Ewing's sarcoma of the urinary bladder - the urologic and pathologic differential diagnosis and current therapeutic options.

BACKGROUND: Bladder cancer is 11th most common cancer worldwide. Histologically, most of the tumors are classified as urothelial carcinomas. Less common variants (squamous cell or adenocarcinomas) usually comprise up to 10% of cases. Other types of tumors are exceptional. The finding of Ewing's sarcoma in the bladder is considered extremely rare. CASE: We present the case of a 54-year-old female patient examined for painless hematuria. During the follow-up examination, a bulky tumor of the bladder was detected, but considering the extent of the bladder tumor, only a diagnostic transurethral resection was possible. According to the primary staging, the disease was already advanced at the time of admission with metastatic spread, anemia and present obstruction of the upper urinary tract. RESULTS: Histologically, Ewing's sarcoma was surprisingly demonstrated in the urinary bladder. Anemia caused by hematuria and advanced disease was corrected by blood transfusions and obstruction of the right kidney by puncture nephrostomy. However, despite a very quick diagnosis, completion of staging and preparation of the patient for further treatment, the patient had died before the planned systemic treatment began. CONCLUSION: The diagnosis of Ewing's sarcoma is identical to that of the other bladder tumors, i.e. transurethral resection. In the case of confirmation of this histological type, it is necessary to complete staging examinations and start multimodal treatment. Early systemic chemotherapy plays a key role and if metastatic spread is excluded, radical cystectomy or radiotherapy are included, too. The aim of our communication is to present a rare case of this disease, discuss the differential diagnosis and point out the principles and possibilities of its treatment.

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment.

BACKGROUND: The combination of intensity modulated radiation therapy (IMRT) and image guided radiotherapy (IGRT) plays a significant role in sparing normal tissue during prostate cancer treatment. We report the clinical outcomes of 260 patients treated with high-dose IGRT as well as the toxicity of high-dose IGRT in these patients. MATERIALS AND METHODS: From September 2008 to February 2012, 260 men with clinically localized prostate cancer underwent radical radiotherapy. Two hundred patients were treated with IMRT (78 Gy in 39 fractions) to the prostate and base of seminal vesicles using an adaptive protocol combining cone-beam computed tomography (CBCT) and kilovoltage image matching with individualized safety margin calculation. Sixty patients underwent treatment with the same prescribed dose using RapidArc with a reduced safety margin of 6 mm and daily online matching using CBCT. Late toxicity was scored prospectively according to the RTOG/FC-LENT scale. RESULTS: Eighteen patients (6.9%) experienced acute grade 2 gastrointestinal toxicity. There was no acute grade 3 or 4 gastrointestinal toxicity. Thirty-nine patients (15%) experienced acute grade 2 genitourinary toxicity and 6 patients (2.3%) had grade 3 gerourinary toxicity. Genitourinary toxicity grade 4 was observed in 5 (1.9%) patients, due to installation of a urinary catheter. At a median follow up of 84.2 months, the estimated 7-year cumulative incidences of grade 2 gastrointestinal and genitourinary toxicity were 4.4 and 7.1% respectively. The estimated 7-year prostate specific antigen relapse free survival was 97.1% for low-risk disease, 83.6% for intermediate-risk disease and 75% for high-risk patients. CONCLUSION: The use of IMRT in combination with IGRT results in a low rate of late toxicity. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 9. 2019 Accepted: 25. 10. 2019.

Acute and sub-acute oral toxicity studies of standardized extract of Nasturtium officinale in Wistar rats.

