Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: contemporary approach, current clinical significance and sources of pathology discrepancies

The Gleason grading system is a powerful tool to prognosticate and aid in the treatment of men with prostate cancer. The needle biopsy Gleason score correlates with virtually all other pathological variables, including tumour volume and margin status in radical prostatectomy specimens, serum prostate-specific antigen levels and many molecular markers. The Gleason score assigned to the tumour at radical prostatectomy is the most powerful predictor of progression after radical prostatectomy. However, there are significant deficiencies in the practice of this grading system. Not only are there problems among practising pathologists but also a relative lack of interobserver reproducibility among experts.     

Effects of waterproof covering on hand immersion tests using water at 10°C, 12°C and 15°C for diagnosis of hand–arm vibration syndrome

Objectives: To compare effects of waterproof covering on finger skin temperature (FST) and subjective hand pain during immersion tests using cold water at 10°C, 12°C and 15°C. In the (Draft International Standard) of the International Organization for Standardization (ISO/DIS 14835-1), a water temperature of 12°C and use of water covering are proposed. Methods: Six healthy male subjects took part in the immersion tests and immersed both hands into water at 10°C, 12°C and 15°C for 5 min, repeatedly, with waterproof covering (polyethylene gloves) or without (bare hands). The FST data from middle fingers and subjective pain scores for hand pain were analyzed. Furthermore, the test with water at 12°C was repeated to assess the repeatability of the test. Results: The glove and water temperature factors for FST were significant at every minute from 1 min during immersion up to 2 min after recovery, showing higher values for waterproof covering than for bare hands and showing lowest values for water temperature of 10°C and highest for 15°C. The glove and water temperature factors for subjective pain score were significant at the 1-min and 2-min points during immersion, showing lower scores for waterproof covering than for bare hands and showing highest scores for water temperature of 10°C and lowest for 15°C. The results of the first and second tests using water of 12°C showed no systematic difference in FST and hand pain between the tests, with a few exceptions. Conclusions: Subjective pain during the cold immersion test with polyethylene gloves and water at 12°C can be reduced, while the differences in FST between water temperatures of 10°C and 12°C were small or not apparent at some points during immersion and recovery. The test also seems to be suitable for repeatability. Further investigation on hand–arm vibration syndrome (HAVS) patients to validate the use of the immersion test with gloves to obtain sufficient data for diagnostic value is required.     

Increasing the number of biopsy cores improves the concordance of biopsy Gleason score to prostatectomy Gleason score

OBJECTIVE: To evaluate taking more biopsy cores for predicting the radical prostatectomy (RP) Gleason score compared with the biopsy Gleason score, as although random sextant biopsies are the standard for a tissue diagnosis of prostate cancer, and taking more biopsies increases the detection rate, it is uncertain whether taking more cores improves the prediction of the RP Gleason score. PATIENTS AND METHODS: We analysed retrospectively 404 patients from three centres (Seattle 162, Washington 107 and Chicago 135) who had RP for prostate cancer. Six, eight or 10 biopsies were taken based on the physician's preference and the patient's characteristics. RESULTS: Before RP, 158 (39%) patients had six, 65 (16%) had eight and 181 (45%) had 10 biopsy cores taken. The accuracy of the Gleason sum of the three groups was 65/158 (41%), 26/65 (40%) and 104/181 (57.5%), respectively (P < 0.004, 10-core vs six-core). However, when comparing the Gleason score separately (i.e. 4 + 3 is not equal to 3 + 4), the accuracy of the three groups was 48/158 (30%), 20/65 (31%), and 95/181 (52.5%), respectively (P < 0.001, 10-core vs six core). CONCLUSIONS: Taking more biopsy cores improves the accuracy of the biopsy Gleason score in predicting the final Gleason score at RP; the predictive accuracy of the final Gleason score may be increased from 41% to 58% by increasing the number of biopsies from six to 10.     

Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

Switch from bicarbonate hemodialysis to hemodiafiltration with online regeneration of the ultrafiltrate (HFR): effects on nutritional status, microinflammation, and beta-microglobulin

BACKGROUND: Hemodiafiltration (HFR) with on-line regeneration of the ultrafiltrate, a technique of hemodiafiltration in which the ultrafiltrate passes through a cartridge containing uncoated charcoal, has been shown to be safe, simple, and well tolerated and has been claimed to improve nutritional status or to prevent its deterioration while decreasing the inflammatory response via a reduced production of proinflammatory cytokines. The purpose of the present prospective study was to ascertain whether HRF improves the nutritional status, reduces microinflammation, and decreases serum beta2-microglobulin levels in patients with end-stage renal disease (ESRD). METHODS: Eight patients, four males and four females, with a mean age of 49.4 +/- 16.8 years, stable on hemodialysis over a period of 8.7 +/- 6.1 years and on standard 4-4.5 h three-times-a-week bicarbonate hemodialysis, were switched to three-times-a-week, 4-h HFR. At baseline and every two months for 12 months at mid-week, serum levels of urea, creatinine, albumin, total cholesterol, C-reactive protein, fibrinogen, complement, ferritin, beta2-microglobulin, intact parathyroid hormone (PTH), hemoglobin concentrations, and hematocrit and the EPO weekly dose were determined. At baseline and at the end of the study, the Malnutrition Inflammatory Score (MIS) was calculated. RESULTS: Nutritional and inflammatory parameters remained constant during the 12-month period of the study. After 12 months of HFR, the MIS trended to be lower, but the difference was not statistically significant. Serum beta2-microglobulin and PTH levels remained constant during all time intervals. Neither hematocrit nor hemoglobin changed over the course of the study as well as the weekly EPO dose. CONCLUSION: The change from bicarbonate hemodialysis to HFR was safe and well tolerated but was not associated with an improvement of nutritional and inflammatory parameters or a reduction of serum beta2-microglobulin levels.     

Staging systems in hepatocellular carcinoma

Staging systems are key to predict the prognosis of patients with cancer, to stratify the patients according to prognostic variables in the setting of clinical trials, to allow the exchange of information among researchers, and finally to guide the therapeutic approach. The current knowledge of the disease, however, prevents recommendation of a staging system that can be used world-wide. The conventional staging systems for hepatocellular carcinoma (HCC), such as the Okuda stage or the TNM stage have shown important limitations in classifying patients. Several new systems have been proposed recently, and only three of them have been validated at this point. The BCLC staging classification links the stage of the disease to a specific treatment strategy. The JIS score has been proposed and used in Japan, although it needs Western validation. The CLIP score is used in patients with advanced tumors. Several reasons explain the difficulty in identifying a world-wide system. First, HCC is a complex neoplasm inserted on a pre-neoplastic cirrhotic liver, and thus variables of both diseases leading to death should be taken into account. Second, the disease is very heterogeneous around the world, and this reflects different underlying epidemiological backgrounds and risk factors. Third, HCC is the sole cancer treated by transplantation in a small proportion of patients. Fourth, only around 20% of the cases are currently treated by surgery, thus precluding the wide use of pathology-based systems, such as TNM. Finally, the potential relevance of a molecular signature identified in terms of outcome prediction is unknown, and further research is needed to obtain this valuable biological information that may aid in classifying the patients.     

Assessing the risk of mortality in paediatric cancer patients admitted to the paediatric intensive care unit: a novel risk score?

Intensive front-line protocols have improved survival in children with malignancies; however, intensive multimodal therapy of paediatric malignancies can be associated with a significant risk of serious adverse events. Common risk scores (PRISM, PRISM III, APACHE-II) fail to predict mortality in these patients. A retrospective chart analysis of 32 paediatric cancer patients admitted to the Paediatric Intensive Care Unit (PICU) at the University Hospital of Saarland between January 2001 and December 2003 for life-threatening complications was performed. The aim of this study was to assess risk factors for short-term outcome (survival vs. non-survival when leaving the PICU) and to develop a risk score to estimate outcome in these patients. Overall survival was good (25 of 32 patients). Mortality rate was significantly related to leukaemia/lymphoma ( P =0.029), to the number of organ failures ( P <0.0001), neutropenia ( P =0.001), septic shock ( P =0.025), mechanical ventilation ( P =0.01) and inotropic support ( P =0.01). Employing multiple logistic regression, the strongest predictor for poor outcome was the number of organ failures ( P <0.05). A risk score (cut-off value: >3 points for non-survival) which included the following risk factors (non-solid tumour, number of organ failures ( n >2), neutropenia, septic shock, mechanical ventilation, and inotropic medication) yielded a sensitivity of 7/7 (95% CI: 4.56–7.00), a specificity of 23/25 (95% CI: 18.49–24.75), a positive predictive value of 23/23 (95% CI: 19.80–23.00), and a negative predictive value of 7/9 (95% CI: 3.60–8.74) for the time of admission to the PICU. Conclusion:Although our risk of mortality score is of prognostic value in assessing short-term outcome in these patients, prospective validation in a larger study cohort is mandatory. Furthermore, it must be emphasised that this risk score must not be used for decision-making in an individual patient.     

