Is retina affected in Huntington's disease? Is optical coherence tomography a good biomarker?

AIM OF THE STUDY: Comparative cross-sectional study of retinal parameters in Huntington's disease and their evaluation as marker of disease progression. CLINICAL RATIONALE FOR THE STUDY: Huntington's disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted. MATERIALS AND METHODS: This is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington's disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure. RESULTS: HD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology. CONCLUSIONS: The results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington's disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington's disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test. CLINICAL IMPLICATIONS: Current retinal parameters are not appropriate for monitoring HD disease progression.

Symptom-severity-related brain connectivity alterations in functional movement disorders.

BACKGROUND: Functional movement disorders, a common cause of neurological disabilities, can occur with heterogeneous motor manifestations including functional weakness. However, the underlying mechanisms related to brain function and connectivity are unknown. OBJECTIVE: To identify brain connectivity alterations related to functional weakness we assessed network centrality changes in a group of patients with heterogeneous motor manifestations using task-free functional MRI in combination with different network centrality approaches. METHODS: Task-free functional MRI was performed in 48 patients with heterogeneous motor manifestations including 28 patients showing functional weakness and 65 age- and sex-matched healthy controls. Functional connectivity differences were assessed using different network centrality approaches, i.e. global correlation, eigenvector centrality, and intrinsic connectivity. Motor symptom severity was assessed using The Simplified Functional Movement Disorders Rating Scale and correlated with network centrality. RESULTS: Comparing patients with and without functional weakness showed significant network centrality differences in the left temporoparietal junction and precuneus. Patients with functional weakness showed increased centrality in the same anatomical regions when comparing functional weakness with healthy controls. Moreover, in the same regions, patients with functional weakness showed a positive correlation between motor symptom severity and network centrality. This correlation was shown to be specific to functional weakness with an interaction analysis, confirming a significant difference between patients with and without functional weakness. CONCLUSIONS: We identified the temporoparietal junction and precuneus as key regions involved in brain connectivity alterations related to functional weakness. We propose that both regions may be promising targets for phenotype-specific non-invasive brain stimulation.

Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID-19) mainly due to respiratory muscle weakness, older age and long-term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID-19 in MG patients and risk of MG exacerbation during COVID-19. METHODS: We evaluated clinical features and outcomes after COVID-19 in 93 MG patients. RESULTS: Thirty-five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID-19. Higher forced vital capacity (FVC) values tested before COVID-19 were shown to be protective against severe infection (95% CI 0.934-0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047-1.232). Long-term chronic corticosteroid treatment worsened the course of COVID-19 in MG patients (95% CI 1.784-111.43) and this impact was positively associated with dosage (p = 0.005). Treatment using azathioprine (95% CI 0.448-2.935), mycophenolate mofetil (95% CI 0.91-12.515) and ciclosporin (95% CI 0.029-2.212) did not influence the course of COVID-19. MG patients treated with rituximab had a high risk of death caused by COVID-19 (95% CI 3.216-383.971). Exacerbation of MG during infection was relatively rare (15%) and was not caused by remdesivir, convalescent plasma or favipiravir (95% CI 0.885-10.87). CONCLUSIONS: As the most important predictors of severe COVID-19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long-term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.

Morbidity and mortality after open radical cystectomy and ileal diversion - 10 years experience and a comprehensive assessment in a single tertiary center.

Open radical cystectomy (ORC) remains the gold standard for the treatment of muscle-invasive and high-risk non-muscle invasive bladder cancer unsuitable for bladder preservation techniques. Despite improvements in operative technique and perioperative care, it continues to be associated with significant complications. We analyzed our series of prospectively collected data of patients who underwent ORC at a tertiary referral academic center and evaluated early and late postoperative complications and mortality. The records of 391 ORCs with ileal diversion performed at our institution between January 2008 and July 2018 for non-metastatic transitional bladder carcinoma and other distinct pathological types were analyzed. Perioperative mortality was determined and 30-day and 90-day complications were reported according to the Martin Criteria and the European Association of Urology and graded according to the five-grade Clavien-Dindo classification. Univariate and multivariate analyses were used to evaluate predictors of complications and mortality. Gastrointestinal and infectious complications represented 41% and 43% of the total complications observed at 30 and 90 days after the surgery, respectively. The strongest predictor of infectious complications was the choice of ileal neobladder as the urinary diversion (p≤0.0001). Diabetes was a predictor of the overall, major and major infectious complications (p<0.05). The 30-day mortality rate was 1% while the 90-day mortality rate was 1.5%. Age ≥75 was the single predictor of mortality at both 30-days (p-value 0.003) and 90-days (p-value 0.01) in univariate and multivariate analyses. ORC is a morbid procedure, associated with a high mortality rate. Elderly patients should have proper counseling before the indication of this procedure. Gastrointestinal and infectious complications represent the most common and serious complications, and the study of their predictors is of the utmost importance.