Nasturtium officinale (watercress) is a perennial dicotyledonous plant, rich in vitamins, minerals and chemical compounds. The leaves of this plant, which contain glucosinolate, are used for its diuretic and hypoglycemic effects. The purpose of the study was to investigate the safety of the standardized extract of Nasturtium officinale (SENO) with phenylethyl glucosinolate 5.0 mg/ml-1, using acute and sub-acute oral dosage in Wistar rats. High-Performance Liquid Chromatography (HPLC) analyzed the chemical composition, from aerial parts of watercress. In the acute toxicity study, dose estimated was LD50 in the range of 2000-5000 mg/kg, signs of mortality and toxicity on female rats were observed for 14 days, after single doses of 2000 and 5000 mg/kg. In the sub-acute study, female and male rats, age 10 weeks, were supplemented at doses of 250, 500 and 1000 mg/kg for 28 days. On the 29th day, rats were fasted, anesthetized, euthanized, then their blood used for hematological and biochemical evaluation. No significant changes in general behavior were reported regarding the acute study, while the sub-acute study demonstrated no toxicity of the hematopoietic and biochemical systems. The results showed that SENO at dosage up to 5000 mg/kg in acute study was safe, and NOAEL (no-observed-adverse-effect levels) in the sub-acute, was up to 1000 mg/kg.

Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte-Induced Lysis.

The integrity of the vasculature plays an important role in the success of allogeneic organ and haematopoietic stem cell transplantation. Endothelial cells (EC) have previously been shown to be the target of activated cytotoxic T lymphocytes (CTL) resulting in extensive cell lysis. Mesenchymal stromal cells (MSC) are multipotent cells which can be isolated from multiple sites, each demonstrating immunomodulatory capabilities. They are explored herein for their potential to protect EC from CTL-targeted lysis. CD8(+) T cells isolated from human PBMC were stimulated with mitotically inactive cells of a human microvascular endothelial cell line (CDC/EU.HMEC-1, further referred to as HMEC) for 7 days. Target HMEC were cultured in the presence or absence of MSC for 24 h before exposure to activated allogeneic CTL for 4 h. EC were then analysed for cytotoxic lysis by flow cytometry. Culture of HMEC with MSC in the efferent immune phase (24 h before the assay) led to a decrease in HMEC lysis. This lysis was determined to be MHC Class I restricted linked and further analysis suggested that MSC contact is important in abrogation of lysis, as protection is reduced where MSC are separated in transwell experiments. The efficacy of multiple sources of MSC was also confirmed, and the collaborative effect of MSC and the endothelium protective drug defibrotide were determined, with defibrotide enhancing the protection provided by MSC. These results support the use of MSC as an adjuvant cellular therapeutic in transplant medicine, alone or in conjunction with EC protective agents such as defibrotide.

[Five-year results of IMRT for prostate cancer - toxicity]. / Petileté výsledky IMRT karcinomu prostaty - toxicita.

BACKGROUND: Intensity modulated radiotherapy (IMRT) plays a crucial role in the treatment of prostate cancer thanks to its capacity for healthy tissue sparing. This work reports on the acute and late toxicity rates among 233 patients treated with high-dose IMRT. MATERIAL AND METHODS: From June 2003 to December 2007, 233 men with clinically localized prostate cancer underwent radical radiotherapy. One hundred sixty patients were treated with IMRT to the prostate and the base of seminal vesicles to 78 Gy in 39 fractions, 73 patients underwent simultaneous integrated boost. Prescribed doses were 82 Gy and 73,8 Gy in 41 fractions to the prostate and seminal vesicles, respectively. Late toxicity was evaluated prospectively using a RTOG/FC-LENT score. RESULTS: Thirty patients (12.8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. No acute Grade 3 or 4 GI toxicity developed. Forty two patients (18.1%) experienced acute Grade 2 genitourinary toxicity and 23 patients (9.9%) had Grade 3 GU toxicity. Grade 4 Genitourinary toxicity was observed in nine (3.8%) patients, due to a need of short-term urinary catheterization. With a median follow-up of 49.2 months, the estimated 5-year cumulative incidence of Grade 2 gastrointestinal toxicity was 22.4%. The estimated 5-year cumulative incidence of Grade 2 genitourinary toxicity was 17.7%. CONCLUSION: Intensity modulated radiotherapy enables dose escalation to 78-82 Gy with an acceptable toxicity.

Neoadjuvant hormonal therapy in prostate cancer - impact of PSA level before radiotherapy.