Pharmacodynamics of chloral hydrate in former preterm infants

The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (bradycardic events, apnoeas) before and after administration of chloral hydrate (oral, 30 mg/kg) were prospectively evaluated in former preterm infants during procedural sedation. Characteristics at birth, during neonatal stay and at inclusion were collected. Paired Wilcoxon and McNemar tests were used to study the impact of chloral hydrate. Characteristics of infants who displayed severe bradycardic events were compared to infants in whom no bradycardic events were recorded (Mann Whitney U, Fischers exact). A significant increase in sedation (decrease COMFORT scale) was observed up to 12 h after administration. There was a minor but significant decrease in oral intake (161 to 156 ml/kg/day, P <0.01). A significant increase in the number of bradycardic events (<80/min: 38 to 82 events, of which <70/min: 30 to 79 of which <60/min: 15 to 45; at least P <0.01) and in the duration of the most severe bradycardic event (8–12.5 s) was observed. Therefore, further inclusion was stopped when 26 neonates were included. Infants who displayed severe bradycardic (<60/min) events ( n =13) after administration of chloral hydrate had a lower gestational age at birth without difference in post-conception age at inclusion. Conclusion:Chloral hydrate was associated with an increase in unintended side-effects in former preterm infants, likely reflecting population specific pharmacodynamics and kinetics of chloral hydrate.     

Parkinsonism with excessive daytime sleepiness

Abstract Background Parkinsonian patients with excessive daytime sleepiness (EDS), hallucinations, REM sleep behavior disorder (RBD), short mean sleep latencies, and sleep-onset REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been reported. In these patients a narcolepsy-like pathophysiology of sleep-wake disturbances has been suggested. Patients and methods We studied 14 consecutive patients with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn & Yahr score), Epworth sleepiness score (ESS), history of REM-symptoms (RBD/hallucinations/sleep paralysis/cataplexy-like episodes), polysomnography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin A). Results There were 12 men and 2 women (mean age 69 years; range 54–82). The mean duration and the Hoehn & Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinsons disease (IPD, n=10), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was 10 in all patients (mean 12; range 10–18). REM-symptoms were reported by all but two patients (hallucinations: n=9; RBD: n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS-index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compared with controls (n=20, mean 497 pg/ml; range 350–603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients (221 and 307 pg/ml, respectively). Conclusion These findings do not support the hypothesis of a final common pathway in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep apnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patients.     

Comparison of different screening tests for detecting diabetic foot neuropathy

INTRODUCTION: Regarding the major role of sensory neuropathy in diabetic foot ulcers, the use of an appropriate screening test for early detection of this neuropathy has a crucial role in the management of diabetic foot disorders. As there were no previous studies that performed all screening tests in the same group of patients, we performed all tests in a single group of diabetic patients and compared them to find out the possible differences between the results. METHODS: A total of 142 diabetic outpatients at Shariati Teaching Hospital were chosen by systematic randomized selection. Different screening tests for detecting neuropathy in diabetic foot such as symptom and sign scores, Michigan Neuropathy Disability Score (MNDS), and testing by a monofilament were performed for each patient. RESULTS: According to the neuropathy symptom score, 54.9% of the patients were neuropathic, their score was higher than 5, and by neuropathy sign score, 10.1% were neuropathic with a score higher than 6. Regarding MNDS, 42.7% of the subjects were neuropathic, with a score higher than 3. Finally, 23.9% were unable to sense at least one point in the monofilament examination. CONCLUSIONS: There were obvious differences between the results of different methods in our study. However, there were significant correlations between them, except between sign and symptom score methods. For determining the most reliable screening test, further studies are needed to compare these methods with a gold standard test and reveal the specificity and sensitivity of these tests.