Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non-muscle-invasive Spectrum.

BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive 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 bladder 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 progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable 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 analyses 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 concomitant 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.

T1G1 Bladder Cancer: Prognosis for this Rare Pathological Diagnosis Within the Non-muscle-invasive Bladder Cancer Spectrum.

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.

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.

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.

Tumor carcinoide primario de ovario que se presenta como enfermedad cardiaca carcinoide / Primary carcinoid tumor of the ovary presenting with carcinoid heart disease / Primary carcinoid tumor of the ovary presenting with carcinoid heart disease

RESUMEN El tumor carcinoide primario de ovario es una entidad poco frecuente que se caracteriza por la producción de sustancias vasoactivas que pasan directamente al torrente circulatorio y producen el llamado síndrome carcinoide. Estas sustancias también son las causantes de la formación de placas de fibrosis en las válvulas cardiacas, principalmente las derechas. Presentamos un caso de tumor carcinoide primario de ovario con afectación de la válvula tricúspide, que fue diagnosticado a partir de la lesión cardiaca. En la literatura están descritos casos clínicos aislados y revisiones de casos que nos pueden ayudar en el diagnóstico y en la toma de decisiones terapéuticas. Debemos conocer la existencia de estos tumores; la clínica debe alertarnos sobre su presencia. Es primordial un manejo multidisciplinar junto con endocrinólogos, cardiólogos, oncólogos, anatomo-patólogos, anestesistas, ginecólogos y cirujanos cardiacos, para ofrecer un tratamiento completo.

ABSTRACT Primary ovarian carcinoid tumor is a rare neoplasm characterized by the production of vasoactive substances that enter the bloodstream and give rise to the so-called carcinoid syndrome. These substances may also cause fibrotic plaques in the heart valves, mainly those in the right cardiac chambers. We describe the case of a primary ovarian carcinoid tumor with tricuspid valve involvement in which the diagnosis was prompted by identification of cardiac involvement. Knowledge of the clinical manifestations of neuroendocrine tumors is important in diagnosis and patient management. Recognition of typical clinical features may help suggest the correct diagnosis. Multidisciplinary discussion allows the formulation of a comprehensive management strategy involving endocrinologists, cardiologists, oncologists, pathologists, anaesthesiologists, gynaecologists and heart surgeons.

Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer.

Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization. Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples. Results: A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0-1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Toll-like receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: SFTPA1 (P = 0.023), SFTPA2 (P = 0.027), SFTPB (P = 0.02), and SFTPC (P = 0.047). Conclusions: We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

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.

Solitary Fibrous Tumor of the Vulva: Report of 2 Cases, Including a De Novo Dedifferentiated Solitary Fibrous Tumor Diagnosed After Molecular Demonstration of NAB2-STAT6 Gene Fusion.

Solitary fibrous tumor (SFT) is a neoplasm of fibroblastic lineage that has been documented in almost every anatomic location. Vulval SFT is very rare with only 10 cases reported to date. We present 2 additional SFTs located in the vulva, in adult women of 59 and 25 yr of age. The first showed a classic morphology and immunophenotype with uniform and strong STAT6 nuclear expression. The other one was a spindle-cell de novo dedifferentiated SFT with heterogeneous nuclear and cytoplasmic STAT6 staining, which could only be correctly diagnosed after molecular analysis with demonstration of a NAB2-STAT6 gene fusion. This genetic aberration is considered to represent the major pathogenic driver in SFT and is highly specific for this neoplasm. The differential diagnosis of vulval SFT is wide and varies depending on the histologic SFT subtype. Molecular analysis is mandatory for a correct diagnosis in cases without the characteristic histopathologic and immunophenotypical features.

Weight of the resected specimen after transurethral resection as a new predictive variable for recurrence of non-muscle-invasive bladder tumour.

OBJECTIVE: To evaluate the role of the weight of the resected specimen after transurethral resection as a predictive factor for recurrence and progression of non-muscle-invasive bladder tumour (NMIBT). PATIENTS AND METHODS: The weight of the resected tumour was measured consecutively in 144 subjects who underwent transurethral resection of bladder tumours at our institution. The median (interquartile range [IQR]) follow-up was 58 (61.3) months. The probability of recurrence and progression at 1 and 5 years were calculated using the currently accepted variables. Thresholds for the specimen weight were determined according to percentiles and receiver-operating characteristic curves. RESULTS: The median (IQR) weight of the specimen was 6 (16) g. Multivariate analysis showed that the weight of the resected specimen was an independent predictive risk factor for recurrence at a threshold value of 6 g with a hazard ratio of 1.7 (95% confidence interval: 1.048-2.761) P = 0.03. Progression was not associated with the weight of the resected specimen. CONCLUSIONS: The weight of the resected specimen is a new variable for predicting the risk of recurrence of NMIBT. Tumours weighing >6 g, according to the present data, have a 1.7-fold higher likelihood of recurrence than those tumours that weigh less.