PURPOSE: To retrospectively investigate the impact of prostate specific antigen (PSA) level after neoadjuvant androgen- deprivation therapy (ADT) on biochemical relapse-free survival in patients with prostate cancer who received radical radiotherapy (RT). METHODS: Between March 2003 and March 2008, 128 men with localized prostate cancer underwent neoadjuvant ADT for 4-6 months followed by radical RT. Biochemical relapse-free survival was compared between patients with pre-RT PSA ≤ 0.1 vs > 0.1 ng/mL. RESULTS: At a median follow up of 47.3 months, biochemical relapse-free survival was significantly higher in patients with a pre-RT PSA ≤ 0.1 ng/mL compared with pre-RT PSA > 0.1 ng/mL (85.6 vs 63.2%, p = 0.0025). CONCLUSION: The current analysis demonstrating better treatment outcome in patients with excellent biochemical response to neoadjuvant ADT, supports an individualized treatment strategy.

[Testicular appendix torsion can mimic a tumour of the paratesticular tissues]. / Die Hydatidentorsion kann einen Tumor des paratestikulären Gewebes vortäuschen.

The authors present a case of testicular appendix torsion that mimicked a tumour of the paratesticular tissues due its calm clinical course, objective palpation and ultrasound finding. The torsion of the big testicular appendix was found during surgery from an inguinal approach. The histological examination confirmed only minimal inflammation changes and excluded tumour disease.

[Right-ventricular dysfunction and the pulmonary vascular obstruction index: predictable variables of the clinical course over 3 months in patients with acute lung emboli]. / Rechterventrikeldisfunctie en index voor pulmonale vasculaire obstructie: voorspellende variabelen voor het klinische beloop gedurende 3 maanden bij patiënten met acute longembolie.

OBJECTIVE: To quantify right-ventricular dysfunction and the pulmonary artery obstruction index, in patients with acute pulmonary embolism, using helical CT, and to assess the prognostic value of these parameters. DESIGN: Prospective. METHOD: In 120 consecutive patients with proven acute pulmonary embolism, the extent of right-ventricular dysfunction was assessed by quantifying the ratios of the right to left-ventricular short-axis diameters (RV/LV ratio) and the extent ofobstruction ofthe pulmonary-artery circulation by using helical CT images. Regression analysis was used to correlate these parameters with patient outcome. RESULTS: Right-ventricular dysfunction (RV/LV ratio > 1.0) was seen in 69 patients (57.5%). Seven patients died as a direct result of pulmonary embolism. Both the RV/LV ratio and the obstruction index were significant risk factors for mortality within three months (p = 0.04 and 0.01 respectively). The positive predictive value for pulmonary embolism-related mortality of an RV/LV ratio > 1.0 was 10.1% (95% CI: 2.9-17.4). The negative predictive value for an uneventful outcome of an RV/LV ratio < or = 1.0 was 100% (95% CI: 94.3-100). There was a 11.2-fold risk of dying of pulmonary embolism in patients with an obstruction index > or = 40% (95% CI: 1.3-93.6). CONCLUSION: Markers of right-ventricular dysfunction and pulmonary vascular obstruction, assessed by helical CT-examination at baseline, help to predict mortality during follow-up of patients with acute pulmonary embolism.

Maternal insertion of 18q11.2-q12.2 in 18p11.3 of the same chromosome analysed by microdissection and multicolour banding (MCB).

OBJECTIVES: Different aberrations in one chromosome 18 were prenatally detected during each of three different pregnancies of a healthy woman. Routine cytogenetic analysis revealed a morphologically altered maternal chromosome 18 as well. The purpose of the current study was to characterize these cytogenetic changes in detail and thus to clarify the reason for the recurrent appearance of morphologically altered chromosomes 18 in this family. METHODS: As GTG banding did not allow resolution of the kind of aberrations present in these four cases, the following molecular cytogenetic approaches were used: microdissection combined with reverse painting and multicolour banding (MCB) analysis using a chromosome 18 specific probe set. RESULTS: Molecular cytogenetic approaches revealed that fetus 1 had a derivative chromosome del(18)(q11.2q12.2), fetus 2 and the mother had the identical derivative chromosomes ins(18)(pterp11.32::q12.2q11.2::p11.32q11.2::q12.3qter) and fetus 3 had a dup(11.2q12.2). CONCLUSION: Partial monosomy in fetus 1 and partial trisomy in fetus 3 can be explained by crossing over events during maternal meiosis.