Simultaneous tonic and phasic REM sleep without atonia best predicts early phenoconversion to neurodegenerative disease in idiopathic REM sleep behavior disorder.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep without atonia (RWA) is the main polysomnographic feature of idiopathic REM sleep behavior disorder (iRBD) and is considered to be a promising biomarker predicting conversion to manifested synucleinopathy. Besides conventionally evaluated tonic, phasic and any RWA, we took into consideration also periods, when phasic and tonic RWA appeared simultaneously and we called this activity "mixed RWA." The study aimed to evaluate different types of RWA, to reveal the most relevant biomarker to the conversion. METHODS: A total of 55 patients with confirmed iRBD were recruited with mean follow-up duration 2.3 ± 0.7 years. Scoring of RWA was based on Sleep Innsbruck Barcelona rules. Positive phenocoversion was ascertained according to standard diagnostic criteria during follow-up. Receiver operator characteristic analysis was applied to evaluate predictive performance of different RWA types. RESULTS: A total of nine patients (16%) developed neurodegenerative diseases. Yearly phenoconversion rate was 5.5%. Significantly higher amounts of mixed (p = 0.009), tonic (p = 0.020), and any RWA (p = 0.049) were found in converters. Optimal cutoffs differentiating the prediction were 16.4% (sensitivity 88.9; specificity 69.6) for tonic, 4.4% (sensitivity 88.9; specificity 60.9) for mixed, and 36.8% (sensitivity 77.8; specificity 65.2) for any RWA. With area under the curve (AUC) 0.778, mixed RWA has proven to be the best predictive test followed by tonic (AUC 0.749) and any (AUC 0.710). CONCLUSIONS: Mixed, tonic and any RWA may serve as biomarkers predicting the conversion into neurodegenerative disease in iRBD. The best predictive value lies within mixed RWA, thus it should be considered as standard biomarker.

Fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder.

Fragmentary myoclonus is a result of muscle activity consisting of brief potentials in surface electromyography during polysomnography. Excessive fragmentary myoclonus is defined by increased intensity of the potentials. A few studies report excessive fragmentary myoclonus occurrence in neurodegenerative diseases. Because idiopathic rapid eye movement sleep behaviour disorder is considered as an early stage of neurodegeneration with involvement of the brainstem, we charted the prevalence and quantified the intensity of excessive fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder. Twenty-nine patients (one woman, 28 men, mean age 68 years, SD 6.2) and 29 controls (two women, 27 men, mean age 65.6 years, SD 8.6) underwent polysomnography. Fragmentary myoclonus potentials were identified and counted according to internationally used criteria. Fragmentary myoclonus intensity was quantified by the fragmentary myoclonus index. Excessive fragmentary myoclonus was diagnosed in 75.9% (22 subjects) in idiopathic rapid eye movement sleep behaviour disorder, while in 34.5% (10 subjects) among the controls (p = 0.003). Quantitative analysis showed a wide-range fragmentary myoclonus index in idiopathic rapid eye movement sleep behaviour disorder (4.0-632.4; median 60.7) and in the controls (0.8-938.1; median 34.3). The overall difference in fragmentary myoclonus index was not significant between the groups; however, patients with idiopathic rapid eye movement sleep behaviour disorder showed trends for higher fragmentary myoclonus index scores in wakefulness (p = 0.027), N1 (p = 0.032), N3 (p = 0.046) and R (p = 0.007). Fragmentary myoclonus index does not correlate with age, idiopathic rapid eye movement sleep behaviour disorder duration or R stage atonia deficiency. The prevalence of excessive fragmentary myoclonus is higher in idiopathic rapid eye movement sleep behaviour disorder compared with the controls, so fragmentary myoclonus should be taken into account in future research of rapid eye movement sleep behaviour disorder and motor control in sleep.

