differentiation were not significantly different between acantholytic SCC and non-acantholytic SCC. One PNI case was found in 82 acantholytic SCC cases. A total of 77 acantholytic SCC cases were followed up over a median 25 months finding histologic proven recurrence at three acantholytic SCC excision sites. CONCLUSIONS: Acantholytic SCC were more likely to be located on head sites with less median depth than non-acantholytic SCC. Increasing percentage of acantholysis within acantholytic SCC was not associated with a shift towards poor differentiation. Histologic margins of 1.2 mm may adequately excise small acantholytic SCC. No recorded deaths, low PNI and low recurrence rates suggests acantholytic SCC is low-risk.

The clinical and dermoscopic features of invasive cutaneous squamous cell carcinoma depend on the histopathological grade of differentiation.

BACKGROUND: Little is known about the variability of the dermoscopic criteria of squamous cell carcinoma (SCC) according to the histopathological differentiation grade. OBJECTIVES: To evaluate whether specific dermoscopic criteria can predict the diagnosis of poorly differentiated SCC compared with well- and moderately differentiated SCC. METHODS: Clinical and dermoscopic images of SCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves. RESULTS: Of 143 SCCs included, 48 (33·5%) were well differentiated, 45 (31·5%) were moderately differentiated and 50 (35·0%) were poorly differentiated. Flat tumours had a fourfold increased probability of being poorly differentiated. Dermoscopically, the presence of a predominantly red colour posed a 13-fold possibility of poor differentiation, whereas a predominantly white and white-yellow colour decreased the odds of poorly differentiated SCC by 97% each. The presence of vessels in more than 50% of the tumour's surface, a diffuse distribution of vessels and bleeding were significantly associated with poor differentiation, while scale/keratin was a potent predictor of well- or moderately differentiated tumours. CONCLUSIONS: Dermoscopy may be regarded as a reliable preoperative tool to distinguish poorly from well- and moderately differentiated SCC. Given that poor differentiation of SCC represents an independent risk factor for recurrence, metastasis and disease-specific death, identifying poorly differentiated tumours in vivo may enhance their appropriate management.

Toxicological assessment of kretek cigarettes Part 4: mechanistic investigations, smoke chemistry and in vitro toxicity.

The smoke chemistry and in vitro toxicity of mainstream smoke (MS) was investigated in American-blended cigarettes with or without the addition of 2.5%, 5% or 10% eugenol to the tobacco and in Indonesian-blended cigarettes with and without the addition of cloves, cloves extracted with hot ethanol, and extracted cloves replenished with eugenol or clove oil. The addition of eugenol reduced the concentration of nearly all toxicants measured in MS as well as the in vitro cytotoxicity of the gas/vapor phase. Reductions were also seen in bacterial mutagenicity of the total particulate matter (TPM) assessed by the Ames Assay. The addition of extracted cloves led to increases and decreases of toxicant concentrations in MS. Replenishment with eugenol or clove oil decreased the toxicant concentrations; with most smoke constituent concentrations reduced below the concentration found in tobacco-only cigarettes. Cytotoxicity of the TPM was not affected by the clove preparations. However, GVP cytotoxicity was reduced (untreated cloves showing the highest reductions). Mutagenicity of TPM was decreased by the clove preparations. Mechanisms for the reductions, (up to 40%), are most likely due to dilution effects by eugenol, changed burning characteristics of the tobacco, and free radical scavenging by eugenol.

The economic burden of schizophrenia in Canada in 2004.