Podocyte injury underlies the progression of focal segmental glomerulosclerosis in the fa/fa Zucker rat.

BACKGROUND: The progression of diabetic nephropathy to chronic renal failure is based on the progressive loss of viable nephrons. The manner in which nephrons degenerate in diabetic nephropathy and whether the injury could be transferred from nephron to nephron are insufficiently understood. We studied nephron degeneration in the fa/fa Zucker rat, which is considered to be a model for non-insulin-dependent diabetes mellitus. METHODS: Kidneys of fa/fa rats with an established decline of renal function and of fa/+ controls were structurally analyzed by advanced morphological techniques, including serial sectioning, high-resolution light microscopy, transmission electron microscopy, cytochemistry, and immunohistochemistry. In addition, tracer studies with ferritin were performed. RESULTS: The degenerative process started in the glomerulus with damage to podocytes, including foot process effacement, pseudocyst formation, and cytoplasmic accumulation of lysosomal granules and lipid droplets. The degeneration of the nephron followed the tuft adhesion-mediated pathway with misdirected filtration from capillaries included in the adhesion toward the interstitium. This was followed by the formation of paraglomerular spaces that extended around the entire glomerulus, as well as via the glomerulotubular junction, to the corresponding tubulointerstitium. This mechanism appeared to play a major role in the progression of the segmental glomerular injury to global sclerosis as well as to the degeneration of the corresponding tubule. CONCLUSIONS: The way a nephron undergoes degeneration in this process assures that the destructive effects remain confined to the initially affected nephron. No evidence for a transfer of the disease from nephron to nephron at the level of the tubulointerstitium was found. Thus, each nephron entering this pathway to degeneration appears to start separately with the same initial injuries at the glomerulus.

Technegas versus (81m)Kr ventilation-perfusion scintigraphy: a comparative study in patients with suspected acute pulmonary embolism.

UNLABELLED: 81mKr is widely used as a ventilation agent to diagnose pulmonary embolism (PE). However, (81m)Kr is expensive, which limits its continuous availability. Technegas can be an alternative ventilation agent with the advantage of being less expensive and available daily. The aim of this study was to compare the value of technegas with that of (81m)Kr in the detection of PE. METHODS: Ninety-two consecutive patients (29 men; mean +/- SD, 53 +/- 17 y old) with at least one segmental perfusion defect (Hull criteria) were studied prospectively. Perfusion and ventilation (V/Q) lung scintigraphy with both technegas and (81m)Kr were performed within 24 h on all patients. V/Q lung scan results were classified as high probability for PE (normal ventilation study) or nondiagnostic (abnormal ventilation study). All V/Q lung scans were read by two experienced nuclear physicians in consensus. For the intra- and interobserver variabilities, two experienced observers independently read the V/Q lung scans. RESULTS: (81m)Kr and technegas showed a good agreement (kappa, 0.68; 95% confidence interval [CI], 0.53-0.82). However, technegas significantly increased the number of nondiagnostic V/Q lung scans (P: = 0.035). In 15 patients, a discrepancy was found between (81m)Kr and technegas. False-positive V/Q lung scan results occurred in 4 of 12 patients (33%) with (81m)Kr and in 2 of 3 patients (66%) with technegas. The intra- and interobserver variabilities were 0.71-0.88 (95% CI, 0.56-1.0) for perfusion/(81m)Kr and 0.74-0.96 (95% CI, 0.58-1.0) for perfusion/technegas. CONCLUSION: In comparison with (81m)Kr, technegas does not result in more false-positive V/Q lung scan results. The use of technegas, however, increases the number of nondiagnostic V/Q lung scan results, which would increase the demand for further additional testing to confirm or refute PE.

Acute pulmonary embolism: impact of selection bias in prospective diagnostic studies. ANTELOPE Study Group. Advances in New Technologies Evaluating the Localization of Pulmonary Embolism.