The impact of non-motor symptoms on the health-related quality of life in patients with functional movement disorders.

OBJECTIVE: Pain, fatigue, cognitive complaints and psychiatric comorbidities are common in patients with functional movement disorder and may significantly affect their quality of life. The aim of the study was to assess the impact of motor and non-motor symptoms on health-related quality of life in patients with functional movement disorder. METHODS: Sixty-one patients with clinically established functional movement disorder and 61 matched healthy controls completed standardized questionnaires for depression, anxiety, cognitive complaints, fatigue, pain, sleepiness, apathy and health-related quality of life. Motor disorder severity was assessed using The Simplified Functional Movement Disorders Rating Scale. Personality traits were assessed using the 44-Item Big Five Inventory. RESULTS: Compared to controls, patients reported significantly lower health-related quality of life and higher levels of all assessed non-motor symptoms except for apathy. No difference was found in personality traits. In both groups, health-related quality of life scores negatively correlated with depression, anxiety, pain, cognitive complaints, apathy, and neuroticism. No correlation was found between health-related quality of life and motor symptom severity in patients with functional movement disorder. Multiple regression analysis of the predictors of health-related quality of life showed significant impact of trait anxiety and cognitive complaints scores. CONCLUSIONS: Multiple non-motor symptoms but not motor symptom severity correlated with impaired health-related quality of life in patients with functional movement disorder. Impaired health-related quality of life was predicted by anxiety and cognitive complaints. Our results highlight the importance of assessing and treating both motor and non-motor symptoms in patients with functional movement disorder.

Mitochondrial membrane protein-associated neurodegeneration: a case report and literature review.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an autosomal recessive disorder caused by mutation in the C19orf12 gene. We report a compound heterozygous c.[32C>T];[205G>A;424A>G] (p.[Thr11Met];[Gly69Arg;Lys142Glu]) Czech patient who manifested with right foot dystonia, impaired handwriting, attention deficit, and signs of iron accumulation on brain MRI. Gradually, he developed dysarthria, spastic-dystonic gait, pedes cavi, and atrophy of leg muscles. Additionally, we report demographic parameters, clinical signs, and allelic frequencies of C19orf12 mutations of all published MPAN cases. We compared the most frequent mutations, p.Thr11Met and p.Gly69ArgfsX10; the latter was associated with younger age at onset and more frequent optic atrophy in homozygotes.

Prospective memory impairment in idiopathic REM sleep behavior disorder.

OBJECTIVE: The aim of the present study was to investigate if prospective memory (PM) is impaired in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). RBD is a parasomnia characterized by dream enactment and by REM sleep without muscle atonia. iRBD is considered as the initial stage of neurodegeneration with pathological storage of alpha-synuclein. METHOD: Sixty iRBD patients with polysomnography-confirmed RBD without parkinsonism and dementia and 30 demographically matched normal controls (NC) were enrolled in the present study. Clinical assessment included Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), dopamine transporter single-photon emission computed tomography (DaT-SPECT) for imaging synapses of dopaminergic neurons in the striatum and a neuropsychological battery with embedded time-based and event-based PM measures. RESULTS: iRBD differed significantly from NC in event-based PM, a number of event-based failures to recall intention and total PM performance (all p < .001) but did not differ in time-based PM and recognition. PM did not contribute to impairment of instrumental activities of daily living in iRBD. Despite being preserved in iRBD in comparison to NC, time-based PM correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT. CONCLUSIONS: We show evidence for a differential pattern of PM impairment in iRBD with severe impairment of event-based and concurrent preservation of time-based PM. We theorize that event-based PM impairment in iRBD is caused by severe impairment of retention and recognition mechanisms in episodic memory whereas time-based PM seems to be affected by reduced striatal dopaminergic synapses.