Xantoma verruciforme de esófago tras radioterapia / Esophageal verruciform xanthoma following radiotherapy

Resumen El xantoma verruciforme (XV) es una lesión benigna poco frecuente y de etiología desconocida que se ha documentado solo dos veces en el esófago. Se describe a un varón de 70 años de edad que presentaba una lesión exofítica de esófago, descubierta de forma incidental durante una endoscopia 2,7 años después de recibir radioterapia por un carcinoma escamoso en la carina traqueal sin posibilidad de resección. Histológicamente, la lesión mostraba una superficie papilar, con numerosos histiocitos espumosos dentro de las papilas de la lámina propia. Las células xantomatosas resultaron positivas para vimentina y CD68 (KP1). La reacción en cadena de la polimerasa no detectó la presencia del virus del papiloma humano (VPH). Nuestros resultados indican que el XV esofágico no es una lesión inducida por el VPH, y sugieren una relación causal entre el XV y la radioterapia, como ya se ha señalado con anterioridad. Se realiza el diagnóstico diferencial histológico y se hace hincapié en la obtención de material de biopsia adecuado para llevar a cabo un diagnóstico preciso (AU)

Abstract Verruciform xanthoma (VX) is an uncommon benign lesion of unclear etiology which has only been reported twice before in the esophagus. We describe a 70-year-old male who presented an exophytic esophageal lesion incidentally found upon endoscopy 2.7 years following radiation therapy for unresectable squamous cell carcinoma of the tracheal carina. Histologically, the lesion showed a papillary surface change with numerous foamy histiocytes within the lamina propia papillae. Xanthoma cells were strongly positive for vimentin and CD68 (KP1). Polymerase chain reaction did not demonstrate human papillomavirus (HPV) infection. Our results indicate that esophageal VX is not an HPV-induced lesion and suggest a causal relationship between VX and radiotherapy, as previously noted. Histological differential diagnosis is discussed and emphasis is placed on obtaining adequate biopsy material for accurate diagnosis (AU)

Esophageal verruciform xanthoma following radiotherapy.

Verruciform xanthoma (VX) is an uncommon benign lesion of unclear etiology which has only been reported twice before in the esophagus. We describe a 70-year-old male who presented an exophytic esophageal lesion incidentally found upon endoscopy 2.7 years following radiation therapy for unresectable squamous cell carcinoma of the tracheal carina. Histologically, the lesion showed a papillary surface change with numerous foamy histiocytes within the lamina propia papillae. Xanthoma cells were strongly positive for vimentin and CD68 (KP1). Polymerase chain reaction did not demonstrate human papillomavirus (HPV) infection. Our results indicate that esophageal VX is not an HPV-induced lesion and suggest a causal relationship between VX and radiotherapy, as previously noted. Histological differential diagnosis is discussed and emphasis is placed on obtaining adequate biopsy material for accurate diagnosis.

Primary melanoma of the vagina. A clinical case.

Primary melanoma of the vagina is a rare neoplasm that appears in the 6(th) and 7(th) decades of life. It has a poor prognosis, for which there is no consensus regarding treatment; indeed, the literature describes a number of therapeutic options. This paper describes a patient with vaginal melanoma treated by local excision and immunotherapy.

Chromatic appreciation in the clinic and the laboratory.

Aesthetic requirement in dentistry is getting more and more important every day. One of its basic principles is the correct selection of colour for the restorations. Colour is a quality which is modulated by a series of factors, environmental and individual, that the clinic must know. Colour measurement by the human eye can induce to an appreciation mistake if it doesn't follow a correct protocol of light conditions and observation technique, checked by the authors, simplifying it with a practical focusing. Colour measurement instruments have appeared recently, trying to correct the problems of conventional technique.

Odontología estética: apreciacion cromática en la clínica y el laboratorio / Chromatic appreciation in the clinic and the laboratory

La demanda estética en Odontología va en aumento, una de sus bases es la correcta selección del color de las restauraciones.El color es una cualidad que se ve modulada por una serie de factores ambientales e individuales que el clínico debe conocer. La valoración ocular del color, puede inducir a error de apreciación si no se sigue un protocolo correcto de iluminación, y técnica de observación los autores lo revisan, simplificándolo con un enfoque práctico. Recientemente, han aparecido instrumentos de medición del color que intentan corregir los defectos de la técnica convencional

Aesthetic requirement in dentistry is getting more and more important every day. One of its basic principles is the correct selection of colour for the restorations. Colour is a quality which is modulated by a series of factors, environmental and individual, that the clinic must know. Colour measurement by the human eye can induce to an appreciation mistake if it doesn’t follow a correct protocol of light conditions and observation technique, checked by the authors, simplifying it with a practical focusing. Colour measurement instruments have appeared recently, trying to correct the problems of conventional technique

Curetagem pulpar em molares permanentes: avaliação clínica / Pulpar curettage in permanent molars: clinical evaluation

Diante da exposição pulpar acidental durante os procedimentos terapêuticos e frente a pulpectomia e as técnicas clássicas de proteção pulpar direta, os autores descrevem a técnica de curetagem pulpar. Mostram que esta técnica é uma alternativa aos tratamentos preconizados com oitenta e cinco por cento de sucesso