OBJECTIVE: To estimate the financial burden of schizophrenia in Canada in 2004. METHODS: A prevalence-based cost-of-illness (COI) approach was used. The primary sources of information for the study included a review of the published literature, a review of published reports and documents, secondary analysis of administrative datasets, and information collected directly from various federal and provincial government programs and services. The literature review included publications up to April 2005 reported in MedLine, EMBASE and PsychINFO. Where specific information from a province was not available, the method of mean substitution from other provinces was used. Costs incurred by various levels/departments of government were separated into healthcare and non-healthcare costs. Also included in the analysis was the value of lost productivity for premature mortality and morbidity associated with schizophrenia. Sensitivity analysis was used to test major cost assumptions used in the analysis. Where possible, all resource utilization estimates for the financial burden of schizophrenia were obtained for 2004 and are expressed in 2004 Canadian dollars (CAN dollars). RESULTS: The estimated number of persons with schizophrenia in Canada in 2004 was 234 305 (95% CI, 136 201-333 402). The direct healthcare and non-healthcare costs were estimated to be 2.02 billion CAN dollars in 2004. There were 374 deaths attributed to schizophrenia. This combined with the high unemployment rate due to schizophrenia resulted in an additional productivity morbidity and mortality loss estimate of 4.83 billion CAN dollars, for a total cost estimate in 2004 of 6.85 billion CAN dollars. By far the largest component of the total cost estimate was for productivity losses associated with morbidity in schizophrenia (70% of total costs) and the results showed that total cost estimates were most sensitive to alternative assumptions regarding the additional unemployment due to schizophrenia in Canada. CONCLUSIONS: Despite significant improvements in the past decade in pharmacotherapy, programs and services available for patients with schizophrenia, the economic burden of schizophrenia in Canada remains high. The most significant factor affecting the cost of schizophrenia in Canada is lost productivity due to morbidity. Programs targeted at improving patient symptoms and functioning to increase workforce participation has the potential to make a significant contribution in reducing the cost of this severe mental illness in Canada.

Health-related quality-of-life measure enhances acute treatment response prediction in depressed inpatients.

BACKGROUND: Many nonbiological variables are reported to predict treatment response for major depression; however, there is little agreement about which variables are most predictive. METHOD: Inpatient subjects (N = 59) diagnosed with current DSM-IV major depressive disorder completed weekly depressive symptom ratings with the Hamilton Rating Scale for Depression (HAM-D-17) and Beck Depression Inventory (BDI), and weekly health-related quality-of-life (HRQL) ratings with the Quality of Well-Being Scale (QWB). Acute responders were identified by a 50% decrease in HAM-D-17 score from baseline within 4 weeks of medication treatment. Predictor variables were initially chosen from a literature review and then tested for their association with acute treatment response. RESULTS: An initial predictive model including age at first depression, admission BDI score, and melancholia predicted acute treatment response with 69% accuracy and was designated as the benchmark model. Adding the admission QWB index score to the benchmark model did not improve the prediction rate; however, adding the admission QWB subscales for physical and social activity to the benchmark model significantly improved acute treatment response prediction to 86% accuracy (p = .001). CONCLUSION: In addition to being designed for use in cost-effectiveness analyses, the QWB subscales appear to be useful HRQL variables for predicting acute inpatient depression treatment response.

Characteristics of patients with schizophrenia who do not believe they are mentally ill.

The purpose of this study was to use a very simple self-report measure to identify patients who did not believe they were mentally ill and describe their characteristics. The study included 177 inpatients and outpatients with schizophrenia. Multivariate regression methods analyzed the relationship between illness belief and sociodemographic, clinical, and attitudinal factors. Thirty-seven percent of subjects did not believe they were mentally ill. Younger age, fewer depressive symptoms, lower perceived medication efficacy, greater satisfaction with current mental health, and less concern about mental illness stigma were associated with not believing one was mentally ill. Outpatients with fewer hospitalizations were less likely to believe they were ill. Inpatients with more hospitalizations were less likely to believe they were ill and had poor medication adherence. Readily identifying patients who do not believe they are mentally ill may be useful to clinicians and policymakers when matching at-risk patients with adherence interventions.

The relationship between quality and outcomes in routine depression care.

OBJECTIVE: This longitudinal, nonexperimental study examined whether depression treatment provided in concordance with guidelines developed by the Agency for Healthcare Research and Quality (AHRQ) is associated with improved clinical outcomes. METHODS: The medical, insurance, and pharmacy records of a community-based sample of 435 subjects who screened positive for current major depression were abstracted to ascertain whether depression treatment was received and whether it was provided in accordance with AHRQ guidelines. Regression analyses estimated the impact of guideline-concordant treatment on the change in depression severity and on mental and physical health over a six-month period. An instrumental variables analysis was used to check the sensitivity of the results to selection bias. RESULTS: A total of 106 subjects were treated for depression by 105 different primary care and specialty providers. Sixty percent of the sample had current major depression, and about 40 percent had subthreshold depression. Only 29 percent of the patients received guideline-concordant treatment. For patients with major depression, guideline-concordant care was significantly and substantially associated with improved depression severity but not with improvements in overall mental or physical health. The instrumental variables analysis indicated that the standard regression analysis underestimated the treatment effect by 21 percent. For those with subthreshold depression, guideline-concordant care was not associated with improved outcomes. DISCUSSION AND CONCLUSIONS: This community-based, nonexperimental study found a positive relationship between the quality of care for depression and clinical outcomes for patients with major depression in routine practice settings.

