AIMS: We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). METHODS AND RESULTS: We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. CONCLUSIONS: En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.

• Klíčová slova
• bladder cancer, en‐bloc TUR, invasion, pT1, pathological diagnosis, progression,
• MeSH
• cystektomie metody   MeSH
• dospělí MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• nádory močového měchýře * patologie   chirurgie   mortalita   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: There is no consensus regarding the indication for postoperative radiotherapy (PORT) for T1- and T2-classified squamous cell carcinoma (SCC) of the external auditory canal (EAC) even with negative surgical margins. This study aimed to evaluate whether PORT provides additional benefits for these cases. METHODS: We collected retrospective data from fourteen international hospitals, including resected pT1- and pT2-classified EAC SCC with negative surgical margins. RESULTS: A total of 112 early-stage radically resected EAC SCC were included, with 48 patients receiving PORT. The 5-year DFS of T1- and T2-classified EAC SCC treated with PORT was not statistically significantly different (92.9% and 76.9%, respectively) compared to the group treated without PORT (100% and 90.9%, respectively; p-values of 0.999 and 0.526, respectively). EAC SCC treated with PORT more frequently exhibited perineural and angioinvasive growth. Eighteen patients experienced side effects related to radiotherapy, of which one patient developed osteoradionecrosis. CONCLUSIONS: Our study suggests that PORT for early-stage radically resected EAC SCC should only be considered in selected cases with perineural, infiltrative growth or angioinvasive growth, and with a close margin. This approach helps mitigate the negative impact on quality of life and the risk of side effects associated with radiotherapy.

• Klíčová slova
• disease-free survival, radiotherapy, squamous cell carcinoma, temporal bone, treatment,
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To assess the clinical significance of repeat transurethral resection (reTUR) and surgical margin status after en bloc resection of bladder tumour (ERBT) for pathological T1 (pT1) bladder cancer. PATIENTS AND METHODS: We retrospectively analysed the record of 106 patients with pT1 high-grade bladder cancer who underwent ERBT between April 2013 and February 2021 at multiple institutions. All specimens were reviewed by a genitourinary pathologist. The primary outcome measures were recurrence-free survival (RFS) and progression-free survival (PFS) between patients with and those without reTUR. We also analysed the predictive value of surgical margin on the likelihood of residual tumour on reTUR. RESULTS: A reTUR was performed in 50 of the 106 patients. The 2-year RFS and 3-year PFS were comparable between patients who underwent reTUR and those who did not (55.1% vs 59.9%, P = 0.6, 80.6% vs 82.6%, P = 0.6, respectively). No patient was upstaged to pT2 on reTUR. Regarding the surgical margin status, there were no recurrences at the original site in 51 patients with negative horizontal margins. Cox proportional hazard analysis revealed that a positive vertical margin was an independent prognostic factor of worse PFS. On reTUR, six pTa/is residues were detected in patients with a positive horizontal margin, and three pT1 residues were detected in one patient with a positive vertical margin or other adverse pathological features. CONCLUSIONS: A reTUR after ERBT for pT1 bladder cancer appears not to improve either recurrence or progression. Surgical margin status affects prognosis and reTUR outcomes. A reTUR can be omitted after ERBT in patients with pT1 bladder cancer and negative margins; for those with positive horizontal or vertical margins, reTUR should remain the standard until proven otherwise.

• Klíčová slova
• Bladder cancer, en bloc TUR, pT1, progression, recurrence, repeat TURs,
• MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• močový měchýř patologie   MeSH
• nádory močového měchýře * chirurgie   patologie   MeSH
• resekční okraje * MeSH
• retrospektivní studie MeSH
• urologické chirurgické výkony MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial. OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation. EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out. EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5. CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended. PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