Frontal Assessment Battery in Parkinson's Disease: Validity and Morphological Correlates.

OBJECTIVES: Executive dysfunction is a common feature in Parkinson's disease (PD). However, there is a lack of brief validated instruments for executive dysfunction in PD. METHODS: The aim of the present study was to assess the relation of Frontal Assessment Battery (FAB) scores to age and education, to verify the utility of FAB in the evaluation of executive dysfunction in PD and to differentiate between controls (n=41), PD patients with normal cognition (PD-NC; n=41; Hoehn and Yahr stages 2-3) and PD with mild cognitive impairment (PD-MCI; n=32; Hoehn and Yahr stages 2-3). In addition, we studied the relation between voxel-based morphometric (VBM) data and FAB results in PD. RESULTS: We found that FAB scores are significantly related to age and education. The FAB has shown discriminative validity for the differentiation of PD-MCI from PD-NC and controls (area under the curve >.80). Also, the VBM analysis revealed lower FAB scores are specifically related to lower gray matter density in the right ventromedial prefrontal areas and precuneus. CONCLUSIONS: The FAB can be recommended as a valid instrument for PD-MCI Level I screening. FAB is sensitive to frontal lobe involvement in PD as reflected by lower gray matter density in prefrontal areas. (JINS, 2017, 23, 675-684).

Diagnostic Efficiency of Serum and Urine Procathepsin B and Cathepsin B in Patients with Carcinoma of the Urinary Bladder.

BACKGROUND: The aim of the study was to evaluate the diagnostic efficiency of cathepsins B (cathepsin B and procathepsin B) in patients with transient cell carcinoma of the urinary bladder. METHODS: Serum and urine concentrations of cathepsin B and procathepsin B were measured by two commercially available enzymatic immunoassays in a group of 125 patients with bladder cell carcinoma without metastases and in a group of 72 healthy individuals. Concentrations in urine were adjusted to creatinine. RESULTS: Concentrations of both cathepsin B and procathepsin B in serum and urine were significantly elevated in patients with bladder cell carcinoma (p < 0.0001 for U-procathepsin B, U-procathepsin B/creatinine, and U-cathepsin B/creatinine, p = 0.0001 for U-cathepsin B, p = 0.0002 for S-procathepsin B and p = 0.02 for S-cathepsin B). Comparison of all diagnostic efficiencies of cathepsin B and procathepsin B in serum and in urine showed the best diagnostic accuracy for procathepsin B in urine (AUC = 0.81 vs. 0.50). The ratio of U-procathepsin B/creatinine was also more efficient than the ratio of U-cathepsin B/creatinine (AUC = 0.81 vs. AUC = 0.70). The diagnostic efficiencies of both parameters in serum were low (S-procathepsin B: AUC = 0.50, S-cathepsin B: AUC = 0.60). U-procathepsin B and U-procathepsin B/creatinine ratio show significantly better diagnostic efficiency in patients with invasive bladder tumors than other parameters (S-procathepsin B, S-cathepsin B, U-cathepsin B and U-Cathepsin B/creatinine; U-procathepsin B: AUC = 0.82, U-procathepsin B/creatinine: AUC = 0.86, S-procathepsin B and cathepsin B: AUC = 0.51 - 0.68). CONCLUSIONS: Procathepsin B concentration in urine is a valuable diagnostic marker in patients with bladder cell carcinoma.

[Hypolipidemic and antihypertensive therapy in diabetic patients in the Czech Republic: notes on the VZP (General Health Insurance Company) Data]. / Terapie diabetiku hypolipidemiky a antihypertenzivy v Ceské republice: poznámky k datum VZP.

