BACKGROUND AND OBJECTIVE:The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS:We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS:Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS:During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.

Background: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a rela-tively rare diagnosis with an ambiguous character owing to the presence of an aggres-sive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive.Objective: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas.Design, setting, and participants: Individual patient data for 5170 primary Ta-T1 blad-der tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018.Outcome measurements and statistical analysis: Time to recurrence and time to progres-sion were analyzed using cumulative incidence functions, log-rank tests, and multivari-able Cox-regression models with interaction terms stratified by institution.Results and limitations: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable anal-yses for recurrence and progression showed similar results. Conclusions: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomi-tant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought.Patient summary: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. Median follow-up was 45.3 (IQR 22.7–81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

Background: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. Objective: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. Design, setting, and participants: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. Outcome measurements and statistical analysis: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. Results and limitations: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. Conclusions: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. Patient summary: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer. (C) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. Design, setting, and participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. Outcome measurements and statistical analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. Results and limitations: A total of 3401 patients treated with TURBT + intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review. Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. Patient summary: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. OBJECTIVES:To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. MATERIALS AND METHODS:Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. RESULTS:PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. CONCLUSIONS:The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.

Macek P, Novak K, Pesl M, Stevens M, Hradec T, Fiala V, Gouveia R, Plincelnerova L, Vavřova L, Bauerova L, Hanus T. Laparoskopicka resekce ledviny - komplexni hodnoceni perioperacnich výsledků jednoho centra. Cil: Zhodnoceni perioperacnich funkcnich a onkologických výsledků laparoskopických nefron‑setřicich operaci pro nador ledvin. Material a metoda: Hodnoceny jsou udaje z prospektivně vedene databaze jednoho centra z obdobi od 1/2013 do 6/2018. Výkony provaděli tři operateři. Finalně bylo vyhodnoceno 174 pacientů. Uvedený pocet výkonů zahrnoval take jeden oboustranný výkon, děvet vicecetných jednodobých resekci (2-5 lezi) a v osmi připadech resekce solitarni ledviny. Celkem bylo odstraněno 190 ložisek (vlevo 102×, vpravo 88×), u 64 žen a 110 mužů. Mediany souboru (IQR = interkvartilove rozpěti): věk 64 (55-70) let, index komorbidit Charlesonove 3 (2-4), kreatinin 78 (68-95) µmol/L, velikost leze 27 (20-35) mm, PADUA skore 8 (7-9). Výsledky: Delka výkonu median 118 (IQR 88-150) min, krevni ztraty median 150 (IQR 80-300) ml, výkon bez ischemie (IT) 51×/190 lezi, delka IT median 15 (IQR 12-17) min, 2× proběhla konverze na otevřenou RL, 2x konverze na laparoskopickou nefrektomii. Během 30 dnů bylo zaznamenano 44 komplikaci Claviena‑Dinda (CD): stupeň 1-17×, 2-13×, 3-10×, 4-1×, 5-3×; tj. CD ≥ 3 u 8 % pacientů. Ve ctyřech připadech bylo zjistěno symptomaticke pseudoaneuryzma, ktere vždy vyřeseno selektivni embolizaci. Pooperacni hospitalizace byla s medianem 6 (IQR 5-7) dni. Histologicky bylo 45 lezi benignich, 145x malignich, z toho 122× pT1a, 16× pT1b, 3× pT2a, 4× pT3a. Pozitivni okraj byl zaznamenam u 11 %. Pouze jedna pacientka podstoupila otevřenou re‑resekci, ostatni byli sledovani. Při sledovani byla zaznamenana jedna lokalni recidiva v ledvině (při R0 výkonu), 1× rychla vzdalena progrese (mozkove metastazy) a 1× soucasně vzdalena (plice) i lokalni progrese v perirenalnim tuku (při R0). Trifekta hodnocena dle Montsouris (R0 výkon + IT ≤ 25 min + absence komplikace CD ≥ 3) dosažena u 74,1 %, dle Khalifeha a kol. (R0 + IT ≤ 25 min + žadna komplikace) u 59,2 %, dle Porpiglii a kol. (R0, IT ≤ 20 min, absence komplikace CD ≥ 3) u 69 %. Zavěr: Laparoskopicka RL je standardnim řesenim solidnich expanzi ledvin poskytujici přiznive výsledky. Mira dosaženi komplexniho klinickeho uspěchu (= trifekta) byla srovnatelna s literarnimi udaji.