• Klíčová slova
• Chemotherapy, Meta-analysis, Non–muscle-invasive bladder cancer, Single instillation, Systematic review,
• MeSH
• aplikace intravezikální MeSH
• časové faktory MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   MeSH
• epirubicin aplikace a dávkování   MeSH
• karcinom z přechodných buněk mortalita   patologie   terapie   MeSH
• lidé MeSH
• lokální recidiva nádoru prevence a kontrola   MeSH
• míra přežití MeSH
• mitomycin aplikace a dávkování   MeSH
• nádory močového měchýře mortalita   patologie   terapie   MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• staging nádorů MeSH
• thiotepa aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• doxorubicin MeSH
• epirubicin MeSH
• mitomycin MeSH
• pirarubicin MeSH Prohlížeč
• thiotepa MeSH

PURPOSE: TaG3 bladder cancer is an under-investigated disease and because of its rarity it is commonly studies together with T1G3 disease. We sought to exclusively study TaG3 disease and to determine the factors associated with disease progression. MATERIAL AND METHOD: We retrospectively studied patients with primary TaG3 bladder cancer. Progression to ≥pT1 and pT2 were analyzed using Cox and competing-risk regression analyses. RESULTS: Of 3,505 consecutive patients with nonmuscle invasive bladder cancer, 285 patients had primary TaG3 without concomitant carcinoma in-situ. Progression to ≥pT1 occurred in 21 patients (7.4%). In a multivariable competing-risk regression analysis, intravesical Bacillus Calmette-Guerin (BCG) was significantly associated with a lower risk of progression to ≥pT1 (HR 0.23, 95%CI 0.08-0.64, P = 0.005). Recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥pT1 (HR 7.81, 95%CI 2.50-24.44, P < 0.001). Progression to ≥T2 was observed in 9 patients (3.2%). In univariable competing-risk regression analyses, intravesical BCG was significantly associated with a lower risk of progression to ≥pT2 (HR 0.11, 95%CI 0.04-0.47, P = 0.003). On the other hand, recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥T2 (HR 7.12, 95%CI 1.50-33.77, P = 0.013). In a subgroup of 199 patients who were treated with BCG, there was no statistically significant association between tumor recurrence in the 1st year of diagnosis and stage progression to ≥pT1 (P = 0.14) or ≥pT2(P = 0.19). CONCLUSION: Patients with TaG3 bladder cancer are considered high risk but if appropriately treated with BCG that risk is considerably mitigated. Our data support that TaG3 without concomitant carcinoma in-situ should not be considered as aggressive as T1G3 as it has a lower risk of progression to muscle-invasive bladder cancer. Recurrence in the first year after diagnosis is the strongest predictor of progression to muscle-invasive bladder cancer.

• Klíčová slova
• Bladder cancer, NMIBC, TaG3, progression, recurrence,
• MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře patologie   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: This review aims to analyze the current place of active surveillance (AS) in non-muscle-invasive bladder cancer (NMIBC). RECENT FINDINGS: A growing body of evidence suggests that AS protocols for pTa low-grade (TaLG) NMIBC are safe and feasible. However, current guidelines have not implemented AS due to a lack of high-quality data. Available studies included pTa tumors, with only one study excluding pT1-NMIBC. Inclusion/exclusion criteria were heterogeneously defined based on tumor volume, number of tumors, carcinoma in situ (CIS), or high-grade (HG) NMIBC. Tumor volume <10 mm and <5 lesions were used as cut-offs. Positive urinary cytology (UC) or cancer-related symptoms precluded inclusion. Surveillance within the first year consisted of quarterly cystoscopy. AS stopped upon the presence of cancer-related symptoms, change in tumor morphology, positive UC, or patient's request. With a median time on AS of 16 months, two-thirds of the patients failed AS. Progression to muscle-invasive bladder cancer (MIBC) was rare and occurred only in patients with pT1-NIMBC at inclusion. SUMMARY: AS in NMIBC is an attractive concept in the era of personalized medicine, but strong evidence is still awaited. A more precise definition of patient inclusion, follow-up, and failure criteria is required to improve its implementation in daily clinical practice.