Diabetes mellitus and in particular type 2 diabetes mellitus is one of the most important risk factors of cardiovascular disease. To influence cardiovascular risk there is enormous important not only positive influence of glycemia, but also the treatment of diabetic dyslipidemia and hypertension. The present work provides an analysis of lipid-lowering and antihypertensive therapy for all diabetics registered with General Health Insurance Company in the period 2010-2013. In this time 866,570 patients with diabetes mellitus registered with General Health Insurance Company were treated, the majority of them were diabetics independent on insulin. Approximately half of the patients were observed by dialectologists and half of them by the doctors of other specialization. Out of antihypertensive medi-cation, patients were most often treated by drugs that affect the renin-angiotensin system, as well as beta-blockers and diuretics. Prescription of the lipid-lowering therapy, especially prescription of statins, in accordance with the guidelines, is increasing, but remains insufficient (at 2013 43.6% diabetics treated by dialectologists and 51.3% diabetics treated by GP´s didn´t have lipid lowering therapy). Inadequate use of combination lipid-lowering therapy was recorded too, still represented mainly by combination of statin and fibrate, but in coming years we expect (based on the positive results of the subanalysis IMPROVE-IT study), an increase of combination therapy statin and ezetimibe.

The use of early postoperative prostate-specific antigen to stratify risk in patients with positive surgical margins after radical prostatectomy.

BACKGROUND: It is well recognized that the presence of positive surgical margins (PSM) after radical prostatectomy (RP) adversely affects cancer specific outcomes and recent evidence from randomized trials supports the use of adjuvant radiotherapy in these cases. However, not all of the patients with PSM develop disease recurrence and the policy of adjuvant radiation could result in considerable over-treatment. We investigated the ability of early postoperative prostate specific antigen (PSA) and PSA decline rates to stratify the risk of disease progression during the first weeks after the surgery thereby allowing adequate time for planning eventual adjuvant therapy. METHODS: We studied 116 consecutive patients with the finding of PSM after RP for localized prostate cancer between 2001 and 2012. No patients were treated with radiation or hormonal therapy. An intensive postoperative PSA monitoring using ultrasensitive assay started first at day 14 after the surgery, then at day 30, 60, 90 and 180, and subsequently in 3 monthly intervals. Biochemical recurrence (BCR) presented the failure of surgical treatment and it was defined as PSA ≥0.2 ng/ml. The ability of PSA decline parameters to predict BCR was assessed using Cox regression model and area under the curve (AUC) calculation. RESULTS: Overall 55 (47%) patients experienced BCR during median follow-up of 31.4 months (range 6-69). Preoperative PSA, pathologic Gleason sum and pathologic grade failed to reveal any association with observation of BCR. Postoperative PSA levels achieved significant predictive accuracy already on day 30 (AUC 0.74). PSA >0.073 ng/ml at day 30 increased significantly the risk of BCR (HR 4.35, p < 0.001). Predictive accuracy was significantly exceeded on day 60 (AUC 0.84; p < 0.001), while further enhancements on day 90 (AUC 0.84) and 180 (AUC 0.91) were not significant. CONCLUSIONS: The level of ultrasensitive PSA yields valuable information about the prostatectomy outcome already at the first month after the surgery and should aid risk stratification in patients with PSM. Patients not likely to experience subsequent disease progression may be spared the toxicity of immediate adjuvant radiotherapy.

Parameters derived from the postoperative decline in ultrasensitive PSA improve the prediction of radical prostatectomy outcome.

PURPOSE: Contemporary tools estimating increased risk of prostate cancer (PCa) relapse after radical prostatectomy (RP) are far from perfect and there has been an intensive search for additional predictive variables. We aimed to explore whether the parameters of postoperative ultrasensitive prostate-specific antigen (PSA) decline provide additional information for predicting PCa progression. METHODS: A total of 319 consecutive men, with at least 2 years of follow-up after RP for clinically localized PCa were subjected to this study. Intensive postoperative measurements of ultrasensitive PSA resulted in total of 4028 PSA values available for statistical evaluation. Biochemical recurrence (BCR) was defined as PSA ≥0.2 ng/ml. The accuracy of predictive models was quantified with the area under the curve. RESULTS: Over a median follow-up of 43 months (24-99 months), 107 patients (34%) experienced BCR after RP. In patients with BCR, significantly higher values of PSA nadir (p < 0.001) and a decreased time interval from surgery to reach PSA nadir (p < 0.001) were observed. A multivariable Cox regression model confirmed that PSA nadir >0.01 ng/ml (HR 6.01, 95% CI: 3.89-9.52) and time to PSA nadir <3 months (HR 2.86, 95% CI: 1.74-5.01) were independent predictors of BCR. The inclusion of PSA nadir and the time to PSA nadir into the model resulted in improvement of predictive accuracy by 16% over the model designed on the basis of established parameters. CONCLUSIONS: Our results demonstrate that the level of PSA nadir and the time to PSA nadir determined by ultrasensitive assay significantly improve the identification of patients who are at high risk of disease recurrence after RP.