The role of psychiatrists in primary care of patients with severe mental illness.

OBJECTIVE: This study sought to identify health conditions for which a primary care psychiatrist would be an appropriate treatment provider in an integrated model of health care delivery for persons with serious mental illness. A primary care psychiatrist is a psychiatrist with primary care training who is supervised by an on-site internist. METHODS: Rating methods for health conditions were adapted from those jointly developed by Rand and the University of California, Los Angeles. A consensus panel of 14 hospital administrators, internists, psychiatrists, and nursing service representatives from three southern California Veterans Affairs health care systems was convened. Eleven physician-panelists, including five psychiatrist, five internists, and a medical specialist, rated whether a general psychiatrist, a primary care psychiatrist, an internist, or a medical specialist could reasonably provide evaluation, treatment, or preventive care for uncomplicated instances of each of 344 physical health conditions or procedures. RESULTS: A primary care psychiatrist, with supervision by an internist, was rated as an appropriate treatment provider for most of the 344 conditions. The conditions included many of those cited by patients as the most common reasons for ambulatory care visits. Panelists identified some intrusive elements of primary care, such as a pelvic examination, as potentially injurious to the psychiatrist-patient relationship and inappropriate for performance by psychiatrists. CONCLUSIONS: This study took the first essential step in evaluating the integration of primary care into the psychiatric setting. Further research is needed to determine whether use of primary care psychiatrists will increase access to primary care by persons with serious mental illness and improve outcomes.

Assessment of the quality of life of patients with major depression.

OBJECTIVE: This study examined the relationship between a measure of quality of life and measures of depressive symptoms among patients with major depression. METHODS: One hundred patients with primary major depression and 61 control subjects from the San Diego Veterans Affairs Medical Center and surrounding area were compared using a variety of measures, including the Quality of Well-Being (QWB) scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory. RESULTS: After analyses controlled for age, gender, family history of mental illness, and comorbid axis III diagnosis, subjects' scores on the QWB were significantly correlated with their scores on the Hamilton scale and Beck inventory. The severity of depressive symptoms was inversely related to quality of life as measured by the QWB, independent of the variables that were controlled for. CONCLUSIONS: The QWB is sensitive to symptoms of depression among patients diagnosed with major depression. The reduction in quality of life associated with psychiatric symptoms of depression is comparable to that observed among physically ill patients.

Preliminary longitudinal assessment of quality of life in patients with major depression.

This study examines the longitudinal relationships between a health-related quality of life measure and depressive symptoms in patients with major depression. One hundred eighteen patients with primary major depression and 81 controls were evaluated. The patients were divided into three groups based on Diagnostic Interview Schedule criteria for a major depressive episode at baseline (T1) and 6 months later (T2). Results indicate that the Quality of Well-Being (QWB) measure is sensitive to different levels of depressive symptoms over a 6-month period. The QWB is a health-related quality of life and cost/utility measure that may be useful for pharmacoeconomic analysis. The reduction in quality of life associated with symptoms of depression is comparable to that observed with chronically physically ill patients. As a generic symptom/function measure, the QWB may be very useful in evaluating public health policy.

Varicella immunity and clinical disease in HIV-infected adults.

Varicella is an infrequent but potentially severe infection in adult HIV-infected patients. We reviewed five cases of varicella in HIV-seropositive men; two were complicated by severe headache and meningismus, and one of these patients also had hepatitis and thrombocytopenia. All five patients responded well to acyclovir therapy, but one patient had dermatomal zoster 2 years later, and another failed to have detectable antibody after infection. We also performed a serosurvey on 181 consecutive HIV-infected patients presenting themselves for evaluation. A total of 95% of these patients had demonstrable antibody to varicella-zoster virus. Immune status to varicella did not correlate with the declining CD4 count, which was well preserved even in patients with fewer than 200 CD4 cells/mm3.

Hand tendon injuries in athletics.