• MeSH
• cystoskopie MeSH
• invazivní růst nádoru MeSH
• karcinom in situ * epidemiologie   terapie   MeSH
• lidé MeSH
• nádory močového měchýře * diagnóza   epidemiologie   terapie   MeSH
• pozorné vyčkávání MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Hop is an important source of medicinally valuable secondary metabolites including bioactive prenylated chalcones. To gain in-depth knowledge of the regulatory mechanisms of hop flavonoids biosynthesis, full-length cDNA of HlMyb8 transcription factor gene was isolated from lupulin glands. The deduced amino acid sequence of HlMyb8 showed high similarity to a flavonol-specific regulator of phenylpropanoid biosynthesis AtMYB12 from Arabidopsis thaliana. Transient expression studies and qRT-PCR analysis of transgenic hop plants overexpressing HlMyb8 revealed that HlMYB8 activates expression of chalcone synthase HlCHS_H1 as well as other structural genes from the flavonoid pathway branch leading to the production of flavonols (F3H, F'3H, FLS) but not prenylflavonoids (PT1, OMT1) or bitter acids (VPS, PT1). HlMyb8 could cross-activate Arabidopsis flavonol-specific genes but to a much lesser extent than AtMyb12. Reciprocally, AtMyb12 could cross-activate hop flavonol-specific genes. Transcriptome sequence analysis of hop leaf tissue overexpressing HlMyb8 confirmed the modulation of several other genes related to flavonoid biosynthesis pathways (PAL, 4CL, ANR, DFR, LDOX). Analysis of metabolites in hop female cones confirmed that overexpression of HlMyb8 does not increase prenylflavonoid or bitter acids content in lupulin glands. It follows from our results that HlMYB8 plays role in a competition between flavonol and prenylflavonoid or bitter acid pathways by diverting the flux of CHS_H1 gene product and thus, may influence the level of these metabolites in hop lupulin.

• Klíčová slova
• Bitter acids, Chalcone synthase, Flavonoids, Humulus lupulus, R2R3 myb, RNA sequencing,
• MeSH
• flavonoidy biosyntéza   MeSH
• fylogeneze MeSH
• geneticky modifikované rostliny genetika   metabolismus   MeSH
• Humulus genetika   metabolismus   MeSH
• listy rostlin metabolismus   MeSH
• rostlinné proteiny chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• stanovení celkové genové exprese MeSH
• tabák genetika   metabolismus   MeSH
• transkripční faktory chemie   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• flavonoidy MeSH
• rostlinné proteiny MeSH
• transkripční faktory MeSH

BACKGROUND: The effect of radical resection in gallbladder cancer is still area of debate. AIM OF STUDY: To determine the criteria of surgery in primary and incidental gallbladder cancer. method: Eighty-four patients with gallbladder cancer were evaluated between 1999 and 2008. Sixty patients (72.4%) were symptomatic. Explorative laparotomy was performed in 40 (66.7%), palliative procedure in 5 (8.3%) patients in stage pT3-4, N1, M0-1. Cholecystectomy only or completed with wedge resection of the gallbladder bed and lymfadenectomy as radical procedure was performed only in 7 (1.7%) patients in pT1-2, N0-1, M0. Twenty four (28.6%) patients had incidental gall bladder carcinoma. Radical cholecystectomy was performed in 4 (16.7%) - pT1a, N0, M0, palliative cholecystectomy in 3 patients (12.5%) - pT3, N1, M0. Radical reoperation was performed in 15 (62.5%) patients in stage pT1b-2, N0-1, M0. RESULTS: Patients survival after explorative laparotomy and palliative procedures was no longer than 7 months. Four from seven patients died after radical operation 12-18 months after operation. Six from 15 radically re-operated patients are alive in interval 4 months and 8 years. Nine patients died in interval 9 months and 4 years after re-operation. CONCLUSION: Radical surgical procedure is the treatment of choice for patients with gall bladder carcinoma especially in stage pT1-2, N0, M0.