Urine and serum cathepsin B concentrations in the transitional cell carcinoma of the bladder.

BACKGROUND: It has been shown that expression and activity of lysosomal proteolytic enzymes (i.e., cathepsin B) correlate with tumor progression in various neoplasms. We investigate possible correlation of cathepsin B concentrations with grading and invasivity of tumorous bladder tissue. METHOD: Cathepsin B concentrations in serum and urine were measured in 40 patients (29 men, 11 women, mean age 68 years) with transitional cell carcinoma (TCC) of the bladder without metastases and in control group of 64 healthy subjects (28 men, 36 women, mean age 55 years) using commercially available enzymatic immunoassay. Concentration of cathepsin B in urine was adjusted on creatinine. Urinary creatinine in all samples was measured by enzymatic creatinase method. Patients were divided into groups according to the grading (low grading: 18 patients, high grading: 22 patients) and invasivity of the carcinoma (nonmuscle-invasive tumors: 23 patients, invasive tumors: 17 patients). RESULT: Concentrations of cathepsin B in urine were significantly elevated in patients than in control group (Median = 3.87 µg/L vs. 1.35 µg/L, P = 0.0002). Similarly, the ratio of U-cathepsin B/creatinine was significantly higher in patients (Median: 0.44 µg/mmol creatinine vs. 0.17 µg/mmol creatinine, P < 0.0001). U-cathepsin B may prove to be useful biomarker (area under the curve [AUC] = 0.72 and 0.73 for the U-cathepsin B/creatinine ratio, respectively). S-cathepsin B significantly correlated with grading of carcinoma (P = 0.02) and U-cathepsin B and U-cathepsin B/creatinine are positively associated with invasive tumors (P = 0.0001 and P = 0.002). CONCLUSION: Cathepsin B concentrations correlate well with grading and invasivity of tumors and may have diagnostic value in investigation of bladder cell carcinoma. New index U-cathepsin B/Creatinine ratio is more appropriate biomarker to monitor TCC, than U-cathepsin B so far.

Influence of tumour-associated symptoms on the prognosis of patients with renal cell carcinoma.

OBJECTIVE: To evaluate the prognostic significance of symptoms related to renal cell carcinoma (RCC) in comparison with incidentally detected tumours in a group of long-term observed patients. MATERIAL AND METHODS: The study included 396 patients operated for RCC between 1982 and 2001. The patients were classified according to age, gender, detection mode, pathological stage and grade, tumour size, nodal involvement and Eastern Cooperative Oncology Group (ECOG) performance status. Special attention was given to the analysis of duration and quality of symptoms. The endpoint of the study was overall survival, which was assessed with univariate and multivariate analyses using the Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: Of the 396 patients, 135 (34%) and 261 (66%) presented with incidental and symptomatic RCC, respectively. Compared with incidental cases, symptomatic tumours had significantly larger size (p < 0.0001), and higher pathological stage (p < 0.0001) and grade (p < 0.02). Five-year survival in patients with incidental and symptomatic tumours was 88.1% and 59.4% (p < 0.0001), respectively. In relation to the quality of symptoms, the 5-year survival in patients with local and systemic symptoms was 75.4% and 44.4% (p < 0.0001), respectively. In the group of patients with a history of tumour-related symptoms shorter and longer than 3 months, the 5-year survival was 62.2% and 55.6% (p < 0.0001), respectively. Multivariate analysis found tumour size [hazard ratio (HR) 1.22, p = 0.05] tumour grade (HR 1.44, p = 0.002), tumour stage (HR 1.35, p = 0.001), presence of symptoms (HR 1.36, p = 0.004) and ECOG (HR 1.25, p = 0.005) to be independent prognostic variables. CONCLUSION: Preoperative somatic symptoms and performance status in patients with RCC provide readily available prognostic information in addition to tumour size, stage and grade.