We report six cases of anastomosing hemangioma of the ovary. All lesions were unilateral and arose in 43 to 81 year old females. In all but one patient, the tumor was asymptomatic and represented incidental finding. The exception was a tumor associated with massive ascites and elevated CA 125. The tumors were, on cut section, spongy and dark violet in color. The size of tumors ranged from 0.5 to 3.5 cm. All lesions showed the same histological features and consisted of capillary sized anastomosing vessels with sinusoid-like pattern intermingled with sporadic medium sized vessels. Interestingly, in all cases there were areas of luteinized cells at the tumor periphery, which ranged from rare small nests to multiple and commonly confluent areas. In one tumor, components of mature adipose tissue were present. Immunohistochemically, all tumors were CD31 and CD34 positive. Other markers examined were negative, including; estrogen receptor, progesterone receptor, androgen receptor, and D2–40. Proliferative activity (Ki-67 index) was very low in all cases. Anastomosing hemangioma is a rare entity, only 8 lesions occurring in ovary has been described from its initial description in 2009. We report six additional cases with their clinicopathological correlation.

The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in β-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied.

We report on a 61-year-old woman with a history of right-sided nephrectomy for clear cell renal cell carcinoma (RCC) occurring 21 years ago; she currently presented with a bilateral ovarian tumour. Histologically, the tumour of both ovaries was clear cell carcinoma. Immunohistochemically, the tumour cells were positive for vimentin, RCC marker, epithelial membrane antigen, cytokeratin AE1/3 and CD10. Cytokeratin 7, CA125, HMWCK, estrogen and progesterone receptors were all negative. Based on the morphology and immunophenotype of the tumour, we established a diagnosis of late metastasis of RCC in the ovaries. A postoperative abdominal computed tomography scan, however, revealed a tumour mass solely in the left kidney, which had not been visible in the preoperative ultrasound. The patient underwent nephron-sparing surgery and a biopsy showed the tumour to be clear cell RCC. Metastasis of RCC to the ovaries is rare, and to the best of our knowledge, only 24 cases have been reported to date. However, due to the different treatments and prognosis, the distinction between a primary ovarian tumour and metastasis of RCC is important.

The presented case displays a clinical study of a cancer phenotype with a poor clinical outcome. Prediction of cancer development and effects of treatment at the beginning of the clinical stage is difficult as the knowledge of cancer process and all necessary parameters of the host body are limited. Cancer is mainly studied on the basis of biochemical-genetic processes and their morphological manifestation. However, the malignant process is assumed to be of essential biophysical nature and develops after mitochondrial dysfunction, which is a direct result of oncogene mutation. Cancers based on the normal and the reverse Warburg effect should be distinguished. The cancer tumors with the reverse Warburg effect display aggressiveness associated with a high rate of recurrence and metastatic implantation. Besides the nature of the two basic types of breast cancer tumors the outcome depends not only on their type, size, and site but also on reactions and interaction with the surrounding tissue and the body aptitude for metastatic activity connected with individual blood or lymphatic vessels for metastatic transport. It is necessary to assess all favourable and adverse factors for cancer development. General reliable method of their specification for all cancers is not available. Nevertheless, the main factor seems to be aggressiveness of cancer cells as follows from interpretation. To reveal the aggressive reverse Warburg effect tumors, metabolic biomarkers of the fibroblast stress should be examined.

Since it is known that UV-C radiation kills fungus, we wanted to verify the hypothesis that the use of excimer laser could be an alternative method for treating onychomycosis - nail fungus. The aim of the first stage of this work was to determine the transmission, reflection and absorption of nails. In the following stage we focused on irradiation of fungi. Our final task is to assess whether it is possible to determine the parameters of radiation (a total dose, a dose per pulse frequency, a repetition rate, a number of pulses) for which the elimination of fungi would be the most effective but without damaging the nail and soft tissue underneath it. The results so far have showed that UV-C radiation does not pass through a fingernail to such an extent that it could damage the soft tissue beneath it. Fungi are destroyed by the application of only small doses of radiation using the excimer laser. Additional measurements will be required to determine the modulation parameters of the excimer laser radiation for the treatment of onychomycosis.