Hand tendon injuries may be caused by acute trauma or chronic overuse. Although these injuries are common in athletics, specific diagnoses can be difficult to make and are often delayed. Early diagnosis is the key to a good outcome. Most hand tendon injuries do well with nonoperative treatment when initiated early. Long-term disruption of the delicate balance of muscle forces in the hand will lead to secondary changes that are often difficult to correct. Delay in treatment of overuse injuries may produce chronic inflammation that does not respond to conservative care and requires operative management. A sound knowledge of hand anatomy, awareness of the differential diagnosis, and a high index of suspicion are needed for proper care of the athletic hand injury.

Solubilization of Leonardite by an Extracellular Fraction from Coriolus versicolor.

Coriolus versicolor has previously been shown to degrade leonardite, an oxidized form of lignite. An extracellular fraction containing protein purified from a C. versicolor culture solubilized leonardite in vitro. Expression of the activity did not require the presence of leonardite and appeared during idiophase. During ion-exchange and gel filtration column chromatography, leonardite-biosolubilizing activity eluted with syringaldazine oxidase activity and with protein, as measured by A(280) and the biuret protein assay. Syringaldazine is a substrate of the polyphenol oxidase formed by C. versicolor. Comparison of leonardite-biosolubilizing activity with the effects of chelators and surface-active agents on leonardite showed that biosolubilization was not due to either surfactant or chelating ability. Heat treatment of the preparation at 60 degrees C for 30 min significantly reduced both syringaldazine oxidase and leonardite-biosolubilizing activities. Cyanide, azide, and thioglycolate, which are known inhibitors of syringaldazine oxidase activity of C. versicolor, also inhibited leonardite biosolubilization. From these data, we conclude that the purified protein fraction from C. versicolor contains a syringaldazine oxidase activity that participates in leonardite biosolubilization by enzymatic action.

Observations on spermatogenesis and inseminative behavior of Megalodiscus temperatus adults in frogs.

Upon in vitro exposure to 3H-adenosine, spermatogonial cells in adult Megalodiscus temperatus were readily labeled on autoradiograms. At least 20 days were required for these cells to produce labeled sperm, the longest time reported so far for digenetic trematodes. Labelled worms transplanted to hosts for 24--31 days showed both self- and cross-insemination in multiple infections. When alone, half of the transplanted adults self-inseminated.

Halothane-induced renal vasodilation.

Halothane-induced changes in renal function have generally been attributed to alterations in systemic hemodynamics, sympathetic tone, and various hormones. Studies were performed to determine whether halothane directly affects the kidney. Twenty-one canine kidneys were perfused in vitro utilizing hemodilution, pulsatile flow, and membrane oxygenation. Temperature and arterial blood-gas variables were controlled and mean and pulse pressures were maintained. Four experimental periods (I-IV)(each consisting of two 10-min sample collection periods) were conducted, with a 20-min "rest" period between succeeding experimental periods (elapsed time = 140 min). Responsiveness was assured by obtaining a normal response to furosemide, acetylcholine, or epinephrine after Period IV. In eight additional kidney preparations halothane was administered to achieve either a "low" (17 +/- 3 mg/100 ml) or "high" (35 +/- 5 mg/100 ml) concentration in Period II, the sequence reversed for Period III, and halothane eliminated by Period IV. Halothane produced marked increases in blood flow (21-26 per cent), total (203-267 per cent) and fractional (173-179 per cent) sodium excretion, osmolal clearance (62-111 per cent) and urinary volume (130-161 per cent). These changes were associated with a shift of microspheres from outer to inner cortex, and were completely reversible by eliminating the halothane. In the absence of external influences, halothane produces renal vasodilation and natriuresis. Direct tubular depression cannot be ruled out.

Efficient ribosome binding of brome mosaic virus (BMV) RNA4 contributes to its ability to outcompete the other BMV RNAs for translation.

Analysis of translation products synthesized in vitro in the presence of a mixture of brome mosaic virus (BMV) RNAs 1, 2, 3, and 4 usually shows a predominance of coat protein, coded by RNA4. The proportion of products directed by RNAs 1 and 2 decreased at saturating concentrations of BMV RNA and in the presence of 7-methylguanosine 5'-phosphate (m7G5'p) at nonsaturating concentrations of RNA. No differences in the relative proportions of the various proteins produced were detected in the presence of T-2 toxin, which interferes with the formation of the first peptidyl bond rather than competing for initiation factor, as has been suggested for m7G5'p. These data show that the ability of BMV RNA4 to outcompete BMV RNAs 1, 2, and 3 results, at least in part, from its ability to bind more efficiently to ribosomes.