We evaluated selection bias in a prospective study of 1,162 consecutive patients with suspected pulmonary embolism. Of these, 983 were eligible, and 627 could actually be included. During two months extensive data were collected on all non-included patients. Finally, our patient characteristics were compared with those of the PIOPED study (1990) and the study of Hull et al. (1994). Compared with included patients, the non-included patients had more often non-diagnostic V/Q scans (50% vs. 36%, p <0.01) and were more often already hospitalized (31% vs. 22%, P = 0.04). The subgroup of patients not included due to refusal or inability to give informed consent (IC) was older (mean age 61 vs. 53 years, P <0.01), more often suffered from malignancies (26% vs. 11%, P <0.01) and frequently had non-diagnostic V/Q scans (57%) as compared to included patients. In our study, 54% of all patients screened was eventually included versus 27% in the PIOPED study. In the PIOPED study patients who had contra-indications for pulmonary angiography were excluded, while in the study of Hull et al. those with inadequate cardiorespiratory reserve were excluded. In studies on new diagnostic technologies, patient selection bias does occur. The potential for such a selection bias should be taken into account when diagnostic strategies are devised to improve their generalizability and acceptability.

An immunoassay for terbutryn using direct hapten linkage to a glutaraldehyde network on the polystyrene surface of standard microtiter plates.

2-Aminobutylamino-4-ethylamino-6-isopropylamino-1,3,5-triazine (ABA-atrazine) has been synthesized and used as a coating hapten in an immunoassay with a monoclonal antibody against terbutryn. Coating was achieved by covalently linking ABA-atrazine to a glutaraldehyde polymer network directly bound to the polystyrene surface of a standard 96-well microtiter plate. The assay was carefully optimized. In particular, the coating hapten concentration had a strong effect on the ELISA sensitivity. By including a pre-incubation step a low test midpoint (IC50-value) of 0.130 microg L(-1) was achieved. As far as we are aware this is the most sensitive ELISA for terbutryn yet reported. The coating-hapten-format presented is proposed as generally applicable, because the glutaraldehyde-modified microtiter plate surface enables stable immobilization of a broad variety of coating haptens.

Diagnosing acute pulmonary embolism: effect of chronic obstructive pulmonary disease on the performance of D-dimer testing, ventilation/perfusion scintigraphy, spiral computed tomographic angiography, and conventional angiography. ANTELOPE Study Group. Advances in New Technologies Evaluating the Localization of Pulmonary Embolism.

In patients with chronic obstructive pulmonary disease (COPD), differentiating a pulmonary embolism (PE) from an exacerbation of COPD can be difficult, since clinical signs and symptoms of the two conditions overlap. Development of reliable noninvasive or minimally invasive techniques for the diagnosis of PE is, especially in these patients, necessary. In this study we assessed the effect of COPD on the accuracy of the clinical probability estimate (CPE), spiral computed tomographic angiography (SCTA), D-dimer analysis, ventilation perfusion (V/Q) scintigraphy, and pulmonary angiography for the diagnosis of PE. From May 1997 through March 1998, 627 consecutive patients with suspected PE were investigated in six teaching hospitals. In these patients, D-dimer testing, CPE, V/Q scintigraphy, and SCTA and/or pulmonary angiography were performed according to a strict diagnostic protocol. The patients were also independently categorized as having COPD or not. A diagnosis of COPD was established in 91 patients (15%). The prevalence of PE was similar in patients with and without COPD (29% and 31%, respectively), notwithstanding the larger proportion of nondiagnostic V/Q scan results in patients with COPD (46% versus 21%, p < 0.001). The distribution of CPEs, diagnostic value of the D-dimer assay and SCTA, and reproducibility of pulmonary angiography were comparable among patients with and without COPD. The presence of COPD does not affect the diagnostic performance of CPE, D-dimer testing, SCTA, or pulmonary angiography. Furthermore, although more nondiagnostic V/Q scan results can be expected in the presence of COPD, V/Q scintigraphy remains a valuable screening test in patients with COPD.

Normal perfusion scintigraphy in pulmonary embolism. Causes and diagnostic alternatives.

Diagnosing pulmonary embolism (PE) is a challenge for many physicians as it is a frequently occurring disease with nonspecific symptoms and signs. Ventilation-perfusion (V/Q) scintigraphy is widely used as the first step in diagnosing PE since it is non-invasive and highly sensitive. With a normal perfusion scan, clinically relevant pulmonary thrombo-emboli are considered to be absent. In an ongoing study assessing the value of spiral CT in the diagnosis of PE, we encountered a patient who had a normal perfusion scan while a large partially occluding thrombus in the right lower lobe artery and its branches was depicted by spiral CT and pulmonary angiography. In this article, we discuss the significance of normal findings in perfusion scintigraphy, the causes of false-negative perfusion scans and the role of alternative techniques such as spiral CT and pulmonary angiography.

The prognostic significance of subclinical hepatic encephalopathy.

OBJECTIVE: Subclinical hepatic encephalopathy may have prognostic significance with regard to the development of clinical hepatic encephalopathy and survival. METHODS: We studied 116 consecutive patients with histologically proven cirrhosis of the liver for subclinical hepatic encephalopathy, using Number Connection Test A, Digit Symbol Test, and spectral analysis of the electroencephalogram. RESULTS: Twenty-five patients (22%) were diagnosed as having subclinical hepatic encephalopathy. Patients with subclinical hepatic encephalopathy were older, had a higher Child-Pugh score, and more often had esophageal or gastric varices and episode(s) of clinical hepatic encephalopathy in their history. During a median follow-up of 29 months (range, 1-49 months), patients with subclinical hepatic encephalopathy significantly more often had episodes of clinical hepatic encephalopathy; survival, however, was similar to that of patients without subclinical hepatic encephalopathy, and was determined mainly by the Child-Pugh score. The Child-Pugh score was also superior to subclinical hepatic encephalopathy in predicting episodes of clinical hepatic encephalopathy. CONCLUSIONS: The prognostic significance of subclinical hepatic encephalopathy appears limited.

New developments in immunochemical water analysis down to 30 mul sample volume.

The determination of trace levels of pesticides like atrazine in water samples of small, restricted volumes is one of the future demands of environmental analysis. In a brief review existing chromatographic and immunochemical methods for atrazine are critically discussed. Then a simple rapid enzyme-linked immunosorbent assay (ELISA) using the tip of an inoculation needle as a solid surface is presented. The sample volume could be reduced to 30 mul. The assay had a centre of the test IC(50) of 0.12 mug l(-1) and permitted the characterisation of atrazine at levels of 0.022-2.90 mug l(-1). A first outlook for automatisation is given. The new method was compared with an ELISA using 96 well microtiter plates as a solid phase. Surface water samples with low atrazine contents were analysed to check the new method.

Subclinical hepatic encephalopathy impairs daily functioning.

Subclinical hepatic encephalopathy (SHE) is assumed to have a negative effect on patients' daily functioning; therefore, treatment is recommended. However, no studies have been performed that document the clinical relevance of SHE. We performed a study in which the prevalence of SHE was determined in 179 outpatients with cirrhosis using two psychometric tests (Number Connection Test Part A [NCT-A] and the Digit Symbol Test [DGT]) and automated analysis of the electroencephalogram (EEG). SHE was defined by the presence of at least one abnormal psychometric test and/or abnormal slowing of the EEG. The influence of cirrhosis and SHE on patients' daily functioning was assessed using the Sickness Impact Profile (SIP) questionnaire. The distribution of SIP scores of the patients with cirrhosis differed from the reference scores of the general population. Patients with cirrhosis and SHE (n = 48) reported significantly more impairment in all 12 scales of the SIP, in the psychosocial subscore, the physical subscore, as well as in the total SIP score, compared with cirrhotic patients without SHE (n = 131). Multivariate analysis taking into account severity of liver disease (Child-Pugh score), presence of varices, and alcoholic etiology, showed that SHE independently was related to a diminished total SIP score. The reproducibility of the SIP was high when the test was repeated after a 3-month period. We conclude that SHE implies impaired daily functioning and warrants attempts at treatment.