• MeSH
• cholecystektomie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory žlučníku diagnóza   chirurgie   MeSH
• reoperace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

BACKGROUND: Radical cystectomy with pelvic lymphadenectomy and urinary diversion is standard treatment in patients with muscle-invasive and selected high-risk superficial bladder cancers. The aim of our study was to evaluate oncological results and correlate prognosis with the extent of the disease. METHODS AND RESULTS: Data of 125 patients (33 females and 92 males) with mean age of 59.8 years were analysed. Histological diagnosis was urothelial carcinoma in 114, squamous cell carcinoma in 8 and small-cell carcinoma in 3 patients respectively. During the mean follow-up of 22.4 months the disease-free survival (DFS) and disease-specific survival (DSS) were evaluated according to the extent of the disease. Tumours were classified as pTa, pT1, pTis in 31 (24.8%), as pT2 in 39 (31.2%), as pT3 in 24 (19.2%) and pT4 in 20 (16%) patients respectively. There was no tumour detected in the specimen in 11 (8.8%) of cases (pT0). Lymph node metastases were confirmed in 36 (28.8%) of patients. Three-year DFS and DSS were 100% and 100% in pT0, 76% and 87.1% in pTa, pT1, pTis, 69.2% and 82.9% in pT2, 32.9% and 62.4% in pT3 and 39.5% and 36.8% in pT4 tumours respectively (p = 0.0001, p = 0.0004). Three-year DFS and DSS reached 69.4% and 51.8% in patients with negative lymph nodes and 51.8% and 44.8% in patients with lymph node involvement (p = 0.0008, p < 0.0001). CONCLUSIONS: DFS and DSS after radical cystectomy depend from the local extent of the tumour and from lymph node status, which is a strong argument for its timely indication.

• MeSH
• cystektomie * MeSH
• dospělí MeSH
• karcinom z přechodných buněk mortalita   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie MeSH
• nádory močového měchýře mortalita   chirurgie   MeSH
• přežití bez známek nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom mortalita   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

PURPOSE: Detrusor muscle (DM) in the resected specimen of patients with pT1 bladder cancer (BCa) is a quality-of-care criteria. We aimed to assess whether obtaining adequate DM is dependent on surgeon's experience, whether is a surrogate for resection quality, and whether the degree of DM thickness is related to postoperative outcomes in en bloc resection for bladder tumors (ERBT). MATERIALS AND METHODS: We retrospectively analyzed the records of 106 pT1 high-grade BCa patients who underwent ERBT at several institutions. All specimens were reviewed by a single pathologist who assessed the presence or absence of DM and its thickness measured by a micrometer, when present. Early recurrence, defined as pathologically confirmed BCa on repeat resection or tumor recurrence at the first follow-up cystoscopy (within 3 months), was the endpoint reflective of the resection quality. RESULTS: Of 106 patients, DM was detected in 99 (93%), and the median DM thickness was 1.8 mm. Large tumor size (>30 mm) was associated with adequate DM sampling (>1.8mm) (odds ratio [OR]: 6.10, 95% confidence intervals [CIs]: 2.08-17.9, P = 0.001), while surgeon's experience was not. DM presence and DM thickness were both not associated with early recurrence, while positive surgical margin was an independent prognosticator for early recurrence (OR: 3.38, 95% CI: 1.12-10.2, P = 0.031). Excessive DM sampling (>2.1 mm) was associated with prolonged urethral catheterization (OR: 28.8, 95% CI: 3.36-248, P = 0.002). CONCLUSIONS: In ERBT, surgeon's experience seems irrelevant to obtain DM. Resection quality relies on surgical margin status, not the degree of DM. Obtaining excessive DM incurs adverse events/unnecessary medical care.

• Klíčová slova
• Detrusor muscle, En bloc resection, Muscularis propria, Non–muscle-invasive bladder cancer, T1, TURBT,
• MeSH
• cystektomie MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   MeSH
• nádory močového měchýře * chirurgie   patologie   MeSH
• retrospektivní studie MeSH
• svaly patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH